獣医学博士, 北海道大学

博士（医学）, 北海道大学

性差を理解する：生殖腺の性差構築と性特異的エピゲノム制御･維持機構の分子基盤の解明

Global Topics in Animal Science, 農学部, 2019

応用動物学各論, 農学部, 2019

応用動物学実験, 農学部, 2019

外国書講読 I, 農学部, 2019

形態機能学Ⅰ－１, 農学部, 2019

形態機能学Ⅰ－２, 農学部, 2019

形態機能学Ⅱ－１, 農学部, 2019

形態機能学Ⅱ－２, 農学部, 2019

高度教養セミナー農学部応用動物学, 農学部, 2019

高度教養セミナー農学部応用動物学入門, 農学部, 2019

高度教養セミナー農学部応用動物学入門, 農学部, 2019

資源生命科学入門Ⅰ－１, 農学部, 2019

資源生命科学入門Ⅰ－２, 農学部, 2019

実験動物の技術と応用１, 農学部, 2019

実験動物の技術と応用２, 農学部, 2019

実験動物マネジメント, 農学部, 2019

卒業研究, 農学部, 2019

課題開発演習, 大学院農学研究科, 2019

資源生命科学プレゼンテーション演習Ⅰ（オーラル・ペーパー）, 大学院農学研究科, 2019

資源生命科学プレゼンテーション演習Ⅱ（オーラル・ペーパー）, 大学院農学研究科, 2019

動物生殖生理論, 大学院農学研究科, 2019

動物分子形態学１, 大学院農学研究科, 2019

動物分子形態学２, 大学院農学研究科, 2019

特定課題演習 I-1, 大学院農学研究科, 2019

特定課題演習 I-2, 大学院農学研究科, 2019

特定課題演習 II-1, 大学院農学研究科, 2019

特定課題演習 II-2, 大学院農学研究科, 2019

環境・交通 ／ 農業

性分化

成熟

生殖腺

ネオニコチノイド系農薬

環境ホルモン

環境・農学 / 化学物質影響

Shuji Ohno, Yoshinori Ikenaka, Kanoko Onaru, Shizuka Kubo, Nanami Sakata, Tetsushi Hirano, Youhei Mantani, Toshifumi Yokoyama, Keisuke Takahashi, Keisuke Kato, Koji Arizono, Takahiro Ichise, Shouta M M Nakayama, Mayumi Ishizuka, Nobuhiko Hoshi

Neonicotinoids (NNs), a widely used class of systemic pesticides, are regarded as exhibiting selective toxicity in insects. However, NNs are suspected of exerting adverse effects on mammals as well, including humans. To date, only adult male animal models have been subjected to general toxicity studies of NNs; fetuses have yet to be considered in this context. Here, we focused on the NN clothianidin (CLO) for the first quantitative LC-MS/MS analysis of maternal-to-fetal transfer and residual property of once-daily (single or multiple days), orally administered CLO and its metabolites in mice. The results revealed the presence of CLO and its five metabolites at approximately the same respective blood levels in both dams and fetuses. In the dams, CLO showed a peak value 1 h after administration, after which levels rapidly decreased at 3 and 6 h. In the fetuses of each group, levels of CLO were almost the same as those observed in the corresponding dams. The present results clearly demonstrated rapid passage of CLO through the placental barrier. However, metabolite-dependent differences observed in blood pharmacokinetics and residual levels. This is the first quantitative demonstration of the presence of CLO and its metabolites in fetal mouse blood.

2020年04月01日, Toxicology letters, 322, 32 - 38, 英語, 国際誌

[査読有り]

研究論文（学術雑誌）

Chinatsu Hasegawa, Toshifumi Yokoyama, Yuria Umemura, Kohei Kawanishi, Yuuka Miura, Nanako Takada, Shuji Ohno, Kanoko Onaru, Takuya Omotehara, Tetsushi Hirano, Yohei Mantani, Takanori Miki, Nobuhiko Hoshi

Organ culture systems are useful for elucidating the process of testicular differentiation from mammalian undifferentiated genetically male gonads, as they permit various experiments, including experiments involving the control of gene expression. However, without addition of testicular differentiation-related factors, it is difficult to induce the formation of testis cord from immature gonads by a time point earlier 12 tail somites (ts) that corresponding to 11.0 days post coitum (dpc). In this study, we attempted to establish an organ culture system that induces testis formation from immature gonads (around 8 ts: 10.5 dpc) just before Sry (sex-determining region of the Y chromosome) expression. A paired gonad-mesonephros complex of around 8 ts was placed in the groove of an agarose gel block and put the semi-cylindrical piece of agarose gel to maintain the gonad morphology. The gonads were cultured in the gas phase for 96 hr. As a result, testis cord-like structures appeared in many genetically male gonads. Cells expressing the Sertoli cell markers Sox9 (SRY-box 9) and Amh (anti-Müllerian hormone) were observed, while granulosa cell marker Foxl2 (forkhead box L2) was not detected. In addition, Sox9- and Amh-expressing cells were observed throughout the entire gonad in many individuals. Amh mRNA expression was also upregulated. Surprisingly, formation of a partial testicular structure was observed from more immature gonads (6 ts). These results show that our gonadal organ culture system is useful for elucidating the regulation mechanism of Sry expression in undifferentiated bipotential gonads.

2020年02月21日, The Journal of veterinary medical science, 英語, 国内誌

[査読有り]

Kanoko Onaru, Shuji Ohno, Shizuka Kubo, Satoki Nakanishi, Tetsushi Hirano, Youhei Mantani, Toshifumi Yokoyama, Nobuhiko Hoshi

Neonicotinoid pesticides (NNs) act as agonists on nicotinic acetylcholine receptors (nAChRs) of insects, and there has been concern about the effects of NNs on the health of mammals. Since nAChRs are expressed in immune cells, it is possible that NNs disturb the immune system. However, few reports have examined the immunotoxicity of clothianidin (CLO), a widely-used NN. Here, we report the effects of CLO on immune organs and type IV allergic reactions in ear auricles. We orally administered CLO at 0, 30 and 300 mg/kg/day (CLO-0, 30 and 300) to Sprague-Dawley rats for 28 days. The effects were evaluated by organ and body weights, histopathology, and immunohistochemistry (TCRαβ, CD4, CD8, CD11b, CD68, CD103). In addition, some cecal contents were subjected to preliminary gut microbiota analysis, because microbiota contribute to host homeostasis, including the immunity. Our results showed loose stool, suppression of body weight gain, significant changes in organ weights (thymus: decreased; liver: increased) and changes of the gut microbiota in the CLO-300 group. There were no obvious histopathological changes in immune organs. Granulomas of the ear auricles were found in one rat of each of the CLO-30 and 300 groups, but CLO had no apparent effect on the thickness or immunohistochemistry in the ear auricles. We present new evidence that CLO affects the thymus and intestine, and might enhance the local inflammatory response. These findings should contribute to the appropriate evaluation of the safety of NNs in the future.

2020年01月27日, The Journal of veterinary medical science, 英語, 国内誌

[査読有り]

Tadashi Takada, Naoki Yoneda, Tetsushi Hirano, Kanoko Onaru, Youhei Mantani, Toshifumi Yokoyama, Hiroshi Kitagawa, Yoshiaki Tabuchi, Colins Nimako, Mayumi Ishizuka, Yoshinori Ikenaka, Nobuhiko Hoshi

Dinotefuran (DIN) belongs to the neonicotinoids (NNs), a class of globally applied pesticides originally developed to exhibit selective toxicity in insects. However, several reports have suggested that NNs also exert neurotoxic effects in mammals. We previously demonstrated neurobehavioral effects of DIN on mice under non-stressful conditions. For further toxicity assessments in the present study, we investigated the effects of DIN on mice exposed to stressful conditions. After subacutely administering a no-observed-effect-level (NOEL) dose of DIN and/or chronic unpredictable mild stress (CUMS) to mice, we conducted three behavioral tests (i.e., open field test [OFT], tail suspension test [TST] and forced swimming test [FST]). In addition, serotonin (5-HT) and tryptophan hydroxylase 2 (TPH2) of the dorsal raphe nuclei (DRN) and median raphe nuclei (MRN) and tyrosine hydroxylase (TH) of the ventral tegmental area and substantia nigra (SN) were evaluated immunohistochemically. A NOEL dose of DIN or CUMS alone increased of the total distance in OFT, decreased or increased the immobility time in TST or FST, respectively, and increased the positive intensity of 5-HT and TPH2 in the DRN/MRN, and TH in the SN. These changes were suppressed under the conditions of combined exposure to DIN and CUMS, though the blood corticosterone level was increased depending on the blood DIN values and the presence of CUMS. The present study suggests the multifaceted toxicity of the neurotoxin DIN.

2020年01月27日, The Journal of veterinary medical science, 英語, 国内誌

[査読有り]

Reiko Yasuda, Shungo Adachi, Atsuhito Okonogi, Yohei Anzai, Tadataka Kamiyama, Keiji Katano, Nobuhiko Hoshi, Katsuo Mogi, Tohru Natsume

2020年

[査読有り]

Tetsushi Hirano, Satsuki Minagawa, Yukihiro Furusawa, Tatsuya Yunoki, Yoshinori Ikenaka, Toshifumi Yokoyama, Nobuhiko Hoshi, Yoshiaki Tabuchi

Neonicotinoids are one of most widely used pesticides targeting nicotinic acetylcholine receptors (nAChRs) of insects. Recent epidemiological evidence revealed increasing amounts of neonicotinoids detected in human samples, raising the critical question of whether neonicotinoids affect human health. We investigated the effects of a neonicotinoid pesticide clothianidin (CTD) on human neuroblastoma SH-SY5Y cells as in vitro models of human neuronal cells. Cellular and functional effects of micromolar doses of CTD were evaluated by changes in cell growth, intracellular signaling activities and gene expression profiles. We examined further the effects of CTD on neuronal differentiation by measuring neurite outgrowth. Exposure to CTD (1-100 μM) significantly increased the number of cells within 24 h of culture. The nAChRs antagonists, mecamylamine and SR16584, inhibited this effect, suggesting human α3β4 nAChRs could be targets of neonicotinoids. We observed a transient intracellular calcium influx and increased phosphorylation of extracellular signal-regulated kinase 1/2 shortly after exposure to CTD. Transcriptome analysis revealed that CTD down-regulated genes involved in neuronal function (e.g., formation of filopodia and calcium ion influx) and morphology (e.g., axon guidance signaling and cytoskeleton signaling); these changes were reflected by a finding of increased neurite length during neuronal differentiation. These findings provide novel insight into the potential risks of neonicotinoids to the human nervous system.

2019年11月15日, Toxicology and applied pharmacology, 383, 114777 - 114777, 英語, 国際誌

[査読有り]

池中 良徳, 一瀬 貴大, Nimako Collins, 中山 翔太, 平野 哲史, 市川 剛, 加藤 恵介, 高橋 圭介, 長谷川 浩, 平 久美子, 有薗 幸司, 星 信彦, 藤岡 一俊, 石塚 真由美

(一社)日本毒性学会, 2019年06月, The Journal of Toxicological Sciences, 44 (Suppl.), S53 - S53, 日本語

[査読有り]

Toshifumi Yokoyama, Yuuka Miura, Anzu Yamamoto, Chinatsu Hasegawa, Kohei Kawanishi, Nanako Takada, Takuya Omotehara, Tetsushi Hirano, Yohei Mantani, Takanori Miki, Nobuhiko Hoshi

C57BL/6J-XYPOS (B6J-XYPOS) mice, which have the Y chromosome derived from Mus musculus poschiavinus on a B6J genetic background, form ovotestes or ovaries. Previously, we replaced the genetic background of B6J-XYPOS mice with B6N and found that individuals with testes also appeared in addition to those with ovaries or ovotestes. To investigate the effect of the B6J genetic sequence on the testis differentiation, the genetic background of B6N-XYPOS mice was replaced with B6J again. The recovery of the B6J genetic background significantly decreased the incidence of testes; only ovaries developed. These results indicate that the testicular differentiation process tends to be perturbed especially in the B6J substrain. This shows the importance of substrain differences in mice usually treated as B6 collectively.

2019年04月27日, The Journal of veterinary medical science, 81 (4), 608 - 611, 英語, 国内誌

[査読有り]

研究論文（学術雑誌）

池中 良徳, 平 久美子, 有薗 幸司, 星 信彦, 藤岡 一俊, 石塚 真由美, 一瀬 貴大, Collins NIMAKO, 中山 翔太, 平野 哲史, 市川 剛, 加藤 恵介, 高橋 圭介, 長谷川 浩

ネオニコチノイド（NNs）は、現在世界で最も使用されている殺虫剤の一つである。特に日本では、果物や野菜における残留基準値が諸外国と比べ高く設定され、かつ複数種が使用されるため、全体的にNNsの摂取量が多いと考えられる。

そこで本研究では、日本人におけるNNs曝露実態を明らかにする事を目的に、新生児、幼児を含む延べ数百人から尿を採取し、尿中に含まれる7種のNNs（アセタミプリド、イミダクロプリド、チアメトキサム、チアクロプリド、ニテンピラム、クロチアニジン、ジノテフラン）及び代謝物（N-デスメチルアセタミプリド）をLC/MS/MSで定量した。更に、得られた尿中データより、推定摂取量を算出し、一日摂取許容量（ADI）と比較した。

分析の結果、日本人の尿から何らかのNNsが検出され、特に、N-デスメチルアセタミプリド（90％）、クロチアニジン（50％）、ジノテフラン（50％）の検出頻度が高かった。一方、尿中濃度から推定した各NNs摂取量は、10～50 µg/dayであり、ADIに比べアセタミプリドで最大1％程度、他のNNsは1％未満であった。更に本研究では、生後48時間以内の新生児の尿も分析した。その尿中濃度は‹LOD～0.7 ng/mLと極めて低かったが、分析した57サンプルのうち14サンプルから検出された。

本研究の結果、多くの日本人は胎児を含めNNsの曝露を受けていることが明らかにされた。NNsの慢性低濃度曝露の健康影響については、胎児移行のメカニズムや神経発達を含む毒性に不明な点が多いが、最近の報告においてNNsは現在のNOAELの1/10程度の曝露でも実験動物に対し不安などの情動認知行動に影響を与える事が示されている。

NNsの毒性について、再度リスク評価を実施した上で、継続的なモニタリングを行う必要がある。

日本毒性学会, 2019年, 日本毒性学会学術年会, 46 (0), S7 - 2, 日本語

[査読有り]

Reiko Yasuda, Shungo Adachi, Atsuhito Okonogi, Youhei Anzai, Tadataka Kamiyama, Keiji Katano, Nobuhiko Hoshi, Tohru Natsume, Katsuo Mogi

2019年

[査読有り]

MANTANI YOUHEI, HARUTA TOMOHIRO, NISHIDA MIHO, YOKOYAMA TOSHIFUMI, HOSHI NOBUHIKO, KITAGAWA HIROSHI

2019年, The Journal of Veterinary Medical Science, 81 (3), 454 - 465, 英語

[査読有り]

研究論文（学術雑誌）

YUASA HIDETO, MANTANI YOUHEI, MIYAMOTO KAZUKI, NISHIDA MIHO, ARAI MASAYA, TSURUTA HIROKI, YOKOYAMA TOSHIFUMI, HOSHI NOBUHIKO, KITAGAWA HIROSHI

2019年, The Journal of Veterinary Medical Science, 81 (4), 555 - 566, 英語

[査読有り]

研究論文（学術雑誌）

Toshifumi Yokoyama, Takuya Omotehara, Tetsushi Hirano, Naoto Kubota, Shogo Yanai, Chinatsu Hasegawa, Tadashi Takada, Yohei Mantani, Nobuhiko Hoshi

Stable reference genes are important for gene expression analyses such as quantitative PCR. The stability of 15 candidate reference genes that can be used to developing mouse gonads was thoroughly verified using combinations of multiple algorithms. The expression of these genes fluctuated greatly depending on the analysis period and/or gender. Peptidylprolyl isomerase A (Ppia) and polymerase (RNA) II (DNA directed) polypeptide A (Polr2a) were the reference genes that were used stably for a wide analysis period in developing mouse gonads. Furthermore, the stable reference genes corresponding to the analysis period and/or gender were ranked. These results are useful for the selection of the optimal reference gene required for high-precision measurements.

2018年11月01日, The Journal of veterinary medical science, 80 (10), 1534 - 1539, 英語, 国内誌

[査読有り]

研究論文（学術雑誌）

Youhei Mantani, Miho Nishida, Kyouji Yamamoto, Kazuki Miyamoto, Hideto Yuasa, Natsumi Masuda, Takuya Omotehara, Hiroki Tsuruta, Toshifumi Yokoyama, Nobuhiko Hoshi, Hiroshi Kitagawa

Paneth cells secrete bactericidal substances in response to bacterial proliferation on the mucosal surface without directly contacting bacteria. However, the induction mechanism of this transient secretion has not been clarified, although nervous system and/or immunocompetent cells in the lamina propria (LP) might be involved. In this study, we ultrastructurally and immunohistochemically investigated which LP cells are localized beneath Paneth cells and examined the relationship between the Paneth cell-derived cellular processes which extended into the LP and the LP cells. The results showed that various cells-including blood capillary, subepithelial stromal cell, and nerve fiber-were present in the LP beneath Paneth cells. Endothelial cells of blood capillary were the cells most frequently found in this location; they were situated within 1 μm of the Paneth cells and possessed fenestration on the surfaces adjacent to Paneth cells. The Paneth cells rarely extended the cellular processes toward the LP across the basal lamina. Most of the cellular processes of Paneth cells contacted the subepithelial stromal cells. Immunohistochemistry revealed that the CD34+ CD31- αSMA- stromal cells preferentially localized in the LP beneath the intestinal crypt base, while PDGFRαhi αSMA+ stromal cells mainly localized around the lateral portions of the intestinal crypt and PDGFRαhi αSMA- stromal cells localized in the intestinal villus. From these findings, the existence of blood capillaries beneath Paneth cells might reflect the active exocrine function of Paneth cells. Furthermore, subepithelial stromal cells, probably with a CD34+ CD31- αSMA- PDGFRα-/lo phenotype, beneath the crypt base might affect Paneth cell activity by interacting with their cellular processes. Anat Rec, 301:1074-1085, 2018. © 2018 Wiley Periodicals, Inc.

2018年06月, Anatomical record (Hoboken, N.J. : 2007), 301 (6), 1074 - 1085, 英語, 国際誌

[査読有り]

研究論文（学術雑誌）

YAMAMOTO ANZU, OMOTEHARA TAKUYA, MIURA YUUKA, TAKADA TADASHI, YONEDA NAOKI, HIRANO TETSUSHI, MANTANI YOUHEI, KITAGAWA HIROSHI, YOKOYAMA TOSHIFUMI, HOSHI NOBUHIKO

Anti-Müllerian hormone (AMH) produced in the developing testis induces the regression of the Müllerian duct, which develops into the oviducts, uterus and upper vagina. In our true hermaphrodite mouse with an ovary on one side and a testis on the other (O/T), the oviduct and uterus are present only on the ovary side, and nothing derived from the Müllerian duct is present on the testis side. Here, we investigate the mechanism underlying the unilateral Müllerian duct regression and the mode of AMH signaling, by performing immunohistology, Western blotting, and organ culture analyses. The histological analysis revealed that during the start of the Müllerian duct regression, the duct in the O/T mice was clearly regressed on the AMH-positive testis side compared to the AMH-negative ovary side. The immunohistochemistry showed a diffuse immunoreaction of AMH in the interstitium surrounding the testis cord and boundary region between the testis and mesonephros, especially in the cranial portion. Western blotting revealed that the amount of AMH in the cranial half of the mesonephros was larger than that in the caudal half. AMH injected into the gonads in organ culture induced the regression of the Müllerian duct via the interstitium of the organ. These results suggest that AMH acts on the Müllerian duct in male mice by exuding into the interstitium surrounding the testis cord and infiltrating through the cranial region from the testis to the mesonephros.

2018年04月18日, The Journal of Veterinary Medical Science, 80 (4), 557 - 567, 英語, 国内誌

[査読有り]

研究論文（学術雑誌）

Tadashi Takada, Naoki Yoneda, Tetsushi Hirano, Shogo Yanai, Anzu Yamamoto, Youhei Mantani, Toshifumi Yokoyama, Hiroshi Kitagawa, Yoshiaki Tabuchi, Nobuhiko Hoshi

It has been suggested that an increase in the use of pesticides affects neurodevelopment, but there has been no animal experiment showing a causal relation between neonicotinoid pesticides (NNs) and depression. We examined whether dinotefuran (DIN), the most widely used NN in Japan, induces depression. Male mice were administered DIN between 3 and 8 weeks of age, referring to the no-observed-effect level (NOEL). The mice were then subjected to a tail suspension test (TST) and a forced swimming test (FST). After these tests, their brains were dissected for immunohistochemical analyses of serotonin (5-HT). Antidepressant activity in TST and no decrease in 5-HT-positive cells were observed. The subchronic exposure to DIN alone in juvenile male mice may not cause depression-like indication.

Japanese Society of Veterinary Science, 2018年04月01日, Journal of Veterinary Medical Science, 80 (4), 720 - 724, 英語

[査読有り]

研究論文（学術雑誌）

Naoki Yoneda, Tadashi Takada, Tetsushi Hirano, Shogo Yanai, Anzu Yamamoto, Youhei Mantani, Toshifumi Yokoyama, Hiroshi Kitagawa, Yoshiaki Tabuchi, Nobuhiko Hoshi

Although neonicotinoid pesticides are expected to have harmful influence on mammals, there is little animal experimental data to support the effect and mechanisms. Since acetylcholine causes the release of dopamine, neonicotinoids may confer a risk of developmental disorders via a disturbance in the monoamine systems. Male mice were peripubertally administered dinotefuran (DIN) referring to no observed effect level (NOEL) and performed behavioral and immunohistological analyses. In an open field test, the total locomotor activity was increased in a dose-dependent manner. The immunoreactivity of tyrosine hydroxylase in the substantia nigra was increased in DIN-exposed mice. These results suggest that exposure to DIN in peripubertal male mice causes hyperactivity and a disturbance of dopaminergic signaling.

Japanese Society of Veterinary Science, 2018年04月01日, Journal of Veterinary Medical Science, 80 (4), 634 - 637, 英語

[査読有り]

研究論文（学術雑誌）

Natsumi Masuda, Youhei Mantani, Chiaki Yoshitomi, Hideto Yuasa, Miho Nishida, Masaya Arai, Junichi Kawano, Toshifumi Yokoyama, Nobuhiko Hoshi, Hiroshi Kitagawa

The host defense system with lysozyme and secretory phospholipase A2 (sPLA2) was immunohistochemically investigated in rat respiratory tract under healthy conditions. In the nasal epithelium, a large number of non-ciliated and non-microvillous cells (NC) and a small number of goblet cells (GC) were immunopositive for lysozyme and sPLA2. A few acinar cells and almost all epithelial cells of intercalated ducts were immunopositive for both bactericidal substances in the nasal glands. In the laryngeal and tracheal epithelia, few NC and GC were immunopositive for both bactericidal substances. In the laryngeal and tracheal glands, a few acinar cells and most ductal epithelial cells were immunopositive for both bactericidal substances. In extra-pulmonary bronchus, small numbers of NC and GC were immunopositive for lysozyme and sPLA2, whereas few NC and no GC were immunopositive in the intra-pulmonary bronchus. No secretory source of either bactericidal substance was located in the bronchioles. In the alveolus, many glandular epithelial cells and alveolar macrophages were immunopositive for lysozyme but immunonegative for sPLA2. Moreover, lysozyme and sPLA2 were detected in the mucus layer and in the periciliary layer from the nose to the extra-pulmonary bronchus. These findings suggest that secretory sources of lysozyme and sPLA2 are distributed in almost all the respiratory tract. Their secretory products are probably transported to the pharynx and contribute to form the first line of defense against inhaled bacteria throughout the respiratory tract.

Japanese Society of Veterinary Science, 2018年02月01日, Journal of Veterinary Medical Science, 80 (2), 323 - 332, 英語

[査読有り]

研究論文（学術雑誌）

Naoto Kubota, Toshifumi Yokoyama, Nobuhiko Hoshi, Mikita Suyama

Cerebral palsy (CP) is a major neuronal disease and the most common movement disorder in children. Although environmental factors leading to CP have been greatly investigated, the genetic mechanism underlying CP is not well understood. Here we focused on two clinical reports that characterized a deletion involving the KANK1 gene locus in the 9p24.3 region. One report shows spastic CP and the other shows no spastic CP phenotype. Based on the epigenetic status and evolutionary conservation, we first found a functional genomic element at the noncoding region that was deleted only in patients with spastic CP. This element contains the retinoic acid receptor/retinoid X receptor (RAR/RXR) complex-binding motif that is widely conserved among placental mammals. RAR/RXR ChIP-seq data from mouse F9 embryonal carcinoma cells that were treated with trans-retinoic acids showed that the element has a binding ability. In addition, data regarding chromosome conformation capture from mouse neural progenitor and ES cells suggested that the element spatially interacts with the Doublesex and mab-3 related transcription factor 3 (Dmrt3) gene promoter that is located approximately 120 kb downstream of the RAR/RXR-binding site. Dmrt3 is detected in the developing mouse forebrain and in some interneurons in the spinal cord, and it works as a locomotion coordinator in horses and mice. Thus, the deletion of the cis-regulatory element for DMRT3 in humans may cause impaired development of the forebrain and gait abnormalities, resulting in spastic CP. In conclusion, this study provides new mechanistic insights into the genetic basis of CP.

Elsevier B.V., 2018年01月29日, Biochemical and Biophysical Research Communications, 496 (1), 133 - 139, 英語

[査読有り]

研究論文（学術雑誌）

Tetsushi Hirano, Shogo Yanai, Tadashi Takada, Naoki Yoneda, Takuya Omotehara, Naoto Kubota, Kiichi Minami, Anzu Yamamoto, Youhei Mantani, Toshifumi Yokoyama, Hiroshi Kitagawa, Nobuhiko Hoshi

Neonicotinoids are novel systemic pesticides acting as agonists on the nicotinic acetylcholine receptors (nAChRs) of insects. Experimental studies have revealed that neonicotinoids pose potential risks for the nervous systems of non-target species, but the brain regions responsible for their behavioral effects remain incompletely understood. This study aimed to assess the neurobehavioral effects of clothianidin (CTD), a later neonicotinoid developed in 2001 and widely used worldwide, and to explore the target regions of neonicotinoids in the mammalian brain. A single-administration of 5 or 50 mg/kg CTD to male C57BL/6N mice at or below the no-observed-adverse-effect level (NOAEL) induced an acute increase in anxiety during the elevated plus-maze test. In addition, mice in the CTD-administered group spontaneously emitted human-audible vocalizations (4-16 kHz), which are behavioral signs of aversive emotions, and showed increased numbers of c-fos immunoreactive cells in the paraventricular thalamic nucleus and dentate gyrus of the hippocampus. In conclusion, mice exposed to NOAEL-dose CTD would be rendered vulnerable to a novel environment via the activation of thalamic and hippocampal regions related to stress responses. These findings should provide critical insight into the neurobehavioral effects of neonicotinoids on mammals.

ELSEVIER IRELAND LTD, 2018年01月, TOXICOLOGY LETTERS, 282, 57 - 63, 英語

[査読有り]

研究論文（学術雑誌）

MASUDA NATSUMI, MANTANI YOUHEI, YUASA HIDETO, YOSHITOMI CHIAKI, ARAI MASAYA, NISHIDA MIHO, Qi WANG-MEI, KAWANO JUNICHI, YOKOYAMA TOSHIFUMI, HOSHI NOBUHIKO, KITAGAWA HIROSHI

The distributions of β-defensin 1 and 2 in secretory host defense system throughout respiratory tract of healthy rats were immunohistochemically investigated. In the nasal epithelium, a large number of non-ciliated and non-microvillous cells (NCs) were immunopositive for both β-defensin 1 and 2, whereas a small number of goblet cells (GCs) were immunopositive only for β-defensin 1. Beta-defensin 2-immunopositive GCs were few. In the nasal glands, a small number of acinar cells and a large number of ductal epithelial cells were immunopositive for both β-defensins. In the laryngeal and tracheal epithelia, a very few NCs and GCs were immunopositive for both β-defensins. In laryngeal and tracheal glands, a very few acinar cells and a large number of ductal epithelial cells were immunopositive for both β-defensins. In the extra-pulmonary bronchus, a small number of NCs were immunopositive for both β-defensins. A small number of GCs were immunopositive for β-defensin 1, whereas few GCs were immunopositive for β-defensin 2. From the intra-pulmonary bronchus to alveoli, a very few or no epithelial cells were immunopositive for both β-defensins. In the mucus and periciliary layers, β-defensin 1 was detected from the nose to the extra-pulmonary bronchus, whereas β-defensin 2 was weakly detected only in the nose and the larynx. These findings suggest that the secretory sources of β-defensin 1 and 2 are mainly distributed in the nasal mucosa and gradually decrease toward the caudal airway in healthy rats.

Japanese Society of Veterinary Science, 2018年, The Journal of Veterinary Medical Science, 80 (3), 395 - 404, 英語

[査読有り]

研究論文（学術雑誌）

YUASA HIDETO, MANTANI YOUHEI, MASUDA NATSUMI, NISHIDA MIHO, ARAI MASAYA, YOKOYAMA TOSHIFUMI, TSURUTA HIROKI, HOSHI NOBUHIKO, KITAGAWA HIROSHI

The mechanism by which indigenous bacteria on the follicle-associated epithelium (FAE) of lymphatic follicles (LFs) accelerate the differentiation of microvillous columnar epithelial cells (MV) into M-cells was immunohistochemically investigated in rat Peyer's patches. The results showed that the number of Toll-like receptor (TLR) -4(+) M-cells was greater in the FAE with expansion of bacterial colonies (LFs with bacterial colonies on the FAE: b-LF) than the FAE without expansion of bacterial colonies (nb-LF). TLR-4 was also expressed in the striated borders of MV upstream next to M-cells in the FAE of the b-LF. TLR-4(+) vesicles were frequently detected in the cytoplasms of MV with TLR-4(+) striated borders upstream next to TLR-4(+) M-cells in the FAE of b-LF. These findings suggest that TLR-4(+) MV take up TLR-4 ligands and differentiate into M-cells in the b-LF. Neither the distribution of RANK nor that of RANKL was coincident with that of M-cells in the b-LF. Moreover, RANK, but not RANKL, was expressed in intestinal villi, whereas cleaved caspase-3 was immunonegative in the MV and M-cells of the FAE, unlike in villous epithelial cells. Therefore, RANK/RANKL signaling in the LF might contribute to the down-regulation of epithelial apoptosis to facilitate the differentiation of MV into M-cells in rat Peyer's patches.

JAPAN SOC VET SCI, 2017年11月, The Journal of Veterinary Medical Science, 79 (11), 1826 - 1835, 英語

[査読有り]

研究論文（学術雑誌）

Shogo Yanai, Tetsushi Hirano, Takuya Omotehara, Tadashi Takada, Naoki Yoneda, Naoto Kubota, Anzu Yamamoto, Youhei Mantani, Toshifumi Yokoyama, Hiroshi Kitagawa, Nobuhiko Hoshi

Neonicotinoids are pesticides used worldwide. They bind to insect nicotinic acetylcholine receptors (nAChRs) with high affinity. We previously reported that clothianidin (CTD), one of the latest neonicotinoids, reduced antioxidant expression and induced germ cell death in the adult testis of vertebrates. Here, we investigated the male reproductive toxicity of prenatal and early postnatal exposure to CTD, because it is likely that developmental exposure more severely affects the testis compared to adults due to the absence of the blood-testis barrier. Pregnant C57BL/6 mice were given water gel blended with CTD (0, 10 or 50 mg/kg/day; noobserved- adverse-effect-level [NOAEL for mice]: 47.2 mg/kg/day) between gestational day 1 and 14 days post-partum. We then examined the testes of male offspring at postnatal day 14. The testis weights and the numbers of germ cells per seminiferous tubule were decreased in the CTD-50 group, and abnormal tubules containing no germ cells appeared. Nevertheless, the apoptotic cell number and proliferative activity were not significantly different between the control and CTD-exposed groups. There were no significant differences in the androgen-related parameters, such as the Leydig cell volume per testis, the Sertoli cell number and the tubule diameter. The present study is the first demonstration that in utero and lactational exposures to CTD at around the NOAEL for mice reduce the germ cell number, but our findings suggest that these exposures do not affect steroidogenesis in Leydig cells during prenatal or early postnatal life.

JAPAN SOC VET SCI, 2017年07月, JOURNAL OF VETERINARY MEDICAL SCIENCE, 79 (7), 1196 - 1203, 英語

[査読有り]

研究論文（学術雑誌）

Takuya Omotehara, Kiichi Minami, Youhei Mantani, Yuria Umemura, Miho Nishida, Tetsushi Hirano, Hidefumi Yoshioka, Hiroshi Kitagawa, Toshifumi Yokoyama, Nobuhiko Hoshi

Background: The left male gonad in the chicken embryo has a thickened cortical layer, but it eventually becomes flattened after the onset of testicular development. Because the destination of the cortical cells migrating from the left gonad remains unclear, we examined this issue herein. Results: The testis-inducing gene doublesex-and mab-3-related transcription factor 1 (DMRT1) was detected in a proportion of the columnar and cubic epithelial cells in the cortex of the left testis as well as Sertoli cells in both testes. Interestingly, some of the DMRT1-expressing cortical cells were contiguous with Sertoli cells in the testis cord. Some cortical cells exhibited a vimentin-positive cytoplasm that was elongated all the way to the medulla. In addition, a desmosome-like structure was observed between the elongated cytoplasm in these cells and the adjacent Sertoli cell. After the organ culture, a few cells labeled with a fluorescent dye that stained only the cortical cells at the beginning of the culture were located in the testis cord of the left testis. Conclusions: Some cortical cells expressing DMRT1 were suggested to contribute to the Sertoli cells in the testis cord only after the onset of testicular development and only in the left testis. (C) 2016 Wiley Periodicals, Inc.

WILEY, 2017年02月, DEVELOPMENTAL DYNAMICS, 246 (2), 148 - 156, 英語

[査読有り]

研究論文（学術雑誌）

平野 哲史, 柳井 翔吾, 高田 匡, 米田 直起, 表原 拓也, 久保田 直人, 南 貴一, 万谷 洋平, 横山 俊史, 北川 浩, 星 信彦

環境ホルモン学会(日本内分泌撹乱化学物質学会), 2016年12月, 環境ホルモン学会研究発表会要旨集, 19回, 63 - 63, 日本語

[査読有り]

柳井 翔吾, 平野 哲史, 表原 拓也, 高田 匡, 米田 直起, 岩本 遥, 万谷 洋平, 横山 俊史, 北川 浩, 星 信彦

環境ホルモン学会(日本内分泌撹乱化学物質学会), 2016年12月, 環境ホルモン学会研究発表会要旨集, 19回, 67 - 67, 日本語

[査読有り]

米田 直起, 平野 哲史, 柳井 翔吾, 高田 匡, 岩本 遥, 表原 拓也, 片田 裕亮, 万谷 洋平, 横山 俊史, 北川 浩, 星 信彦

環境ホルモン学会(日本内分泌撹乱化学物質学会), 2016年12月, 環境ホルモン学会研究発表会要旨集, 19回, 101 - 101, 日本語

[査読有り]

高田 匡, 平野 哲史, 柳井 翔吾, 米田 直起, 岩本 遥, 表原 拓也, 万谷 洋平, 横山 俊史, 北川 浩, 星 信彦

環境ホルモン学会(日本内分泌撹乱化学物質学会), 2016年12月, 環境ホルモン学会研究発表会要旨集, 19回, 102 - 102, 日本語

[査読有り]

Hideto Yuasa, Youhei Mantani, Natsumi Masuda, Miho Nishida, Junichi Kawano, Toshifumi Yokoyama, Nobuhiko Hoshi, Hiroshi Kitagawa

The expressions of Toll-like receptor (TLR) -2, -4 and -9 were immunohistochemically investigated in the follicle-associated epithelium (FAE), and epithelia of the follicle-associated intestinal villus (FAIV) and ordinary intestinal villus (IV) in rat Peyer's patch regions with no bacterial colonies on the mucous membranes. TLR-2 was expressed in the striated borders of microvillous columnar epithelial cells (MV) in both FAIV and IV except in the apices. However, TLR-2 expression in the striated borders was weaker in the epithelium of the follicular side of FAIV (f-FAIV) than in epithelia of IV and the anti-follicular side of FAIV. TLR-4 and-9 were not expressed in the FAIV and IV. In the FAE, TLR-2,-4 and-9 were not expressed in the striated borders of MV, but the roofs of some typical M-cells were immunopositive for all TLRs. Especially, no TLR-positive MV were found at the FAE sites where M-cells appeared most frequently. In the follicle-associated intestinal crypt (FAIC), immunopositivity for all TLRs was observed in the striated borders of MV and the luminal substances. In conclusion, the lower levels of TLR-2 in both FAE and the epithelium of f-FAIV probably reduce recognition of indigenous bacteria. TLR-2,-4 and-9 appear not to participate directly in differentiation of MV into M-cells, because TLRs were not expressed in any MV in the upstream region of M-cells in FAE with no settlement of indigenous bacteria in the rat Peyer's patches.

JAPAN SOC VET SCI, 2016年12月, JOURNAL OF VETERINARY MEDICAL SCIENCE, 78 (12), 1797 - 1804, 英語

[査読有り]

研究論文（学術雑誌）

梅村 ゆりあ, 横山 俊史, 田渕 圭章, 南 貴一, 表原 拓也, 久保田 直人, 山本 杏, 広川 千英, 平野 哲史, 柳井 翔吾, 米田 直起, 高田 匡, 万谷 洋平, 北川 浩, 星 信彦

(公社)日本獣医学会, 2016年08月, 日本獣医学会学術集会講演要旨集, 159回, 312 - 312, 日本語

[査読有り]

山本 杏, 表原 拓也, 久保田 直人, 南 貴一, 広川 千英, 平野 哲史, 磯江 美智子, 柳井 翔吾, 高田 匡, 米田 直起, 三浦 由佳, 岩本 遥, 万谷 洋平, 北川 浩, 横山 俊史, 星 信彦

(公社)日本獣医学会, 2016年08月, 日本獣医学会学術集会講演要旨集, 159回, 312 - 312, 日本語

[査読有り]

平野 哲史, 柳井 翔吾, 高田 匡, 米田 直起, 表原 拓也, 久保田 直人, 南 貴一, 山本 杏, 岩本 遥, 三浦 由佳, 磯江 美智子, 万谷 洋平, 横山 俊史, 北川 浩, 星 信彦

(公社)日本獣医学会, 2016年08月, 日本獣医学会学術集会講演要旨集, 159回, 314 - 314, 日本語

[査読有り]

米田 直起, 平野 哲史, 柳井 翔吾, 高田 匡, 表原 拓也, 久保田 直人, 南 貴一, 山本 杏, 岩本 遥, 三浦 由佳, 磯江 美智子, 万谷 洋平, 横山 俊史, 北川 浩, 星 信彦

(公社)日本獣医学会, 2016年08月, 日本獣医学会学術集会講演要旨集, 159回, 315 - 315, 日本語

[査読有り]

高田 匡, 平野 哲史, 柳井 翔吾, 米田 直起, 表原 拓也, 久保田 直人, 南 貴一, 山本 杏, 岩本 遥, 三浦 由佳, 磯江 美智子, 万谷 洋平, 横山 俊史, 北川 浩, 星 信彦

(公社)日本獣医学会, 2016年08月, 日本獣医学会学術集会講演要旨集, 159回, 315 - 315, 日本語

[査読有り]

平野 哲史, 柳井 翔吾, 高田 匡, 米田 直起, 表原 拓也, 久保田 直人, 南 貴一, 広川 千英, 山本 杏, 万谷 洋平, 横山 俊史, 北川 浩, 星 信彦

(一社)日本毒性学会, 2016年06月, The Journal of Toxicological Sciences, 41 (Suppl.), S339 - S339, 日本語

[査読有り]

Hiroko Ishiniwa, Kazuhiro Sogawa, Ken-Ichi Yasumoto, Nobuhiko Hoshi, Tsuneo Sekijima

Tohoku University, 2016年, Japanese Journal of Ecology, 66 (1), 69 - 79, 日本語

[査読有り]

研究論文（学術雑誌）

平野 哲史, 万谷 洋平, 横山 俊史, 北川 浩, 星 信彦, 柳井 翔吾, 高田 匡, 米田 直起, 表原 拓也, 久保田 直人, 南 貴一, 広川 千英, 山本 杏

【背景】ネオニコチノイドは1990年代に昆虫型ニコチン性アセチルコリン受容体（nAChRs）を標的として開発された農薬成分である．しかし近年，ネオニコチノイドは哺乳類型nAChRsを介して神経細胞に興奮反応を引き起こすことが示され，昆虫以外の生物に対して不測の影響を与える可能性が懸念されている．我々はこれまでに成熟雄マウスをネオニコチノイドの1種，クロチアニジン（CTD）に4週間曝露すると，新規環境（オープンフィールド）における不安様行動が引き起こされ，その影響は環境ストレス下においてより顕在化することを報告してきた．本研究では，ネオニコチノイドによる行動影響発現に関与する脳領域を明らかにすることを目的とした．
【材料と方法】C57BL/6成熟雄マウスに5または50 mg/kgの CTDを単回経口投与し，投与1時間後に高架式十字迷路試験による行動解析を行った．さらに2時間後に脳を摘出し，c-fos発現を指標とした組織学的解析により投与後誘導された神経活動を評価した．
【結果と考察】行動解析の結果，CTD 5 mg/kg投与群においては溶媒投与対照群と比較してOpen arm滞在時間および侵入回数の減少がみられた．CTD 50 mg/kg投与群においては，さらに総移動距離の減少ならびに迷路探索時における異常啼鳴（Abnormal vocalization）およびすくみ行動（Freezing）が観察された．組織学的解析の結果，情動およびストレス反応に関与する視床下部，海馬においてc-fos陽性細胞数の増加がみられた．
以上の結果から，CTD投与下においては，新規環境ストレスに曝露された際にコリン作動性神経投射を受ける視床下部や海馬における過剰な神経興奮が生じ，不安様行動やストレス応答を濃度依存的に誘発する可能性が示唆された．

日本毒性学会, 2016年, 日本毒性学会学術年会, 43 (0), P - 252, 日本語

[査読有り]

石庭寛子, 十川和博, 安元研一, 星 信彦, 関島恒夫

2016年, 日本生態学会誌, 66 (1), 69 - 79, 日本語

[査読有り]

研究論文（学術雑誌）

柳井 翔吾, 平野 哲史, 表原 拓也, 高田 匡, 米田 直起, 梅村 ゆりあ, 久保田 直人, 南 貴一, 広川 千英, 山本 杏, 万谷 洋平, 横山 俊史, 北川 浩, 星 信彦

環境ホルモン学会(日本内分泌撹乱化学物質学会), 2015年12月, 環境ホルモン学会研究発表会要旨集, 18回, 109 - 109, 日本語

[査読有り]

平野 哲史, 柳井 翔吾, 表原 拓也, 高田 匡, 米田 直起, 梅村 ゆりあ, 久保田 直人, 南 貴一, 広川 千英, 山本 杏, 万谷 洋平, 横山 俊史, 北川 浩, 星 信彦

環境ホルモン学会(日本内分泌撹乱化学物質学会), 2015年12月, 環境ホルモン学会研究発表会要旨集, 18回, 118 - 118, 日本語

[査読有り]

表原 拓也, 万谷 洋平, 南 貴一, 梅村 ゆりあ, 平野 哲史, 横山 俊史, 北川 浩, 星 信彦

(公社)日本生化学会, 2015年12月, 日本生化学会大会・日本分子生物学会年会合同大会講演要旨集, 88回・38回, [2P0993] - [2P0993], 日本語

[査読有り]

Yuria Umemura, Ryosuke Miyamoto, Rie Hashimoto, Kyoko Kinoshita, Takuya Omotehara, Daichi Nagahara, Tetsushi Hirano, Naoto Kubota, Kiichi Minami, Shogo Yanai, Natsumi Masuda, Hideto Yuasa, Youhei Mantani, Eiko Matsuo, Toshifumi Yokoyama, Hiroshi Kitagawa, Nobuhiko Hoshi

Mammalian sexual fate is determined by the presence or absence of sex determining region of the Y chromosome (Sly) in the "bipotential" gonads. Recent studies have demonstrated that both male and female sexual development are induced by distinct and active genetic pathways. Breeding the Y chromosome from Mus m. domesticus poschiavinus (POS) strains into C57BL/6J (B6J) mice (B6J-XYPOS) has been shown to induce sex reversal (75%: bilateral ovary, 25%: true hermaphrodites). However, our B6N-XYPOS mice, which were generated by backcrossing of B6J-XYPOS on an inbred B6N-XX, develop as males (36%: bilateral testis with fertility as well as bilateral ovary (34%), and the remainder develop as true hermaphrodites. Here, we investigated in detail the expressions of essential sex-related genes and histological features in B6N-XYPOS mice from the fetal period to adulthood. The onsets of both Sry and SRY-box 9 (Sox9) expressions as determined spatiotemporally by whole-mount immunohistochemistry in the B6N-XYPOS gonads occurred 2-3 tail somites later than those in B6N-XYB6 gonads, but earlier than those in B6J-XYPOS, respectively. It is possible that such a small difference in timing of the Sry expression underlies testicular development in our B6N-XYPOS. Our study is the first to histologically show the expression and ectopic localization of a female-related gene in the XYPOS testes and a male -related gene in the XYPOS ovaries. The results from these and previous experiments indicate that the interplay between genome variants, epigenetics and developmental gene regulation is crucial for testis development.

JAPAN SOC VET SCI, 2015年12月, JOURNAL OF VETERINARY MEDICAL SCIENCE, 77 (12), 1587 - 1597, 英語

[査読有り]

研究論文（学術雑誌）

Yoshihiro Kobayashi, Tetsushi Hirano, Takuya Omotehara, Rie Hashimoto, Yuria Umemura, Hideto Yuasa, Natsumi Masuda, Naoto Kubota, Kiichi Minami, Shogo Yanai, Mitsuko Ishihara-Sugano, Youhei Mantani, Toshifumi Yokoyama, Hiroshi Kitagawa, Nobuhiko Hoshi

Dioxins are widespread persistent environmental contaminants with adverse impacts on humans and experimental animals. Behavioral and cognitive functions are impaired by 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) exposure. TCDD exerts its toxicity via the aryl hydrocarbon receptor (AhR), a ligand-activated transcription factor. The hippocampus, which plays important roles in episodic memory and spatial function, is considered vulnerable to TCDD-induced neurotoxicity, because it contains the AhR. We herein investigated the effects of TCDD toxicity on hippocampal development in embryonic mice. TCDD was administered to dams at 8.5 days postcoitum with a single dose of 20, 200, 2,000 and 5,000 ng/kg body weight (groups T20, T200, T2000 and T5000, respectively), and the brains were dissected from their pups at embryonic day 18.5. Immunohistochemical analysis demonstrated that the Glial Fibrillary Acidic Protein (GFAP) immunoreactivities in the dentate gyrus (DG) were reduced in the T5000 group. Granular GFAP immunoreactivity was observed in the hippocampal fimbria, and the number of immunoreactive fimbria was significantly decreased in the T5000 group. The number of Proliferating Cell Nuclear Antigen (PCNA)-positive cells was decreased in all TCDD-exposed groups and significantly reduced in the T20, T200 and T5000 groups. Together, these results demonstrate that maternal TCDD exposure has adverse impacts on neural stem cells (NSCs), neural precursor cells (NPCs) and granular cells in the DG and disrupts the NSC maintenance and timing of differentiation in the hippocampal fimbria, which in turn interrupt neuronal development in future generations of mice.

JAPAN SOC VET SCI, 2015年11月, JOURNAL OF VETERINARY MEDICAL SCIENCE, 77 (11), 1355 - 1361, 英語

[査読有り]

研究論文（学術雑誌）

Tetsushi Hirano, Shogo Yanai, Takuya Omotehara, Rie Hashimoto, Yuria Umemura, Naoto Kubota, Kiichi Minami, Daichi Nagahara, Eiko Matsuo, Yoshiko Aihara, Ryota Shinohara, Tomoyuki Furuyashiki, Youhei Mantani, Toshifumi Yokoyama, Hiroshi Kitagawa, Nobuhiko Hoshi

Neonicotinoids, some of the most widely used pesticides in the world, act as agonists to the nicotinic acetylcholine receptors (nAChRs) of insects, resulting in death from abnormal excitability. Neonicotinoids unexpectedly became a major topic as a compelling cause of honeybee colony collapse disorder, which is damaging crop production that requires pollination worldwide. Mammal nAChRs appear to have a certain affinity for neonicotinoids with lower levels than those of insects; there is thus rising concern about unpredictable adverse effects of neonicotinoids on vertebrates. We hypothesized that the effects of neonicotinoids would be enhanced under a chronic stressed condition, which is known to alter the expression of targets of neonicotinoids, i.e., neuronal nAChRs. We performed immunohistochemical and behavioral analyses in male mice actively administered a neonicotinoid, clothianidin (CTD; 0, 10, 50 and 250 mg/kg/day), for 4 weeks under an unpredictable chronic stress procedure. Vacuolated seminiferous epithelia and a decrease in the immunoreactivity of the antioxidant enzyme glutathione peroxidase 4 were observed in the testes of the CTD+stress mice. In an open field test, although the locomotor activities were not affected, the anxiety-like behaviors of the mice were elevated by both CTD and stress. The present study demonstrates that the behavioral and reproductive effects of CTD become more serious in combination with environmental stress, which may reflect our actual situation of multiple exposure.

JAPAN SOC VET SCI, 2015年10月, JOURNAL OF VETERINARY MEDICAL SCIENCE, 77 (10), 1207 - 1215, 英語

[査読有り]

研究論文（学術雑誌）

Youhei Mantani, Eri Ito, Miho Nishida, Hideto Yuasa, Natsumi Masuda, Wang-Mei Qi, Junichi Kawano, Toshifumi Yokoyama, Nobuhiko Hoshi, Hiroshi Kitagawa

Indigenous bacteria in the alimentary tract are exposed to various bactericidal peptides and digestive enzymes, but the viability status and morphological changes of indigenous bacteria are unclear. Therefore, the present study aimed to ultrastructurally clarify the degeneration and viability status of indigenous bacteria in the rat intestine. The majority of indigenous bacteria in the ileal mucous layer possessed intact cytoplasm, but the cytoplasm of a few bacteria contained vacuoles. The vacuoles were more frequently found in bacteria of ileal chyme than in those of ileal mucous layer and were found in a large majority of bacteria in both the mucous layer and chyme throughout the large intestine. In the dividing bacteria of the mucous layer and chyme throughout the intestine, the ratio of area occupied by vacuoles was almost always less than 10%. Lysis or detachment of the cell wall in the indigenous bacteria was more frequently found in the large intestine than in the ileum, whereas bacterial remnants, such as cell walls, were distributed almost evenly throughout the intestine. In an experimental control of long-time-cultured Staphylococcus epidermidis on agar, similar vacuoles were also found, but cell-wall degeneration was never observed. From these findings, indigenous bacteria in the mucous layer were ultrastructurally confirmed to be the source of indigenous bacteria in the chyme. Furthermore, the results suggested that indigenous bacteria were more severely degenerated toward the large intestine and were probably degraded in the intestine.

JAPAN SOC VET SCI, 2015年09月, JOURNAL OF VETERINARY MEDICAL SCIENCE, 77 (9), 1121 - 1128, 英語

[査読有り]

研究論文（学術雑誌）

平野 哲史, 柳井 翔吾, 表原 拓也, 梅村 ゆりあ, 久保田 直人, 南 貴一, 高田 匡, 米田 直起, 広川 千英, 山本 杏, 万谷 洋平, 横山 俊史, 北川 浩, 星 信彦

(公社)日本獣医学会, 2015年08月, 日本獣医学会学術集会講演要旨集, 158回, 280 - 280, 日本語

[査読有り]

Ei-ichirou Takahara, Hideto Yuasa, Miho Nishida, Youhei Mantani, Kankanam Gamage Sanath Udayanga, Wang-Mei Qi, Takashi Takeuchi, Toshifumi Yokoyama, Nobuhiko Hoshi, Hiroshi Kitagawa

A portion of the minute chylomicrons less than 75 nm in diameter are transcytosed from the extravascular tissue into the subepithelial blood capillaries (sBC) in the villous apices of the rat jejunum. However, the details of the transportation mechanism have not been clarified. In this study, the endothelial receptor involved in the transportation of minute chylomicrons into the sBC's lumina was immunohistochemically and histoplanimetrically examined in intestinal villi of the rat jejunum. Immunopositivity for very low density lipoprotein (VLDL) receptor was detected on the luminal and basal surfaces of the endothelial cells of sBC in approximately 68% of those apices of jejunal villi that possessed numerous chylomicrons in the lamina propria, while VLDL receptor was detected on the endothelial cells of sBC in only approximately 8% of intestinal villi that possessed few or no chylomicrons in the lamina propria. No immunopositivity for VLDL receptor was detected in the sBC of all intestinal villi. These findings suggest that VLDL receptor is expressed by the endothelial cells of the sBC in conjunction with the filling of the lamina propria of jejunal villi with many chylomicrons produced by the villous columnar epithelial cells and that the VLDL receptor mediates the transportation of minute chylomicrons, maybe VLDL, into the subepithelial portal blood from the extravascular tissue of the rat jejunal villi.

JAPAN SOC VET SCI, 2015年04月, JOURNAL OF VETERINARY MEDICAL SCIENCE, 77 (4), 387 - 393, 英語

[査読有り]

研究論文（学術雑誌）

平野 哲史, 柳井 翔吾, 表原 拓也, 橋本 理恵, 梅村 ゆりあ, 久保田 直人, 南 貴一, 万谷 洋平, 横山 俊史, 北川 浩, 星 信彦

環境ホルモン学会(日本内分泌撹乱化学物質学会), 2014年12月, 環境ホルモン学会研究発表会要旨集, 17回, 132 - 132, 日本語

[査読有り]

Katsuhiko Warita, Tomoko Mitsuhashi, Nobuhiko Hoshi, Ken-Ichi Ohta, Shingo Suzuki, Yoshiki Takeuchi, Takanori Miki

We investigated the toxicity of bisphenol A (BPA) by determining the gene expression of nerve growth factor (Ngf) in the embryonic mouse cell line mHypoE-N44 derived from the hypothalamus exposed to BPA dose range between 0.02 and 200 μmol L-1 for 3 h. Ngf mRNA levels decreased in a dose-dependent manner, with significant reductions observed in the 2 to 50 μmol L-1 BPA treatment groups compared to controls. However, at 100 to 200 μmol L-1 the Ngf mRNA gradually increased and was significantly higher than control, while the expression of the apoptosis-related genes Caspase 3 and transformation-related protein 73 decreased significantly. These results suggest that in an embryonic hypothalamic cell line the higher doses of BPA induce a unique pattern of Ngf gene expression and that BPA has the potential to suppress apoptosis essential for early-stage brain development.

Institute for Medical Research and Occupational Health, 2014年09月01日, Arhiv za Higijenu Rada i Toksikologiju, 65 (3), 293 - 299, 英語

[査読有り]

研究論文（学術雑誌）

Tetsushi Hirano, Yoshihiro Kobayashi, Takuya Omotehara, Atsutoshi Tatsumi, Rie Hashimoto, Yuria Umemura, Daichi Nagahara, Youhei Mantani, Toshifumi Yokoyama, Hiroshi Kitagawa, Nobuhiko Hoshi

Environmental stress affects various parts of mammals typically through the circulation of stress hormones. It has been identified as one of the possible reasons for male reproductive difficulties, but the complex mechanisms responsible for stress-induced reproductive suppression are poorly understood. Here, we examined the relationship between chronic environmental stress and hypothalamic kisspeptin, a recently discovered upstream regulator of the reproductive endocrine feedback system. We studied male mice under an unpredictable chronic stress procedure to replicate the situation of animals under chronic stress. Histological and immunohistochemical analyses were performed focusing on kisspeptin neurons in the arcuate hypothalamic nucleus (ARC) and DNA fragmented cells in seminiferous tubules. Although the ARC was not morphologically altered in either the stressed or non-stressed group, granular kisspeptin immunoreactivities decreased slightly in the stress group. In the testes of the stress group, several signs of testicular degeneration were observed, including increased numbers of ssDNA-positive cells per seminiferous tubule, thinning, vacuoled seminiferous epithelia and multinucleated giant cells. The decreases in kisspeptin in the stress group might be due to other hypothalamic peptides, such as corticotropin-releasing hormone and leptin, whose receptors are known to coexpress in the ARC. In addition, environmental stress directly and indirectly affects testicular function through stress hormones and gonadotropins. In summary, our findings enhance the understanding of stress-induced reproductive suppression possibly mediated by kisspeptin in the ARC.

JAPAN SOC VET SCI, 2014年09月, JOURNAL OF VETERINARY MEDICAL SCIENCE, 76 (9), 1201 - 1208, 英語

[査読有り]

研究論文（学術雑誌）

Nobuhiko Hoshi, Tetsushi Hirano, Takuya Omotehara, Junko Tokumoto, Yuria Umemura, Youhei Mantani, Takashi Tanida, Katsuhiko Warita, Yoshiaki Tabuchi, Toshifumi Yokoyama, Hiroshi Kitagawa

Neonicotinoids, which were developed in the 1990s as an insecticide having selective toxicity, were later found to cause reproductive abnormalities in experimental animals. In Japan there is an attempt to preserve endangered animals, including the Japanese crested ibis, and there is a question of whether neonicotinoids affect the reproduction of this bird, since they are used in its habitat. Hence, we investigated whether the daily oral administration of the neonicotinoid clothianidin (CTD) has any deleterious effects on the reproductive function of mature male only or both young male and female quails as experimental animals. Vacuolization and the number of germ cells having fragmented DNA in seminiferous tubules, as well as the number and size of vacuoles in hepatocytes, increased dose-dependently. The ovaries showed abnormal histology in the granulosa cells, which produce progesterone. There were significant differences in egg-laying rates and embryo weights between the groups. Glutathione Peroxidase 4 (GPx4) and Manganese Superoxide Dismutase (Mn-SOD), which protect the organism from oxidative damage, showed a dose-dependent decrease. Thus, it is possible neonicotinoids affect the bird's reproductive system through oxidative stress, reflecting an imbalance between the production of reactive oxygen species (ROS) and a biological system's ability to readily detoxify the reactive intermediates or easily repair the resulting damage. Responding to our study, Sado Island has since succeeded in breeding Japanese crested ibis in the wild without the use of neonicotinoids.

PHARMACEUTICAL SOC JAPAN, 2014年09月, BIOLOGICAL & PHARMACEUTICAL BULLETIN, 37 (9), 1439 - 1443, 英語

[査読有り]

研究論文（学術雑誌）

橋本 理恵, 梅村 ゆりあ, 表原 拓也, 平野 哲史, 長原 大知, 湯浅 秀人, 久保田 直人, 南 貴一, 柳井 翔吾, 万谷 洋平, 横山 俊史, 北川 浩, 星 信彦

(公社)日本獣医学会, 2014年08月, 日本獣医学会学術集会講演要旨集, 157回, 318 - 318, 日本語

[査読有り]

表原 拓也, 橋本 理恵, 梅村 ゆりあ, 平野 哲史, 南 貴一, 長原 大知, 湯浅 秀人, 久保田 直人, 柳井 翔吾, 万谷 洋平, 横山 俊史, 北川 浩, 星 信彦

(公社)日本獣医学会, 2014年08月, 日本獣医学会学術集会講演要旨集, 157回, 318 - 318, 日本語

[査読有り]

横山 俊史, 橋本 理恵, 梅村 ゆりあ, 表原 拓也, 長原 大知, 平野 哲史, 久保田 直人, 南 貴一, 柳井 翔吾, 万谷 洋平, 北川 浩, 星 信彦

(公社)日本獣医学会, 2014年08月, 日本獣医学会学術集会講演要旨集, 157回, 319 - 319, 日本語

[査読有り]

平野 哲史, 表原 拓也, 橋本 理恵, 梅村 ゆりあ, 久保田 直人, 南 貴一, 柳井 翔吾, 長原 大知, 湯浅 秀人, 万谷 洋平, 横山 俊史, 北川 浩, 星 信彦

(公社)日本獣医学会, 2014年08月, 日本獣医学会学術集会講演要旨集, 157回, 331 - 331, 日本語

[査読有り]

Youhei Mantani, Miho Nishida, Hideto Yuasa, Kyouji Yamamoto, Ei-Ichirou Takahara, Takuya Omotehara, Kankanam Gamage Sanath Udayanga, Junichi Kawano, Toshifumi Yokoyama, Nobuhiko Hoshi, Hiroshi Kitagawa

Paneth cells (PCs) contribute to the host defense against indigenous bacteria in the small intestine. We found Paneth cell-like cells (PLCs) in the rat ascending colon, but the nature of PLCs is never clarified. Therefore, the present study aimed to clarify the cytological characteristics of PLCs and discuss their cellular differentiation. PLCs were localized in the bases of intestinal crypts, especially follicle-associated intestinal crypts in proximal colonic lymphoid tissue, but were very seldom found in the ordinary intestinal crypts of the ascending colon. PLCs possessed specific granules with highly electron-dense cores and haloes, as well as PCs in the small intestine. The secretory granules of PLCs were positive for PAS reaction, lysozyme and soluble phospholipase A2, but negative for Alcian blue staining, beta-defensin-1 and -2, as well as the ones of PCs. Furthermore, intermediate cells possessing both the PLC-specific granules and the mucus granules similar to those of goblet cells (GCs) were occasionally found in the vicinity of PLCs. Intermediate cells ranged from goblet cell-like cells rich in mucus granules to PLC-like cells with few mucus granules. The cellular condensation and fragmentation were exclusively found in PLCs but never seen in intermediate cells or GCs. The PLCs, which were identified as PC, were suggested to be transformed from GCs through intermediate cells and finally to die by apoptosis in intestinal crypts of proximal colonic lymphoid tissue in the rat ascending colon. (C) 2014 Wiley Periodicals, Inc.

WILEY-BLACKWELL, 2014年08月, ANATOMICAL RECORD-ADVANCES IN INTEGRATIVE ANATOMY AND EVOLUTIONARY BIOLOGY, 297 (8), 1462 - 1471, 英語

[査読有り]

研究論文（学術雑誌）

MANTANI YOUHEI, YUASA HIDETO, NISHIDA MIHO, TAKAHARA EI-ICHIROU, OMOTEHARA TAKUYA, UDAYANGA K. G. S, KAWANO JUNICHI, YOKOYAMA TOSHIFUMI, HOSHI NOBUHIKO, KITAGAWA HIROSHI

The epithelial cell composition was investigated in the follicle-associated intestinal crypt (FAIC) of rat Peyer's patches. The epithelium of the FAIC mainly consisted of columnar epithelial cells, goblet cells and Paneth cells. The characteristics of secretory granules in Paneth cells and goblet cells of both the FAIC and ordinary intestinal crypts (IC) were almost the same in periodic acid-Schiff (PAS) reaction, Alcian blue (AB) staining and the immunohistochemical detection of lysozymes and soluble phospholipase A2. Both goblet cells and Paneth cells were markedly less frequent on the follicular sides than on the anti-follicular sides of the FAIC. Goblet cells were also markedly less frequent in the follicle-associated epithelium (FAR) than in the ordinary intestinal villi (IV). Indigenous bacteria were more frequently adhered to FAR than to follicle-associated intestinal villi or IV. These findings suggest that the host defense against indigenous bacteria is inhibited on the follicular sides of FAIC, which might contribute to the preferential settlement of indigenous bacteria on the FAE; they also suggest that differentiation into secretory cells is inhibited in the epithelium of the follicular sides of FAIC, so that differentiation into M cells might be admitted in the FAR of rat Peyer's patches. Furthermore, intermediate cells possessing characteristics of both Paneth cells and goblet cells were rarely found in the FAIC, but not in the IC. This finding suggests that the manner of differentiation into Paneth cells in the FAIC differs from that in the IC.

JAPAN SOC VET SCI, 2014年06月, The Journal of Veterinary Medical Science, 76 (6), 833 - 838, 英語

[査読有り]

研究論文（学術雑誌）

T. Omotehara, C. A. Smith, Y. Mantani, Y. Kobayashi, A. Tatsumi, D. Nagahara, R. Hashimoto, T. Hirano, Y. Umemura, T. Yokoyama, H. Kitagawa, N. Hoshi

Sex of birds is genetically determined by the inheritance of sex chromosomes (ZZ for male and ZW for female), and the Z-linked gene named doublesex and mab-3 related transcription factor 1 (DMRT1) is a candidate sex- determining gene in avian species. However, the mechanisms underlying sex determination in birds are not yet understood, and the expression patterns of the DMRT1 protein in urogenital tissues have not been identified. In the current study, we used immunohistochemistry to investigate the detailed expression patterns of the DMRT1 protein in the urogenital systems (including Mullerian ducts) in male and female chicken embryos throughout embryonic development. Gonadal somatic cells in the male indifferent gonads showed stronger expressions of DMRT1 compared with those in the female indifferent gonads well before the presumptive period of the sex determination, and Sertoli cells forming testicular cords expressed DMRT1 in the testes after sex determination. Germ cells expressed DMRT1 equally in males and females after sex determination. The expression was continuous in males, but in females it gradually disappeared from the germ cells in the central part of the cortex of the left ovary toward both edges. The DMRT1 was also detected in the tubal ridge, which is a precursor of the Mullerian duct, and at the mesenchyme and outermost coelomic epithelium of the Mullerian duct in both sexes. Strong expression was observed in the males, but it was restricted to coelomic epithelium after the regression of the duct started. Thus, we observed the detailed spatiotemporal expression patterns of DMRT1 in the developing chicken urogenital systems throughout embryonic development, suggesting its various roles in the development of urogenital tissues in the chicken embryo.

OXFORD UNIV PRESS, 2014年04月, POULTRY SCIENCE, 93 (4), 953 - 958, 英語

[査読有り]

研究論文（学術雑誌）

TABUCHI YOSHIAKI, YUNOKI TATSUYA, HOSHI NOBUHIKO, SUZUKI NOBUO, KONDO TAKASHI

2014年04月, International Journal of Molecular Science, 15, 8959 - 8978, 英語

[査読有り]

研究論文（学術雑誌）

Takashi Tanida, Ken Tasaka, Eiichi Akahoshi, Mitsuko Ishihara-Sugano, Michiko Saito, Shigehisa Kawata, Megumi Danjo, Junko Tokumoto, Youhei Mantani, Daichi Nagahara, Yoshiaki Tabuchi, Toshifumi Yokoyama, Hiroshi Kitagawa, Mitsuhiro Kawata, Nobuhiko Hoshi

Fetal exposure to dioxins and related compounds is known to disrupt normal development of the midbrain dopaminergic system, which regulates behavior, cognition and emotion. The toxicity of these chemicals is mediated mainly by aryl hydrocarbon receptor (AhR) signaling. Previously, we identified a novel binding motif of AhR, the AhR-responsive element III (AHRE-III), in vitro. This motif is located upstream from the gene encoding tyrosine hydroxylase (TH), the rate-limiting enzyme of dopamine biosynthesis. To provide in vivo evidence, we investigated whether 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) could regulate AHRE-III transcriptional activity in midbrain dopaminergic neurons. We produced transgenic mice with inserted constructs of the AHRE-III enhancers, TH gene promoter and the c-myc-tagged luciferase gene. Single oral administrations of TCDD (0-2000ngkg(-1) body weight) to the transgenic dams markedly enhanced TH-immunoreactive (ir) intensity in the A9, A10 and A8 areas of their offspring at 3days and 8weeks of age. The offspring of dams treated with 200ngkg(-1) TCDD exhibited significant increases in the numbers of TH- and double (TH and c-myc)-ir neurons in area A9 compared with controls at 8weeks. These results show that fetal exposure to TCDD upregulates TH expression and increases TH-ir neurons in the midbrain. Moreover, the results suggest that TCDD directly transactivates the TH promoter via the AhR-AHRE-III-mediated pathway in area A9. Fetal exposure to TCDD caused stable upregulation of TH via the AhR-AHRE-III signaling pathway and overgrowth of TH-ir neurons in the midbrain, implying possible involvement in the etiology of neurodevelopmental disorders such as attention-deficit/hyperactivity disorder (ADHD). Copyright (c) 2013 John Wiley & Sons, Ltd.

WILEY, 2014年02月, JOURNAL OF APPLIED TOXICOLOGY, 34 (2), 117 - 126, 英語

[査読有り]

研究論文（学術雑誌）

Yoshiaki Tabuchi, Shigehito Wada, Mika Ikegame, Ayako Kariya, Yukihiro Furusawa, Nobuhiko Hoshi, Tatsuya Yunoki, Nobuo Suzuki, Ichiro Takasaki, Takashi Kondo, Yoshihisa Suzuki

We have developed an immortalized oral epithelial cell line, ROE2, from fetal transgenic rats harboring temperature-sensitive simian virus 40 large T-antigen gene. The cells grew continuously at either a permissive temperature of 33 degrees C or an intermediate temperature of 37 degrees C. At the nonpermissive temperature of 39 degrees C, on the other hand, growth decreased significantly, and the Sub-G1 phase of the cell cycle increased, indicating that the cells undergo apoptosis at a nonpermissive temperature. Histological and immunocytochennical analyses revealed that ROE2 cells at 37 degrees C had a stratified epithelial-like morphology and expressed cytokeratins Krt4 and Krt13, marker proteins for oral nonkeratinized epithelial cells. Global-scale comprehensive nnicroarray analysis, coupled with bioinformatics tools, demonstrated a significant gene network that was obtained from the upregulated genes. The gene network contained 16 genes, including Cdkn1a, Fos, Krt13, and Prdm1, and was associated mainly with the biological process of skin development in the category of biological functions, organ development. These four genes were validated by quantitative real-time polymerase chain reaction, and the results were nearly consistent with the microarray data. It is therefore anticipated that this cell line will be useful as an in vitro model for studies such as physiological functions, as well as for gene expression in oral epithelial cells.

INT PRESS EDITING CENTRE INC, 2014年01月, EXPERIMENTAL ANIMALS, 63 (1), 31 - 44, 英語

[査読有り]

研究論文（学術雑誌）

SAKAMOTO YUJI, Okumura N, Koizumi N, Numata R, Kitano J, Yamamoto M, Komada T, HOSHI NOBUHIKO

2014年01月, Animal Eye Research, 32, 15 - 21, 英語

[査読有り]

研究論文（学術雑誌）

小林 泰丈, 表原 拓也, 辰巳 敬哉, 橋本 理恵, 平野 哲史, 梅村 ゆりあ, 長原 大知, 横山 俊史, 北川 浩, 星 信彦

環境ホルモン学会(日本内分泌撹乱化学物質学会), 2013年12月, 環境ホルモン学会研究発表会要旨集, 16回, 150 - 150, 日本語

[査読有り]

Ei-ichirou Takahara, Youhei Mantani, Kankanam Gamage Sanath Udayanga, Wang-Mei Qi, Takashi Tanida, Takashi Takeuchi, Toshifumi Yokoyama, Nobuhiko Hoshi, Hiroshi Kitagawa

Chylomicrons from villous columnar epithelial cells are generally known to be transported only by central lymph vessels (CLV), whereas antigenic particulates derived from the intestinal lumen can also be transported by subepithelial blood capillaries (sBCs) in rat intestinal villi. The possibility of chylomicron absorption by sBCs was histoplanimetrically studied in the rat jejunum under a transmission electron microscope. The chylomicrons more abundantly presented in villous venules than in arterioles. The most frequent size (MFS) of chylomicrons was 75 to 90 nm in diameter in the areas near sBCs, while it was 45 to 60 nm in the epithelial intercellular spaces just above sBCs or the intermediate areas between sBCs. The MFS of chylomicrons was 45 to 60 nm in the intermediate areas between sBCs and in the epithelial intercellular spaces just above these areas. The MFS of chylomicrons in CLV was intermediate between that in the area adjacent to sBCs and that in the intermediate areas between sBCs. Chylomicrons were found in small vesicles in the endothelial cytoplasms of sBCs. No chylomicrons larger than 600 nm were observed in the lamina propria. These findings suggest that some of the chylomicrons smaller than 75 nm, which are probable intestinal very low-density lipoproteins (VLDL), are directly transported to the liver by hepatic portal blood in addition to CLV and that epithelial fat droplets larger than 600 nm are not discharged into lamina propria in rat jejunum under physiological conditions.

JAPAN SOC VET SCI, 2013年12月, JOURNAL OF VETERINARY MEDICAL SCIENCE, 75 (12), 1563 - 1569, 英語

[査読有り]

研究論文（学術雑誌）

表原 拓也, 木下 今日子, 長原 大知, 段上 めぐみ, 徳本 順子, 小林 泰丈, 辰巳 敬哉, 橋本 理恵, 平野 哲史, 梅村 ゆりあ, 横山 俊史, 北川 浩, 星 信彦

(公社)日本獣医学会, 2013年08月, 日本獣医学会学術集会講演要旨集, 156回, 197 - 197, 日本語

[査読有り]

平野 哲史, 長原 大知, 表原 拓也, 小林 泰丈, 辰巳 敬哉, 橋本 理恵, 梅村 ゆりあ, 横山 俊史, 北川 浩, 星 信彦

(公社)日本獣医学会, 2013年08月, 日本獣医学会学術集会講演要旨集, 156回, 201 - 201, 日本語

[査読有り]

徳本 順子, 星 信彦, 橋口 峰雄, 表原 拓也, 小林 泰丈, 辰巳 敬哉, 平野 哲史, 橋本 理恵, 梅村 ゆりあ, 長原 大知, 関島 恒夫, 上曽山 博, 横山 俊史, 北川 浩

(公社)日本獣医学会, 2013年08月, 日本獣医学会学術集会講演要旨集, 156回, 201 - 201, 日本語

[査読有り]

MANTANI YOUHEI, TAKAHARA EI-ICHIRO, TAKEUCHI TAKASHI, KAWANO JUNICHI, YOKOYAMA TOSHIFUMI, HOSHI NOBUHIKO, KITAGAWA HIROSHI

2013年07月, The Journal of Veterinary Medical Science, 75 (5), 939 - 947, 英語

[査読有り]

研究論文（学術雑誌）

Maeda N, Okumura K, Tanaka E, Suzuki T, Miyasho T, Haeno S, Ueda H, HOSHI NOBUHIKO, YOKOTA HIROSHI

2013年07月, Environmental Toxicology, 英語

[査読有り]

研究論文（学術雑誌）

Junko Tokumoto, Megumi Danjo, Yoshihiro Kobayashi, Kyoko Kinoshita, Takuya Omotehara, Atsutoshi Tatsumi, Mineo Hashiguchi, Tsuneo Sekijima, Hiroshi Kamisoyama, Toshifumi Yokoyama, Hiroshi Kitagawa, Nobuhiko Hoshi

Clothianidin (CTD) is a neonicotinoid developed in the 1990s as an insecticide having selective toxicity, but it was later found to cause reproductive abnormalities in rats through oxidative stress. There is an attempt to preserve endangered animals, including the Japanese crested ibis, in Japan. However, there is a concern that neonicotinoid affects the reproduction of this bird, since it is used in its habitat. CTD toxicity in the birds is poorly understood, so we investigated whether or not the daily oral administration of CTD has any deleterious effects on the reproductive functions of mature male quails as experimental animals. The animals were randomly divided into four groups of 6 or 7 quails each, treated orally with 0, 0.02, 1 or 50 mg CTD/kg body weight (Control, CTD0.02, CTD1 and CTD50). After that the males bred with untreated females to estimate the egg weights, and rates of fertilization and normal development, the testes, liver and spleen were examined histologically. Vacuolization and the number of germ cells having fragmented DNA in seminiferous tubules, and the number and size of vacuoles in hepatocytes increased dose-dependently. There were no significant differences in egg weights and fertilization rates between the groups, but some eggs of the CTD1 and CTD50 groups failed to develop, and embryonic length decreased dose-dependently. Thus, it was found that CTD affected the reproduction of the male quail through the fragmentation of germ cells and the inhibition or delay of embryonic development.

JAPAN SOC VET SCI, 2013年06月, JOURNAL OF VETERINARY MEDICAL SCIENCE, 75 (6), 755 - 760, 英語

[査読有り]

研究論文（学術雑誌）

TAKENAKA ASAMI, Kashiwagi Nobuyuki, Maezono YUKO, Nakao Tatsuko, Uwano YUKA, Kakizoe YUKA, Kinoshita KODZUE, Kusunoki hiroshi, HOSHI NOBUHIKO

2013年05月, Japanese Journal of Zoology and Wildlife Medecine, 18 (3), 107 - 114, 英語

[査読有り]

研究論文（学術雑誌）

Warita K, Mitsuhashi T, Fukui S, Ohta K, Suzuki S, Miki T, Takeuchi Y, YOKOYAMA TOSHIFUMI, KITAGAWA HIROSHI, Sugawara T, HOSHI NOBUHIKO

2013年05月, Reproductive Biology, 13 (1), 92 - 95, 英語

[査読有り][招待有り]

研究論文（学術雑誌）

Katsuhiko Warita, Tomoko Mitsuhashi, Ken-ichi Ohta, Shingo Suzuki, Nobuhiko Hoshi, Takanori Miki, Yoshiki Takeuchi

DNA methyltransferases (DNMTs) are associated with epigenetic regulation of gene expression, and methyl-CpG binding protein 2 (MECP2) acts as a long-range regulator of methylated genes. We evaluated the effects of bisphenol A (BPA) on embryonic mouse hypothalamic cells, with particular emphasis on the gene expression of Dnmts (Dnmt1, Dnmt3a, and Dnmt3b) and Mecp2 isoforms. In a dose-dependent (0.02-200 mu M BPA) 3-hr experiment, real-time reverse transcription polymerase chain reaction revealed that gene expression of both Dnmts and Mecp2_e2 was affected at 200 mu M and that of Mecp2_e1 was affected at > 20 mu M. These results suggest that gene expression of Dnmts and Mecp2 are less susceptible to lower doses of BPA in developing hypothalamic cells. However, as BPA concentration increases, this agent has the potential to alter gene expression of key players that provide stability and flexibility of epigenetic gene regulation, which could disrupt the normal development of hypothalamic functions.

JAPANESE SOC TOXICOLOGICAL SCIENCES, 2013年04月, JOURNAL OF TOXICOLOGICAL SCIENCES, 38 (2), 285 - 289, 英語

[査読有り][招待有り]

研究論文（学術雑誌）

Sakamoto YUJI, Okumura N, Koizumi N, Yamasaki K, Kitano J, Numata R, Komada T, HOSHI NOBUHIKO

2013年04月, Animal Eye Research, 31, 3 - 11, 英語

[査読有り]

研究論文（学術雑誌）

Katsuhiko Warita, Tomoko Mitsuhashi, Ken-ichi Ohta, Shingo Suzuki, Nobuhiko Hoshi, Takanori Miki, Yoshiki Takeuchi

We evaluated the effects of bisphenol A (BPA) on embryonic mouse hypothalamic cells. Real-time reverse transcription polymerase chain reaction (RT-PCR) indicated that gonadotropin-releasing hormone 1 (Gnrh1) expression in 0.02-20μM BPA-treated cells did not differ from that in control cells but decreased significantly in 200μM BPA-treated cells. The mRNA level for brain-derived neurotrophic factor (Bdnf), which participates in GNRH1 secretory system development, decreased significantly in 200μM BPA-treated cells, but that for neurotrophic tyrosine kinase, receptor, type 2 (Ntrk2), did not change. This indicates that Gnrh1 gene expression in mice fetuses is not affected by exposure to < 20μM BPA and that the adverse effects of BPA on the BDNF-NTRK2 neurotrophin system are induced by decrease in the mRNA level of the ligand, not of its receptor. © 2012 Japanese Teratology Society.

2013年03月, Congenital Anomalies, 53 (1), 42 - 45, 英語

[査読有り]

研究論文（学術雑誌）

Katsuhiko Warita, Tomoko Mitsuhashi, Shiho Fukui, Ken-ichi Ohta, Shingo Suzuki, Takanori Miki, Yoshiki Takeuchi, Toshifumi Yokoyama, Hiroshi Kitagawa, Teruo Sugawara, Nobuhiko Hoshi

The expression patterns of steroidogenic acute regulatory protein (StAR) and StAR-binding protein (SSP) in fetal Leydig cells were compared by using immunohistochemistry. While StAR immunoreactivity was detected during the first steps of testis differentiation, SBP expression was detected slightly later. The timing of SBP expression closely correlated with that of the testosterone surge, an event which is known to induce masculinization. Our results suggest that SBP plays an important role in male sexual development via interactions with StAR. (C) 2013 Society for Biology of Reproduction & the Institute of Animal Reproduction and Food Research of Polish Academy of Sciences in Olsztyn. Published by Elsevier Urban & Partner Sp. z o.o. All rights reserved.

INST ANIMAL REPRODUCTION FOOD RESEARCH, 2013年03月, REPRODUCTIVE BIOLOGY, 13 (1), 92 - 95, 英語

[査読有り]

研究論文（学術雑誌）

Youhei Mantani, Ei-ichirou Takahara, Takashi Takeuchi, Junichi Kawano, Toshifumi Yokoyama, Nobuhiko Hoshi, Hiroshi Kitagawa

The relationship between the invasion of indigenous bacteria into intestinal crypts and the proliferation of epithelial cells was histoplanimetrically investigated in the rat ascending colon. Indigenous bacteria preferentially adhered to the intestinal superficial epithelial cells in the mesenterium-attached mucosa (MAM) compared to those in the mesenterium-non-attached mucosa (MNM). Intestinal crypts with indigenous bacteria were also significantly more frequently found in MAM than in MNM. Total epithelial cells, columnar epithelial cells and goblet cells were significantly more abundant in the intestinal crypts with no-indigenous bacteria in MAM (MAM-C) than those in MNM (MNM-C), whereas the columnar epithelial cells were less abundant in MAM-C than in the intestinal crypts with indigenous bacteria in MAM (MAM-C-B). Columnar epithelial cells and goblet cells immuno-positive for proliferating cell nuclear antigen (PCNA) in MAM-C were more abundant than those in MNM-C, but less abundant than those in MAM-C-B. Toll-like receptor (TLR)-2, -4 and -9 were immuno-positive in the striated borders of the intestinal superficial epithelial cells, but their positive intensities were weaker in MAM than in MNM. From these findings, indigenous bacteria were confirmed to preferentially settle on the intestinal superficial epithelium of MAM in the rat ascending colon, and low TLRs-expression might contribute to the preferential settlement of indigenous bacteria in MAM. The increase of proliferating epithelial cells is probably induced by the invasion of indigenous bacteria into the intestinal crypts of MAM. © 2013 The Japanese Society of Veterinary Science.

2013年, Journal of Veterinary Medical Science, 75 (7), 939 - 947, 英語

[査読有り]

研究論文（学術雑誌）

小林 泰丈, 段上 めぐみ, 徳本 順子, 長原 大知, 木下 今日子, 表原 拓也, 辰巳 敬哉, 横山 俊史, 北川 浩, 星 信彦

環境ホルモン学会(日本内分泌撹乱化学物質学会), 2012年12月, 環境ホルモン学会研究発表会要旨集, 15回, 60 - 60, 日本語

[査読有り]

Midori Yuji, Masato Fujimoto, Wang-Mei Qi, Ei-ichirou Takahara, Youhei Mantani, Kankanam Gamage Sanath Udayanga, Takashi Takeuchi, Katsuhiko Warita, Toshifumi Yokoyama, Nobuhiko Hoshi, Hiroshi Kitagawa

Previously, the specific antibody-mediated persorption of antigenic molecules and particulates from the small-intestinal lumen into the peripheral blood was clarified in rats, but the intermediation of the receptor for the specific antibodies was not. In this study, the existence of receptor for the specific antibody was experimentally examined in the rat small intestine. Glutaraldehyde-fixed sheep erythrocytes (SEs) coated by Fc-fragments of IgG (IgG-Fc), (Fab')(2)-fragments of IgG (IgG-Fab) or bovine serum albumin (BSA), were injected into 3 jejunal loops each 2 cm in length in non-orally pre-immunized rats, respectively. Thirty minutes after the injection, IgG-Fc-coated SEs were significantly more engulfed by villous columnar epithelial cells than Fab- or BSA-coated SEs. The most frequent absorption sites were the intestinal villous apices. The IgG-Fc-coated SEs were adhered to the striated borders and were engulfed by villous columnar epithelial cells. IgG-Fc-coated SEs passing through the epithelial cells were also detected in the subepithelial blood capillaries just beneath the villous epithelium, but not in the connective tissue and the lymph vessels. These findings suggest that the absorption of luminal antigenic particulates is probably mediated by the Fc-receptor, and that the absorbed antigenic particulates are directly transferred to the hepatic portal blood by passing through the endothelium of the subepithelial blood capillaries.

JAPAN SOC VET SCI, 2012年11月, JOURNAL OF VETERINARY MEDICAL SCIENCE, 74 (11), 1447 - 1452, 英語

[査読有り]

研究論文（学術雑誌）

Youhei Mantani, Yuh Yokoo, Aosa Kamezaki, Kankanam Gamage Sanath Udayanga, Ei-ichirou Takahara, Takashi Takeuchi, Junichi Kawano, Toshifumi Yokoyama, Nobuhiko Hoshi, Hiroshi Kitagawa

Localization of Toll-like receptors (TLRs) in the exocrine glands associated with the rat alimentary tract was immunohistochemically studied using anti-TLR antibodies. TLR-2, -4 and -9 were detected in the secretory granules of acinar cells or the luminal substances of the gustatory gland, extraorbital lacrimal gland, Harderian gland, proper gastric gland and pancreas. TLR-2 and -9 were also detected in the mucous acinar cells of the sublingual gland. Positivity for all TLRs was found in the striated borders of columnar epithelial cells and the luminal substances of the intestinal crypts throughout the small intestine, and also in the goblet cells throughout the large intestine. Only TLR-4 was detected in the secretory granules of Paneth cells. A reduction of TLR-4-positive secretory granules and the formation of TLR-4-positive vacuoles were found in the ileal Paneth cells under the hyper-proliferation of indigenous bacteria. In the apical to middle intervillous portions of the ileum, Gram-positive bacterial colonies were significantly more abundant than Gram-negative bacterial colonies, whereas this difference disappeared in the basal intervillous portions. These findings suggest that there are distribution differences in the secretory sources of soluble TLRs that possibly neutralize their luminal ligands, in the rat alimentary tract. Therefore, the bacterial ligand-recognition system composed of the membranous TLRs of villous columnar epithelial cells and soluble TLRs from crypt epithelial cells might contribute to host defense mechanisms for the selective elimination of Gram-positive bacteria rather than Gram-negative bacteria in the rat small intestine.

JAPAN SOC VET SCI, 2012年11月, JOURNAL OF VETERINARY MEDICAL SCIENCE, 74 (11), 1429 - 1438, 英語

[査読有り]

研究論文（学術雑誌）

長原 大知, 森實 真由美, 蛯名 康彦, 木下 今日子, 段上 めぐみ, 徳本 順子, 安田 玲子, 表原 拓也, 小林 泰丈, 辰巳 敬哉, 横山 俊史, 北川 浩, 山田 秀人, 星 信彦

(公社)日本獣医学会, 2012年08月, 日本獣医学会学術集会講演要旨集, 154回, 176 - 176, 日本語

[査読有り]

小林 泰丈, 長原 大知, 木下 今日子, 段上 めぐみ, 徳本 順子, 安田 玲子, 表原 拓也, 辰巳 敬哉, 横山 俊史, 北川 浩, 星 信彦

(公社)日本獣医学会, 2012年08月, 日本獣医学会学術集会講演要旨集, 154回, 180 - 180, 日本語

[査読有り]

SAKAMOTO YUJI, OKUMURA NAOKI, KOIZUMI NORIKO, YAMASAKI KENTA, KITANO JUNJI, NUMATA RYOUHEI, KOMADA TAKAFUMI, HOSHI NOBUHIKO

2012年06月, Animal Eye Research, 31, 3 - 11, 英語

[査読有り]

研究論文（学術雑誌）

Kankanam Gamage Sanath Udayanga, Kyoji Yamamoto, Hidenori Miyata, Yuh Yokoo, Youhei Mantani, Ei-ichrou Takahara, Junichi Kawano, Toshifumi Yokoyama, Nobuhiko Hoshi, Hiroshi Kitagawa

The apoptosis process in rat esophageal epithelium was investigated using enzyme-immunohistochemistry and transmission electron microscopy. As a result, Fas and Fas-L were expressed in the epithelial cell membrane and cytoplasm from the stratum spinosum (SS) to the stratum granulosum (SG). No TNF-R1 show immunopositivity in the cell membranes. TNF-alpha and caspase-8 were not observed in any layer. Caspase-10, cleaved caspase-3, XIAP and DNase-1 were found in the epithelial cytoplasm from the SS to the SG, whereas Bid, Apaf-1 and cleaved caspase-9 were detected only in the SG. Cytochrome c was observed as cytoplasmic granular positivity from the stratum basale (SB) and altered into homogeneous immunopositivity in the SG. Bcl-2 and Bcl-X immunopositivity was detected in cytoplasm from the SB to the SG. Immunoreactions of Bak in the cytoplasm and Bax beneath the cell membrane were observed from the upper portion of the SS with increasing intensity toward the SG. In the sites with the hyperproliferation of indigenous bacteria, TNF-R1, TNF-alpha and caspase-8 were detected in the SG and the immunopositive intensities of Bid, Apaf-1 and cleaved caspase-9 were altered to be strong. Prominently swollen cells and decreased mitochondria were ultrastructurally confirmed in the uppermost layers of stratum corneum. These findings suggest that the Fas-Fas-L-interaction initially induces apoptosis through a mitochondria-independent pathway and secondarily through a mitochondria-dependent pathway, leading to eventual epithelial cell death in the rat esophageal epithelium. The bacterial stimuli probably enhance the mitochondria-dependent pathway through the TNF-R1-TNF-alpha interaction.

JAPAN SOC VET SCI, 2012年05月, JOURNAL OF VETERINARY MEDICAL SCIENCE, 74 (5), 597 - 605, 英語

[査読有り]

研究論文（学術雑誌）

Hiroko Ishiniwa, Kazuhiro Sogawa, Ken-ichi Yasumoto, Nobuhiko Hoshi, Toshifumi Yokoyama, Ken Tasaka, Tsuneo Sekijim

InTech, 2012年02月, Immunosuppression - Role in Health and Diseases

[査読有り]

WARITA KATSUHIKO, MITSUHASHI TOMOKO, TABUSHI YOSHIAKI, OHTA KEN-ICHI, SUZUKI SHINGO, HOSHI NOBUHIKO, MIKI TAKANORI, TAKEUCHI YOSHIKI

2012年02月, Journal Toxicology Science, 37 (2), 287 - 295, 英語

[査読有り]

研究論文（学術雑誌）

Youhei Mantani, Aosa Kamezaki, Kankanam Gamage Sanath Udayanga, Ei-ichirou Takahara, Wang-Mei Qi, Junichi Kawano, Toshifumi Yokoyama, Nobuhiko Hoshi, Hiroshi Kitagawa

Toll-like receptors (TLRs) are known to recognize pathogen-associated molecular patterns and might function as receptors to detect microbes. In this study, the distribution of TLR-2, -4 and -9 were immunohistochemically investigated in the rat small intestine. As a result, TLR-2 was detected in the striated borders of villous columnar epithelial cells throughout the small intestine, except for the apices of a small number of intestinal villi. TLR-4 and -9 were detected in the striated borders of the villous columnar epithelial cells only in the duodenum. TLR-4-immunopositive minute granules were found in the apical cytoplasms of epithelial cells, subepithelial spaces and blood capillary lumina. TLR-2 and -4 were detected in the striated borders of undifferentiated epithelial cells and in the luminal substances of the intestinal crypts throughout the small intestine, but TLR-9 was not detected in the crypts throughout the small intestine. Only TLR-4 was detected in the secretory granules of Paneth cells in both the jejunal and ileal intestinal crypts. These findings suggest that duodenal TLRs might monitor indigenous bacteria proliferation in the upper alimentary tract, that TLR-2 might also monitor the proliferation of colonized indigenous bacteria throughout the small intestine, that the lack of TLR-2 at the villous apices might contribute to the settlement of indigenous bacteria, and that TLR-2 and -4 are secreted from intestinal crypts.

F HERNANDEZ, 2011年10月, HISTOLOGY AND HISTOPATHOLOGY, 26 (10), 1295 - 1303, 英語

[査読有り]

研究論文（学術雑誌）

Yuh Yokoo, Hidenori Miyata, Kankanam Gamage Sanath Udayanga, Wang-Mei Qi, Ei-ichirou Takahara, Youhei Mantani, Toshifumi Yokoyama, Junichi Kawano, Nobuhiko Hoshi, Hiroshi Kitagawa

To clarify the regulatory mechanism by bactericidal peptides secretion, the secretion of bactericidal peptides was immunohistochemically and histoplanimetrically compared with the degree of Gram-positive/negative bacterial colonization throughout the rat alimentary tract. In the associated exocrine glands from the oral cavity to the stomach, no comparable differences were observed under the changes of development of indigenous bacterial colonies. In the small intestine, immunopositive granules for lysozyme and secretory phospholipase A2 (sPLA2) were markedly decreased, whereas immunopositive vacuoles in the Paneth cells were more increased at sites with hyper-development of indigenous bacterial colonies in the intervillous spaces than at sites with no or less development. No changes in exocrine glands were observed in the large intestine because of the constant existence of large quantities of bacteria. Gram-positive bacterial colonies on the mucosal surfaces were dominant from the oral cavity to the stomach. Gram-negative bacteria were dominant in the large intestine, and the distributions of both Gram-positive and negative bacteria were intermediate in the small intestine. These findings suggest that lysozyme and sPLA2 secreted from the Paneth cells contribute to the regulation of the proliferation of indigenous bacteria in the intervillous spaces of the small intestine, and that the inversion of distributions of Gram-positive and -negative bacteria in the alimentary tract might be caused by the secretion of lysozyme and sPLA2 in the small intestine.

JAPAN SOC VET SCI, 2011年08月, JOURNAL OF VETERINARY MEDICAL SCIENCE, 73 (8), 1043 - 1050, 英語

[査読有り]

研究論文（学術雑誌）

K. G. S. Udayanga, H. Miyata, Y. Yokoo, W. -M. Qi, E. Takahara, Y. Mantani, T. Yokoyama, N. Hoshi, H. Kitagawa

Epidermal homeostasis is maintained by both epithelial proliferation in the stratum basale (SB) and the apoptosis of epithelial cells under physiological conditions. In this study, the induction and regulation mechanisms of epidermal apoptosis were immunohistochemically investigated in the epidermis from Wistar rat's palm and foot pad by using several apoptotic related proteins under a physiological condition. The results showed that Fas and Fas-L were expressed in cellular membranes of the stratum spinosum (SS), whereas TNF-R1 did not show any membranous expression in any epidermal layers. TNF-alpha was not observed in the epidermis. Caspase-10, cleaved caspase-3 and DNase-1 were found in the epithelial cytoplasms from the SS to stratum granulosum (SG), whereas caspase-8 was not detected in the epidermis. XIAP and Bak were found in the cytoplasm from the SS to SG, and the intensity of Bak-positivity was stronger in the SG than the SS, whereas Bid, Apaf-1 and cleaved caspase-9 were restricted in the SG. Homogenous cytoplasmic immunoreactivity of Bcl-2 was found in the SB and the intensity was gradually decreased from the SB to the SG. The granular-cytoplasmic immuno-positivity of cytochrome C gradually altered into homogenous cytoplasmic expression in the upper half of the SG. Single-stranded DNA was rarely detected in the upper portion of the SG. These results suggest that epidermal apoptosis is induced by the interaction between Fas and Fas-L and the activation of caspase-10, and might initially proceed through a mitochondrial-independent pathway, and that a mitochondrial-dependent pathway finally accelerated under physiological conditions.

F HERNANDEZ, 2011年07月, HISTOLOGY AND HISTOPATHOLOGY, 26 (7), 811 - 820, 英語

[査読有り]

研究論文（学術雑誌）

Toshifumi Yokoyama, Takahiko Etoh, Kankanam Gamage Sanath Udayanga, Eiichiro Takahara, Wang-Mei Qi, Katsuhiko Warita, Yoshiki Matsumoto, Takanori Miki, Yoshiki Takeuchi, Nobuhiko Hoshi, Hiroshi Kitagawa

The hypothesis that apoptotic factors play some roles in the denucleation of erythroblasts has been confirmed by the immunohistological detection of both phosphatidylserine and thrombospondin as phagocytosis-inducing factors in general apoptotic events. Both phosphatidylserine and thrombospondin were detected on the surface of cell membrane of mature erythroblasts, while thrombospondin was also detected in more immature erythroblasts. The intensities of their immune reactions increased as the erythroids matured. During denucleation, the positivities of both phosphatidylserine and thrombospondin were restricted on the surface of the cell membrane surrounding the protruding nuclei. Thus, the apoptotic process involves denucleation of erythroblasts and phosphatidylserine, and thrombospondin acts as phagocytosis-inducing factors in the denucleation event.

JAPAN SOC VET SCI, 2011年07月, JOURNAL OF VETERINARY MEDICAL SCIENCE, 73 (7), 949 - 952, 英語

[査読有り]

研究論文（学術雑誌）

Yuh Yokoo, Hidenori Miyata, Kankanam Gamage Sanath Udayanga, Wang-Me Qi, Ei-ichioru Takahara, Toshifumi Yokoyama, Junichi Kawano, Nobuhiko Hoshi, Hiroshi Kitagawa

To clarify the fundamental regulation mechanism against indigenous bacterial proliferation in the alimentary tract, we immunohistochemically examined the localization of 4 bactericidal peptides (BP) in the rat digestive exocrine glands. In the upper alimentary tract, lysozyme was detected in the gustatory, extraorbital lacrimal and parotid glands. Secretory phospholipase A2 (sPLA2) was detected in the extraorbital lacrimal glands. β -defensin1 was detected in the gustatory and extraorbital lacrimal glands. β -defensin2 was detected in the Harderian glands. In the stomach, β -defensins were detected in the gastric superficial epithelial cells. In the small and large intestines, only lysozyme and sPLA2 were detected in the Paneth cells. In the cecum, all 4 BP were detected in the middle to apical portions of the crypts, and only sPLA2 was detected in the basal portion. No BP were localized in other exocrine glands associated with the alimentary tract. In addition, all 4 BP were also detected in the columnar epithelial cells of the apical portions of intestinal villi. In the intestinal superficial epithelial cells, lysozyme and β -defensins were detected in the ascending colon, whereas only β -defensin1 was detected in the descending colon and rectum. These results suggest that BP are mainly secreted from exocrine tissues in the initial portion of the digestive tract and play a role in host defense against indigenous bacteria throughout the digestive tract. Part of the BP in the chyme might be absorbed by the epithelium at the most inner sites of mucosae in the small and large intestines.

2011年02月, Journal of Veterinary Medical Science, 73 (2), 217 - 225, 英語

[査読有り]

研究論文（学術雑誌）

Kenkichi Yamamoto, Wang-Mei Qi, Yuh Yokoo, Hidenori Miyata, Kankanam Gamage Sanath Udayanga, Junichi Kawano, Toshifumi Yokoyama, Nobuhiko Hoshi, Hiroshi Kitagawa

Surfaces of the most luminal positions of mucosae are fundamental settlement sites of indigenous bacteria throughout the rat alimentary tract. In these positions, also epithelial cell-shedding sites, the special sugar expression in the glycocalyx is very important as it provides possible ligands of bacterial lectins for attachment to epithelial cells. Therefore, the sugar expression in glycocalyx of epithelial cells was lectin-histochemically surveyed using 21 lectins throughout the rat alimentary tract. From the tongue to the nonglandular part of the stomach, alpha-D-Man, alpha-D-Glc and alpha-D-GalNAc were detected on the surface of the keratinized stratified squamous epithelium. In the glandular part of the stomach, alpha-D-Man, beta-D-Gal-4GlcNAc, D-Gal, D-GalNAc, D-GlcNAc, alpha-L-Fuc-alpha-D-Gal-beta(1-4)GlcNAc and bisected triantennary N-glycans were detected on the surface of gastric superficial epithelial cells. From the duodenum to the ileum, (GlcNAc)(2-4) was expressed exclusively on the epithelial cells in the apical portions of the intestinal villi. From the cecum to the rectum, alpha-D-Man, beta-D-Gal-4GlcNAc, D-Gal, D-GalNAc, alpha-D-Gal(1-3)D-GalNAc, (GalNAc)(n) and NeuNAc were expressed on the intestinal superficial epithelial cells. These results suggest that special sugars are expressed on the most luminal portions of mucosae as exclusive epithelial cell-shedding sites, and that sugar expression differs among the various segments of the alimentary tract. These site differences might reflect differences in resident bacterial species in the rat alimentary tract.

JAPAN SOC VET SCI, 2010年09月, JOURNAL OF VETERINARY MEDICAL SCIENCE, 72 (9), 1119 - 1127, 英語

[査読有り]

研究論文（学術雑誌）

Katsuhiko Warita, Tomoko Mitsuhashi, Teruo Sugawara, Yoshiaki Tabuchi, Takashi Tanida, Zhi-Yu Wang, Yoshiki Matsumoto, Toshifumi Yokoyama, Hiroshi Kitagawa, Takanori Miki, Yoshiki Takeuchi, Nobuhiko Hoshi

Aims: To investigate the precise mechanisms underlying the action of estrogenic endocrine disruptors, we evaluated the direct effects of synthetic estrogen diethylstilbestrol (DES) on steroidogenesis in Leydig cells, with particular emphasis on the expression of the cholesterol side-chain cleavage enzyme P450scc. Furthermore, the mechanism underlying the action of DES was compared with that of endogenous estrogen 17 beta-estradiol (E2), which has a potency equivalent to that of DES.Main methods: TTE1 Leydig cells were treated with 5 x 10(-8) mu M to 5 mu M DES or E2 for 24 h, and P450scc gene expression and the histone modifications underlying their transcriptional activation were examined using reverse transcription-polymerase chain reaction (RT-PCR) and chromatin immunoprecipitation (ChIP), respectively.Key findings: P450scc mRNA expression in the DES-treated and E2-treated cells reduced in inverse proportion to the dose of DES and E2, respectively; however, cAMP stimulation induced a recovery in the expression to a level approximately equal to those in the controls. In the DES-treated cells, ChIP assay revealed histone deacetylation in the P450scc promoter region. Interestingly, E2 did not cause histone deacetylation.Significance: In the early stages of steroidogenesis, DES and E2 directly induced a reduction in P450scc mRNA expression in inverse proportion to their doses, and treatment with CAMP restored the decreased P450scc mRNA expression. Furthermore, DES can induce alterations in the histone modification of the P450scc gene, and natural estrogen and synthetic estrogenic compounds such as DES may induce reproductive disorders through different molecular mechanisms. (C) 2010 Elsevier Inc. All rights reserved.

PERGAMON-ELSEVIER SCIENCE LTD, 2010年08月, LIFE SCIENCES, 87 (9-10), 281 - 285, 英語

[査読有り]

研究論文（学術雑誌）

Tomoko Mitsuhashi, Katsuhiko Warita, Teruo Sugawara, Yoshiaki Tabuchi, Ichiro Takasaki, Takashi Kondo, Fumio Hayashi, Zhi-Yu Wang, Yoshiki Matsumoto, Takanori Miki, Yoshiki Takeuchi, Yasuhiko Ebina, Hideto Yamada, Noriaki Sakuragi, Toshifumi Yokoyama, Takashi Nanmori, Hiroshi Kitagawa, Jeffrey A. Kant, Nobuhiko Hoshi

In normal ontogenetic development, the expression of the sex-determining region of the Y chromosome (SRY) gene, involved in the first step of male sex differentiation, is spatiotemporally regulated in an elaborate fashion. SRY is expressed in germ cells and Sertoli cells in adult testes. However, only few reports have focused on the expressions of SRY and the other sex-determining genes in both the classical organ developing through these genes (gonad) and the peripheral tissue (skin) of adult XY females. In this study, we examined the gonadal tissue and fibroblasts of a 17-year-old woman suspected of having disorders of sexual differentiation by cytogenetic, histological, and molecular analyses. The patient was found to have the 46,X,inv(Y)(p11.2q11.2) karyotype and streak gonads with abnormally prolonged SRY expression. The sex-determining gene expressions in the patient-derived fibroblasts were significantly changed relative to those from a normal male. Further, the acetylated histone H3 levels in the SRY region were significantly high relative to those of the normal male. As SRY is epistatic in the sex-determination pathway, the prolonged SRY expression possibly induced a destabilizing effect on the expressions of the downstream sex-determining genes. Collectively, alterations in the sex-determining gene expressions persisted in association with disorders of sexual differentiation not only in the streak gonads but also in the skin of the patient. The findings suggest that correct regulation of SRY expression is crucial for normal male sex differentiation, even if SRY is translated normally.

WILEY, 2010年06月, CONGENITAL ANOMALIES, 50 (2), 85 - 94, 英語

[査読有り]

研究論文（学術雑誌）

Tomoko Mitsuhashi, Katsuhiko Warita, Yoshiaki Tabuchi, Ichiro Takasaki, Takashi Kondo, Teruo Sugawara, Fumio Hayashi, Zhi-Yu Wang, Yoshiki Matsumoto, Takanori Miki, Yoshiki Takeuchi, Yasuhiko Ebina, Hideto Yamada, Noriaki Sakuragi, Toshifumi Yokoyama, Takashi Nanmori, Hiroshi Kitagawa, Jeffrey A. Kant, Nobuhiko Hoshi

XY females are rare individuals who carry a Y chromosome but are phenotypically female. In approximately 80-90% of these cases, there are no mutations in the SRY gene, a testis-determining gene on the short arm of the Y chromosome, and the pathophysiology of XY females without SRY mutation remains unclear. In the present study, we used a molecular data mining technique to analyze the pathophysiology of an XY female with functional SRY and pericentric inversion of the Y chromosome, and compared the results with those of a normal male. Interestingly, upregulations of numerous genes included in the development category of the Biological Process ontology, including genes associated with sex determination and organ morphogenesis, were seen in the patient. Additionally, the transforming growth factor-beta (TGF-beta) signaling pathway and Wnt signaling pathway, in which most cell-cell interactions during embryonic development are involved, were altered. Alterations in the expression of numerous genes at the developmental stage, including alterations at both the gene and pathway levels, may persist as a vestige of anomalies of sex differentiation that presumably began in the fetal period. The present study indicates that a data mining technique using bioinformatics contributes to identification of not only genes responsible for birth defects, but also disorders of sex development (DSD)-specific pathways, and that this kind of analysis is an important tool for clarifying the pathophysiology of human idiopathic XY gonadal dysgenesis. Our findings could serve as one of the basic datasets which will be used for future follow-up investigations.

WILEY, 2010年03月, CONGENITAL ANOMALIES, 50 (1), 40 - 51, 英語

[査読有り]

研究論文（学術雑誌）

Kana Ishihara, Seiichiroh Ohsako, Ken Tasaka, Hiroshi Harayama, Masashi Miyake, Katsuhiko Warita, Takashi Tanida, Tomoko Mitsuhashi, Takashi Nanmori, Yoshiaki Tabuchi, Toshifumi Yokoyama, Hiroshi Kitagawa, Nobuhiko Hoshi

Recent animal experiments confirmed that paternal 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) exposure decreases the sex ratio of offspring at birth without altering litter size. However, the timing of this decrease remained unclear. Male mice were administered TCDD at 7-12 weeks of age and mated with non-treated females. The Y-bearing/X-bearing sperm ratio was examined by real-time PCR and FISH methods, and the sex ratio of the 2-cell embryos collected from non-treated females that had been mated with TCDD-exposed males were investigated by nested PCR. The Y-bearing/X-bearing sperm ratio was not significantly decreased in the TCDD group. However, the sex ratio of the 2-cell embryos of the TCDD group was significantly lower than that of the control group. These results may have resulted from a decrease in fertility of Y-bearing sperm. Thus, the results of this study suggested that the sex ratio of the offspring was decreased at fertilization and not during the spermatozoa stage. (C) 2009 Elsevier Inc. All rights reserved.

PERGAMON-ELSEVIER SCIENCE LTD, 2010年01月, REPRODUCTIVE TOXICOLOGY, 29 (1), 68 - 73, 英語

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研究論文（学術雑誌）

TANIDA TAKASHI, WARITA KATSUHIKO, ISHIHARA KANA, FUKUI SHIHO, MITSUHASHI TOMOKO, SUGAWARA TERUO, TABUSHI YOSHIAKI, NANMORI TAKASHI, QI WANG-MEI, INAMOTO TETSUROU, YOKOYAMA TOSHIFUMI, KITAGAWA HIROSHI, HOSHI NOBUHIKO

A major question is whether exposure to mixtures of low-dose endocrine disruptors (EDs) having different action mechanisms affects neurodevelopment differently than exposure to EDs individually. We therefore investigated the effects of fetal and neonatal exposure to three typical EDs - bisphenol A (BPA), di-(2-ethylhexyl)-phthalate (DEHP), and 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) - on the midbrain dopaminergic system associated with functions - including motor activity, emotion, and cognition affected by neuropsychiatric diseases such as attention-deficit/hyperactivity disorder. ICR mouse dams and their pups were orally treated with BPA (5 mg/(kgday)), DEHP (1 mg/(kgday)), or TCDD (8ng/kg) individually, or with mixtures thereof, to compare the effects between sole and mixed administration. We analyzed tyrosine hydroxylase (TH)- and Fos-immunoreactive (it) neurons as markers of dopamine and neuronal activation, respectively. The numbers of TH- and/or Fos-ir neurons and the intensity of TH-immunoreactivity within midbrain dopaminergic nuclei (A9, A10, and A8) of each sole administration group significantly differed from controls at 2, 4, and 6 weeks of age. In contrast, no significant differences were detected in the mixture groups, suggesting counteractions among those chemicals. These results indicate that ED mixtures as pollution have unique and elusive effects. Thyroid hormones and/or aryl hydrocarbon receptor-related mechanisms may be responsible for this counteraction. (C) 2009 Published by Elsevier Ireland Ltd.

ELSEVIER IRELAND LTD, 2009年08月, Toxicology Letters, 189 (1), 40 - 47, 英語

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研究論文（学術雑誌）

Takashi Tanida, Katsuhiko Warita, Tomoko Mitsuhashi, Kana Ishihara, Toshifumi Yokoyama, Hiroshi Kitagawa, Nobuhiko Hoshi

While it is commonly hypothesized that sexual differentiation in the mammalian brain is initiated mainly by gonadal sex steroids, recent evidence has suggested that dopaminergic (DA) neurons within the rodent midbrain have sex differences independent of gonadal secretions. More recently, it has been reported that Sty (the sex-determining region of the Y chromosome) is directly involved in this difference. The possibility of sexual dimorphism in the mouse midbrain needs to be elucidated. In the present Study, the midbrain of C3H mice, which is little understood, was investigated histologically and immuno-histoplanimetrically to reveal sexual and developmental differences. The female ventral tegmental area appeared to contain higher immunoreactivity to tyrosine hydroxylase (TH) than that of males at 11 weeks of age, whereas general histological differences between the sexes were not clearly found. The TH-immunoreactive (TH-ir) neurons within the A8, A9, and A10 mesencephalic areas were examined separately. There was the sex difference in the time period when TH-ir cell numbers significantly increased, indicating that the growth rate of midbrain DA nuclei also differs and that the midbrain DA system may trace different processes of sexual maturation between the sexes. These differences between female and male may reflect the direct regulation by Sry or the multiple effects of both Sty and sex steroids. Further experiments are needed to determine which factor forms this difference in the growth pattern in the numbers of TH-ir neurons.

JAPAN SOC VET SCI, 2009年07月, JOURNAL OF VETERINARY MEDICAL SCIENCE, 71 (7), 855 - 863, 英語

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研究論文（学術雑誌）

Shigeki Shimada, Hideto Yamada, Nobuhiko Hoshi, Gen Kobashi, Kazuhiko Okuyama, Kaoru Hanatani, Seiichiro Fujimoto

Cytogenetic amniocentesis (CA) has been performed as a reliable prenatal diagnostic method for decades. The aims of the present study were to reveal the frequency of fetal chromosome abnormalities according to medical indications of CA, and to assess the risks of specific abnormal ultrasound findings. Data on chromosome karyotypes of fetuses from 5043 Japanese mothers were collected. Group I comprised 4626 fetuses whose mothers underwent CA due to a variety of parental reasons. Group II comprised 417 fetuses whose mothers underwent CA due to fetal abnormality, abnormality of amniotic fluid volume and fetal growth restriction. The frequency of chromosome abnormalities in Group II (17.7%) was significantly higher than in Group I (1.8%). The frequencies of chromosome abnormalities in Group II singleton fetuses with fetal abnormality, polyhydramnios and fetal growth restriction were 21.5, 22.9 and 19.6%, respectively. By multivariate analyses, we found that cystic hygroma (odds ratio 5.6, 95% CI 2.7-11.6), abnormal extremity (5.0, 1.7-14.4) and cardiovascular abnormality (3.3, 1.1-10.1) were significant variants associated with fetal chromosomal abnormalities. Information revealed in the present study constitutes a beneficial reference for genetic counseling. © 2009 Japanese Teratology Society.

2009年06月, Congenital Anomalies, 49 (2), 61 - 65, 英語

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研究論文（学術雑誌）

Wang-Mei Qi, Kenkichi Yamamoto, Yuh Yokoo, Hidenori Miyata, Kankanam Gamage Sanath Udayanga, Junichi Kawano, Toshifumi Yokoyama, Nobuhiko Hoshi, Hiroshi Kitagawa

The aim of this study was to clarify the regulatory effects of epithelial kinetics on indigenous bacterial proliferation in the large intestine. The lifespan, migration speed and proliferation rate of crypt epithelial cells in the initial 20% of the colon (proximal colon) and the 50% of the colon (middle colon) in bromodeoxyuridine-administrated rats were histoplanimetrically and chronologically compared. The proximal colon possessed well-developed mucosal folds and a large amount of indigenous bacteria which filled the crypt lumen, whereas no folds or bacteria were found to occupy the crypt lumen in the middle colon. The cell lifespans were 32.2, 42.5 and 33.6 hr in the apical and the basal parts of the mucosal folds of the proximal colon, and in the middle colon, respectively. The migration speeds were 4.2, 2.1 and 3.3 mu m/hr, respectively, while the appearance frequencies of proliferating cell nuclear antigen (PCNA)-positive crypt epithelial cells were 35.0, 24.6 and 33.8%. These findings suggest that the lifespan was shortened and the migration speed increased in the most luminal mucosa of colon, contributing to the elimination of the adhered bacteria from the most luminal mucosa. By contrast, the elongation of the lifespan and deceleration of the migration of epithelial cells in the basal parts of the mucosal folds might contribute to reliable settlement of indigenous bacteria, resulting in the maintenance of a large amount of indigenous bacteria in the lumen of the proximal colon.

JAPAN SOC VET SCI, 2009年06月, JOURNAL OF VETERINARY MEDICAL SCIENCE, 71 (6), 745 - 752, 英語

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研究論文（学術雑誌）

Kenkichi Yamamoto, Wang-Mei Qi, Yuh Yokoo, Hidenori Miyata, Kankanam Gamage Sanath Udayanga, Junichi Kawano, Toshifumi Yokoyama, Nobuhiko Hoshi, Hiroshi Kitagawa

The spatial relationship between the distribution of indigenous bacteria (IB) and the Situation of mucosal lymphatic follicles (LF) is histoplanimetrically studied in the rat alimentary tract. From the oral cavity to the nonglandular part of the stomach, IB adhered to the corneal layer of the most luminal mucosa. In the glandular part of the stomach, IB adhered only to the most luminal mucosa but not in the gastric pits. In the small intestine, IB consistently adhered around the apices of both intestinal villi and the doilies, and their amounts decreased toward their basal portions. No IB entered the intestinal crypts. In the large intestine, IB consistently adhered to the most luminal mucosa. Numerous IB were Suspended in the intestinal crypts of both the cecum and the proximal colon, whereas there were no IB in the crypts of the distal colon and the rectum. When IB spread over the basal portions of the intestinal villi, IB with the same morphology were detected on the neighboring LF, whereas no bacteria were detected on the neighboring LF, when IB were located in the apical to middle portions of the intestinal villi. This close relationship between the distribution of IB and mucosal LF was also observed in the large intestine. These results Suggest that the most luminal mucosae are a fundamental settlement site of IB throughout the alimentary tract and that the hyperproliferation of IB's colonies might be detected by neighboring LF in the rat intestine.

JAPAN SOC VET SCI, 2009年05月, JOURNAL OF VETERINARY MEDICAL SCIENCE, 71 (5), 621 - 630, 英語

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研究論文（学術雑誌）

Wang-Mei Qi, Kenkichi Yamamoto, Yuh Yokoo, Hidenori Miyata, Tetsurou Inamoto, Kankanam Gamage Sanath Udayanga, Junichi Kawano, Toshifumi Yokoyama, Nobuhiko Hoshi, Hiroshi Kitagawa

The relationship between the kinetics of villous columnar epithelial cells and the expansion of colonies of indigenous bacteria from the narrow apical portions of intestinal villi was immunohistochemically and histoplanimetrically investigated in the small intestine of bromodeoxyuridine administred Wistar rats. As a result, the lifespan Of villous columnar epithelial cells was slightly shorter in the distal ileum than in other portions of small intestine, accompanying the minimum height of the intestinal villi of the distal ileum in the small intestine. The migration speed of villous columnar epithelial cells was significantly decreased toward the distal small intestine. The migration speed in the distal ileum was about one-fourth of that in the duodenum. The migration speed of the villous columnar epithelial cells was greater and their lifespans were shorter in the sites with Wide expansion of the indigenous bacterial colony from the narrow apical portions of the intestinal villi than that in sites with no or less expansion. Additionally, the expansion of the indigenous bacterial colony from narrow villous apices also immediately shortened the heights of the intestinal villi. These findings suggest that the migration speed of villous columnar epithelial cells might contribute to the regulation of the settlement of bacteria at the villous apices and the inevitable proliferation of indigenous bacteria at the intervillous spaces in the rat small intestine.

JAPAN SOC VET SCI, 2009年04月, JOURNAL OF VETERINARY MEDICAL SCIENCE, 71 (4), 463 - 470, 英語

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研究論文（学術雑誌）

Tetsurou Inamoto, Makiko Namba, Wang-Mei Qi, Kenkichi Yamamoto, Yuh Yokoo, Hidenori Miyata, Junichi Kawano, Toshifumi Yokoyama, Nobuhiko Hoshi, Hiroshi Kitagawa

The mechanism of physical elimination of indigenous bacteria was ultrastructurally and immunohistochemically investigated in microvillous columnar epithelial cells of Peyer's patches and intestinal villi of the rat jejunoileum. From ultrastructural observation, the microfilaments accumulated to form several electron-dense layers beneath the bacteria adhering to the cell membrane, which was slightly invaginated in the epithelial cells of Peyer's patches and intestinal villi. As the microfilamentous layers were forming, the end portions of invaginations were deformed into a cone-shape and were finally collapsed. At the same time, the end portions of the adhered bacteria were also deformed into cone-shapes. The bacterial cells were moved back toward the invagination orifices with no morphological change in their inner structure. From immunohistochemical observation, beta-actin and nonmuscle-type myosin were detected at the thin layer just beneath the invaginated cell membrane. These findings suggest that indigenous bacteria which adhere to epithelia] cells are removed by only a physical action of actin and myosin filaments, but are not killed. This bacterial cell removal system might lead to the establishment of a settlement of indigenous bacteria on host cells.

JAPAN SOC VET SCI, 2008年11月, JOURNAL OF VETERINARY MEDICAL SCIENCE, 70 (11), 1153 - 1158, 英語

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研究論文（学術雑誌）

Tetsurou Inamoto, Yuko Kawata, Wang-Mei Qi, Kenkichi Yamamoto, Katsuhiko Warita, Junichi Kawano, Toshifumi Yokoyama, Nobuhiko Hoshi, Hiroshi Kitagawa

The ultrastructure of epithelial responses against the membrane adhesion of indigenous bacteria was investigated in the follicle-associated epithelium (FAE) of rat small intestine. The most frequent adherence of the various morphological types of bacteria to the epithelial membranes was found at the apex of the FAE. The attachment sites were deeply invaginated, and their bottoms were deformed into a sharp cone shape. Four layers with different electron densities were formed just beneath the apical membranes by microfilaments which surrounded the invaginations. The electron density of each layer was gradually decreased as being apart from the invaginations. The extremities of some bacteria in the invaginations were deformed into sharpened shapes. The cell walls of the extremities of the bacteria were occasionally dissolved in the invaginations, and their cytoplasms were slightly swollen with low electron densities. In some invaginations, the attached bacteria were eliminated to leave their fragments such as filamentous debris and a part of cell walls. Finally these remnants disappeared completely. When the bacterial colonies existed in the middle region of the FAE, the attachment of bacteria resulted in the engulfment of bacteria by M cells. The degenerated bacteria whose cytoplasmic matrices were separated into high electron dense materials and cleared materials were occasionally engulfed by ordinary microvillous columnar epithelial cells or goblet cells throughout the FAE. These findings suggest that the epithelial cells reject the attachment of live indigenous bacteria and that the M cells absorb indigenous bacteria in rat Peyer's patches.

JAPAN SOC VET SCI, 2008年03月, JOURNAL OF VETERINARY MEDICAL SCIENCE, 70 (3), 235 - 241, 英語

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研究論文（学術雑誌）

Teruo Sugawara, Eiji Nomura, Nobuhiko Hoshi

Steroidogenic acute regulatory (SCAR) protein plays a crucial role in the intramitochondrial movement of cholesterol, where P450 side chain cleavage enzyme resides. Cholesterol sulphate (CS), which is present ubiquitously in mammalian tissues, is not only a precursor of sulphated adrenal steroids but also an inhibitor of cholesterol biosynthesis. This study was designed to examine the biological roles of CS in steroidogenesis in adrenocortical cells. Human adrenocortical carcinoma H295R cells were cultured with various amounts of CS. To evaluate steroid hormone synthesis, pregnenolone production in cells was assayed. The amount of pregnenolone produced by H295R cells in culture medium, to which over 50 mu g/ml CS was added, was significantly (P<0.05) decreased compared with that produced by control cells. Western blot analysis was performed to determine StAR protein level using whole cell extracts from cells. StAR protein level decreased when the concentration of CS in the medium was 50 mu g/ml, whereas the level of glyceraldehyde-3-phosphate dehydrogenase did not change. To examine the mechanism by which SCAR gene expression is controlled, we performed RT-PCR and measured promoter activity in cells transfected with pGL(2) StAR reporter constructs. StAR mRNA level and promoter activity were decreased in cells. The decrease in StAR protein level is a result of the low StAR gene expression level. In conclusion, CS affects the production of steroid hormones by reducing StAR protein level in adrenocortical cells.

SOC ENDOCRINOLOGY, 2007年12月, JOURNAL OF ENDOCRINOLOGY, 195 (3), 451 - 458, 英語

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研究論文（学術雑誌）

Sachiko Onishi, Hidenori Miyata, Tetsurou Inamoto, Wang-Mei Qi, Kenkichi Yamamoto, Toshifumi Yokoyama, Katsuhiko Warita, Nobuhiko Hoshi, Hiroshi Kitagawa

It is well known that some caspases in apoptosis is involved in determinant of terminal differentiation and maturation of various cells. Our previous study ultrastructurally clarified the differentiation into M cells from immature microvillous epithelial cells and the redifferentiation from M cells to microvillous epithelial cells in the follicle-associated epithelium (FAE) of rat Peyer's patch. In this study, the difference of epithelial apoptosis between the FAE of Peyer's patch and intestinal villi was immunohistochemically investigated in rat jejunoileum. As a result, cleaved caspase-3 was limited to several epithelial cells at the tip of FAE, whereas almost all of the epithelial cells were cleaved caspase-3 positive in intestinal villi. Cleaved caspase-9 was detected only in a few exfoliating or exfoliated epithelial cells of both FAE and intestinal villi. Nuclear DNA-fragmentation was detected only in several epithelial cells of the tip of FAE, while it was expressed from the middle regions in the intestinal villi. The DNase I expression of the epithelial cytoplasm was much weaker in FAE than in intestinal villi. Bcl-x expression was restricted in the apical cytoplasms of epithelial cells in the FAE, whereas it was restricted in whole cytoplasms in villous epithelial cells. These findings suggest that the progression of the apoptotic process in the epithelial cells of FAE is later than in the intestinal villi, so that the possibility of epithelial differentiation might be remained in the FAE, unlike in the intestinal villi.

2007年11月, Journal of Veterinary Medical Science, 69 (11), 1123 - 1129, 英語

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研究論文（学術雑誌）

Sachiko Onishi, Toshifumi Yokoyama, Keigi Chin, Midori Yuji, Tetsurou Inamoto, Wang-Mei Qi, Katsuhiko Warita, Nobuhiko Hoshi, Hiroshi Kitagawa

The differentiation process of immature microvillous epithelial cells to M cells and the fate of M cells in the follicle-associated epithelium (FAE) of the mucosa-associated lymphoid tissues are still unclear. In this study, the differentiation process and the fate of M cells were clarified in rat Peyer's patches under a transmission electron microscope. Almost all immature epithelial cells were found to possess long, slender microvilli, which gradually shortened, thickened and dispersed as the immature epithelial cells migrated away from the crypt orifices. These morphological changes started in the centers and moved to the peripheries of the apical surfaces of epithelial cells, accompanied by the protrusion of apical cytoplasm out of the terminal web. During these changes, the bundles of microfilaments of microvilli never shortened, and both small vesicles in the apical cytoplasm and tiny invaginations of the apical membranes were found. The intraepithelial migrating cells gradually accumulated to form typical intraepithelial pockets. In all FAE, there was no morphological sign of cell death in M cells. The rearrangement of microfilament bundles, the reconstruction of microvilli and the disappearance of pockets resulted in the transformation of M cells into microvillous epithelial cells. These serial ultrastructural changes suggest that M cells are a temporal and transitional cell type caused by the active engulfment of luminal substances and that when the engulfment ceases, the M cells transform into mature microvillous epithelial cells.

2007年05月, Journal of Veterinary Medical Science, 69 (5), 501 - 508, 英語

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研究論文（学術雑誌）

Kana Ishihara, Katsuhiko Warita, Takashi Tanida, Teruo Sugawara, Hiroshi Kitagawa, Nobuhiko Hoshi

In 1976, men who were exposed to the highest concentrations of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) after an explosion at a chemical plant near Seveso, Italy, produced more girls than boys. However, few studies have examined the possibility that the exposure of laboratory animals to TCDD, especially that of males, could lead to a lower male/female sex ratio. The aim of this study was to investigate whether direct paternal exposure to TCDD affects the sex ratio of offspring using a relatively large-scale experimental design. Male ICR mice (n=120) were randomly assigned to three, one of which served as a vehicle control, the other two were administered TCDD orally with an initial loading dose of 2 or 2,000 ng TCDD/kg, followed by a weekly maintenance dose of 0.4 (T2/0.4 group) or 400 (T2000/400 group) ng/kg prior to mating. The major organs of each mouse were weighed and histopathologically and immunohistologically investigated, and the sex ratio of offspring [males/(males + females) x 100] was calculated in each dam. There were no significant effects on organ weights, or on the structure of the testis and epididymis between the control and TCDD-exposed males, but TCDD administration produced a significantly lower proportion of male offspring from T2000/400-exposed sires despite no alteration in litter size (Control: 53.1 ± 1.7 T2/0.4: 48.8 ± 2.5 T2000/400: 46.2 ± 2.1). In addition, we further divided the T2000/400 group into 3 subgroups based on the proportion of CYP1A1- immunoreactive areas in the liver there was a significant correlation between sex ratio and CYP1A1 immunoreactivity. Thus, the present study confirms that direct paternal exposure to TCDD might be associated with an alteration in the sex ratio of offspring. Possible mechanisms through which TCDD might decrease the fertility potential of Ybearing gametes before conception are discussed.

2007年04月, Journal of Veterinary Medical Science, 69 (4), 347 - 352, 英語

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研究論文（学術雑誌）

Midori Yuji, Masato Fujimoto, Hidenori Miyata, Tetsurou Inamoto, Wang-Mei Qi, Kenkichi Yamamoto, Katsuhiko Warita, Toshifumi Yokoyama, Nobuhiko Hoshi, Hiroshi Kitagawa

The possibility of persorption of prefixed bovine serum albumin-coated sheep erythrocytes (BSA-SEs) from mucous epithelial cells and its mechanisms were investigated in rats orally immunized by BSA for 14 consecutive days. On the day after the final oral immunization, the rats were duodenally perfused by BSA-SEs or non-coated SEs. BSA-SEs were also duodenally perfused in nonimmunized rats. Thirty min after perfusion, BSA-SEs were significantly more engulfed by late-apoptotic-stage villous columnar epithelial cells in the orally immunized rats than those in other experiments. The specific antibody (SpAb) was detected on the surfaces of BSA-SEs in rats with oral immunization. In Peyer's patches of all animals, no SEs reached the follicle-associated epithelium, because of the close attachment of follicle-associated intestinal villi and the thick mucous layer. BSA-SEs were more frequently persorbed into portal blood in the orally immunized rats than in other rats. Small numbers of BSA-SEs or SEs were detected in the systemic blood of all animals. BSA-SEs were also histologically found in the blood vessels of the liver, but not in mesenteric lymph nodes. These findings suggest that sensitized antigenic particulates are taken up by late-apoptotic-stage villous columnar epithelial cells in the small intestine and are finally persorbed into the systemic blood circulation. The uptake of antigenic particulates might be mediated by its luminal SpAb.

2007年04月, Journal of Veterinary Medical Science, 69 (4), 339 - 346, 英語

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研究論文（学術雑誌）

Keigi Chin, Sachiko Onishi, Midori Yuji, Tetsurou Inamoto, Wang-Mei Qi, Kenkichi Yamamoto, Katsuhiko Warita, Toshifumi Yokoyama, Nobuhiko Hoshi, Hiroshi Kitagawa

Our previous study clarified that the apical regions of both the follicle-associated epithelium (FAE) of Peyer's patches and the intestinal villi are the only adhesion sites of indigenous bacteria in rat jejuno-ileum. To survey the ligands against bacterial lectins, sugar expression patterns on epithelial cells were lectin-histochemically investigated using 21 lectins in the jejuno-ileal Peyer's patches of rats. As a result, (D-glcNAc)2-4, detected by Solanum tuberosum (STL) and by Lycopersicon esculentum (LEL), and β?D-gal(1-3)-D-galNAc detected by Peanut agglutinin (PNA), were strongly expressed on the brush borders of the apical regions of the FAE and the intestinal villi. On the other hand, neither sugar was expressed on the brush borders of the basal regions of both FAE and intestinal villi. The positive intensities for the lectins correlated with the progression of epithelial apoptosis in the FAE and in the intestinal villi. Moreover, the double staining with lectin histochemical method and the in situ nick end-labeling method could simultaneously detect the strong expression of both sugars and nuclear DNA fragmentation in epithelial cells at the late apoptotic stage. Other sugar expression patterns in the intestinal villi were similar with those in the FAE. There were no lectins specific for M cells in the FAE. From these findings, the possible sugars of ligands against some indigenous bacterial lectins, expressing specially on the apoptotic epithelial cells, might be narrowed down in rat jejuno-ileum.

2007年02月, Journal of Veterinary Medical Science, 69 (2), 193 - 199, 英語

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研究論文（学術雑誌）

Katsuhiko Warita, Teruo Sugawara, Zhan-Peng Yue, Shinji Tsukahara, Ken-Ichiro Mutoh, Yoshihisa Hasegawa, Hiroshi Kitagawa, Chisato Mori, Nobuhiko Hoshi

For the purpose of investigation of working mechanisms in endocrine disruptors, we evaluated the dose-related effects of fetal and/or neonatal exposure to an estrogenic compound on the male reproductive organs in adult mice, particularly with respect to gene expression of steroidogenic acute regulatory protein (StAR). The pregnant ICR mice were given subcutaneous injections of 10 μg/day/animal of diethylstilbestrol (DES) to subject the fetal mice to in utero exposure (IUE). Subsequently, the newborn male mice were subjected to neonatal exposure (NE) by treatment with vehicle or 0.1-10 μg/day/animal of DES. Fertility rates of each group were as follows: control, 100% IUE only, 60% IUE+NE 0.1 μg, 25% IUE+NE 1 μg, 0% IUE+NE 10 μg, 0%. In general histology, germ cell layers in the seminiferous tubules were thinned in the group of IUE+NE 10 μg. Hypoplasia of the Leydig cells, in which the staining intensity of eosin was diminished, was also observed in the groups of IUE+NE 0.1-10 μg. The androgen receptor (AR) and estrogen receptor alpha (ERα) immunoexpression in the Leydig cells of IUE+NE 1-10 μg was slightly lower than that in the controls. Longterm dysfunction of the hypothalamo-pituitary-testicular axis, including sustained hypoproduction of gonadotropin and testosterone, and altered expressions of steroid hormone receptors and StAR genes were observed. The hypothalamo-pituitary control of gonadotropin secretion may be affected by the smaller doses of estrogenic agents than the reproductive organs. Furthermore, the fertility rate in the male mice exposed to this estrogenic agent was closely correlated with the testosterone levels, and even more so with the rate-limiting factor of steroidogenesis, StAR. This finding suggests that endocrine disruptors have an important pronounced effect on StAR gene expression.

2006年12月, Journal of Veterinary Medical Science, 68 (12), 1257 - 1267, 英語

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研究論文（学術雑誌）

YUJI Midori, TSUBATA Masahito, CHIN Keigi, ONISHI Sachiko, INAMOTO tetsurou, QI Wang-Mei, WARITA Katsuhiko, YOKOYAMA Toshifumi, HOSHI Nobuhiko, 北川 浩

The possibility of persorption of bovine serum albumin (BSA) molecules from mucous epithelial cells and its mechanism were investigated in rats orally pre-immunized by BSA for 14 consecutive days. In the small and large intestines, both the BSA antigen (BSA-Ag) and its specific antibody (SpAb) were absorbed by the epithelial cells at the late apoptotic stage (ApoEp), and were subsequently transcytosed by membranes of the small vesicles. The basal cytoplasms containing highly-concentrated BSA-Ag and SpAb were occasionally fragmented into small cytoplasmic droplets that were secreted into the lamina propria. In Peyer's patches, both BSA-Ag and SpAb were more actively absorbed and transcytosed toward the dome area by the ApoEp of the dome apex than by the M cells. BSA-Ag and SpAb were finally persorbed into the portal blood and lymph, but were never secreted into the bile. They were also engulfed by macrophage-like cells in the villous lamina propria, mesenteric lymph node and spleen, and by hepatocytes in the liver. These findings suggest that sensitized soluble luminal antigens are taken up by ApoEp in the small intestine and are finally persorbed into the peripheral blood. The uptake of luminal antigen might be mediated by its luminal SpAb.

JAPAN SOC VET SCI, 2006年12月, The Journal of Veterinary Medical Science, 68 (12), 1297 - 1305, 英語

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研究論文（学術雑誌）

Keigi Chin, Sachiko Onishi, Midori Yuji, Tetsurou Inamoto, Wang-Mei Qi, Katsuhiko Warita, Toshifumi Yokoyama, Nobuhiko Hoshi, Hiroshi Kitagawa

To clarify the relationship between M cells and intestinal microflora, histoplanimetrical investigation into the bacterial colonization and the differentiation to M cells was carried out in rat Peyer's patch under physiological conditions. The follicle-associated epithelium (FAE), except for the narrow area of apical region, was closely covered with both neighboring intestinal villi and a thick mucous layer, the latter of which also filled the intervillous spaces as well as the space between the FAE and the neighboring intestinal villi. Indigenous bacteria adhered almost constantly to the narrow areas of apical regions of both intestinal villi and the FAE. Bacterial colonies were occasionally located on the basal to middle region of FAE, where M cells also appeared, forming large pockets. When bacterial colonies were located on the basal to middle region of FAE, bacteria with the same morphological characteristics also proliferated in the intervillous spaces neighboring the Peyer's patch. In cases with no bacterial colonies on the basal to middle region of FAE, however, M cells were rare in the FAE. Histoplanimetrical analysis showed the similar distribution pattern of bacterial colonies on the FAE and M cells in the FAE. M cells ultrastructurally engulfed indigenous bacteria, which were then transported to the pockets. These results suggest that indigenous bacterial colonization on the FAE stimulates the differentiation of M cells in the FAE under physiological conditions. The uptake of bacteria by M cells might contribute the regulation of the development of indigenous bacterial colonies in the small intestine.

JAPAN SOC VET SCI, 2006年10月, JOURNAL OF VETERINARY MEDICAL SCIENCE, 68 (10), 1023 - 1028, 英語

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研究論文（学術雑誌）

T Sugawara, E Nomura, N Hoshi

Steroid sulfatase (STS) is localized in the endoplasmic reticulum and catalyzes desulfation of 3 beta-hydroxysteroid sulfates. X-linked ichthyosis (XLI) is an inherited skill disorder caused by deficiency of STS enzyme activity. We previously reported a case in which XLI with a one-base change in the STS gene and variation in amino acid Q560P developed. In this study, we performed molecular analysis to determine the importance of terminal regions of STS and the effect of mutant STS oil STS enzyme activity. To examine the effect of terminal truncated STS on the enzyme activity, N- and C-terminal truncated STS expression vectors were transfected into COS-1 cells. The activity of truncated STS lacking the N-terminal regions declined, and the activity of C-terminal-truncated STS declined with extension of the truncated C-terminal region. Although the results of pulse-chase experiments showed that a one-base mutant STS (Q560P) and C-terminal-truncated STS (Delta C2 (1-559)) had no effects on protein synthesis and degradation, the mutant STS and C-terminal-truncated STS have dominant negative effect oil STS enzyme activity when the STS mutant or truncated STS protein and a wild-type STS protein coexist in cells. Results of coprecipitation of the truncated STS with all STS-FLAG fusion protein showed that STS formed a dimer conformation in cells. In this study, we have shown that both the N-terminal region and C-terminal region are important for STS enzyme activity. The C-terminal mutant has a dominant negative effect on wild-type STS.

SOC ENDOCRINOLOGY, 2006年02月, JOURNAL OF ENDOCRINOLOGY, 188 (2), 365 - 374, 英語

[査読有り]

研究論文（学術雑誌）

WARITA K, OKAMOTO K, SUGAWARA T, Yue Z.-P, TSUKAHARA S, ISHIHARA K, KITAGAWA Hiroshi, MORI C, HOSHI Nobuhiko

2006年, Reproduction of Toxicology (accepted), 英語

[査読有り]

研究論文（学術雑誌）

S Tsukahara, S Tanaka, K Ishida, N Hoshi, H Kitagawa

The present study examined the effects of aging and sex differences on the suprachiasmatic nucleus (SCN) of F344/N rats. In juveniles (1.6-1.9 months of age), adults (11.7-16.3 months of age), and old (29.2-34 months of age) rats, the volume, size of neuronal nucleus and neuronal cell number of the SCN were determined with cresyl fast violet-stained sections. In addition, immunohistochemical analysis was performed for glial fibrillary acidic protein (GFAP). There was no significant effect of aging and sex differences on the SCN volume. The number of neurons in the SCN gradually decreased from juvenile to old age in females. However, in males, the number was significantly decreased in adult and old age rats. The size of neuronal nuclei in the SCN was significantly decreased by increasing age in both sexes, except for the ventrolateral part of the SCN of males. In the dorsomedial part of the SCN of females, the density of GFAP-immunoreactive components was significantly higher in adult age rats than in rats of other ages. However, there was no significant increase in the density of the SCN in adult males. These results suggest that morphological changes in neuronal and astroglial cells occur in the SCN with aging in a sex-specific manner. (c) 2004 Elsevier Inc. All rights reserved.

PERGAMON-ELSEVIER SCIENCE LTD, 2005年03月, EXPERIMENTAL GERONTOLOGY, 40 (3), 147 - 155, 英語

研究論文（学術雑誌）

HOSHI Nobuhiko, OKUYAMA K, YAMADA H, YAMADA T, SUGAWARA T, SAGAWA T, FUJIMOTO S

2004年, Chromosome Science, 7,pp.7-13, 英語

研究論文（学術雑誌）

T Sugawara, H Shimizu, N Hoshi, A Nakajima, S Fujimoto

Steroidogenic acute regulatory ( StAR) protein plays a key role in the transport of cholesterol from the outer mitochondrial membrane to the inner membrane. A StAR mutant protein lacking the first 62 amino acids (N-62 StAR protein) has been reported to be as effective as wild-type StAR protein. In the present study, we examined the mechanism by which StAR protein stimulates steroidogenesis. A Gal4-based yeast two-hybrid system was used to identify proteins interacting with N-62 StAR protein. Nine positive clones were obtained from screening 1 x 10(6) clones. The results of pull-down assays and mammalian two-hybrid assays confirmed interaction between N-62 StAR protein and the clone 4 translated product. The clone 4 translated product was named StAR-binding protein (SBP). We prepared an expression plasmid (pSBP) by inserting SBP cDNA into the pTarget vector. After cotransfection with the human cytochrome P450scc system, StAR expression vector, and pSBP, the amount of pregnenolone produced by COS-1 cells was increased. The amount of steroid hormones produced by steroidogenic cells subjected to small interfering RNA treatment was less than that produced by control cells. In conclusion, SBP binds StAR protein in cells and enhances the ability of StAR protein to promote syntheses of steroid hormones.

AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC, 2003年10月, JOURNAL OF BIOLOGICAL CHEMISTRY, 278 (43), 42487 - 42494, 英語

研究論文（学術雑誌）

S Kataoka, H Yamada, N Hoshi, M Kudo, H Hareyama, N Sakuragi, S Fujimoto

Objective: The aim of this study was to elucidate the clinical characteristics of uterine leiomyomas having abnormal chromosome karyotype. Study design: A total of 394 myomas were obtained from 213 patients for cytogenetic analysis. The size (number of nodules = 144), histopathology (n = 302), and gonadotropin-releasing hormone analogue (GnRHa)-response (it = 58) were investigated in relation to chromosome karyotype in myomas. Results: 302 myomas from 166 patients were successfully karyotyped. A total of 21 myomas from 21 patients showed abnormal chromosome karyotype. The high frequencies of involved chromosomes 12, 14, 1, 7 were observed. The diameters of myomas with abnormal karyotype were significantly larger than those of myomas with normal karyotype. The frequency of the degeneration in myomas with abnormal karyotype was significantly higher than that with normal karyotype. The reduction rate in size of myomas by GnRHa treatments did not differ between the two types (karyotype normal versus abnormal) of nodules. Conclusions: Chromosomally abnormal myomas were larger in diameter and showed a higher frequency of degeneration, suggesting that the cytogenetic background in uterine leiomyoma affects a tumor's growth potential. (C) 2003 Elsevier Science Ireland Ltd. All rights reserved.

ELSEVIER SCI IRELAND LTD, 2003年09月, EUROPEAN JOURNAL OF OBSTETRICS GYNECOLOGY AND REPRODUCTIVE BIOLOGY, 110 (1), 58 - 62, 英語

研究論文（学術雑誌）

HOSHI Nobuhiko

2003年, The Hokkaido Journal of Medical Science., 78,pp.139-145, 英語

研究論文（学術雑誌）

Osamu Hashimoto, Kunihiro Tsuchida, Yuuki Ushiro, Yuko Hosoi, Nobuhiko Hoshi, Hiromu Sugino, Yoshihisa Hasegawa

We cloned human activin βE subunit cDNA from a liver cDNA library using the polymerase chain reaction (PCR) technique. The deduced amino acid sequence was 97 and 96% homologous to the mouse and rat activin βE subunits. Human activin βE subunit tagged with Myc and polyhistidine residues at the COOH terminus was expressed in mammalian cells and secreted into the medium as a disulphide-linked homodimer protein. We also found that the human activin βE protein could bind to follistatin, an activin-binding protein. Northern blot analysis showed that this gene was expressed as a major transcript of 2.7 kb predominantly in human liver. These findings suggest that activin E (dimeric protein) may play a role in humans. © 2002 Elsevier Science Ireland Ltd. All rights reserved.

2002年08月30日, Molecular and Cellular Endocrinology, 194 (1-2), 117 - 122, 英語

[査読有り]

研究論文（学術雑誌）

Ritsu Yamamoto, Masaki Azuma, Nobuhiko Hoshi, Tatsuro Kishida, Shinji Satomura, Seiichiro Fujimoto

Background: Three serum tests, α-fetoprotein (AFP), human chorionic gonadotrophin and unconjugated oestriol, are now widely used for screening for Down's syndrome. Lens culinaris agglutinin-reactive α-fetoprotein (AFP-L3) is a variant of α-fetoprotein with α1→6 fucose appended to the reducing terminal N-acetylglucosamine. It is the most prominent AFP detected in the serum of patients with hepatocellular carcinoma. Methods: We investigated microheterogeneities of the carbohydrate chain on AFP in fetal liver tissues, amniotic fluids and maternal sera obtained from pregnancies with Down's syndrome using lectin affinity electrophoresis with four lectins. The percentages of AFP-L3 in maternal sera from 22 Down's syndrome and 227 unaffected pregnancies were determined. Results: Unlike the case with AFP concentration, the percentage of AFP-L3 in maternal serum and amniotic fluid was similar, and apparently not influenced by membrane permeability. Knowing the percentage of AFP-L3 in maternal serum was effective for discriminating between Down's syndrome-affected pregnancies and unaffected pregnancies. The percentage of AFP-L3 in maternal serum identified 55% of Down's syndrome cases with a 5% false-positive rate. Conclusions: AFP-L3 should be an effective replacement for AFP in prenatal Down's syndrome screening.

Oxford University Press, 2001年, Human Reproduction, 16 (11), 2438 - 2444, 英語

[査読有り]

研究論文（学術雑誌）

H Yamada, N Hoshi, EH Kato, Y Ebina, T Kishida, T Sagawa, K Matsuno, S Fujimoto

A 35-year-old Japanese woman with a low level (42-54%) of blood antithrombin (AT) III, experienced two induced abortions due to deep venous thrombosis at 8 weeks of gestation (GW) and cerebral thrombosis at 10 GW, The present pregnancy was successfully managed with intravenous administration of AT III (6,000-8,000 U/wk), Analysis of polymerase chain reaction (PCR)-single strand conformation polymorphism (SSCP) for exons 3A and 4 of the AT III gene (AT3) using her DNA revealed extra expansion bands with altered migration. The DNA sequencing demonstrated novel mutations in exon 3A of AT3: a G to T substitution at nucleotide position 5333 in codon GAG for Glu 113, causing a stop codon (E113X), and an A to T substitution at position 5338 in codon AAA for Lys 114, forming Asn (K114N). These novel mutations, especially E113X, in AT3 may be related to recurrent thrombosis in the pregnancy. (C) 2000 Wiley-Liss, Inc.

WILEY-LISS, 2000年04月, AMERICAN JOURNAL OF MEDICAL GENETICS, 91 (5), 348 - 350, 英語

[査読有り]

研究論文（学術雑誌）

Tatsuro Kishida, Nobuhiko Hoshi, Rifumi Hattori, Hiroaki Negishi, Hideto Yamada, Kazuhiko Okuyama, Kaoru Hanatani, Tsukasa Takagi, Tadashi Sagawa, Seiichiro Fujimoto

Objective: This prospective study assesses the efficacy of maternal serum screening for use in prenatal diagnosis of fetal anomaly and chromosome imbalance in Japanese women. Methods: Maternal serum α-fetoprotein, human chorionic gonadotropin, and unconjugated estriol were measured in 1055 singleton pregnant women between 14 and 20 weeks of gestation. A calculated risk for trisomy 21 of ≥ 1/299 or α-fetoprotein ≥ 2.5 multiples of the median was adopted as positive. Results: Three hundred and seventy-eight of the 1055 women screened (35.8%) were identified as positive. Sensitivity, false-positive rate, and positive predictive value in women aged < 35 years were 60.0, 10.6, and 6.8%, respectively, and these values were 87.5, 49.3, and 4.2%, respectively, in women aged ≥ 35 years. The false-positive rate in women aged < 35 years was significantly lower than that for women aged ≥ 35 years (p < 0.001). Chromosomal abnormalities were identified in 21 cases, including 10 with trisomy 21, 5 with trisomy 18, 2 with trisomy 13, and 4 with other chromosomal disorders. Seventeen of the 21 cases (81.0%) showed screen-positive results, and among these all 10 cases with trisomy 21 were detectable. Two cases with trisomy 18, 1 with trisomy 13 and 1 with isochromosome X showed extremely low human chorionic gonadotropin levels (0.4 ± 0.1 multiples of the median, mean ± SE), although they were screen negative. Of the 264 women who did not undergo amniocentesis, none had any clinical findings consistent with aneuploidy after birth. Conclusions: Our results suggest that the evaluation of each serum marker, as well as of the calculated risk, was significantly important in the prenatal detection of fetal aneuploidy. Copyright (C) 2000 S. Karger AG, Basel.

S. Karger AG, 2000年, Fetal Diagnosis and Therapy, 15 (2), 112 - 117, 英語

[査読有り]

研究論文（学術雑誌）

Yasushi Handa, Nobuhiko Hoshi, Hideto Yamada, Shin-Ichiro Wada, Masataka Kudo, Katsuya Tsuda, Tadashi Sagawa, Seiichiro Fujimoto

Objective: To report a case of tubal pregnancy in a unicornuate uterus with rudimentary horn on the side of the rudiment and its pathology. Design: Case report. Setting: University hospital. Patient: An 18-year-old woman, primigravida, with tubal pregnancy. Intervention(s): Systemic administration of methotrexate, salpingectomy by laparotomy, and laparoscopic surgery for resection of rudimentary horn. Main Outcome Measure(s): Emergent laparotomy revealed that the intraperitoneal hemorrhage was caused by the rupture of the tubal pregnancy on the same side as the rudimentary horn of the unicornuate uterus. A corpus luteum was found at the ipsilateral ovary of the rudimentary horn. Result(s): Image diagnosis and pathological examination of the rudimentary horn revealed that this uterine malformation was a unicornuate uterus with a noncommunicated, noncavitary rudimentary horn, corresponding to class IIc of the American Fertility Society classification of mullerian anomalies. Conclusion(s): This is the first report of a tubal pregnancy on the side of the noncommunicating rudimentary horn with the ipsilateral ovary carrying a corpus luteum in a unicornuate uterus.

1999年08月, Fertility and Sterility, 72 (2), 354 - 356, 英語

[査読有り]

研究論文（学術雑誌）

Nobuhiko Hoshi, Rifumi Hattori, Kaoru Hanatani, Kazuhiko Okuyama, Hideto Yamada, Tatsuro Kishida, Takahiro Yamada, Tadashi Sagawa, Yoshio Sumiyoshi, Seiichiro Fujimoto

The aims of the present study were to determine recent trends in the prevalence of Down syndrome (DS) in Japan, and to determine whether recent changes in demographic and social habits and access to prenatal diagnosis have influenced the livebirth rates of DS. Livebirth statistics indicate that the birth rate in Japan has decreased for women in their 20s and has increased for those in their 30s and 40s. During an 18-year period between 1980 and 1997, 1,299 consecutive DS infants were born among a total of 2,232,694 births, a rate corresponding to approximately 10% of all births in Japan over the same period. The increasing risk of DS with advancing maternal age was confirmed. The overall prevalence was 5.82 DS births per 10,000 livebirths (8.3-9.7 per 10,000 after correction according to the estimated ascertainment ratio: 60-70%). The prevalence rate by year of child birth represents a statistically significant increase (P = 0.001). In conclusion, recent trends in the prevalence of DS in Japan from 1980 to 1997 failed to show a consistent tendency to decrease, probably because of the concomitant increase in pregnancy in advanced maternal age.

Wiley-Liss Inc., 1999年06月04日, American Journal of Medical Genetics, 84 (4), 340 - 345, 英語

[査読有り]

研究論文（学術雑誌）

Shinya Nishi, Nobuhiko Hoshi, Masanori Kasahara, Teruo Ishibashi, Seiichiro Fujimoto

The human deleted in azoospermia-like autosomal (DAZLA) gene is thought to be a candidate gene for azoospermia. cDNA encoding the C-terminal 94 amino acid residues of human DAZLA was used to express a bacterial fusion protein which was then used to raise polyclonal antibodies in rabbits. Immunohistochemical analyses with the human DAZLA antiserum showed that the DAZLA protein is expressed at a cytoplasmic location in female germ cells. Available evidence suggests that the DAZLA gene is a participant in human oogenesis.

1999年06月, Molecular Human Reproduction, 5 (6), 495 - 497, 英語

[査読有り]

研究論文（学術雑誌）

Shigeki Uehara, Nobuo Yaegashi, Tohru Maeda, Nobuhiko Hoshi, Seiichiro Fujimoto, Keiya Fujimori, Kaoru Yanagida, Michiko Yamanaka, Fumiki Hirahara, Akira Yajima

Objective: To evaluate the risk of recurrence of fetal chromosomal aberrations in women who had offspring with numeric chromosomal abnormalities. Subjects and Methods: This collaborative study consisted of 1076 Japanese women with a history of offspring with trisomy-21, -18, -13, or 45,X. Second-trimester amniocenteses were performed, resulting in 1248 fetal karyotypes that were analyzed with reference to prior offspring karyotypes and maternal age. Results: Of the 842 women with trisomy-21 offspring, 10 conceived another such fetus. In 2 women with 3 or more such offspring, parental mosaicism of trisomy-21 was suspected. The incidence of recurrence of trisomy-21 increased with age, and significantly exceeded the incidence of trisomy-21 fetuses in the general population. None of the 170 women with trisomy-18 offspring, and none of the 46 women with trisomy-13 offspring, had another such fetus. Of the 18 women with 45,X offspring, 1 with mos 45,X/46,XX had another such fetus. Conclusions: The risk of recurrence of trisomy-21 is affected by maternal age and parental germline mosaicism. The risk of recurrence of trisomy-18 or -13 appears to be much lower than that of trisomy-21. Women who give birth to more than 1 offspring with 45,X should be examined for mos 45,X/46,XX.

University of Tokyo Press, 1999年, Journal of Obstetrics and Gynaecology Research, 25 (6), 373 - 379, 英語

[査読有り]

研究論文（学術雑誌）

Tadashi Matsuda, Kazuhiko Okuyama, Kazutoshi Cho, Nobuhiko Hoshi, Yoshinori Matsumoto, Yoshiyasu Kobayashi, Seiichiro Fujimoto

OBJECTIVES: Our purpose was to determine whether systemic hypotension induced by rapid withdrawal of fetal blood would induce periventricular leukomalacia in the brain of premature fetal sheep. STUDY DESIGN: At 113 days' gestation, systemic hypotension (mean blood pressure < 30 mm Hg) was induced by withdrawing approximately 35% of the fetoplacental blood volume in the hemorrhage group (n = 6), whereas in the control group (n = 4) isovolemic exchange transfusion was carried out. Six days after the insult, fetal brains were removed and processed for histologic analysis. RESULTS: Five of the 6 fetuses in the hemorrhage group exhibited periventricular white-matter lesions, consisting of nodular coagulation necrosis or diffuse axonal swellings or both. No abnormal findings other than these lesions were detected in the fetal brains in either experimental group. CONCLUSION: Hemorrhagic hypotension antenatally induced brain lesions similar to those of periventricular leukomalacia, suggesting that it is an essential element in the pathogenesis of periventricular leukomalacia in premature fetuses.

Mosby Inc., 1999年, American Journal of Obstetrics and Gynecology, 181 (3), 725 - 730, 英語

[査読有り]

研究論文（学術雑誌）

Takahiro Yamada, Nobuhiko Hoshi, Kazuhiko Okuyama, Hiroaki Negishi, Satoko Sudo, Tatsuro Kishida, Hideto Yamada, Tadashi Sagawa, Hiroaki Fujii, Akihiro Ishizu, Hiroshi Ishikura, Seiichiro Fujimoto

Ectopia cordis is a rare congenital anomaly. We present 4 cases of ectopia cordis, 1 of which is the first report of an affected fetus in a triplet pregnancy. The morphological relationship between the types of ectopia cordis and their outcomes were investigated in all 4 cases. In addition, the literature on ectopia cordis in Japan was reviewed and discussed.

University of Tokyo Press, 1999年, Journal of Obstetrics and Gynaecology Research, 25 (4), 237 - 243, 英語

[査読有り]

研究論文（学術雑誌）

Nobuhiko Hoshi, Miri Fujita, Masato Mikuni, Takafumi Fujino, Kazuhiko Okuyama, Yasushi Handa, Hideto Yamada, Tadashi Sagawa, Hitoshi Hareyama, Yutaka Nakahori, Kenji Fujieda, Jeffrey A. Kant, Kazuo Nagashima, Sciichiro Fujimoto

We report an unusual case of a 55 year old Japanese woman with a seminoma but relatively normal menses. The patient was a phenotypic female with late onset menarche (18 years of age), who was amenorrhoeic for the first year, followed by menses of one to three days' slight flow with dysmenorrhoea, but an otherwise normal menstrual history. A typical seminoma was removed from the left adnexal region and an immature testis was identified separately as an associated right adnexal mass. Repeated karyotypic studies on peripheral 770, Japan blood lymphocyte cultures showed only Y Nal ahori 46,X,-Y,t(Y 15)(q12 p13). Cytogenetic examination of the patient's younger brother, who had fathered three healthy children, showed an identical karyotype. Mosaicism of 46,X,-Y,t(Y 15)(q12 p13)/45,X cell lines was found in skin samples from the patient's elbow and genital regions, although there were no clinical stigmata of Turner syndrome. An androgen receptor binding assay of cultured genital skin fibroblasts was negative. Molecular analysis using Southern blot hybridisation, PCR, and direct DNA sequencing showed that neither the patient nor her brother had a detectable deletion or other abnormalities of Y chromosome sequences, including the SRY (sex determining region of the Y chromosome) gene sequence. These findings suggest that Turner mosaicism of the 45,X cell line may have contributed to this atypical presentation in an XY female, although we cannot exclude abnormalities of other genes related to sex differentiation.

1998年, Journal of Medical Genetics, 35 (10), 852 - 856, 英語

[査読有り]

研究論文（学術雑誌）

Nobuhiko Hoshi, Hidefumi Tonoki, Yasushi Handa, Takafumi Fujino, Kazuhiko Okuyama, Yasutsugu Koga, Yoshinori Matsumoto, Takahiro Yamada, Hideto Yamada, Tatsuro Kishida, Tadashi Sagawa, Kenji Fujieda, Yutaka Nakahori, Jeffrey A. Kant, Sehchiro Fujimoto

We report a case of mos 45,X/46,X,+mar, diagnosed prenatally by amniocentesis, whose physical examination, including external and internal organs, along with serum testosterone values were normal five years after delivery. The mosaic karyotype was seen in 146 of 240 cells examined (amniotic fluid cells, 110/65 placental chorionic vilii: 5/4 cord blood, 21/81 cultured skin fibroblasts, 10/90) from 386 metaphases, and the marker chromosome appeared as a small non-fluorescent acrocentric chromosome. All autosomes appeared normal, and no normal Y chromosome could be demonstrated. Analysis of 26 Y-chromosome loci by molecular techniques such as PCR, Southern analysis using multiple Y-specific DNA probes, and Hae III restriction endonuclease assessment of male-specific repeated DNA in the heterochromatic region of the Y chromosome, and fluorescence in situ hybridization (FISH), revealed the marker was derived from a Y chromosome including p terminal to q11.23, and paracentric inversion in the remaining Y long arm. The formation of testes can be considered as existence of SRY (sex-determining region of Y) as a testis-determining factor. The present report illustrates the importance of FISH and molecular techniques as a complement to cytogenetic methods for accurate identification and characterization of chromosome rearrangements in prenatal diagnosis.

1998年, Prenatal Diagnosis, 18 (12), 1316 - 1322, 英語

[査読有り]

研究論文（学術雑誌）

Hideto Yamada, Emi H. Kato, Itsuko Furuta, Nobuhiko Hoshi, Kazuki Koizumi, Kenichi Sawada, Seiichiro Fujimoto

Fetal anemia causes hydrops fetalis and fetal ascites/hydrothorax, and in severe cases the prognosis is poor. Little other than alloimmunity and viral infections are known as mechanisms causing fetal anemia. The aim of this study was to elucidate any pathogenesis in fetal anemia due to otherwise idiopathic etiology. The levels of three hematopoietic cytokines, IL-3, erythropoietin (EPO), and granulocyte colony-stimulating factor (G-CSF) were measured in blood samples obtained by cordocentesis from six fetuses with anemia (Hb < 10.0 g/dl) and 34 fetuses without anemia. Cordocentesis was performed prior to the onset of labor or uterine contractions in all pregnant women. The concentration of IL-3 in fetuses with anemia [M ± (SD), 8.3 (10.1) pg/ml] was significantly lower than that in fetuses without anemia [59.9 (71.0) pg/ml]. EPO and G-CSF levels were not different between the two groups. In addition, through in vitro colony formation assay, using blood stem cells from two fetuses with severe anemia and three fetuses without anemia, it was found that colony forming unit-erythroid, burst forming unit- erythroid and granulocyte macrophage-colony forming unit were significantly suppressed in blood stem cells from the two fetuses with severe anemia. Thus, the malfunction of differentiation and proliferation of blood stem cells and the decrease of hematopoietic cytokine levels in the fetal circulation may be responsible for the occurrence of fetal anemia.

Thieme Medical Publishers, Inc., 1998年, Seminars in Thrombosis and Hemostasis, 24 (5), 485 - 490, 英語

[査読有り]

研究論文（国際会議プロシーディングス）

Hideto Yamada, Tatsuro Kishida, Noriko Kobayashi, Emi H. Kato, Nobuhiko Hoshi, Seiichiro Fujimoto

The aim of this trial was to investigate the efficacy of massive i.v. immunoglobulin (MIVIg) treatment for women with a history of recurrent spontaneous abortion (RSA) due to unexplained aetiology. The study included nine women (11 pregnancies) with a history of four or more consecutive RSA with unexplained aetiology and no live births. The mean number of fetal losses was 4.5 (range 4-6 abortions). Over the course of 5 days, immunoglobulin (20 g/day) was infused i.v. at gestational weeks 4-7. No additional infusions were carried out. Two pregnancies out of the 11 conceptions resulted in missed abortions at gestational weeks 6 and 7 respectively. Mosaicism (46XX/ 48XX, + 16, + 20), and tetraploidy (92XXXX) were found by chromosome analyses of the two aborti. Eight out of the other nine pregnancies resulted in full term deliveries of healthy neonates. One pregnancy developed intrauterine growth retardation and fetal distress, resulting in a premature delivery (30 gestational weeks) by Caesarean section. Thus, excluding the two abortions with chromosome aberrations, the MIVIg treatment was effective in all nine pregnancies of RSA women with unexplained aetiology. This MIVIg treatment (100 g administered in early gestation) may be a beneficial alternative to previous IVIg infusion methods, and should be further evaluated in a multicentric, placebo-controlled study, employing a larger number of homogeneous patients who fall into a high risk catagory of first trimester abortions.

1998年, Human Reproduction, 13 (9), 2620 - 2623, 英語

[査読有り]

研究論文（学術雑誌）

Nobuhiko Hoshi, Kaoru Hanatani, Tatsuro Kishida, Tadashi Sagawa, Seiichiro Fujimoto

Objective: To clarify the prenatal sex ratio, and types and frequencies of chromosome anomalies in relation to gestational weeks in women of advanced maternal age. Methods: Chromosomal analysis was performed in 894 induced abortuses derived from elderly pregnant women 35 or more years of age. Results: The embryonic sex ratio in the chromosomally normal (abnormal) gave a preponderance of females over males in lower gestational weeks [366/458 (53/73) 79.9 to 100 (86.3 to 100) in 4-10 weeks] the reversal of dominancy in those from females to males occurred in the 11th gestational week [41/29 (5/4) 141.4 to 100 (125.0 to 100) in 11-20 weeks]. The frequency of trisomy in females at 10 weeks of gestation was significantly high (7/28 25%). Conclusions: This study showed that the existence of a difference of and a reversal of the sex ratio in gestational weeks. It was considered that there might be a lower viability of genetically handicapped males as compared to such females. However, the reversal of the sex ratio, such as that observed between 9th and 10th gestational weeks, might reflect events occurring after implantation.

Blackwell Publishing, 1997年, Journal of Obstetrics and Gynaecology Research, 23 (1), 1 - 7, 英語

[査読有り]

研究論文（学術雑誌）

Nobuhiko Hoshi, Yukiko Yamagami, Kaoru Hanatani, Toshinobu Tanaka, Seiichiro Fujimoto

A total of 934 induced abortuses of middle‐aged pregnant women (35–48 years old) were chromosomally surveyed. The mean gestational age was 7.6±2.0 (S.D.) weeks after the first day of the last menstrual period, and the mean maternal age was 39.6±2.7 (S.D.) years. There was a high incidence of chromosomally abnormal fetuses in induced abortions, which markedly increased with the advancing age of the women: 9.6% (40/418) for the 35–39‐year‐old age group, 20.7% (100/484) for the 40–44‐year‐old age group, and 43.8% (14/32) for the 45–48‐year‐old age group, averaging 16.5%. © 1990 Japanese Society of Obstetrics and Gynaecology

1990年, Asia‐Oceania Journal of Obstetrics and Gynaecology, 16 (3), 275 - 281, 英語

[査読有り]

研究論文（学術雑誌）

N HOSHI, Y HASHIMOTO, H KITAGAWA, Y KON, N KUDO

HOKKAIDO UNIV, 1988年01月, JAPANESE JOURNAL OF VETERINARY RESEARCH, 36 (1), 15 - 29, 英語

[査読有り]

研究論文（学術雑誌）

星 信彦, 橋本 善春, 北川 浩, 昆 泰寛, 工藤 規雄

1988年, Jpn. J. Vet. Sci.,, 50 (1), 83 - 92

N HOSHI, Y HASHIMOTO, H KITAGAWA, Y KON, N KUDO

JAPAN SOC VET SCI, 1986年12月, JAPANESE JOURNAL OF VETERINARY SCIENCE, 48 (6), 1097 - 1107, 英語

[査読有り]

研究論文（学術雑誌）

大野周嗣, 大成果乃子, 久保静花, 坂田奈那美, 平野哲史, 万谷洋平, 横山俊史, 石塚真由美, 池中良徳, 星信彦

2018年12月, 日本内分泌かく乱化学物質学会研究発表会要旨集, 21st, 79, 日本語

杉田晄佑, 高田匡, 万谷洋平, 横山俊史, 石塚真由美, 池中良徳, 星信彦

2018年12月, 日本内分泌かく乱化学物質学会研究発表会要旨集, 21st, 82, 日本語

大野周嗣, 大成果乃子, 久保静花, 坂田奈那美, 杉田晄佑, 宮田結佳, 高田匡, 平野哲史, 万谷洋平, 横山俊史, 石塚真由美, 池中良徳, 星信彦

2018年08月21日, 日本獣医学会学術集会講演要旨集, 161st, 467, 日本語

表原 拓也, 永堀 健太, 河田 晋一, 李 忠連, 宮宗 秀伸, 伊藤 正裕, 南 貴一, 万谷 洋平, 梅村 ゆりあ, 西田 美穂, 平野 哲史, 北川 浩, 横山 俊史, 星 信彦, 吉岡 秀文

東京医科大学医学会, 2018年01月, 東京医科大学雑誌, 76 (1), 139 - 140, 英語

表原 拓也, 永堀 健太, 河田 晋一, 李 忠連, 宮宗 秀伸, 伊藤 正裕, 南 貴一, 万谷 洋平, 梅村 ゆりあ, 西田 美穂, 平野 哲史, 北川 浩, 横山 俊史, 星 信彦, 吉岡 秀文

東京医科大学医学会, 2018年01月, 東京医科大学雑誌, 76 (1), 139 - 140, 英語

星 信彦

2016年, Endocrine Disrupter News Letter, 19 (2), 3, 日本語

記事・総説・解説・論説等（学術雑誌）

辰巳敬哉, 亀崎直樹, 藍原祥子, 山下真路, 谷口真理, 三根佳奈子, 坂本未来, 表原拓也, 小林泰丈, 横山俊史, 北川浩, 今川智敬, 星信彦

2013年08月30日, 日本獣医学会学術集会講演要旨集, 156th, 191, 日本語

辰巳敬哉, 亀崎直樹, 藍原祥子, 山下真路, 谷口真理, 三根佳奈子, 坂本未来, 木下今日子, 横山俊史, 北川浩, 今川智敬, 金沢和樹, 星信彦

2013年03月31日, は虫両棲類学会報, 2013 (1), 66, 日本語

辰巳敬哉, 亀崎直樹, 藍原祥子, 山下真路, 谷口真理, 三根佳奈子, 坂本未来, 表原拓也, 小林泰丈, 横山俊史, 北川浩, 今川智敬, 星信彦

2013年, 日本野生動物医学会大会・講演要旨集, 19th, 98, 日本語

段上 めぐみ, 田阪 健, 須谷 真巳, 木下 今日子, 徳本 順子, 表原 拓也, 小林 泰丈, 辰巳 敬哉, 谷田 任司, 菅野 美津子, 赤星 英一, 横山 俊史, 北川 浩, 星 信彦

環境ホルモン学会(日本内分泌撹乱化学物質学会), 2012年12月, 環境ホルモン学会研究発表会要旨集, 15回, 59 - 59, 日本語

辰巳敬哉, 亀崎直樹, 山下真路, 長原大知, 木下今日子, 段上めぐみ, 徳本順子, 安田玲子, 表原拓也, 小林泰丈, 横山俊史, 北川浩, 今川智敬, 星信彦

2012年08月31日, 日本獣医学会学術集会講演要旨集, 154th, 175, 日本語

星 信彦, 石川 恭子, 須谷 真己, 藤井 裕香, 段上 めぐみ, 木下 今日子, 安田 玲子, 長原 大知, 谷田 任司, 横山 俊史, 北川 浩

(一社)日本解剖学会, 2012年06月, 解剖学雑誌, 87 (2), 37 - 37, 日本語

段上 めぐみ, 須谷 真己, 石川 恭子, 藤井 裕香, 木下 今日子, 安田 玲子, 長原 大知, 谷田 任司, 横山 俊史, 北川 浩, 星 信彦

(一社)日本解剖学会, 2012年06月, 解剖学雑誌, 87 (2), 37 - 37, 日本語

横山 俊史, 石川 恭子, 須谷 真巳, 藤井 裕香, 段上 めぐみ, 木下 今日子, 安田 玲子, 谷田 任司, 北川 浩, 星 信彦

(公社)日本獣医学会, 2011年08月, 日本獣医学会学術集会講演要旨集, 152回, 173 - 173, 日本語

段上 めぐみ, 須谷 真巳, 石川 恭子, 藤井 裕香, 木下 今日子, 安田 玲子, 谷田 任司, 横山 俊史, 北川 浩, 星 信彦

(公社)日本獣医学会, 2011年08月, 日本獣医学会学術集会講演要旨集, 152回, 177 - 177, 日本語

三觜 友子, 割田 克彦, 菅原 照夫, 田渕 圭章, 松本 由樹, 三木 崇範, 石原 可奈, 谷田 任司, 蝦名 康彦, 櫻木 範明, 横山 俊史, 竹内 義喜, 北川 浩, 星 信彦

(公社)日本獣医学会, 2008年09月, 日本獣医学会学術集会講演要旨集, 146回, 148 - 148, 日本語

割田 克彦, 菅原 照夫, 田渕 圭章, 三觜 友子, 松本 由樹, 三木 崇範, 石原 可奈, 谷田 任司, 横山 俊史, 竹内 義喜, 北川 浩, 星 信彦

(公社)日本獣医学会, 2008年03月, 日本獣医学会学術集会講演要旨集, 145回, 163 - 163, 日本語

Katsuhiko Warita, Kazutaka Okamoto, Ken-ichiro Mutoh, Yoshihisa Hasegawa, Zhan-Peng Yue, Toshifumi Yokoyama, Yoshiki Matsumoto, Takanori Miki, Yoshiki Takeuchi, Hiroshi Kitagawa, Teruo Sugawara, Nobuhiko Hoshi

We aimed to elucidate the mechanism of action of estrogenic endocrine disruptors and the rescue of reproductive function, particularly the responsiveness of testes to eCG and/or activin A (ACT) after establishing reproductive disorders. Newborn male mice (n = 29) were randomly divided into an untreated group and three treatment groups that received diethylstilbestrol (DES; 100 mu g per animal) subcutaneously on Postnatal Day 3 to establish reproductive disorders and daily treatment with PBS (controls: DES + PBS), eCG (eCG group: DES + eCG), or eCG + ACT (eCG + ACT group: DES + eCG + ACT) at 6-8 wit of age prior to mating. After treatment, the controls showed diminished Leydig cells in the testes anti thin germ cell layers containing pyknotic germ cells and multinucleated cells. in the eCG and eCG + ACT groups, spermatids and Leydig cells increased markedly. The immunoexpression of androgen receptors in the eCG group and steroidogenic acute regulatory (STAR) protein in the eCG and eCG + ACT groups recovered to approximately the levels in the untreated group; plasma LH and testosterone levels also increased relative to those in the controls. in addition, the cell proliferation index, which is estimated from 5-bromo-2'-deoxyuridine immunoexpression in spermatogonia, increased significantly under eCG treatment, and even more with eCG + ACT. However, the numbers of germ and Leydig cells decreased at 12 wit of age. Thus, ACT and eCG help the! testes to recover from the dysfunction induced by neonatal DES administration. Furthermore, the permanent male reproductive disorder induced by neonatal exposure to estrogenic agents may be more likely to result from dysfunction of the hypothalamic-pituitary axis than from dysfunction of the lower reproductive organs.

SOC STUDY REPRODUCTION, 2008年01月, BIOLOGY OF REPRODUCTION, 78 (1), 59 - 67, 英語

割田 克彦, 菅原 照夫, 田渕 圭章, 三觜 友子, 松本 由樹, 三木 崇範, 石原 可奈, 谷田 任司, 横山 俊史, 竹内 義喜, 北川 浩, 星 信彦

環境ホルモン学会(日本内分泌撹乱化学物質学会), 2007年12月, 環境ホルモン学会研究発表会要旨集, 10回, 178 - 178, 日本語

星 信彦

その他, 学窓社, 2017年, 日本語

教科書・概説・概論

星 信彦

その他, 学窓社, 2013年04月, 日本語

教科書・概説・概論

武田 義明, 林 美鶴, 堀江 修, 星 信彦, 梶並 昭彦, 上田 裕清, 竹中 信幸, 島村 健, 竹内 憲司, 國部 克彦, 松田 毅, 米谷 淳, 吉村 知里

その他, アドスリー, 2011年10月, 日本語

教科書・概説・概論

山田 秀人, 星 信彦, 藤本 征一郎

共著, ヘルス出版, 1999年04月, 日本語

教科書・概説・概論

星 信彦, 山田 秀人, 藤本 征一郎

共著, へるす出版, 1999年04月, 日本語

教科書・概説・概論

星 信彦, 山田 秀人, 藤本 征一郎

共著, へるす出版, 1999年04月, 日本語

教科書・概説・概論

SAGAWA TADASHI, YAMASHITA YOICHI, FURUYA MITSUKO, FUJIMOTO TOSHIO, YAMADA HIDETO, HOSHI NOBUHIKO, YAMAMOTO RITSU, SAKURAGI NORIAKI, FUJIMOTO SEIICHIRO

共著, Ares Serono Symposia, 1999年04月, 英語

学術書

YAMADA TAKASHI, HOSHI NOBUHIKO, SAITO CHIAKI, YAMASHITA YOICHI, SAGAWA TADASHI, FUJINO TAKAFUMI, SAKURAGI NORIAKI, FUMIMOTO SEIICHIRO

共著, Monduzzi Editore, 1998年04月, 英語

学術書

星 信彦, 藤本 征一郎

共著, 医歯薬出版, 1997年04月, 日本語

一般書・啓蒙書

星 信彦, 藤本 征一郎, 牧野田 知

共著, 六法出版社, 1992年04月, 日本語

一般書・啓蒙書

三浦由佳, 横山 俊史, 山本杏, 川西航平, 長谷川千夏, 高田菜々子, 万谷洋平, 星 信彦

第32回モロシヌス研究会, 2019年06月, 日本語, 千葉市, 国内会議

口頭発表（一般）

万谷洋平, 春田知洋, 中西怜稀, 横山 俊史, 星 信彦, 北川 浩

第124回日本解剖学会総会全国学術集会, 2019年03月, 日本語, 新潟市, 国内会議

ポスター発表

安田玲子, 足達, 小此木孝仁, ANZAI Y, KAMIYAMA T, KATANO K, 星 信彦, NATSUME T, 茂木

International Conference on PharmScience Research & Development 2019, 2019年03月, 英語, Paris, 国際会議

口頭発表（一般）

星 信彦, 池中良徳, 大野周嗣, 大成果乃子, 久保静花, 前田瑞稀, 宮田結佳, 杉田晄佑, 石塚真由美, 万谷洋平, 横山 俊史

Chemical Hazard Symposium in Hokkaido, 2019年03月, 英語, Sapporo, 国際会議

[招待有り]

シンポジウム・ワークショップパネル（指名）

星 信彦

ダイオキシン・環境ホルモン対策国民会議設立20周年記念議演会, 2019年01月, 日本語, 東京, 国内会議

[招待有り]

口頭発表（招待・特別）

久保静花, 宮田結佳, 大成果乃子, 大野周嗣, 高田匡, 平野哲史, 横山 俊史, 星 信彦

環境ホルモン学会第21回研究発表会, 2018年12月, 日本語, 東京都文京区, 国内会議

ポスター発表

大野周嗣, 大成果乃子, 久保静花, 坂田奈那美, 平野哲史, 万谷洋平, 横山 俊史, 石塚真由美, 池中良徳, 星 信彦

環境ホルモン学会第21回研究発表会, 2018年12月, 日本語, 東京都文京区, 国内会議

ポスター発表

杉田晄佑, 高田匡, 万谷洋平, 横山 俊史, 石塚真由美, 池中良徳, 星 信彦

環境ホルモン学会第21回研究発表会, 2018年12月, 日本語, 東京都文京区, 国内会議

ポスター発表

長谷川千夏, 梅村ゆりあ, 三浦由佳, 川西航平, 高田菜々子, 大野周嗣, 万谷洋平, 横山 俊史, 星 信彦

関西実験動物研究会第140回研究会, 2018年12月, 日本語, 京都市, 国内会議

口頭発表（一般）

大成果乃子, 大野周嗣, 久保静花, 中西怜稀, 荒井真也, 横山 俊史, 星 信彦

環境ホルモン学会第21回研究発表会, 2018年12月, 日本語, 東京都文京区, 国内会議

ポスター発表

宮田結佳, 久保静花, 大野周嗣, 前田瑞稀, 荒井真也, 中西怜稀, 高田匡, 平野哲史, 横山 俊史, 星 信彦

環境ホルモン学会第21回研究発表会, 2018年12月, 日本語, 東京都文京区, 国内会議

ポスター発表

長谷川千夏, 梅村ゆりあ, 三浦由佳, 川西航平, 高田菜々子, 大野周嗣, 万谷洋平, 横山 俊史, 星 信彦

第94回日本解剖学会近畿支部学術集会, 2018年11月, 日本語, 神戸市, 国内会議

口頭発表（一般）

荒井真也, 万谷洋平, 西田美穂, 湯浅秀人, 横山 俊史, 星 信彦, 北川 浩

第94回日本解剖学会近畿支部学術集会, 2018年11月, 日本語, 神戸市, 国内会議

口頭発表（一般）

中西怜稀, 万谷洋平, 田村彩貴, 荒井真也, 横山 俊史, 星 信彦, 北川 浩

第94回日本解剖学会近畿支部学術集会, 2018年11月, 日本語, 神戸市, 国内会議

口頭発表（一般）

三浦由佳, 山本杏, 川西航平, 長谷川千夏, 高田菜々子, 高田匡, 万谷洋平, 横山 俊史, 星 信彦

第161回日本獣医学会学術集会, 2018年09月, 日本語, つくば市, 国内会議

口頭発表（一般）

久保静花, 宮田結佳, 大成果乃子, 大野周嗣, 杉田晄佑, 前田瑞稀, 高田匡, 平野哲史, 万谷洋平, 横山 俊史, 星 信彦

第161回日本獣医学会学術集会, 2018年09月, 日本語, つくば市, 国内会議

口頭発表（一般）

大野周嗣, 大成果乃子, 久保静花, 坂田奈那美, 杉田晄佑, 宮田結佳, 高田匡, 平野哲史, 万谷洋平, 横山 俊史, 石塚真由美, 池中良徳, 星 信彦

第161回日本獣医学会学術集会, 2018年09月, 日本語, つくば市, 国内会議

口頭発表（一般）

荒井真也, 万谷洋平, 西田美穂, 湯浅秀人, 横山 俊史, 星 信彦, 北川 浩

第161回日本獣医学会学術集会, 2018年09月, 日本語, つくば市, 国内会議

口頭発表（一般）

斉旺梅, 増田なつみ, 万谷洋平, 横山 俊史, 星 信彦, 北川 浩

第161回日本獣医学会学術集会, 2018年09月, 日本語, つくば市, 国内会議

口頭発表（一般）

万谷洋平, 春田知洋, 西田美穂, 横山 俊史, 星 信彦, 北川 浩

第161回日本獣医学会学術集会, 2018年09月, 日本語, つくば市, 国内会議

口頭発表（一般）

中西怜稀, 万谷洋平, 田村彩貴, 荒井真也, 横山 俊史, 星 信彦, 北川 浩

第161回日本獣医学会学術集会, 2018年09月, 日本語, つくば市, 国内会議

口頭発表（一般）

大成果乃子, 大野周嗣, 久保静花, 中西怜稀, 荒井真也, 杉田晄佑, 宮田結佳, 高田匡, 平野哲史, 万谷洋平, 横山 俊史, 星 信彦

第161回日本獣医学会学術集会, 2018年09月, 日本語, つくば市, 国内会議

口頭発表（一般）

宮田結佳, 大成果乃子, 大野周嗣, 久保静花, 杉田晄佑, 高田匡, 前田瑞稀, 中西怜稀, 平野哲史, 万谷洋平, 横山 俊史, 星 信彦

第161回日本獣医学会学術集会, 2018年09月, 日本語, つくば市, 国内会議

口頭発表（一般）

米田直起, 高田 匡, 大成果乃子, 大野周嗣, 久保静花, 杉田晄佑, 宮田結佳, 平野哲史, 万谷洋平, 横山 俊史, 北川 浩, 星 信彦

環境ホルモン学会第20回研究発表会, 2017年12月, 日本語, 神戸市, 国内会議

ポスター発表

高田 匡, 米田直起, 大成果乃子, 大野周嗣, 久保静花, 杉田晄佑, 宮田結佳, 平野哲史, 万谷洋平, 横山 俊史, 北川 浩, 星 信彦

環境ホルモン学会第20回研究発表会, 2017年12月, 日本語, 神戸市, 国内会議

ポスター発表

三浦由佳, 山本 杏, 川西航平, 長谷川千夏, 横山 俊史, 星 信彦

第136回関西実験動物研究会, 2017年12月, 日本語, 京都市, 国内会議

口頭発表（一般）

田村彩貴, 万谷洋平, 西田美穂, 湯浅秀人, 増田なつみ, 横山 俊史, 星 信彦, 北川 浩

第93回日本解剖学会近畿支部学術集会, 2017年11月, 日本語, 大津市, 国内会議

口頭発表（一般）

万谷洋平, 春田知洋, 西田美穂, 湯浅秀人, 増田なつみ, 横山 俊史, 星 信彦, 北川 浩

第93回日本解剖学会近畿支部学術集会, 2017年11月, 日本語, 大津市, 国内会議

口頭発表（一般）

山本杏, 表原拓也, 三浦由佳, 川西航平, 長谷川千夏, 万谷洋平, 北川 浩, 横山 俊史, 星 信彦

第93回日本解剖学会近畿支部学術集会, 2017年11月, 日本語, 大津市, 国内会議

口頭発表（一般）

吉冨千晶, 増田なつみ, 湯浅秀人, 西田美穂, 万谷洋平, 河野潤一, 横山 俊史, 星 信彦, 北川 浩

第160回日本獣医学会学術集会, 2017年09月, 日本語, 鹿児島市, 国内会議

口頭発表（一般）

宮本和樹, 万谷洋平, 湯浅秀人, 西田美穂, 増田なつみ, 横山 俊史, 星 信彦, 北川 浩

第160回日本獣医学会学術集会, 2017年09月, 日本語, 鹿児島市, 国内会議

口頭発表（一般）

万谷洋平, 春田知洋, 西田美穂, 湯浅秀人, 増田なつみ, 横山 俊史, 星 信彦, 北川 浩

第160回日本獣医学会学術集会, 2017年09月, 日本語, 鹿児島市, 国内会議

口頭発表（一般）

星 信彦

第64回生態学会シンポジウム「ネオニコチノイド系農薬研究の最前線」, 2017年03月, 日本語, 新宿区, 国内会議

[招待有り]

口頭発表（招待・特別）

表原拓也, 南貴一, 万谷 洋平, 朝克吉楽, 梅村ゆりあ, 西田美穂, 平野哲史, 青山裕彦, 吉岡秀文, 北川 浩, 横山 俊史, 星 信彦

第122回日本解剖学会総会・全国学術集会, 2017年03月, 日本語, 長崎市, 国内会議

[招待有り]

口頭発表（招待・特別）

米田直起, 平野哲史, 柳井翔吾, 高田匡, 岩本遥, 表原拓也, 片田裕亮, 万谷 洋平, 横山 俊史, 北川 浩, 星 信彦

第19回環境ホルモン学会研究発表会, 2016年12月, 日本語, つくば市, 国内会議

ポスター発表

久保田直人, 表原拓也, 山本杏, 三浦由佳, 平野哲史, 南貴一, 柳井翔吾, 高田匡, 米田直起, 岩本遥, 万谷 洋平, 横山 俊史, 北川 浩, 星 信彦

第39回日本分子生物学会年会, 2016年12月, 日本語, 横浜市, 国内会議

ポスター発表

平野哲史, 柳井翔吾, 高田匡, 米田直起, 表原拓也, 南貴一, 久保田直人, 万谷 洋平, 横山 俊史, 北川 浩, 星 信彦

第19回環境ホルモン学会研究発表会, 2016年12月, 日本語, つくば市, 国内会議

口頭発表（一般）

高田匡, 平野哲史, 柳井翔吾, 米田直起, 岩本遥, 表原拓也, 万谷 洋平, 横山 俊史, 北川 浩, 星 信彦

第19回環境ホルモン学会研究発表会, 2016年12月, 日本語, つくば市, 国内会議

口頭発表（一般）

柳井翔吾, 平野哲史, 表原拓也, 高田匡, 米田直起, 岩本遥, 万谷 洋平, 横山 俊史, 北川 浩, 星 信彦

第19回環境ホルモン学会研究発表会, 2016年12月, 日本語, つくば市, 国内会議

口頭発表（一般）

増田なつみ, 万谷 洋平, 西田美穂, 湯浅秀人, 河野潤一, 横山 俊史, 星 信彦, 北川 浩

第92回日本解剖学会近畿支部学術集会, 2016年11月, 日本語, 東大阪市, 国内会議

口頭発表（一般）

万谷 洋平, 宮本和樹, 西田美穂, 湯浅秀人, 増田なつみ, 横山 俊史, 星 信彦, 北川 浩

第92回日本解剖学会近畿支部学術集会, 2016年11月, 日本語, 東大阪市, 国内会議

口頭発表（一般）

湯浅秀人, 万谷 洋平, 増田なつみ, 西田美穂, 河野潤一, 横山 俊史, 星 信彦, 北川 浩

第92回日本解剖学会近畿支部学術集会, 2016年11月, 日本語, 東大阪市, 国内会議

口頭発表（一般）

山本杏, 表原拓也, 久保田直人, 南貴一, 平野哲史, 万谷 洋平, 北川 浩, 横山 俊史, 星 信彦

第92回日本解剖学会近畿支部学術集会, 2016年11月, 日本語, 東大阪市, 国内会議

口頭発表（一般）

南貴一, 表原拓也, 田渕圭章, 平野哲史, 横山 俊史, 万谷 洋平, 北川 浩, 星 信彦

第92回日本解剖学会近畿支部学術集会, 2016年11月, 日本語, 東大阪市, 国内会議

口頭発表（一般）

湯浅秀人, 増田なつみ, 西田美穂, 河野潤一, 横山 俊史, 万谷 洋平, 星 信彦, 北川 浩

第159回日本獣医学会学術集会, 2016年09月, 日本語, 藤沢市, 国内会議

口頭発表（一般）

増田なつみ, 万谷 洋平, 西田美穂, 湯浅秀人, 河野潤一, 横山 俊史, 星 信彦, 北川 浩

第159回日本獣医学会学術集会, 2016年09月, 日本語, 藤沢市, 国内会議

口頭発表（一般）

万谷 洋平, 宮本和樹, 西田美穂, 湯浅秀人, 増田なつみ, 横山 俊史, 星 信彦, 北川 浩

第159回日本獣医学会学術集会, 2016年09月, 日本語, 藤沢市, 国内会議

口頭発表（一般）

山本杏, 表原拓也, 久保田直人, 南貴一, 広川千英, 平野哲史, 磯江美智子, 柳井翔吾, 高田匡, 米田直起, 三浦由佳, 岩本遥, 万谷 洋平, 北川 浩, 横山 俊史, 星 信彦

第159回日本獣医学会学術集会, 2016年09月, 日本語, 藤沢市, 国内会議

口頭発表（一般）

高田匡, 平野哲史, 柳井翔吾, 米田直起, 表原拓也, 磯江美智子, 久保田直人, 南貴一, 山本杏, 岩本遥, 三浦由佳, 万谷 洋平, 横山 俊史, 北川 浩, 星 信彦

第159回日本獣医学会学術集会, 2016年09月, 日本語, 藤沢市, 国内会議

口頭発表（一般）

米田直起, 平野哲史, 柳井翔吾, 高田匡, 表原拓也, 久保田直人, 南貴一, 山本杏, 岩本遥, 三浦由佳, 磯江美智子, 万谷 洋平, 横山 俊史, 北川 浩, 星 信彦

第159回日本獣医学会学術集会, 2016年09月, 日本語, 藤沢市, 国内会議

口頭発表（一般）

平野哲史, 柳井翔吾, 高田匡, 米田直起, 表原拓也, 久保田直人, 南貴一, 山本杏, 岩本遥, 三浦由佳, 磯江美智子, 万谷 洋平, 横山 俊史, 北川 浩, 星 信彦

第159回日本獣医学会学術集会, 2016年09月, 日本語, 藤沢市, 国内会議

口頭発表（一般）

米田直起, 平野哲史, 柳井翔吾, 高田匡, 表原拓也, 磯江美智子, 久保田直人, 南貴一, 広川千英, 山本杏, 岩本遥, 三浦由佳, 万谷 洋平, 横山 俊史, 北川 浩, 星 信彦

第56回 先天異常学会学術集会, 2016年07月, 日本語, 姫路市, 国内会議

ポスター発表

高田匡, 平野哲史, 柳井翔吾, 米田直起, 表原拓也, 磯江美智子, 久保田直人, 南貴一, 広川千英, 山本杏, 岩本遥, 三浦由佳, 万谷 洋平, 横山 俊史, 北川 浩, 星 信彦

第56回 先天異常学会学術集会, 2016年07月, 日本語, 姫路市, 国内会議

ポスター発表

平野哲史, 柳井翔吾, 高田匡, 米田直起, 表原拓也, 磯江美智子, 久保田直人, 南貴一, 広川千英, 山本杏, 岩本遥, 三浦由佳, 万谷 洋平, 横山 俊史, 北川 浩, 星 信彦

第56回 先天異常学会学術集会, 2016年07月, 日本語, 姫路市, 国内会議

ポスター発表

星 信彦

第30回環境ホルモン学会講演会「ネオニコチノイド系農薬をめぐって」, 2016年06月, 日本語, 文京区, 国内会議

[招待有り]

口頭発表（招待・特別）

平野哲史, 柳井翔吾, 高田匡, 米田直起, 表原拓也, 久保田直人, 南貴一, 広川千英, 山本杏, 万谷 洋平, 横山 俊史, 北川 浩, 星 信彦

第43回日本毒性学会学術年会, 2016年06月, 日本語, 名古屋市, 国内会議

ポスター発表

星 信彦

Post-Neonics –What Next ? Symposium, 2016年06月, 英語, 新宿区, 国際会議

[招待有り]

口頭発表（招待・特別）

表原拓也, 南貴一, 万谷洋平, 梅村ゆりあ, 西田 美穂, 平野哲史, 吉岡 秀文, 北川浩, 横山俊史, 星信彦

第121回日本解剖学会総会・全国学術集会, 2016年03月, 日本語, 郡山市, 国内会議

口頭発表（一般）

平野哲史, 柳井翔吾, 表原拓也, 高田匡, 米田直起, 梅村ゆりあ, 久保田直人, 南貴一, 広川千英, 山本杏, 万谷洋平, 横山俊史, 北川浩, 星信彦

環境ホルモン学会第18回研究発表会, 2015年12月, 日本語, 下野市, 国内会議

ポスター発表

柳井翔吾, 平野哲史, 表原拓也, 高田匡, 米田直起, 梅村ゆりあ, 久保田直人, 南貴一, 広川千英, 山本杏, 万谷洋平, 横山俊史, 北川浩, 星信彦

環境ホルモン学会第18回研究発表会, 2015年12月, 日本語, 下野市, 国内会議

ポスター発表

表原拓也, 万谷洋平, 南貴一, 梅村ゆりあ, 平野哲史, 横山俊史, 北川浩, 星信彦

第38回日本分子生物学会年会・第88回日本生化学会大会合同大会, 2015年12月, 日本語, 神戸市, 国内会議

口頭発表（一般）

湯浅秀人, 万谷洋平, 増田なつみ, 西田美穂, 河野潤一, 横山俊史, 星信彦, 北川浩

第91回日本解剖学会・近畿支部学術集会, 2015年11月, 日本語, 京都市, 国内会議

口頭発表（一般）

梅村ゆりあ, 表原拓也, 平野哲史, 久保田直人, 柳井翔吾, 増田なつみ, 湯浅秀人, 万谷洋平, 北川浩, 横山俊史, 星信彦

第91回日本解剖学会・近畿支部学術集会, 2015年11月, 日本語, 京都市, 国内会議

口頭発表（一般）

増田なつみ, 万谷洋平, 西田美穂, 湯浅秀人, 河野潤一, 横山俊史, 星信彦, 北川浩

第91回日本解剖学会・近畿支部学術集会, 2015年11月, 日本語, 京都市, 国内会議

口頭発表（一般）

万谷洋平, 西田美穂, 湯浅秀人, 増田なつみ, 横山俊史, 星信彦, 北川浩

第91回日本解剖学会・近畿支部学術集会, 2015年11月, 日本語, 京都市, 国内会議

口頭発表（一般）

表原拓也, 南貴一, 万谷洋平, 梅村ゆりあ, 西田美穂, 平野哲史, 吉岡秀文, 横山俊史, 北川浩, 星信彦

第91回日本解剖学会・近畿支部学術集会, 2015年11月, 日本語, 京都市, 国内会議

口頭発表（一般）

南 貴一, 表原拓也, 田渕圭章, 梅村ゆりあ, 平野哲史, 横山俊史, 北川 浩, 星 信彦

第91回日本解剖学会・近畿支部学術集会, 2015年11月, 日本語, 京都市, 国内会議

口頭発表（一般）

平野哲史, 柳井翔吾, 表原拓也, 梅村ゆりあ, 久保田直人, 南貴一, 高田匡, 米田直起, 広川千英, 山本杏, 万谷洋平, 横山俊史, 北川浩, 星信彦

第158回日本獣医学会, 2015年09月, 日本語, 十和田市, 国内会議

口頭発表（一般）

万谷洋平, 西田美穂, 湯浅秀人, 増田なつみ, 横山俊史, 星信彦, 北川浩

第158回日本獣医学会, 2015年09月, 日本語, 十和田市, 国内会議

口頭発表（一般）

増田なつみ, 万谷洋平, 西田美穂, 湯浅秀人, 河野潤一, 横山俊史, 星信彦, 北川浩

第158回日本獣医学会, 2015年09月, 日本語, 十和田市, 国内会議

口頭発表（一般）

湯浅秀人, 万谷洋平, 増田なつみ, 西田美穂, 河野潤一, 横山俊史, 星信彦, 北川浩

第158回日本獣医学会, 2015年09月, 日本語, 十和田市, 国内会議

口頭発表（一般）

表原拓也, 万谷洋平, 南貴一, 梅村ゆりあ, 平野哲史, 横山俊史, 北川浩, 星信彦

日本家禽学会2015年度秋季大会, 2015年09月, 日本語, 江別市, 国内会議

口頭発表（一般）

南 貴一, 表原拓也, 田渕圭章, 梅村ゆりあ, 平野哲史, 北川 浩, 横山俊史, 星 信彦

日本家禽学会2015年度秋季大会, 2015年09月, 日本語, 江別市, 国内会議

口頭発表（一般）

MANTANI YOUHEI, MIYAMOTO KAZUKI, MATSUMORI SEIKO, YUASA HIDETO, MASUDA NATSUMI, YOKOYAMA TOSHIFUMI, HOSHI NOBUHIKO, KITAGAWA HIROSHI

17th International Congress of Mucosal Immunology, 2015年07月, 英語, Berlin, Germany, 国際会議

ポスター発表

梅村ゆりあ, 橋本理恵, 表原拓也, 長原大知, 平野哲史, 久保田直人, 南貴一, 柳井翔吾, 万谷 洋平, 横山 俊史, 北川 浩, 星 信彦

第62回日本実験動物学会, 2015年05月, 日本語, 京都市, 国内会議

ポスター発表

星 信彦

第60回日本生殖医学会学術集会, 2015年04月, 日本語, 横浜市, 国内会議

[招待有り]

口頭発表（招待・特別）

梅村 ゆりあ, 橋本 理恵, 表原 拓也, 平野 哲史, 長原 大知, 湯浅 秀人, 久保田 直人, 南 貴一, 柳井 翔吾, 万谷 洋平, 横山 俊史, 北川 浩, 星 信彦

第120回 日本解剖学会総会･全国学術集会, 2015年03月, 日本語, 神戸市, 国内会議

ポスター発表

横山 俊史, 橋本 理恵, 梅村 ゆりあ, 表原 拓也, 平野 哲史, 長原 大知, 柳井 翔吾, 南 貴一, 久保田 直人, 万谷 洋平, 北川 浩, 星 信彦

第120回 日本解剖学会総会･全国学術集会, 2015年03月, 日本語, 神戸市, 国内会議

ポスター発表

平野 哲史, 柳井 翔吾, 表原 拓也, 橋本 理恵, 梅村 ゆりあ, 久保田 直人, 南 貴一, 万谷 洋平, 横山 俊史, 北川 浩, 星 信彦

第120回 日本解剖学会総会･全国学術集会, 2015年03月, 日本語, 神戸市, 国内会議

ポスター発表

MANTANI YOUHEI, NISHIDA MIHO, YUASA HIDETO, MASUDA NATSUMI, TAKAHARA EIICHIROU, YOKOYAMA TOSHIFUMI, HOSHI NOBUHIKO, KITAGAWA HIROSHI

第120回 日本解剖学会総会･全国学術集会, 2015年03月, 日本語, 神戸市, 国内会議

ポスター発表

表原 拓也, 橋本 理恵, 梅村 ゆりあ, 平野 哲史, 南 貴一, 長原 大知, 湯浅 秀人, 久保田 直人, 柳井 翔吾, 万谷 洋平, 横山 俊史, 北川 浩, 星 信彦

第120回 日本解剖学会総会･全国学術集会, 2015年03月, 日本語, 神戸市, 国内会議

ポスター発表

湯浅 秀人, 万谷 洋平, 西田 美穂, 高原 英一郎, 増田 なつみ, 河野 潤一, 横山 俊史, 星 信彦, 北川 浩

第120回 日本解剖学会総会･全国学術集会, 2015年03月, 日本語, 神戸市, 国内会議

ポスター発表

湯浅 秀人, 万谷 洋平, 横山 俊史, 星 信彦, 北川 浩

神戸大学研究基盤センター若手フロンティア研究会2014, 2014年12月, 日本語, 神戸市, 国内会議

ポスター発表

平野 哲史, 柳井 翔吾, 表原 拓也, 橋本 理恵, 梅村 ゆりあ, 久保田 直人, 南 貴一, 万谷 洋平, 横山 俊史, 北川 浩, 星 信彦

環境ホルモン学会第17回研究発表会, 2014年12月, 日本語, 京都市, 国内会議

口頭発表（一般）

横山 俊史, 橋本 理恵, 梅村 ゆりあ, 表原 拓也, 長原 大知, 平野 哲史, 久保田 直人, 南 貴一, 湯浅 秀人, 柳井 翔吾, 万谷 洋平, 北川 浩, 星 信彦

第157回日本獣医学会学術集会, 2014年09月, 日本語, 札幌市, 国内会議

口頭発表（一般）

万谷 洋平, 西田 美穂, 湯浅 秀人, 高原 英一郎, 河野 潤一, 横山 俊史, 星 信彦, 北川 浩

第157回日本獣医学会学術集会, 2014年09月, 日本語, 札幌市, 国内会議

口頭発表（一般）

池邊 正大, 万谷 洋平, 西田 美穂, 湯浅 秀人, 高原 英一郎, 河野 潤一, 横山 俊史, 星 信彦, 北川 浩

第157回日本獣医学会学術集会, 2014年09月, 日本語, 札幌市, 国内会議

口頭発表（一般）

湯浅 秀人, 万谷 洋平, 西田 美穂, 高原 英一郎, 河野 潤一, 横山 俊史, 星 信彦, 北川 浩

第157回日本獣医学会学術集会, 2014年09月, 日本語, 札幌市, 国内会議

口頭発表（一般）

橋本 理恵, 梅村 ゆりあ, 表原 拓也, 平野 哲史, 長原 大知, 湯浅 秀人, 久保田 直人, 南 貴一, 柳井 翔吾, 万谷 洋平, 横山 俊史, 北川 浩, 星 信彦

第157回日本獣医学会学術集会, 2014年09月, 日本語, 札幌市, 国内会議

口頭発表（一般）

平野 哲史, 表原 拓也, 橋本 理恵, 梅村 ゆりあ, 久保田 直人, 南 貴一, 柳井 翔吾, 長原 大知, 湯浅 秀人, 万谷 洋平, 横山 俊史, 北川 浩, 星 信彦

第157回日本獣医学会学術集会, 2014年09月, 日本語, 札幌市, 国内会議

口頭発表（一般）

表原 拓也, 橋本 理恵, 梅村 ゆりあ, 平野 哲史, 南 貴一, 長原 大知, 湯浅 秀人, 万谷 洋平, 横山 俊史, 北川 浩, 星 信彦

日本家禽学会2014年度秋季大会, 2014年09月, 日本語, 鹿児島市, 国内会議

口頭発表（一般）

表原 拓也, 橋本 理恵, 梅村 ゆりあ, 平野 哲史, 南 貴一, 長原 大知, 湯浅 秀人, 久保田 直人, 柳井 翔吾, 万谷 洋平, 横山 俊史, 北川 浩, 星 信彦

第157回日本獣医学会学術集会, 2014年09月, 日本語, 札幌市, 国内会議

口頭発表（一般）

平野 哲史, 徳本 順子, 横山 俊史, 北川 浩, 星 信彦

日本薬学会第134年会, 2014年03月, 日本語, 国内会議

[招待有り]

シンポジウム・ワークショップパネル（指名）

表原 拓也, 木下 今日子, 長原 大知, 段上 めぐみ, 徳本 順子, 小林 泰丈, 辰巳 敬哉, 橋本 理恵, 平野 哲史, 梅村 ゆりあ, 横山 俊史, 北川 浩, 星 信彦

第156回日本獣医学会学術集会, 2013年09月, 日本語, 岐阜市, 国内会議

口頭発表（一般）

万谷 洋平, 高原 英一郎, 河野 潤一, 横山 俊史, 星 信彦, 北川 浩

第156回日本獣医学会学術集会, 2013年09月, 日本語, 岐阜市, 国内会議

口頭発表（一般）

万谷 洋平, 高原 英一郎, 河野 潤一, 横山 俊史, 星 信彦, 北川 浩

第89回日本解剖学会近畿支部学術集会, 2013年09月, 日本語, 岐阜市, 国内会議

口頭発表（一般）

高原 英一郎, 万谷 洋平, 横山 俊史, 星 信彦, 北川 浩

第156回日本獣医学会学術集会, 2013年09月, 日本語, 岐阜市, 国内会議

口頭発表（一般）

又吉 緑, 万谷 洋平, 高原 英一郎, 横山 俊史, 河野 潤一, 星 信彦, 北川 浩

第156回日本獣医学会学術集会, 2013年09月, 日本語, 岐阜市, 国内会議

口頭発表（一般）

徳本 順子, 星 信彦, 橋口 峰雄, 表原 拓也, 小林 泰丈, 辰巳 敬哉, 平野 哲史, 橋本 理恵, 梅村 ゆりあ, 長原 大知, 関島 恒夫, 上曽山 博, 横山 俊史, 北川 浩

第156回日本獣医学会学術集会, 2013年09月, 日本語, 岐阜市, 国内会議

口頭発表（一般）

辰巳 敬哉, 亀崎 直樹, 藍原 祥子, 山下 真路, 谷口 真理, 三根 佳奈子, 坂本 未来, 表原 拓也, 小林 泰丈, 横山 俊史, 北川 浩, 今川 智敬, 星 信彦

第156回日本獣医学会学術集会, 2013年09月, 日本語, 岐阜市, 国内会議

口頭発表（一般）

平野 哲史, 小林 泰丈, 表原 拓也, 辰巳 敬哉, 橋本 理恵, 梅村 ゆりあ, 長原 大知, 横山 俊史, 北川 浩, 星 信彦

第19回日本野生動物医学会大会, 2013年08月, 日本語, 京都市, 国内会議

ポスター発表

辰巳 敬哉, 亀崎 直樹, 藍原 祥子, 山下 真路, 谷口 真理, 三根 佳奈子, 坂本 未来, 表原 拓也, 小林 泰丈, 横山 俊史, 北川 浩, 今川 智敬, 星 信彦

第19回日本野生動物医学会大会, 2013年08月, 日本語, 京都市, 国内会議

ポスター発表

MAEDA NAOYUKI, TANAKA EMI, MASU KANAE, HAENO SATOKO, YASUDA KAORI, HOSHI NOBUHIKO, SAKAKI TOSHIYUKI, UEDA HIROMI, HOKOTA HIROSHI

7th Copenhagen Workshops on Endocrine Disrupters, 2013年05月, 英語, COPENHAGEN, DENMARK, 国際会議

口頭発表（一般）

段上 めぐみ, 田阪 健, 長原 大知, 木下 今日子, 徳本 順子, 表原 拓也, 小林 秦丈, 辰巳 敬哉, 谷田 任司, 横山 俊史, 菅野 美津子, 赤星 英一, 北川 浩, 星 信彦

第88回日本解剖学会近畿支部学術集会, 2012年12月, 日本語, 神戸市, 国内会議

口頭発表（一般）

段上 めぐみ, 田阪 健, 木下 今日子, 徳本 順子, 表原 拓也, 小林 泰丈, 辰巳 敬哉, 谷田 任司, 赤星 英一, 菅野 美津子, 横山 俊史, 北川 浩, 星 信彦

第15回環境ホルモン学会研究発表会, 2012年12月, 日本語, 東京，文京区, 国内会議

口頭発表（一般）

木下 今日子, 長原 大知, 段上 めぐみ, 徳本 順子, 表原 拓也, 小林 泰丈, 辰巳 敬哉, 横山 俊史, 北川 浩, 星 信彦

第88回日本解剖学会近畿支部学術集会, 2012年12月, 日本語, 神戸市, 国内会議

口頭発表（一般）

万谷 洋平, 高原 英一郎, 河野 潤一, 横山 俊史, 星 信彦, 北川 浩

第88回日本解剖学会近畿支部学術集会, 2012年12月, 日本語, 神戸市, 国内会議

口頭発表（一般）

樅山 真丈, 万谷 洋平, 高原 英一郎, 河野 潤一, 横山 俊史, 星 信彦, 北川 浩

第88回日本解剖学会近畿支部学術集会, 2012年12月, 日本語, 神戸市, 国内会議

口頭発表（一般）

高原 英一郎, 万谷 洋平, 樅山真丈, 又吉 緑, 横山 俊史, 星 信彦, 北川 浩

第88回日本解剖学会近畿支部学術集会, 2012年12月, 日本語, 神戸市, 国内会議

口頭発表（一般）

又吉 緑, 万谷 洋平, 高原 英一郎, 河野 潤一, 横山 俊史, 星 信彦, 北川 浩

第88回日本解剖学会近畿支部学術集会, 2012年12月, 日本語, 神戸市, 国内会議

口頭発表（一般）

小林 泰丈, 段上 めぐみ, 徳本 順子, 長原 大知, 木下 今日子, 表原 拓也, 辰巳 敬哉, 横山 俊史, 北川 浩, 星 信彦

第15回環境ホルモン学会研究発表会, 2012年12月, 日本語, 東京，文京区, 国内会議

口頭発表（一般）

徳本 順子, 段上 めぐみ, 小林 泰丈, 木下 今日子, 表原 拓也, 辰巳 敬哉, 橋口 峰雄, 関島 恒夫, 上曽山 博, 横山 俊史, 北川 浩, 星 信彦

第15回環境ホルモン学会研究発表会, 2012年12月, 日本語, 東京，文京区, 国内会議

口頭発表（一般）

徳本 順子, 長原 大知, 木下 今日子, 段上 めぐみ, 表原 拓也, 小林 泰丈, 辰巳 敬哉, 橋口 峰雄, 関島 恒夫, 上曽山 博, 横山 俊史, 北川 浩, 星 信彦

第88回日本解剖学会近畿支部学術集会, 2012年12月, 日本語, 神戸市, 国内会議

口頭発表（一般）

辰巳 敬哉, 亀崎 直樹, 藍原 祥子, 山下 真路, 谷口 真理, 三根 佳奈子, 坂本 未来, 木下 今日子, 横山 俊史, 北川 浩, 今川 智敬, 金沢 和樹, 星 信彦

第51回日本爬虫類両棲類学会, 2012年11月, 日本語, 豊田市, 国内会議

口頭発表（一般）

橋本 理恵, 長原 大知, 木下 今日子, 段上 めぐみ, 徳本 順子, 安田 玲子, 表原 拓也, 小林 泰丈, 辰巳 敬哉, 横山 俊史, 北川 浩, 星 信彦

新学術領域研究「性差構築の分子基盤」若手研究会, 2012年10月, 日本語, 和歌山市, 国内会議

口頭発表（一般）

表原 拓也, 長原 大知, 木下 今日子, 段上 めぐみ, 徳本 順子, 安田 玲子, 小林 泰丈, 辰巳 敬哉, 横山 俊史, 北川 浩, 星 信彦

新学術領域研究「性差構築の分子基盤」若手研究会, 2012年10月, 日本語, 和歌山市, 国内会議

口頭発表（一般）

長原 大知, 森實 真由美, 蛯名 康彦, 木下 今日子, 段上 めぐみ, 徳本 順子, 安田 玲子, 表原 拓也, 小林 泰丈, 辰巳 敬哉, 横山 俊史, 北川 浩, 山田秀人, 星 信彦

新学術領域研究「性差構築の分子基盤」若手研究会, 2012年10月, 日本語, 和歌山市, 国内会議

口頭発表（一般）

星 信彦, 割田(三觜) 友子, 割田 克彦, 田渕 圭章, 横山 俊史, 北川 浩, 櫻木 範明

新学術領域研究「性差構築の分子基盤」若手研究会, 2012年10月, 日本語, 和歌山市, 国内会議

口頭発表（一般）

山本 教司, 樅山 真丈, UDAYANGA KANKANAM, GAMAGE SANATH, 万谷 洋平, 高原 英一郎, 竹内 崇師, 横山 俊史, 河野 潤一, 星 信彦, 北川 浩

第154回日本獣医学会学術集会, 2012年09月, 日本語, 盛岡市, 国内会議

口頭発表（一般）

万谷 洋平, 高原 英一郎, 竹内 崇師, 河野 潤一, 横山 俊史, 星 信彦, 北川 浩

第154回日本獣医学会学術集会, 2012年09月, 日本語, 盛岡市, 国内会議

口頭発表（一般）

小林 泰丈, 長原 大知, 木下 今日子, 段上 めぐみ, 徳本 順子, 安田 玲子, 表原 拓也, 辰巳 敬哉, 横山 俊史, 北川 浩, 星 信彦

第154回日本獣医学会学術集会, 2012年09月, 日本語, 盛岡市, 国内会議

口頭発表（一般）

徳本 順子, 谷口 和美, 竹中 亜紗実, 長原 大知, 木下 今日子, 段上 めぐみ, 安田 玲子, 表原 拓也, 小林 泰丈, 辰巳 敬哉, 橋口 峰雄, 関島 恒夫, 上曽山 博, 横山 俊史, 北川 浩, 星 信彦

第154回日本獣医学会学術集会, 2012年09月, 日本語, 盛岡市, 国内会議

口頭発表（一般）

表原 拓也, 長原 大知, 木下 今日子, 段上 めぐみ, 徳本 順子, 安田 玲子, 小林 泰丈, 辰巳 敬哉, 横山 俊史, 北川 浩, 星 信彦

第154回日本獣医学会学術集会, 2012年09月, 日本語, 盛岡市, 国内会議

口頭発表（一般）

長原 大知, 森實 真由美, 蛯名 康彦, 木下 今日子, 段上 めぐみ, 徳本 順子, 安田 玲子, 表原 拓也, 小林 泰丈, 辰巳 敬哉, 横山 俊史, 北川 浩, 山田 秀人, 星 信彦

第154回日本獣医学会学術集会, 2012年09月, 日本語, 盛岡市, 国内会議

口頭発表（一般）

辰巳 敬哉, 亀崎 直樹, 山下 真路, 長原 大知, 木下 今日子, 段上 めぐみ, 徳本 順子, 安田 玲子, 表原 拓也, 小林 泰丈, 横山 俊史, 北川 浩, 今川 智敬, 星 信彦

第154回日本獣医学会学術集会, 2012年09月, 日本語, 盛岡市, 国内会議

口頭発表（一般）

段上 めぐみ, 須谷 真巳, 石川 恭子, 藤井 裕香, 木下 今日子, 安田 玲子, 谷田 任司, 横山 俊史, 北川 浩, 星 信彦

第87回日本解剖学会近畿支部学術集会, 2011年12月, 日本語, 西宮市, 国内会議

口頭発表（一般）

星 信彦, 石川 恭子, 須谷 真己, 藤井 裕香, 段上 めぐみ, 木下 今日子, 安田 玲子, 長原 大知, 谷田 任司, 横山 俊史, 北川 浩

第87回日本解剖学会近畿支部学術集会, 2011年12月, 日本語, 西宮市, 国内会議

口頭発表（一般）

万谷 洋平, 亀崎 青沙, UDAYANGA KANKANAM, GAMAGE SANATH, 高原 英一郎, 谷田 任司, 河野 潤一, 横山 俊史, 星 信彦, 北川 浩

第87回日本解剖学会近畿支部学術集会, 2011年12月, 日本語, 西宮市, 国内会議

口頭発表（一般）

亀崎 青沙, 万谷 洋平, UDAYANGA KANKANAM, GAMAGE SANATH, 高原 英一郎, 谷田 任司, 河野 潤一, 横山 俊史, 星 信彦, 北川 浩

第87回日本解剖学会近畿支部学術集会, 2011年12月, 日本語, 西宮市, 国内会議

口頭発表（一般）

UDAYANGA KANKANAM, GAMAGE SANATH, YAMAMOTO KYOJI, MANTANI YOUHEI, TAKAHARA EI-ICHIRO, KAMEZAKI AOSA, TANIDA TAKASHI, YOKOYAMA TOSHIFUMI, KAWANO JUNICHI, HOSHI NOBUHIKO, KITAGAWA HIROSHI

第87回日本解剖学会近畿支部学術集会, 2011年12月, 日本語, 西宮市, 国内会議

口頭発表（一般）

UDAYANGA KANKANAM, GAMAGE SANATH, MIYATA HIDENORI, YOKOO YUH, TAKAHARA EI-ICHIRO, MANTANI YOHEI, YOKOYAMA TOSHIFUMI, HOSHI NOBUHIKO, KITAGAWA HIROSHI

2011 Mitochondria, Apoptosis and Cancer Conference, 2011年10月, 英語, Singapore, 国際会議

ポスター発表

木下 こずえ, 木綿 萠, 長原 大知, 前園 優子, 伊藤 修, 楠 比呂志, 坪田 敏男, 星 信彦

第17回日本野生動物医学会大会, 2011年09月, 日本語, 東京, 国内会議

ポスター発表

段上 めぐみ, 須谷 真巳, 石川 恭子, 藤井 裕香, 木下 今日子, 安田 玲子, 谷田 任司, 横山 俊史, 北川 浩, 星 信彦

第152回日本獣医学会学術集会, 2011年09月, 日本語, 堺市, 国内会議

口頭発表（一般）

横山 俊史, 石川 恭子, 須谷 真己, 藤井 裕香, 段上 めぐみ, 木下 今日子, 安田 玲子, 谷田 任司, 北川 浩, 星 信彦

第152回日本獣医学会学術集会, 2011年09月, 日本語, 堺市, 国内会議

口頭発表（一般）

万谷 洋平, UDAYANGA KANKANAM, GAMAGE SANATH, 高原 英一郎, 河野 潤一, 横山 俊史, 星 信彦, 北川 浩

第152回日本獣医学会学術集会, 2011年09月, 日本語, 堺市, 国内会議

口頭発表（一般）

亀崎 青沙, 万谷 洋平, UDAYANGA KANKANAM, GAMAGE SANATH, 高原 英一郎, 谷田 任司, 河野 潤一, 横山 俊史, 星 信彦, 北川 浩

第152回日本獣医学会学術集会, 2011年09月, 日本語, 堺市, 国内会議

口頭発表（一般）

竹中 亜紗実, 柏木 伸幸, 上野 友香, 柿添 裕香, 前園 優子, 中尾 建子, 楠 比呂志, 星 信彦

第17回日本野生動物医学会学術集会, 2011年09月, 日本語, 府中市, 国内会議

ポスター発表

木下 こづえ, 木綿 萌, 長原 大知, 前園 優子, 楠 比呂志, 坪田 敏男, 星 信彦

第17回日本野生動物医学会学術集会, 2011年09月, 日本語, 府中市, 国内会議

ポスター発表

UDAYANGA KANKANAM, GAMAGE SANATH, YAMAMOTO KYOUJI, MANTANI YOUHEI, TAKAHARA EI-ICHIRO, TANIDA TAKASHI, YOKOYAMA TOSHIFUMI, KAWANO JUNICHI, HOSHI NOBUHIKO, KITAGAWA HIROSHI

第152回日本獣医学会学術集会, 2011年09月, 日本語, 堺市, 国内会議

口頭発表（一般）

楠 比呂志, 太田 貴樹, 三保 尚志, 鳥羽 通久, 星 信彦

第19回希少動物人工繁殖研究会議, 2011年07月, 日本語, 姫路, 国内会議

口頭発表（一般）

段上 めぐみ, 田阪 健, 須谷 真巳, 石川 恭子, 横山 俊史, 赤星 英一, 菅野 美津子, 北川 浩, 星 信彦

環境ホルモン学会（日本内分泌攪乱化学物質学会）第13回研究発表会, 2010年12月, 日本語, 東京，文京区, 国内会議

ポスター発表

横山 俊史, 宮本 良介, 土居 弘明, 田阪 健, 橋本 佳樹, 藤井 裕香, 石川 恭子, 須谷 真巳, 長原 大知, 三觜 友子, 北川 浩, 星 信彦

第86回日本解剖学会近畿支部学術集会, 2010年11月, 日本語, 泉佐野市, 国内会議

口頭発表（一般）

万谷 洋平, UDAYANGA KANKANAM, GAMAGE SANATH, 高原 英一郎, 河野 潤一, 横山 俊史, 星 信彦, 北川 浩

第86回日本解剖学会近畿支部学術集会, 2010年11月, 日本語, 泉佐野市, 国内会議

口頭発表（一般）

UDAYANGA KANKANAM, GAMAGE SANATH, 山本教司, 宮田英典, 横尾 諭, 万谷 洋平, 高原 英一郎, 横山 俊史, 星 信彦, 北川 浩

第86回日本解剖学会近畿支部学術集会, 2010年11月, 日本語, 泉佐野市, 国内会議

口頭発表（一般）

横山 俊史, 宮本 良介, 土居 弘明, 田阪 健, 橋本 佳樹, 藤井 裕香, 石川 恭子, 須谷 真巳, 長原 大知, 三觜 友子, 北川 浩, 星 信彦

第150回日本獣医学会学術集会, 2010年09月, 日本語, 帯広市, 国内会議

口頭発表（一般）

万谷 洋平, UDAYANGA KANKANAM, GAMAGE SANATH, 高原 英一郎, 河野 潤一, 横山 俊史, 星 信彦, 北川 浩

第150回日本獣医学会学術集会, 2010年09月, 日本語, 帯広市, 国内会議

口頭発表（一般）

UDAYANGA KANKANAM, GAMAGE SANATH, 高原 英一郎, 河野 潤一, 横山 俊史, 星 信彦, 北川 浩

第150回日本獣医学会学術集会, 2010年09月, 日本語, 帯広市, 国内会議

口頭発表（一般）

星 信彦, 宮本 良介, 横山 俊史, 土居 弘明, 田阪 健, 橋本 佳樹, 藤井 裕香, 石川 恭子, 須谷 真巳, 長原 大知, 三觜 友子, 北川 浩

第50回日本先天異常学会学術集会, 2010年07月, 日本語, 淡路市, 国内会議

ポスター発表

横山 俊史, 土居 弘明, 宮本 良介, 田阪 健, 橋本 佳樹, 藤井 裕香, 石川 恭子, 須谷 真巳, 長原 大知, 三觜 友子, 北川 浩, 星 信彦

第50回日本先天異常学会学術集会, 2010年07月, 日本語, 淡路市, 国内会議

ポスター発表

ISHIHARA KANA, TASAKA KEN, TANIDA TAKASHI, WARITA KATSUHIKO, MITSUHASHI TOMOKO, MIYAKE MASASHI, HARAYAMA HIROSHI, YOKOYAMA TOSHIFUMI, KITAGAWA HIROSHI, HOSHI NOBUHIKO

11th International Symposium on Spermatology, 2010年06月, 英語, 宜野湾市, 国際会議

ポスター発表

伊藤 栄理, 浅田 千枝, 西田 美穂, UDAYANGA KANKANAM, GAMAGE SANATH, 河野 潤一, 横山 俊史, 星 信彦, 北川 浩

第85回日本解剖学会近畿支部学術集会, 2009年11月, 日本語, 橿原市, 国内会議

口頭発表（一般）

西田 美穂, 伊藤 栄理, 宮田 英典, 平野 晶子, 斉 旺梅, UDAYANGA KANKANAM, GAMAGE SANATH, 横山 俊史, 星 信彦, 北川 浩

第85回日本解剖学会近畿支部学術集会, 2009年11月, 日本語, 橿原市, 国内会議

口頭発表（一般）

万谷 洋平, UDAYANGA KANKANAM, GAMAGE SANATH, 横尾 諭, 宮田英典, 河野 潤一, 横山 俊史, 星 信彦, 北川 浩

第85回日本解剖学会近畿支部学術集会, 2009年11月, 日本語, 橿原市, 国内会議

口頭発表（一般）

宮田 英典, 平野 晶子, 斉 旺梅, 横尾 諭, UDAYANGA KANKANAM, GAMAGE SANATH, 横山 俊史, 星 信彦, 北川 浩

第85回日本解剖学会近畿支部学術集会, 2009年11月, 日本語, 橿原市, 国内会議

口頭発表（一般）

横山 俊史, 青木 香保里, 三觜 友子, 石原 可奈, 谷田 任司, 北川 浩, 星 信彦

第85回日本解剖学会近畿支部学術集会, 2009年11月, 日本語, 橿原市, 国内会議

口頭発表（一般）

須谷 真巳, 石庭 寛子, 田阪 健, 藤井 裕香, 土居 弘明, 橋本 佳樹, 宮本 良介, 三觜 友子, 石原 可奈, 谷田 任司, 横山 俊史, 北川 浩, 関島 恒夫, 星 信彦

第85回日本解剖学会近畿支部学術集会, 2009年11月, 日本語, 橿原市, 国内会議

口頭発表（一般）

田阪 健, 石原 可奈, 土居 弘明, 橋本 佳樹, 宮本 良介, 三觜 友子, 谷田 任司, 横山 俊史, 北川 浩, 星 信彦

第85回日本解剖学会近畿支部学術集会, 2009年11月, 日本語, 橿原市, 国内会議

口頭発表（一般）

土居 弘明, 宮本 良介, 田阪 健, 橋本 佳樹, 三觜 友子, 石原 可奈, 谷田 任司, 横山 俊史, 北川 浩, 星 信彦

第85回日本解剖学会近畿支部学術集会, 2009年11月, 日本語, 橿原市, 国内会議

口頭発表（一般）

UDAYANGA KANKANAM, GAMAGE SANATH, MIYATA HIDENORI, YOKOO YUH, QI WANG-MEI, NISHIDA MIHO, YOKOYAMA TOSHIFUMI, HOSHI NOBUHIKO, KITAGAWA HIROSHI

第85回日本解剖学会近畿支部学術集会, 2009年11月, 日本語, 橿原市, 国内会議

口頭発表（一般）

田阪 健, 石原 可奈, 土居 弘明, 橋本 佳樹, 宮本 良介, 三觜 友子, 谷田 任司, 横山 俊史, 北川 浩, 星 信彦

第148回日本獣医学会学術集会, 2009年09月, 日本語, 鳥取市, 国内会議

口頭発表（一般）

藤井 裕香, 横山 俊史, 田阪 健, 須谷 真巳, 万谷 洋平, 三觜 友子, 石原 可奈, 谷田 任司, 北川 浩, 星 信彦

第148回日本獣医学会学術集会, 2009年09月, 日本語, 鳥取市, 国内会議

口頭発表（一般）

宮田 英典, 平野 晶子, 斉 旺梅, 横尾 諭, UDAYANGA KANKANAM, GAMAGE SANATH, 横山 俊史, 星 信彦, 北川 浩

第148回日本獣医学会学術集会, 2009年09月, 日本語, 鳥取市, 国内会議

口頭発表（一般）

万谷 洋平, UDAYANGA KANKANAM, GAMAGE SANATH, 横尾 諭, 宮田 英典, 河野 潤一, 横山 俊史, 星 信彦, 北川 浩

第148回日本獣医学会学術集会, 2009年09月, 日本語, 鳥取市, 国内会議

口頭発表（一般）

伊藤 栄理, 浅田 千枝, 西田 美穂, UDAYANGA KANKANAM, GAMAGE SANATH, 河野 潤一, 横山 俊史, 星 信彦, 北川 浩

第148回日本獣医学会学術集会, 2009年09月, 日本語, 鳥取市, 国内会議

口頭発表（一般）

西田 美穂, 伊藤 栄理, 宮田 英典, 平野 晶子, 斉 旺梅, UDAYANGA KANKANAM, GAMAGE SANATH, 横山 俊史, 星 信彦, 北川 浩

第148回日本獣医学会学術集会, 2009年09月, 日本語, 鳥取市, 国内会議

口頭発表（一般）

横山 俊史, 青木 香保里, 三觜 友子, 石原 可奈, 谷田 任司, 北川 浩, 星 信彦

第148回日本獣医学会学術集会, 2009年09月, 日本語, 鳥取市, 国内会議

口頭発表（一般）

須谷 真巳, 石庭 寛子, 田阪 健, 藤井 裕香, 土居 弘明, 橋本 佳樹, 宮本 良介, 三觜 友子, 石原 可奈, 谷田 任司, 横山 俊史, 北川 浩, 関島 恒夫, 星 信彦

第148回日本獣医学会学術集会, 2009年09月, 日本語, 鳥取市, 国内会議

口頭発表（一般）

ITO ERI, ASADA CHIE, NISHIDA MIHO, YOKOO YUH, UDAYANGA KANKANAM, GAMAGE SANATH, QI WANG-MEI, KAWANO JUNICHI, YOKOYAMA TOSHIFUMI, HOSHI NOBUHIKO, KITAGAWA HIROSHI

The 6th International Symposium on Electron Microscopy in Medicine and Biology, 2009年09月, 英語, 神戸市, 国際会議

ポスター発表

NISHIDA MIHO, ITO ERI, MIYATA HIDENORI, UDAYANGA KANKANAM, GAMAGE SANATH, YOKOO YUH, QI WANG-MEI, YOKOYAMA TOSHIFUMI, HOSHI NOBUHIKO, KITAGAWA HIROSHI

The 6th International Symposium on Electron Microscopy in Medicine and Biology, 2009年09月, 英語, 神戸市, 国際会議

ポスター発表

TAKAHARA EI-ICHIRO, ONISHI SACHIKO, NISHIDA MIHO, QI WANG-MEI, UDAYANGA KANKANAM, GAMAGE SANATH, YOKOYAMA TOSHIFUMI, WARITA KATSUHIKO, HOSHI NOBUHIKO, KITAGAWA HIROSHI

The 6th International Symposium on Electron Microscopy in Medicine and Biology, 2009年09月, 英語, 神戸市, 国際会議

ポスター発表

土居 弘明, 宮本 良介, 田阪 健, 橋本 佳樹, 三觜 友子, 石原 可奈, 谷田 任司, 横山 俊史, 北川 浩, 星 信彦

第148回日本獣医学会学術集会, 2009年09月, 日本語, 鳥取市, 国内会議

口頭発表（一般）

FUKUI YOSHITOMO, YUJI MIDORI, ONISHI SACHIKO, NISHIDA MIHO, INAMOTO TETSUROU, WARITA KATSUHIKO, YOKOYAMA TOSHIFUMI, HOSHI NOBUHIKO, KITAGAWA HIROSHI

The 6th International Symposium on Electron Microscopy in Medicine and Biology, 2009年09月, 英語, 神戸市, 国際会議

ポスター発表

YOKOYAMA TOSHIFUMI, AOKI KAHORI, ISHIHARA KANA, MITSUHASHI TOMOKO, WARITA KATSUHIKO, HIROSHI KITAGAWA, NOBUHIKO HOSHI

The 6th International Symposium on Electron Microscopy in Medicine and Biology, 2009年09月, 英語, 神戸市, 国際会議

ポスター発表

MANTANI YOUHEI, YOKOO YUH, UDAYANGA KANKANAM, GAMAGE SANATH, QI WANG-MEI, NAMBA MAKIKO, NISHIDA MIHO, KAWANO JUNICHI, YOKOYAMA TOSHIFUMI, HOSHI NOBUHIKO, KITAGAWA HIROSHI

The 6th International Symposium on Electron Microscopy in Medicine and Biology, 2009年09月, 英語, 神戸市, 国際会議

ポスター発表

UDAYANGA KANKANAM, GAMAGE SANATH, MIYATA HIDENORI, YOKOO YUH, QI WANG-MEI, NISHIDA MIHO, YOKOYAMA TOSHIFUMI, HOSHI NOBUHIKO, KITAGAWA HIROSHI

第148回日本獣医学会学術集会, 2009年09月, 日本語, 鳥取市, 国内会議

口頭発表（一般）

WARITA KATSUHIKO, MITSUHASHI TOMOKO, YOKOYAMA TOSHIFUMI, MATSUMOTO YOSHIKI, KITAGAWA HIROSHI, MIKI TAKANORI, TAKEUCHI YOSHIKI, HOSHI NOBUHIKO

The 6th International Symposium on Electron Microscopy in Medicine and Biology, 2009年09月, 英語, 神戸市, 国際会議

ポスター発表

香川 真二, 千田 廉, 木村 愛子, 前田 真依子, 米田 稔彦, 星 信彦, 岡田 安弘

PT 学会, 2006年02月, 日本語, 不明, 群馬, 国内会議

口頭発表（一般）

稲元 哲朗, 陳 慶義, 大西 佐知子, 斉 旺梅, 湯地 みどり, 割田 克彦, 星 信彦, 北川 浩

第81 回日本解剖学会近畿支部学術集会, 2005年11月, 日本語, 不明, 京都, 国内会議

口頭発表（一般）

湯地 みどり, 大西 佐知子, 陳 慶義, 稲元 哲朗, 斉 旺梅, 割田 克彦, 星 信彦, 北川 浩

第81回日本解剖学会近畿支部学術集会, 2005年11月, 日本語, 不明, 京都, 国内会議

口頭発表（一般）

割田 克彦, 岡本 一剛, 石原 可奈, 菅原 照夫, 千田 廉, 北川 浩, 星 信彦

第8 回環境ホルモン学会学術集会講演要旨集、 259, 2005年, 日本語, 不明, 名古屋, 国内会議

口頭発表（一般）

坂本 志磨子, 嵐 泰弘, 畠中 みどり, 松岡 健, 函城 悦司, 生田 健太郎, 三隅 隆也, 白鳥 典彦, 古本 彰, 星 信彦, 千田 廉

第139 回日本獣医学会学術集会講演要旨集、182, 2005年, 日本語, 不明, 埼玉, 国内会議

口頭発表（一般）

湯地 みどり, 大西 佐知子, 陳 慶義, 稲元 哲朗, 斉 旺梅, 割田 克彦, 星 信彦, 北川 浩

第140 回日本獣医学会学術集会講演要旨集,58, 2005年, 日本語, 不明, 鹿児島, 国内会議

口頭発表（一般）

稲元 哲朗, 陳 慶義, 大西 佐知子, 斉 旺梅, 湯地 みどり, 割田 克彦, 星 信彦, 北川 浩

第140 回日本獣医学会学術集会講演要旨集,58, 2005年, 日本語, 不明, 鹿児島, 国内会議

口頭発表（一般）

内海 やよい, 湯地 みどり, 陳 慶義, 稲元 哲朗, 斉 旺梅, 割田 克彦, 星 信彦, 北川 浩

第140 回日本獣医学会学術集会講演要旨集， 56, 2005年, 日本語, 不明, 鹿児島, 国内会議

口頭発表（一般）

坂本 志磨子, 嵐 泰弘, 畠中 みどり, 松岡 健, 千田 廉, 星 信彦

第104 回日本畜産学会学術集会, 2005年, 日本語, 不明, 東京, 国内会議

口頭発表（一般）

KAGAWA S, CHIDA Y, KIMURA A, MAEDA M, HOSHI Nobuhiko, OKADA Y

4th World Confederation for Physical Therapy-Asia Western Pacific Region & 9th Asia Confederation for Physical Therapy Congress 2005、Proceedings,218-219, 2005年, 日本語, 不明, Korea, 国内会議

口頭発表（一般）

星 信彦

第14回関西生殖発生毒性フォーラム基礎教育講座, 2004年, 日本語, 未記入, 未記入, 国内会議

口頭発表（一般）

塚原 伸治, 星 信彦, 北川 浩

第138回日本獣医学会学術集会, 2004年, 日本語, 日本獣医学会, 北海道大学, 国内会議

口頭発表（一般）

星 信彦, 町田 佳名子, 松山 道子, 菅原 照夫, 長谷川 喜久

平成15年度科学研究費補助金（特定領域研究（１））「内分泌攪乱物質の環境リスク」研究成果報告会, 2004年, 日本語, 未記入, 未記入, 国内会議

口頭発表（一般）

星 信彦, 町田 佳名子, 松山 道子, 割田 克彦, 千田 廉, 塚原 伸治, 北川 浩, 長谷川 喜久

第138回日本獣医学会学術集会, 2004年, 日本語, 日本獣医学会, 北海道大学, 国内会議

口頭発表（一般）

星 信彦

第12回生命科学実験センター学術セミナー, 2004年, 日本語, 未記入, 富山医科薬科大学, 国内会議

口頭発表（一般）

星 信彦

兵庫医科大学大学院総合セミナー, 2004年, 日本語, 未記入, 兵庫医科大学, 国内会議

口頭発表（一般）

大西 佐知子, 陳 慶義, 湯地 みどり, 横山 俊史, 塚原 伸治, 星 信彦, 北川 浩

第138回日本獣医学会学術集会, 2004年, 日本語, 日本獣医学会, 北海道大学, 国内会議

口頭発表（一般）

大西 佐知子, 陳 慶義, 湯地 みどり, 塚原 伸治, 星 信彦, 北川 浩

第80回日本解剖学会近畿支部学術集会, 2004年, 日本語, 日本解剖学会近畿支部, 関西医科大学, 国内会議

口頭発表（一般）

陳 慶義, 湯地 みどり, 大西 佐知子, 横山 俊史, 塚原 伸治, 星 信彦, 北川 浩

第138回日本獣医学会学術集会, 2004年, 日本語, 日本獣医学会, 北海道大学, 国内会議

口頭発表（一般）

陳 慶義, 大西 佐知子, 湯地 みどり, 塚原 伸治, 星 信彦, 北川 浩

第80回日本解剖学会近畿支部学術集会, 2004年, 日本語, 日本解剖学会近畿支部, 関西医科大学, 国内会議

口頭発表（一般）

塚原 伸治, 井波 広一, 星 信彦, 北川 浩

第31回日本神経内分泌学会学術集会, 2004年, 日本語, 日本神経内分泌学会, 弘前, 国内会議

口頭発表（一般）

星 信彦, 本島 直子, 菅原 照夫, 田渕 圭章, 長谷川 喜久

平成15年度科学研究費補助金（特定領域研究（１））「内分泌攪乱物質の環境リスク」研究成果報告会, 2004年, 日本語, 未記入, 未記入, 国内会議

口頭発表（一般）

塚原 伸治, 星 信彦, 北川 浩

第27回日本神経科学大会および第47回日本神経化学学会大会合同大会学術集会, 2004年, 日本語, 日本神経科学学会, 大阪国際会議場, 国内会議

口頭発表（一般）

HOSHI Nobuhiko, MACHIDA Kanako, MATSUYAMA Michiko, WARITA Katsuhiko, CHIDA Yasushi, TSUKAHARA Shinji, HASEGAWA Yoshihisa, KITAGAWA Hiroshi

7th International Symposium on Environmental Endocrine Disrupters 2004, 2004年, 英語, 未記入, Nagoya Congress Center, 国内会議

口頭発表（一般）

HOSHI Nobuhiko, OKAMOTO Kazutaka, WARITA Katsuhiko, HASEGAWA Yoshihisa, CHIDA Yasushi, TSUKAHARA Shinji, KITAGAWA Hiroshi

16th International Congress of the IFAA., 2004年, 英語, 未記入, Kyoto International Conference Hall, 国内会議

口頭発表（一般）

星 信彦, 町田 佳名子, 松山 道子, 割田 克彦, 千田 廉, 塚原 伸治, 長谷川 喜久, 北川 浩

第7回環境ホルモン学会研究発表会, 2004年, 日本語, 環境ホルモン学会, 未記入, 国内会議

口頭発表（一般）

横山 俊史

学術研究助成基金助成金／基盤研究(C), 2017年04月 - 2020年03月

競争的資金

星 信彦

学術研究助成基金助成金／基盤研究(C), 2016年04月 - 2019年03月, 研究代表者

競争的資金

中塚 雅也

科学研究費補助金／基盤研究(B), 2014年07月 - 2018年03月

競争的資金

横山 俊史

学術研究助成基金助成金／基盤研究(C), 2014年04月 - 2017年03月

競争的資金

星 信彦

科学研究費補助金／基盤研究(C), 2012年04月 - 2015年03月, 研究代表者

競争的資金

星 信彦

科学研究費補助金／基盤研究(C), 2009年, 研究代表者

競争的資金

星 信彦

科学研究費補助金／基盤研究(B), 2005年, 研究代表者

競争的資金

星 信彦

科学研究費補助金／特定領域研究, 2005年, 研究代表者

競争的資金