研究者紹介システム
| 万谷 洋平 |  |
| マンタニ ヨウヘイ | |
| 大学院農学研究科 資源生命科学専攻 | |
| 助教 | |
| 農学関係 |
研究者情報
所属
【主配置】
大学院農学研究科 資源生命科学専攻【配置】
農学部 資源生命科学科
学位
授業科目
- 卒業研究, 農学部, 2022
- 応用動物学実験, 農学部, 2022
- 外国書講読Ａ, 農学部, 2022
- 初年次セミナー（応用動物学コース）, 農学部, 2022
- 応用動物学各論, 農学部, 2022
- 特定課題演習 I-1, 大学院農学研究科, 2022
- 課題開発演習, 大学院農学研究科, 2022
- 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, 2022
- 特定課題演習 II-1, 大学院農学研究科, 2022
- 先端融合科学特論A（食料編）, 大学院農学研究科, 2022
- 特定課題演習 I-2, 大学院農学研究科, 2022
- 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, 2022
- 特定課題演習 II-2, 大学院農学研究科, 2022
ジャンル
コメントテーマ
研究活動
研究分野
論文
- Springer Science and Business Media LLC, 2023年05月06日, Cell and Tissue Research
研究論文（学術雑誌）
Neonicotinoid pesticides (NN) were recently reported to exhibit adverse effects in higher vertebrates. Moreover, NNs are routinely transferred from mother to offspring, raising concerns about their effects on future generations. The fetal and neonatal periods are the most critical to the formation of neural circuits in the brain through neurogenesis and differentiation, neuronal migration, axon guidance, and synaptogenesis. NN exposure throughout the fetal and neonatal periods was found to affect the neurobehavior of the offspring, but the stage-specific neurobehavioral effects are unclear. We exposed fetal and neonatal mice to a no-observed-adverse-effect level (NOAEL) of clothianidin (CLO) for 4 days during each of four developmental stages: neurite proliferation and differentiation (fetal days 9-12, CLO-1), neurite outgrowth (fetal days 15-18, CLO-2), synapse formation and astrocyte differentiation (days 1-4 after birth, CLO-3), and synapse remodeling (days 11-14 after birth, CLO-4). CLO's neurobehavioral effects were evaluated in juveniles and adults, revealing that CLO-1 and CLO-2 caused behavioral abnormalities in adult mice. CLO-3 significantly increased locomotor activity and decreased juvenile neurons in the hippocampal dentate gyrus in adulthood. Comprehensive gene analysis of CLO-3 revealed high expression of genes related to neurite outgrowth and axonal branching in the hippocampus in juveniles and adults. These results revealed developmental stage-specific effects of a NOAEL of CLO in the fetal and neonatal periods, suggesting that the susceptibility of the fetus and neonate to CLO varies by developmental stage.
2023年03月01日, The Journal of veterinary medical science, 85 (4), 486 - 496, 英語, 国内誌研究論文（学術雑誌）
The expression of sex determining region of the Y chromosome (Sry) in the fetal gonads is important for male development. In a mouse model of disorders of sex development (C57BL/6 (B6)-XYPOS), the gonadal phenotype and the timing of Sry expression differ due to differences among the B6 substrain as the genetic background. Since differences in Sry expression among B6 substrains have been speculated, the present study examined Sry expression in B6J, B6JJmsSlc, and B6NCrl mice. These substrains differed in the number of Sry-expressing cells in the gonads of embryonic mice at each developmental stage, with B6NCrl having more than the other strains. The substrains differed also in the number of Sry-expressing cells between the left and right gonads, with B6J and B6NCrl, but not B6JJmsSlc, showing left gonad-dominant Sry expression. Substrain differences existed also in the distribution of Sry-expressing cells in the medial and lateral directions of gonads. In addition, in the left gonad-dominant Sry-expressing substrains B6J and B6NCrl, the medial and central regions of the left gonad had more Sry-expressing cells than those of the right gonad. Substrains of B6 mice have not always been considered in sex differentiation studies. In the present study, however, we observed substrain differences in the number of Sry-expressing cells, left-right distribution, and medial/lateral distribution during the early stages of gonadal development in B6 mice. Therefore, future studies on sex differentiation in B6 mice should consider substrain differences.
2023年02月28日, The Journal of veterinary medical science, 英語, 国内誌研究論文（学術雑誌）
Diamide insecticides activate ryanodine receptors expressed in lepidopteran skeletal muscle and promote Ca2+ release in the sarcoplasmic reticulum, causing abnormal contractions and paralysis, leading to death of the pest. Although they had been thought not to act on nontarget organisms, including mammals, adverse effects on vertebrates were recently reported, raising concerns about their safety in humans. We investigated the neurotoxicity of the acute no-observed-adverse-effect level of chlorantraniliprole (CAP), a diamide insecticide, in mice using clothianidin (CLO), a neonicotinoid insecticide, as a positive control. The CLO-administered group showed decreased locomotor activities, increased anxiety-like behaviors, and abnormal human-audible vocalizations, while the CAP-administered group showed anxiety-like behaviors but no change in locomotor activities. The CAP-administered group had greater numbers of c-fos‒immunoreactive cells in the hippocampal dentate gyrus, and similar to the results in a CLO-administered group in our previous study. Blood corticosterone levels increased in the CLO-administered group but did not change in the CAP-administered group. Additionally, CAP was found to decreased 3-Methoxytyramine and histamine in mice at the time to maximum concentration. These results suggest that CAP-administered mice are less vulnerable to stress than CLO-administered mice, and the first evidence that CAP exposure increases neuronal activity and induces anxiety-like behavior as well as neurotransmitter disturbances in mammals.
2023年02月28日, The Journal of veterinary medical science, 85 (4), 497 - 506, 英語, 国内誌研究論文（学術雑誌）
Recently, the effects of exposure to clothianidin (CLO) on the thymus and gut microbiota have become clear, but no report has examined its next-generation impacts. Pregnant C57BL/6N mice were administered a no-observed-adverse-effect-level dose of CLO until weaning. We examined CLO's effects on the gut microbiota and immune organs of dams and their 3- and 10-week-old male offspring. CLO administration led to several alterations of the top 30 bacterial genera in the gut microbiota in dams and 3-week-old mice. Compared to controls, 10-week-old mice had more thymic Hassall's corpuscles, and both dams and 10-week-old mice had fewer macrophages. These results suggest that fetal and lactational CLO exposure may affect the immune system and gut microbiota of the next generation.
2023年02月17日, The Journal of veterinary medical science, 英語, 国内誌研究論文（学術雑誌）
Our previous studies and others have revealed detailed characteristics of the mucosal nerve network in the small intestine, but much remains unknown about the corresponding network in the large intestine. We herein investigated regional differences in the expression of neurochemical markers, the nerve network structure, and the cells in contact with nerve fibers by histological analysis using both immunohistochemistry and serial block-face scanning electron microscopy (SBF-SEM). Immunohistochemistry revealed that immunopositive structures for protein gene product 9.5, vasoactive intestinal peptide (VIP), calretinin and vesicular acetylcholine transporter were more prevalent in the lamina propria of the ascending colon than the cecum and descending colon (DC). There was no significant difference in the frequency of most neurochemical markers between the cecum and DC, but the frequencies of VIP+ structures were higher in the cecum than in the DC. SBF-SEM analysis showed that the nerve network structure was more developed on the luminal side of the DC than the cecum. The cells that nerve fibers abundantly contacted were subepithelial and lamina propria fibroblast-like cells and macrophages. In addition, nerve fibers in the cecum were in more frequent contact with immune cells such as macrophages and plasma cells than nerve fibers in the DC. Thus, the present histological analysis suggested that the mucosal nerve network in the large intestine possessed both regional universality and various specificities, and revealed the intimate relationship between the nerve network and immune cells, especially in the cecum.
2022年12月13日, The Journal of veterinary medical science, 英語, 国内誌研究論文（学術雑誌）
Neonicotinoid pesticides (NNs) have been reported to have neurobehavioral effects on offspring after fetal and lactational exposure. In this study, clothianidin (CLO), an NN, was administered orally as a single dose (6.5mg/kg: 1/10 of the no-observed-adverse-effect level in the current Pesticide Evaluation Report) to 10-day post-partum ICR mice, and CLO and its metabolites were quantified using liquid chromatography-electrospray ionization/tandem mass spectrometry (LC-ESI/MS/MS) after collecting maternal breast milk and blood samples over time (1, 3, 6, 9, 12, and 24h after administration). CLO and its metabolite desmethyl-CLO (dm-CLO) were detected in the breast milk at 1h after the administration, and their concentrations were significantly higher than those in blood at all time points. The concentrations of CLO and dm-CLO in the breast milk were at their highest levels at 1 and 3h, respectively, and then decreased over time to become almost undetectable at 24h after the administration. These results show that CLO is metabolized in the mother's body and is rapidly transferred to and concentrated in the breast milk. Since CLO concentrations in breast milk are higher than those in the blood, there is concern about the effects of CLO during lactation.
2022年10月31日, Toxicology letters, 373, 33 - 40, 英語, 国際誌研究論文（学術雑誌）
Although neonicotinoids are among the major classes of pesticides that affect mammalian nervous systems, little is known about sex differences in their effects. This study aimed to examine whether the neurobehavioral effects of a neonicotinoid, clothianidin (CLO), differed between sexes. Male and female C57BL/6 N mice were orally administered CLO (5 or 50 mg/kg) at or below the chronic no-observed-adverse-effect-level (NOAEL) and subjected to behavioral tests of emotional and learning functions. Changes in neuroactivity in several brain regions and the concentrations of CLO and its metabolites in blood and urine were measured. Acute CLO exposure caused sex-related behavioral effects; decreases in locomotor activities and elevation of anxiety-like behaviors were more apparent in males than in females. In addition, male-specific impairment of short- and long-term learning memory by CLO exposure was observed in both the novel recognition test and the Barnes maze test. Male-dominant increases in the number of c-fos positive cells were observed in the paraventricular thalamic nucleus in the thalamus and in the dentate gyrus in the hippocampus, which are related to the stress response and learning function, respectively. The concentrations of CLO and most metabolites in blood and urine were higher in males. These results support the notion that male mice are more vulnerable than females to the neurobehavioral effects of CLO and provide novel insights into the risk assessment of neonicotinoids in mammalian neuronal function.
2022年10月14日, Toxicology and applied pharmacology, 456, 116283 - 116283, 英語, 国際誌研究論文（学術雑誌）
Our previous studies using immunohistochemistry and serial block-face scanning electron microscopy (SBF-SEM) clarified that fibroblast-like cells (FBLCs) in the rat ileal mucosa are classifiable into several subtypes, but their characteristics throughout the large intestine remain unknown. In this study, we investigated the region-specific characteristics of FBLCs in the rat large intestine using histological analysis including SBF-SEM. Immunohistochemistry revealed that CD34+CD31- FBLCs were localized in the lamina propria beneath the crypt bases throughout the large intestine and were more abundant in the descending colon than in the other regions. In addition, platelet-derived growth factor receptor α (PDGFRα)+ FBLCs were ubiquitously present just below the epithelium throughout the large intestine, and those at the crypt base were slightly more abundant in the descending colon than in the other regions. SBF-SEM analysis revealed that there were two types of FBLCs around the crypt base in both the cecum and the descending colon: sub-epithelial FBLCs localizing just beneath the epithelium in the manner of PDGFRα+ FBLCs, and lamina propria FBLCs localizing farther away from the epithelium than sub-epithelial FBLCs in the manner of CD34+CD31- FBLCs. The lamina propria FBLCs were closely apposed to various immune cells in the lamina propria, and their endoplasmic reticulum in the descending colon exhibited various dilatation levels, unlike that in the cecum. These findings indicate that FBLCs, especially around the crypt base, differed in each region of the large intestine with respect to localization, abundance, and ultrastructure, which could lead to the region-specific microenvironment around the crypt base.
2022年09月, Cell and tissue research, 389 (3), 427 - 441, 英語, 国際誌[査読有り]
研究論文（学術雑誌）
- Springer Science and Business Media LLC, 2022年04月11日, Cell and Tissue Research
[査読有り]
研究論文（学術雑誌）
- Japanese Society of Veterinary Science, 2022年, Journal of Veterinary Medical Science, 84 (4), 585 - 592
[査読有り]
研究論文（学術雑誌）
Neonicotinoids, which act as agonists of the nicotinic acetylcholine receptors of insects, are widely used pesticides worldwide. Although epidemiological studies revealed that the detection amounts of neonicotinoids in urine are higher in the elderly population than other age-groups, there is no available information regarding the risks of neonicotinoids to older mammals. This study was aimed to investigate aging-related differences in the behavioral effects of the neonicotinoid pesticide clothianidin (CLO). We acutely administered a sub-NOAEL level (5 mg/kg) of CLO to adult (12-week-old) and aging (90-week-old) mice and conducted four behavioral tests focusing on the emotional behavior. In addition, we measured the concentrations of CLO and its metabolites in blood, brain and urine. There were age-related changes in most parameters in all behavioral tests, and CLO significantly decreased the locomotor activity in the open field test and elevated plus-maze test in the aging group, but not in the adult group. The concentrations of most CLO and its metabolites were significantly higher in the blood and brain and were slightly lower in the urine in the aging group compared to the adult group. These findings should contribute to our understanding of age-related differences in the adverse effects of neonicotinoids in mammals.
2021年05月15日, Toxicology letters, 342, 95 - 103, 英語, 国際誌[査読有り]
研究論文（学術雑誌）
Several types of macrophages have been reported in the intestinal mucosa, but their histological localization remains ambiguous. Here, we obtained detailed information about ultrastructural and phenotypical diversity of macrophage-like cells (MLCs) in the rat ileal mucosa using immunofluorescent analysis and serial block-face scanning electron microscopy (SBF-SEM). The results revealed that the cells immunopositive for CD68, the pan-macrophage marker, included CD163-CD4+, CD163+CD4+, and CD163-CD4- cells in the lamina propria (LP) of the intestinal villus and around the crypt. CD68+CD4+CD163- cells seemed to be preferentially localized in the intestinal villus, whereas CD68+CD163+CD4+ cells were frequently localized around the crypt. SBF-SEM analysis identified three types of MLCs in the ileal mucosa, which were tentatively named types I-III MLC based on aspects of the 3D-ultrastructure, such as the localization, quantity of lysosomes, endoplasmic reticulum, and exoplasm. Type I and II MLCs were localized in the villous LP, while type III MLCs were localized around the crypt, although type II MLCs were a minor population. All three MLC types extended their cellular processes into the epithelium, with type I MLCs showing the greatest abundance of extended processes. Type I MLCs in the upper portion of the intestinal villus showed a higher level of attachment to intraepithelial lymphocytes (IELs) compared to type III MLCs around the crypt. These findings suggest that macrophages of the rat ileal mucosa differed by region along the longitudinal axis of the villous tip-crypt from the perspective of ultrastructure, cellular composition, localization, and interactions with IELs.
2021年05月07日, Cell and tissue research, 英語, 国際誌[査読有り]
研究論文（学術雑誌）
Recently, developmental exposure to clothianidin (CLO) has been shown to cause reproductive toxicity in male mice, but the effects in female mice remain to be clarified. Pregnant C57BL/6N mice were given a no-observed-adverse-effect-level (NOAEL) dose of CLO until weaning. We then examined ovaries of 3- or 10-week-old female offspring. In the CLO-administered group, morphological changes, a decrease in the immunoreactivity of the antioxidant enzyme glutathione peroxidase 4 (GPx4), and activation of genes in the steroid hormone biosynthesis pathway were observed in 3-week-old mice, and decreases of GPx4 immunoreactivity, 17OH-progesterone and corticosterone levels were observed in 10-week-old mice, along with high rates of infanticide and severe neglect, providing new evidence that developmental exposure to CLO affects juvenile and adult mice differently.
2021年04月24日, The Journal of veterinary medical science, 83 (4), 746 - 753, 英語, 国内誌[査読有り]
研究論文（学術雑誌）
Recently, it has been reported that neonicotinoid pesticides (NNs) are transferred from mother to child and are assumed to affect the next generation, but the behavioral effects of NN exposure at different developmental stages have not been investigated. We exposed mice to no-observed-adverse-effect level (NOAEL) doses of clothianidin (CLO) during the fetal and lactational period, and then evaluated the neurobehavioral effects in juvenile and adult mice. Significant increases in anxiety-like behavior and locomotor activity were observed in juveniles and adults, respectively, and neuronal activity and neurogenesis in the hippocampal dentate gyrus were affected in both stages. These results suggest that fetal and lactational exposure to CLO may inhibit neurogenesis and cause different behavioral abnormalities at different developmental stages.
2021年04月03日, The Journal of veterinary medical science, 83 (3), 542 - 548, 英語, 国内誌[査読有り]
研究論文（学術雑誌）
Fipronil (FPN) is a systemic insecticide that antagonizes the gamma-aminobutyric acid type A (GABAA) receptors in insects. Recently, adverse effects of FPN on mammals have been reported, but most of those were caused by high doses of FPN and additives in the products. We investigated the effects of low-dose pure FPN on the emotional behavior of mice. Nine-week-old male mice conducted behavioral tests 24 hr after FPN administration by gavage at doses of 0.05 or 5 mg/kg based on the no-observed-effect level (NOEL), showed a significant increase in locomotor activity and dose-dependent responses on the time they spent in the central zone in the open field test. Pure FPN below the NOEL dose may affect the emotional behavior of mice.
2021年03月05日, The Journal of veterinary medical science, 83 (2), 344 - 348, 英語, 国内誌[査読有り]
研究論文（学術雑誌）
Eosinophils are abundantly present in intestinal mucosa. However, the morphological characteristics of their cellular population are still largely unknown. In this study, we examine their characteristics in the rat ileal mucosa using histological and ultrastructural methods. The results indicated that ileal eosinophils could be distinguished into two main groups based on their nuclear shapes and distribution: eosinophils with spheric or reniform nuclei mainly localized in the villous region and eosinophils with annular or bacilliform nuclei as the major population around crypts. Immunohistochemical analysis revealed that all eosinophils in the lamina propria (LP) were immunopositive for CD11b, whereas eosinophils in LP of the intestinal villus but not those in LP around the crypt, were immunopositive for CD11c. Three-dimensional ultrastructural analysis using serial block-face scanning electron microscopy showed that the eosinophils with spheric or reniform nuclei were abundant in the upper portions of the intestinal villus, whereas those with annular nuclei were abundant in the lower portions of the intestinal villus and around crypts. The eosinophils with spheric or reniform nuclei possessed broader cellular bodies with greater abundance of surface projections compared with those with annular nuclei. Eosinophils in the upper portions of intestinal villus frequently extended their cellular bodies into the intraepithelial space. The number of total and eosinophil-specific granules was positively correlated with the minor axis of the nuclear holes in the annular nuclei. These data suggest that ileal eosinophils exhibit not homogenous but rather diverse characteristics, possible due to the mixture of eosinophils at different maturation and/or activation stages.
2020年09月, Cell and tissue research, 381 (3), 439 - 450, 英語, 国際誌[査読有り]
研究論文（学術雑誌）
The comprehensive targets of innervation in the intestinal mucosa are unknown, partly because of the diversity of cell types and the complexity of the neural circuits. Herein, we investigated the comprehensive targets of neural connectivity and analyzed the precise characteristics of their contact structures in the mucosa of rat ileum. We examined target cells of neural connections and the characteristics of their contact structures by serial block-face scanning electron microscopy at four portions of the rat ileal mucosa: the apical and basal portions in the villi, and the lateral and basal portions around/in the crypts. Nerve fibers were in contact with several types of fibroblast-like cells (FBLCs), macrophage-like cells, eosinophils, lymphocyte-like cells, and other types of cells. The nerve fibers almost always ran more inside of lamina propria than subepithelial FBLC, and thus contacts with epithelial cells were very scarce. The contact structures of the nerve fibers were usually contained synaptic vesicle-like structures, and we classified them into patterns based on the number of nerve fiber contacting the target cells at one site, the maximum diameter of the contact structures, and the relationship between nerve fibers and nerve bundles. The contact structures for each type of cells occasionally dug into the cellular bodies of the target cells. We revealed the comprehensive targets of neural connectivity based on the characteristics of contact structures, and identified FBLCs, immunocompetent cells, and eosinophils as the candidate targets for innervation in the rat ileal mucosa.
2020年07月31日, The Journal of veterinary medical science, 82 (7), 990 - 999, 英語, 国内誌[査読有り]
研究論文（学術雑誌）
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04月, J. Vet. Med. Sci., 82 (4), 414 - 421, 英語, 国内誌[査読有り]
研究論文（学術雑誌）
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）
Neonicotinoid pesticides (NNs) act as agonists on nicotinic acetylcholine receptors (nAChRs) of insects, and there have been concerns 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03月24日, The Journal of veterinary medical science, 82 (3), 360 - 372, 英語, 国内誌[査読有り]
研究論文（学術雑誌）
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03月24日, The Journal of veterinary medical science, 82 (3), 350 - 359, 英語, 国内誌[査読有り]
研究論文（学術雑誌）
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）
The effect of bacterial colonies expanded into the intervillous spaces on the localization of several lymphocyte lineages was immunohistochemically investigated in two types of mucosa: ordinary mucosa of rat ileum, which consists of mucosa without any mucosal lymphatic tissue; and follicle-associated mucosa (FAM), which accompanies the parafollicular area under the muscularis mucosae in the rat ileal Peyer's patch. The results showed that bacterial colonies in the intervillous spaces induced increased populations of CD8+ cells in the epithelium of the intestinal villus in ordinary mucosa (IV) and intestinal villus in FAM (IV-FAM). Bacterial colonies in the intervillous spaces were also associated with increased numbers of IgA+ cells, which were mainly localized in the lamina propria of basal portions of IV and IV-FAM, and with expanded localization of IgA+ cells into the villous apex in both IV and IV-FAM. Moreover, IgA+ cells around the intestinal crypts adjacent to IV or IV-FAM were also increased in response to bacterial colonies. In the IV-FAM, but not IV, L-selectin+ cells, which were found to be immunopositive for TCRαβ or CD19, were drastically increased in the lamina propria from the crypt to middle portion of IV-FAM and in the lumen of central lymph vessel of IV-FAM in response to the bacterial colonies in the intervillous spaces. These findings revealed that the expansion of bacterial colonies into the intervillous spaces accompanies the change of histological localization of the lymphocyte lineage in both the ordinary mucosa and FAM.
2019年04月16日, The Journal of veterinary medical science, 81 (4), 555 - 566, 英語, 国内誌[査読有り]
研究論文（学術雑誌）
Serial block-face scanning electron microscopy (SBF-SEM) is useful for three-dimensional observation of tissues or cells at high-resolution. In this study, SBF-SEM was used to three-dimensionally analyze the characteristics of fibroblast-like cells (FBLCs) in the rat ileal lamina propria (LP). The results revealed that FBLCs in LP could be divided into four types, tentatively named FBLC type I-IV, based on the external cellular appearance, abundance or shape of each organelle, detailed distribution in the LP and relationship with surrounding cells. FBLC-I and -II localized around the intestinal crypt (InC), FBLC-III localized from the lateral portion of InC to the apical portion of the intestinal villus (InV), and FBLC-IV localized in the InV. FBLC-I, -II and -III, but not FBLC-IV, localized beneath the epithelium. FBLC-II possessed thin lamellar-shaped endoplasmic reticula, whereas FBLC-I possessed expanded endoplasmic reticula that occasionally showed a spherical shape. FBLC-III and -IV possessed a cytoplasmic region with high-electron density and no organelles immediately beneath the cellular membrane; this region was found at the epithelial sides in FBLC-III and scattered in FBLC-IV. FBLC-IV were in constant close proximity to villous myocytes throughout the InV and also in contact with FBLC-III especially in the apical portion of the InV. FBLC-I, -II and -IV, but not -III, were constantly found to be in contact with various immunocompetent cells in the LP. Three-dimensional analysis using SBF-SEM indicates that four types of FBLC localized in the rat ileal LP.
2019年03月30日, The Journal of veterinary medical science, 81 (3), 454 - 465, 英語, 国内誌[査読有り]
研究論文（学術雑誌）
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）
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）
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27日, The Journal of veterinary medical science, 80 (4), 720 - 724, 英語, 国内誌[査読有り]
研究論文（学術雑誌）
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）
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18日, The Journal of veterinary medical science, 80 (4), 634 - 637, 英語, 国内誌[査読有り]
研究論文（学術雑誌）
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03月24日, The Journal of Veterinary Medical Science, 80 (3), 395 - 404, 英語, 国内誌[査読有り]
研究論文（学術雑誌）
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03月02日, The Journal of veterinary medical science, 80 (2), 323 - 332, 英語, 国内誌[査読有り]
研究論文（学術雑誌）
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 50mg/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 (4-16kHz), 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05日, Toxicology letters, 282, 57 - 63, 英語, 国際誌[査読有り]
研究論文（学術雑誌）
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17日, The Journal of Veterinary Medical Science, 79 (11), 1826 - 1835, 英語, 国内誌[査読有り]
研究論文（学術雑誌）
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; no-observed-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07日, The Journal of veterinary medical science, 79 (7), 1196 - 1203, 英語, 国内誌[査読有り]
研究論文（学術雑誌）
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. Developmental Dynamics 246:148-156, 2017. © 2016 Wiley Periodicals, Inc.
WILEY, 2017年02月, Developmental dynamics : an official publication of the American Association of Anatomists, 246 (2), 148 - 156, 英語, 国際誌[査読有り]
研究論文（学術雑誌）
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, 2017年01月10日, The Journal of veterinary medical science, 78 (12), 1797 - 1804, 英語, 国内誌[査読有り]
研究論文（学術雑誌）
Mammalian sexual fate is determined by the presence or absence of sex determining region of the Y chromosome (Sry) 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-XY(POS)) has been shown to induce sex reversal (75%: bilateral ovary, 25%: true hermaphrodites). However, our B6N-XY(POS) mice, which were generated by backcrossing of B6J-XY(POS) 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-XY(POS) 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-XY(POS) gonads occurred 2-3 tail somites later than those in B6N-XY(B6) gonads, but earlier than those in B6J-XY(POS), respectively. It is possible that such a small difference in timing of the Sry expression underlies testicular development in our B6N-XY(POS). Our study is the first to histologically show the expression and ectopic localization of a female-related gene in the XY(POS) testes and a male-related gene in the XY(POS) 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, 2016年01月, The Journal of veterinary medical science, 77 (12), 1587 - 98, 英語, 国内誌[査読有り]
研究論文（学術雑誌）
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, The Journal of veterinary medical science, 77 (11), 1355 - 61, 英語, 国内誌[査読有り]
研究論文（学術雑誌）
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, The Journal of veterinary medical science, 77 (10), 1207 - 15, 英語, 国内誌[査読有り]
研究論文（学術雑誌）
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, The Journal of veterinary medical science, 77 (9), 1121 - 8, 英語, 国内誌[査読有り]
研究論文（学術雑誌）
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 LDL 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, The Journal of veterinary medical science, 77 (4), 387 - 93, 英語, 国内誌[査読有り]
研究論文（学術雑誌）
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, The Journal of veterinary medical science, 76 (9), 1201 - 8, 英語, 国内誌[査読有り]
研究論文（学術雑誌）
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, β-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.
2014年08月, Anatomical record (Hoboken, N.J. : 2007), 297 (8), 1462 - 71, 英語, 国際誌[査読有り]
研究論文（学術雑誌）
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 (FAE) than in the ordinary intestinal villi (IV). Indigenous bacteria were more frequently adhered to FAE 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 FAE 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 - 8, 英語, 国内誌[査読有り]
研究論文（学術雑誌）
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）
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 (0-2000 ng kg⁻¹ body weight) to the transgenic dams markedly enhanced TH-immunoreactive (ir) intensity in the A9, A10 and A8 areas of their offspring at 3 days and 8 weeks of age. The offspring of dams treated with 200 ng kg⁻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 8 weeks. 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).
WILEY, 2014年02月, Journal of applied toxicology : JAT, 34 (2), 117 - 26, 英語, 国際誌[査読有り]
研究論文（学術雑誌）
- Insight into the mechanism of reproductive dysfunction caused by neonicotinoid pesticides.
Neonicotinoids, which were developed in the 1990 s 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, Biological & pharmaceutical bulletin, 37 (9), 1439 - 43, 英語, 国内誌[査読有り]
研究論文（学術雑誌）
- Ultrastructural demonstration of the absorption and transportation of minute chylomicrons by subepithelial blood capillaries in rat jejunal villi.
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.
THE JAPANESE SOCIETY OF VETERINARY SCIENCE, 2013年12月30日, The Journal of veterinary medical science, 75 (12), 1563 - 9, 英語, 国内誌[査読有り]
研究論文（学術雑誌）
- 2013年07月, The Journal of Veterinary Medical Science, 75 (5), 939 - 947, 英語Histoplanimetrical study on the relationship between invasion of indigenous bacteria into intestinal crypts and proliferation of epithelial cells in rat ascending colon.
[査読有り]
研究論文（学術雑誌）
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, The Journal of veterinary medical science, 74 (11), 1447 - 52, 英語, 国内誌[査読有り]
研究論文（学術雑誌）
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, The Journal of veterinary medical science, 74 (11), 1429 - 38, 英語, 国内誌[査読有り]
研究論文（学術雑誌）
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-α 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-α 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-α interaction.
JAPAN SOC VET SCI, 2012年05月, The Journal of veterinary medical science, 74 (5), 597 - 605, 英語, 国内誌[査読有り]
研究論文（学術雑誌）
- Site differences of Toll-like receptor expression in the mucous epithelium of rat small intestine
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）
- Immunohistochemical and histoplanimetrical study on the spatial relationship between the settlement of indigenous bacteria and the secretion of bactericidal peptides in rat alimentary tract.
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, The Journal of veterinary medical science, 73 (8), 1043 - 50, 英語, 国内誌[査読有り]
研究論文（学術雑誌）
- Immunohistochemical study of the apoptosis process in epidermal epithelial cells of rats under a physiological condition
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）
MISC
- 2021年, 日本先天異常学会学術集会プログラム・抄録集, 61st (CD-ROM)ネオニコチノイド系農薬クロチアニジンのマウス母乳中移行量に関する定量的評価
- 2021年, 日本先天異常学会学術集会プログラム・抄録集, 61st (CD-ROM)ネオニコチノイド系農薬クロチアニジンが次世代マウスの免疫系および腸内細菌叢に及ぼす影響
- 2021年, 日本獣医学会学術集会講演要旨集, 164th (CD-ROM)神経回路形成期におけるステージ別ネオニコチノイド系農薬曝露と発達神経毒性評価
- 2021年, 日本獣医学会学術集会講演要旨集, 164th (CD-ROM)ネオニコチノイド系農薬クロチアニジンの胎子・授乳期曝露が次世代マウスの免疫系および腸内細菌叢に及ぼす影響
- 2021年, 環境ホルモン学会研究発表会プログラム・要旨集, 23rd (Web)低用量クロチアニジンの神経回路形成期におけるステージ別曝露と発達神経毒性評価
- 2021年, 環境ホルモン学会研究発表会プログラム・要旨集, 23rd (Web)ネオニコチノイド系農薬クロチアニジンの胎子・授乳期曝露による次世代マウスの免疫系および腸内細菌叢の変化
- 2020年, 日本先天異常学会学術集会プログラム・抄録集, 60th無毒性量ネオニコチノイド系農薬が次世代のマウス雌性生殖機能に及ぼす影響
- 2020年, 日本先天異常学会学術集会プログラム・抄録集, 60th無毒性量の浸透性農薬のマウス胎子・授乳期曝露による神経行動学的影響
- 2020年, Endocrine Disrupter News Letter (Web), 22 (4)低用量クロチアニジンによる情動変容への加齢の影響評価
- 2019年, 日本分子生物学会年会プログラム・要旨集(Web), 42nd脆弱なSryを有するYPOSマウスの生殖腺形成に及ぼすC57BL/6マウスの亜系統差の影響
- 2019年, 環境ホルモン学会研究発表会プログラム・要旨集, 22nd (Web)ネオニコチノイド系農薬における野生哺乳動物の曝露状況と都道府県別の出荷量との関連
- 環境ホルモン学会(日本内分泌撹乱化学物質学会), 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 - 79, 日本語母子間移行における浸透性農薬およびその代謝産物の定量的な解明
- 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, 日本語兵庫県における野生哺乳動物のネオニコチノイド系農薬への曝露実態調査
- (公社)日本獣医学会, 2018年08月21日, 日本獣医学会学術集会講演要旨集, 161st, 467 - 467, 日本語浸透性農薬とその代謝産物の胎子移行量の解明
- 2018年, 日本アンドロロジー学会総会記事, 37thニワトリの精巣におけるセルトリ細胞の起源の左右差
- 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, 英語ニワトリ胚におけるセルトリ細胞の起源(The origin of Sertoli cells in the chicken embryo)
- 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, 英語ニワトリ胚におけるセルトリ細胞の起源(The origin of Sertoli cells in the chicken embryo)
- 2017年, 日本解剖学会総会・全国学術集会講演プログラム・抄録集, 122ndニワトリの発生過程に特徴的な生殖腺の左右差
- 2016年, 日本先天異常学会学術集会プログラム・抄録集, 56th発達期におけるネオニコチノイド系農薬曝露により多動が引き起こされる
- 2016年, 日本先天異常学会学術集会プログラム・抄録集, 56th胎子期から成獣期にかけてのネオニコチノイド系農薬クロチアニジン曝露が及ぼす行動学的影響
- 2016年, 日本解剖学会総会・全国学術集会講演プログラム・抄録集, 121stニワトリ胚の性腺発生における左右差
- 2016年, 日本分子生物学会年会プログラム・要旨集(Web), 39thマウス胎子性腺における性分化関連遺伝子転写調節領域のDNAメチル化状態
- 2016年, 日本先天異常学会学術集会プログラム・抄録集, 56th発達期におけるネオニコチノイド系農薬ジノテフラン曝露とうつ病発症との関係
- 2015年, 日本家禽学会誌, 52ニワトリ胚における左精巣特異的な発生メカニズム
- 2015年, 日本実験動物学会総会講演要旨集, 62ndC57BL/6マウスの不可思議さ:その遺伝的背景に潜むSry-HMG box&Q-rich領域と性決定
- 2014年, 日本家禽学会誌, 51ニワトリ胚における性腺の形成機構とその左右差
講演・口頭発表等
- 第98回日本解剖学会近畿支部学術集会, 2022年11月, 日本語, 国内会議Serial block-face 走査型電子顕微鏡を用いたラット大腸粘膜におけるマクロファージの超微形態学的部位差に関する研究
- 第98回日本解剖学会近畿支部学術集会, 2022年11月, 日本語, 国内会議ラット腸管における免疫担当細胞の局在への日常的な細菌刺激の影響に関する予備的解析
- 第98回日本解剖学会近畿支部学術集会, 2022年11月, 日本語, 国内会議C57BL/6N マウスの未分化性腺における Sry 上流因子の発現に関する定量組織学的検討
- 第98回日本解剖学会近畿支部学術集会, 2022年11月, 日本語, 国内会議性決定期の Sry 発現に対する C57BL/6 マウスの亜系統差の影響に関する定量組織学的解析
- 第98回日本解剖学会近畿支部学術集会, 2022年11月, 日本語, 国内会議アミド系農薬がマウスの行動および神経活動に及ぼす影響について
- 第165回日本獣医学会学術集会, 2022年09月, 日本語, 国内会議無毒性量クロチアニジンの経口曝露がアトピー性皮膚炎に与える影響の評価
- 第165回日本獣医学会学術集会, 2022年09月, 日本語, 国内会議環境ストレス負荷下におけるネオニコチノイド系農薬曝露が腸内細菌叢に及ぼす影響
- 第165回日本獣医学会学術集会, 2022年09月, 日本語, 国内会議胎子授乳期ネオニコチノイド系農薬曝露が海馬記憶と運動学習に及ぼす次世代影響
- 第165回日本獣医学会学術集会, 2022年09月, 日本語, 国内会議性決定期のC57BL/6マウスにおけるSry発現の亜系統差に関する定量組織学的検討
- 第165回日本獣医学会学術集会, 2022年09月, 日本語, 国内会議性腺分化の臨界期のC57BL/6NマウスにおけるSry上流因子の発現に関する定量組織学的検討
- 第165回日本獣医学会学術集会, 2022年09月, 日本語, 国内会議ラット回腸粘膜内神経ネットワークの生後変化に関する組織学的研究
- 第165回日本獣医学会学術集会, 2022年09月, 日本語, 国内会議ラット大腸粘膜におけるマクロファージの組織学的部位差に関する研究
- International Federation of Associations of Anatomists 2022, 2022年08月, 英語, 国内会議Histological study on postnatal changes of the nerve network in the rat ileal mucosa.
- 第127回日本解剖学会総会・全国学術集会, 2022年03月27日, 日本語, 国内会議ラット回腸粘膜内神経ネットワークの生後変化に関する予備的解析
- 第127回日本解剖学会総会・全国学術集会, 2022年03月27日, 日本語, 国内会議マウス胎子精巣から中腎内へのAMHの移行経路の検討
- 第127回日本解剖学会総会・全国学術集会, 2022年03月27日, 日本語, 国内会議ラット大腸の粘膜内神経ネットワークに関する組織学的研究
- 日本解剖学会第97回近畿支部学術集会, 2021年11月, 日本語, 国内会議発生中のマウスにおける中腎領域へのAMHの移行経路の検討
- 第147回関西実験動物研究会, 2021年12月10日, 日本語, 国内会議マウス胎子における精巣から中腎内へのAMHの移行経路の検討
- 第23回環境ホルモン学会研究発表会, 2021年09月, 日本語, 国内会議低用量クロチアニジンの神経回路形成期におけるステージ別曝露と発達神経毒性評価
- 第23回環境ホルモン学会研究発表会, 2021年09月, 日本語, 国内会議ネオニコチノイド系農薬クロチアニジンの胎子・授乳期曝露による次世代マウスの免疫系および腸内細菌叢の変化
- 第23回環境ホルモン学会研究発表会, 2021年09月, 日本語, 国内会議極微量クロチアニジン曝露による神経学的影響の解明
- 第164回日本獣医学会学術集会, 2021年09月, 日本語, 国内会議Serial block-face走査型電子顕微鏡を用いたラット大腸粘膜における神経ネットワークに関する研究
- 第164回日本獣医学会学術集会, 2021年09月, 日本語, 国内会議神経回路形成期におけるステージ別ネオニコチノイド系農薬曝露と発達神経毒性評価
- 第164回日本獣医学会学術集会, 2021年09月, 日本語, 国内会議ネオニコチノイド系農薬クロチアニジンの胎子・授乳期曝露が次世代マウスの免疫系および腸内細菌叢に及ぼす影響
- 第164回日本獣医学会学術集会, 2021年09月, 日本語, 国内会議クロチアニジン曝露による高次脳機能の維持破綻メカニズムの解明
- 第164回日本獣医学会学術集会, 2021年09月, 日本語, 国内会議発生中のマウス精巣から中腎領域へのAMHの移行経路の検討
- 第164回日本獣医学会学術集会, 2021年09月, 日本語, 国内会議ラット腸管における粘膜内グリア細胞に関する組織学的研究
- 第61回日本先天異常学会学術集会, 2021年08月, 日本語, 国内会議ネオニコチノイド系農薬クロチアニジンのマウス母乳中移行量に関する定量的評価
- 第61回日本先天異常学会学術集会, 2021年08月, 日本語, 国内会議ネオニコチノイド系農薬クロチアニジンが次世代マウスの免疫系および腸内細菌叢に及ぼす影響
- 第61回日本先天異常学会学術集会, 2021年08月, 日本語, 国内会議2光子顕微鏡を用いたクロチアニジン曝露による神経学的影響の解明
- 第96回日本解剖学会近畿支部学術集会, 2020年11月, 日本語, 国内会議性分化撹乱マウス系統（B6J-XYPOS）における性腺原基の卵巣化に関する免疫組織化学的研究
- 第96回日本解剖学会近畿支部学術集会, 2020年11月, 日本語, 国内会議ラット消化管粘膜上皮表面における常在細菌の定着程度の概日リズムに関する定量組織学的解析
- 第163回日本獣医学会学術集会, 2020年09月, 日本語, 国内会議無毒性量ネオニコチノイド系農薬がマウスの継世代雌性生殖器に及ぼす影響
- 第163回日本獣医学会学術集会, 2020年09月, 日本語, 国内会議性分化撹乱マウス系統（B6J-XYPOS）における精巣化破綻機構に関する免疫組織化学的研究
- 第163回日本獣医学会学術集会, 2020年09月, 日本語, 国内会議ラット消化管各部位の粘膜上皮表面における常在細菌の定着程度の日内変動に関する組織学的解析
- 第163回日本獣医学会学術集会, 2020年09月, 日本語, 国内会議腸管各部位の集合リンパ小節における細網細胞の部位差に関する免疫組織化学的研究
- 第163回日本獣医学会学術集会, 2020年09月, 日本語, 国内会議ラット大腸粘膜における線維芽細胞様細胞の部位差に関する組織学的研究
- 第60回日本先天異常学会学術集会, 2020年07月, 日本語, 国内会議無毒性量ネオニコチノイド系農薬が次世代のマウス雌性生殖機能に及ぼす影響
- 第60回日本先天異常学会学術集会, 2020年07月, 日本語, 国内会議無毒性量の浸透性農薬のマウス胎子・授乳期曝露による神経行動学的影響
- 環境ホルモン学会第22回研究発表会, 日本語ネオニコチノイド系農薬における野生哺乳動物の曝露状況と都道府県別の出荷量との関連
ポスター発表
- 環境ホルモン学会第22回研究発表会, 日本語ネオニコチノイド系農薬クロチアニジンが次世代雌性生殖器に及ぼす影響
ポスター発表
- 環境ホルモン学会第22回研究発表会, 日本語クロチアニジンおよびその代謝産物の母子間移行における組織分布・蓄積性の定量的解明
ポスター発表
- 環境ホルモン学会第22回研究発表会, 日本語低用量クロチアニジンの胎子・授乳期曝露による神経行動学的影響
ポスター発表
- 環境ホルモン学会第22回研究発表会, 日本語低用量クロチアニジンによる情動変容への加齢の影響評価
ポスター発表
- 環境ホルモン学会第22回研究発表会, 日本語クロチアニジンの亜急性摂取はラット腸内細菌叢を変化させる
ポスター発表
- 環境ホルモン学会第22回研究発表会, 日本語低用量クロチアニジンによるマウスの物体認識・空間学習記憶障害とその性差
ポスター発表
- 第95回日本解剖学会近畿支部学術集会, 2019年11月, 日本語, 国内会議マウス健常雄個体の性腺におけるSry 発現の左右差に関する定量組織学的研究
口頭発表（一般）
- 第95回日本解剖学会近畿支部学術集会, 2019年11月, 日本語, 国内会議Serial block-face 走査型電子顕微鏡を用いたラット回腸粘膜における神経接続の三次元解析
口頭発表（一般）
- 第95回日本解剖学会近畿支部学術集会, 2019年11月, 日本語, 国内会議ラット小腸粘膜における好酸球の多様性に関する組織学的研究
口頭発表（一般）
- 第162回日本獣医学会学術集会, 2019年09月, 日本語, 国内会議GABA撹乱物質フィプロニルがマウスの情動行動に及ぼす影響
口頭発表（一般）
- 第162回日本獣医学会学術集会, 2019年09月, 日本語, 国内会議性決定期のマウス性腺におけるSry発現の時空間的解析-健常雄個体におけるSry発現の左右差
口頭発表（一般）
- 第162回日本獣医学会学術集会, 2019年09月, 日本語, 国内会議性決定前のマウス未分化XY性腺の精巣化を誘導する器官培養法の確立とその組織学的評価
口頭発表（一般）
- 第162回日本獣医学会学術集会, 2019年09月, 日本語, 国内会議Serial block-face走査型電子顕微鏡(SBF-SEM)を用いたラット回腸の粘膜固有層における神経投射対象の解明
口頭発表（一般）
- 第162回日本獣医学会学術集会, 2019年09月, 日本語, 国内会議Serial block-face走査型電子顕微鏡を用いたラット回腸における単核食細胞系列の細胞と上皮内リンパ球の相互作用に関する研究
口頭発表（一般）
- 19th International Congress of Mucosal Immunology, 2019年07月, 英語, 国際会議Three-Dimensional Observation of Mononuclear Phagocyte Lineages in the Rat Ileum using Serial Block-Face Scanning Electron Microscopy
ポスター発表
- 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C57BL/6マウスの亜系統差による生殖腺表現型の変化
口頭発表（一般）
- 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Serial Block face走査型電子顕微鏡を用いたラット回腸粘膜における単核食細胞系列の細胞の三次元的観察
ポスター発表
- Chemical Hazard Symposium in Hokkaido, 2019年03月, 英語, Sapporo, 国際会議Adverse effects on cognitive-emotional behavior and immune system function in experimental animals administered a NOAEL-dose of neonicotinoids.
[招待有り]
シンポジウム・ワークショップパネル（指名）
- 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, 国内会議母子間移行における浸透性農薬およびその代謝産物の定量的な解明
ポスター発表
- 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, 国内会議兵庫県における野生哺乳動物のネオニコチノイド系農薬への曝露実態調査
ポスター発表
- 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, 国内会議性決定遺伝子発現前のマウス未分化XY性腺の精巣化を誘導する器官培養法
口頭発表（一般）
- 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, 国内会議性決定前のマウス未分化 XY 性腺の精巣化を誘導する器官培養法の確立とその組織学的評価
口頭発表（一般）
- 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, 国内会議ラット回腸粘膜における好酸球系列の細胞の組織学的研究
口頭発表（一般）
- 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, 国内会議ラット回腸の上皮下線維芽細胞様細胞を制御し得る神経伝達物質の同定
口頭発表（一般）
- 第161回日本獣医学会学術集会, 2018年09月, 日本語, つくば市, 国内会議生殖腺の表現型に及ぼすマウス亜系統差の影響に関する遺伝学的研究
口頭発表（一般）
- 第161回日本獣医学会学術集会, 2018年09月, 日本語, つくば市, 国内会議浸透性農薬の行動影響の性差
口頭発表（一般）
- 第161回日本獣医学会学術集会, 2018年09月, 日本語, つくば市, 国内会議浸透性農薬とその代謝産物の胎子移行量の解明
口頭発表（一般）
- 第161回日本獣医学会学術集会, 2018年09月, 日本語, つくば市, 国内会議ラット小腸粘膜におけるCD11b陽性細胞を中心とした各種免疫担当細胞の組織内配置に関する免疫組織化学的研究
口頭発表（一般）
- 第161回日本獣医学会学術集会, 2018年09月, 日本語, つくば市, 国内会議ラット呼吸器系粘膜におけるSP-AおよびSP-D分泌細胞の分布
口頭発表（一般）
- 第161回日本獣医学会学術集会, 2018年09月, 日本語, つくば市, 国内会議ラット回腸腸絨毛における上皮下および非上皮下線維芽細胞様細胞の三次元的解析
口頭発表（一般）
- 第161回日本獣医学会学術集会, 2018年09月, 日本語, つくば市, 国内会議ラット回腸の上皮直下における線維芽細胞様細胞への神経投射に関する免疫組織化学的研究
口頭発表（一般）
- 第161回日本獣医学会学術集会, 2018年09月, 日本語, つくば市, 国内会議ネオニコチノイド系農薬における哺乳動物への免疫毒性の検証
口頭発表（一般）
- 第161回日本獣医学会学術集会, 2018年09月, 日本語, つくば市, 国内会議ネオニコチノイド系農薬が老齢動物に及ぼす影響
口頭発表（一般）
- 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, 国内会議発達期におけるネオニコチノイド系農薬曝露により引き起こされたドーパミン神経系の攪乱を伴う多動
ポスター発表
- 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, 国内会議環境ストレスおよびネオニコチノイド系農薬ジノテフランの複合影響評価
ポスター発表
- 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, 国内会議ラット大腸の上皮直下における間質細胞の部位差に関する免疫組織化学的研究
口頭発表（一般）
- 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, 国内会議ラット回腸における間質細胞を介した細胞間ネットワーク解析へのSerial Block Face走査型電子顕微鏡の有用性
口頭発表（一般）
- 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, 国内会議マウスのミュラー管退行におけるAMH作用様式
口頭発表（一般）
- 第160回日本獣医学会学術集会, 2017年09月, 日本語, 鹿児島市, 国内会議生理的条件下のラット呼吸器系粘膜における補体成分C3と補体受容体C3aRおよびCD11bの局在に関する免疫組織化学的研究
口頭発表（一般）
- 第160回日本獣医学会学術集会, 2017年09月, 日本語, 鹿児島市, 国内会議ラットパイエル板におけるlysozyme陽性細胞を介する生体防御機構に関する免疫組織化学的研究
口頭発表（一般）
- 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Serial block face-走査型電子顕微鏡を用いたラット回腸腸陰窩周囲の間質細胞に関する3次元超微形態学的解析
口頭発表（一般）
- 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, 国内会議ニワトリの発生過程に特徴的な生殖腺の左右差
[招待有り]
口頭発表（招待・特別）
- 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, 国内会議胎子期および発達期におけるネオニコチノイド系農薬曝露がドーパミン神経系および行動に及ぼす影響
ポスター発表
- 第39回日本分子生物学会年会, 2016年12月, 日本語, 横浜市, 国内会議マウス胎子性腺における性分化関連遺伝子転写調節領域のDNAメチル化状態
ポスター発表
- 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, 国内会議ネオニコチノイド系農薬曝露によりみられた神経行動学的異常および標的脳領域の探索
口頭発表（一般）
- 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, 国内会議ネオニコチノイド系農薬ジノテフラン曝露はうつ様行動を引き起こすか？
口頭発表（一般）
- 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, 国内会議ネオニコチノイド系農薬クロチアニジンは胎子型と成獣型，2種類のライディッヒ細胞にそれぞれ異なる影響を及ぼす
口頭発表（一般）
- 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, 国内会議ラット呼吸器系粘膜を覆う粘液層における β-defensin 1 および β-defensin 2 の存在および分泌源の同定
口頭発表（一般）
- 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, 国内会議ラット回腸粘膜における各種間質細胞の局在
口頭発表（一般）
- 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, 国内会議ラットパイエル板における濾胞被蓋上皮のアポトーシスとRANK/RANKLの発現との関係
口頭発表（一般）
- 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, 国内会議マウス真性半陰陽個体のミュラー管退行とAMHの作用様式
口頭発表（一般）
- 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, 国内会議ニワトリ雌右性腺退縮メカニズムの解明
口頭発表（一般）
- 第159回日本獣医学会学術集会, 2016年09月, 日本語, 藤沢市, 国内会議生理学的条件下のラットパイエル板におけるRANK/RANKLの発現および常在細菌の増殖による影響
口頭発表（一般）
- 第159回日本獣医学会学術集会, 2016年09月, 日本語, 藤沢市, 国内会議ラット呼吸器におけるβ-defensin 1およびβ-defensin 2を介した分泌型の生体防御機構に関する免疫組織化学的研究
口頭発表（一般）
- 第159回日本獣医学会学術集会, 2016年09月, 日本語, 藤沢市, 国内会議ラット回腸におけるtelocyteの免疫組織化学的同定
口頭発表（一般）
- 第159回日本獣医学会学術集会, 2016年09月, 日本語, 藤沢市, 国内会議マウス真性半陰陽個体におけるAMHの作用様式に関する組織学的解析
口頭発表（一般）
- 第159回日本獣医学会学術集会, 2016年09月, 日本語, 藤沢市, 国内会議ネオニコチノイド系農薬曝露とうつ発症との関連性の検証
口頭発表（一般）
- 第159回日本獣医学会学術集会, 2016年09月, 日本語, 藤沢市, 国内会議ネオニコチノイド系農薬ジノテフランによるドーパミン神経系の攪乱および多動性の誘発
口頭発表（一般）
- 第159回日本獣医学会学術集会, 2016年09月, 日本語, 藤沢市, 国内会議ネオニコチノイド系農薬クロチアニジン急性投与が及ぼす行動学的影響とその作用点
口頭発表（一般）
- 第56回 先天異常学会学術集会, 2016年07月, 日本語, 姫路市, 国内会議発達期におけるネオニコチノイド系農薬曝露により多動が引き起こされる
ポスター発表
- 第56回 先天異常学会学術集会, 2016年07月, 日本語, 姫路市, 国内会議発達期におけるネオニコチノイド系農薬ジノテフラン曝露とうつ病発症との関係
ポスター発表
- 第56回 先天異常学会学術集会, 2016年07月, 日本語, 姫路市, 国内会議胎子期から成獣期にかけてのネオニコチノイド系農薬クロチアニジン曝露が及ぼす行動学的影響
ポスター発表
- 第43回日本毒性学会学術年会, 2016年06月, 日本語, 名古屋市, 国内会議ネオニコチノイド系農薬クロチアニジン単回投与によりみられた異常啼鳴および神経行動学的影響
ポスター発表
- 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, 国内会議ニワトリ胚の性腺発生における左右差
口頭発表（一般）
- 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, 国内会議環境ストレス下においてネオニコチノイド系農薬クロチアニジンが与える神経行動学的影響
ポスター発表
- 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, 国内会議ネオニコチノイド系農薬クロチアニジンの妊娠期及び授乳期曝露がマウス産子の雄性生殖器に与える影響
ポスター発表
- 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, 国内会議ニワトリ胚の左精巣に特異的なセルトリ細胞の起源
口頭発表（一般）
- 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, 国内会議生理学的条件下におけるラットパイエル板濾胞被蓋上皮におけるToll-like receptor-4の発現とM細胞への分化との関係について
口頭発表（一般）
- 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, 国内会議性逆転系統（B6-XYPOS）マウスにおける性腺分化と遺伝的背景
口頭発表（一般）
- 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, 国内会議ラット呼吸器系粘膜を覆う液相に含まれるlysozymeおよびsPLA2の分泌源の特定
口頭発表（一般）
- 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, 国内会議ラット回腸における間質細胞telocyteに関する超微形態学的研究
口頭発表（一般）
- 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, 国内会議ニワトリ胚の左性腺に特異的な細胞運命の追跡
口頭発表（一般）
- 第158回日本獣医学会, 2015年09月, 日本語, 十和田市, 国内会議環境ストレス下において浸透性農薬クロチアニジンが行動及び生殖機能に与える影響
口頭発表（一般）
- 第158回日本獣医学会, 2015年09月, 日本語, 十和田市, 国内会議ラット小腸のPaneth細胞に連絡する粘膜固有層細胞の超微形態
口頭発表（一般）
- 第158回日本獣医学会, 2015年09月, 日本語, 十和田市, 国内会議ラット呼吸器系におけるlysozymeおよびsPLA2の分泌上皮細胞に関する免疫組織化学的研究
口頭発表（一般）
- 第158回日本獣医学会, 2015年09月, 日本語, 十和田市, 国内会議ラットパイエル板濾胞被蓋上皮におけるToll-like receptor-2, -4および-9の発現に対する常在細菌増殖の影響
口頭発表（一般）
- 日本家禽学会2015年度秋季大会, 2015年09月, 日本語, 江別市, 国内会議ニワトリ胚における左精巣特異的な発生メカニズム
口頭発表（一般）
- 17th International Congress of Mucosal Immunology, 2015年07月, 英語, Berlin, Germany, 国際会議The short-term effect of peptidoglycan injected into the intestinal lumen against host defense responses.
ポスター発表
- 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C57BL/6マウスの不可思議さ：その遺伝的背景に潜むSry-HMG box & Q-rich領域と性決定
ポスター発表
- 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Sex-related genes' asymmetric expression in early mouse gonads
ポスター発表
- 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Selection of stable reference genes for quantitative RT-PCR analyses in developing mouse gonads
ポスター発表
- 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Reproductive and behavioral effects of clothianidin in male mice in a chronically stressed condition
ポスター発表
- 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Light and Electron Microscopical Study on the Particulate Bodies Found in Epithelium of Rat Airway.
ポスター発表
- 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Left-right asymmetry of testicular formation in the chicken embryo
ポスター発表
- 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Differential Expression of Toll-like Receptor-2,-4 and -9 in the Various Type of Epithelia Associated with Rat Peyer’s Patches
ポスター発表
- 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, 国内会議消化管付属リンパ組織、パイエル板の上皮におけるToll-like receptor-2、-4および-9の発現に関する免疫組織化学的研究
ポスター発表
- 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, 国内会議環境ストレス下動物の生殖機能抑制機序に関する形態機能学的研究
口頭発表（一般）
- 第157回日本獣医学会学術集会, 2014年09月, 日本語, 札幌市, 国内会議発生中のマウス胎子生殖腺における内部標準遺伝子の検討
口頭発表（一般）
- 第157回日本獣医学会学術集会, 2014年09月, 日本語, 札幌市, 国内会議通常飼育下のラットの呼吸器系に吸入された粒子状物の粘膜上皮への取り込みに関する組織学的研究
口頭発表（一般）
- 第157回日本獣医学会学術集会, 2014年09月, 日本語, 札幌市, 国内会議ラット呼吸器系粘膜上皮におけるToll-like receptor -1-9の局在に関する網羅的解析
口頭発表（一般）
- 第157回日本獣医学会学術集会, 2014年09月, 日本語, 札幌市, 国内会議ラットパイエル板濾胞被蓋上皮および濾胞付属腸絨毛の上皮におけるToll-like receptor-2，-4および-9の発現特性
口頭発表（一般）
- 第157回日本獣医学会学術集会, 2014年09月, 日本語, 札幌市, 国内会議マウス胎子生殖腺における性分化関連遺伝子発現の左右差に関する分子形態学的研究
口頭発表（一般）
- 第157回日本獣医学会学術集会, 2014年09月, 日本語, 札幌市, 国内会議ネオニコチノイド系農薬クロチアニジンの低用量曝露とストレスの複合影響
口頭発表（一般）
- 日本家禽学会2014年度秋季大会, 2014年09月, 日本語, 鹿児島市, 国内会議ニワトリ胚における性腺の形成機構とその左右差
口頭発表（一般）
- 第157回日本獣医学会学術集会, 2014年09月, 日本語, 札幌市, 国内会議ニワトリ胚における性腺の形成メカニズムと左右差
口頭発表（一般）
- 第156回日本獣医学会学術集会, 2013年09月, 日本語, 岐阜市, 国内会議ラット上行結腸の集合リンパ小節近傍の腸陰窩に出現するパネート細胞様外分泌細胞に関する超微形態学的および組織化学的研究
口頭発表（一般）
- 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, 国内会議ラット上行結腸における酸好性顆粒を有する腸陰窩上皮細胞に関する形態学的研究
口頭発表（一般）
- 第156回日本獣医学会学術集会, 2013年09月, 日本語, 岐阜市, 国内会議ラット空腸の腸絨毛における小型乳ビ球の門脈血への移行の仕組みに関する免疫組織化学的研究
口頭発表（一般）
- 第156回日本獣医学会学術集会, 2013年09月, 日本語, 岐阜市, 国内会議ラットの消化器系における補体成分C3とC4の産生部位に関する免疫組織化学的研究
口頭発表（一般）
- 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, 国内会議ラット上行結腸腸陰窩における常在細菌の増殖に対する生体防御に関する研究
口頭発表（一般）
- 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, 国内会議ラット十二指腸粘膜上皮におけるMyeloid differentiation factor-2とToll-like receptor-2の発現に関する免疫組織化学的研究
口頭発表（一般）
- 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, 国内会議ラット空腸腸絨毛の毛細血管内皮における乳ビ球に対する受容体に関する免疫組織化学的研究
口頭発表（一般）
- 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, 国内会議ラット肝臓における補体C3およびC4の産生に関する免疫組織化学的研究
口頭発表（一般）
- 第154回日本獣医学会学術集会, 2012年09月, 日本語, 盛岡市, 国内会議ラット小腸腸陰窩上皮細胞の細胞死に関する超微形態学的および免疫組織化学的研究
口頭発表（一般）
- 第154回日本獣医学会学術集会, 2012年09月, 日本語, 盛岡市, 国内会議ラットの上行結腸における常在細菌の定着とその制御に関する定量組織学的研究
口頭発表（一般）
- 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, 国内会議ラットの大腸粘膜上皮におけるToll-like receptorの発現と分泌
口頭発表（一般）
- 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, 国内会議ラットの呼吸器粘膜におけるToll-like receptorの発現と分泌
口頭発表（一般）
- 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Acceleration of Epithelial Apoptosis through the Secondary Activation of Mitochondria-Dependent Pathway in the Indigenous Bacteria Settlement Sites of Rat Tongue
口頭発表（一般）
- 第152回日本獣医学会学術集会, 2011年09月, 日本語, 堺市, 国内会議ラット大腸におけるToll-like receptorの局在に関する免疫組織化学的研究
口頭発表（一般）
- 第152回日本獣医学会学術集会, 2011年09月, 日本語, 堺市, 国内会議ラット呼吸器系上皮におけるToll-like receptorの局在に関する免疫組織化学的研究
口頭発表（一般）
- 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Acceleration of epithelial apoptosis in anterior epithelial column of filiform papilla in rat tongue by indigenous bacterial settlement.
口頭発表（一般）
- 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, 国内会議ラット消化管付属分泌腺からのToll-like receptorの分泌に関する免疫組織化学的研究
口頭発表（一般）
- 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Changes in apoptosis process of rat esophageal epithelium with hyperproliferation of the indigenous bacteria under a physiological condition
口頭発表（一般）
- 第150回日本獣医学会学術集会, 2010年09月, 日本語, 帯広市, 国内会議ラット消化管附属分泌腺からのToll-like receptorの分泌に関する免疫組織化学的研究
口頭発表（一般）
- 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, 国内会議ラット小腸腸絨毛におけるToll-like Receptorの発現
口頭発表（一般）
- 第148回日本獣医学会学術集会, 2009年09月, 日本語, 鳥取市, 国内会議成獣雄マウスにおける性決定遺伝子Sry発現の分子学的解析
口頭発表（一般）
- 第148回日本獣医学会学術集会, 2009年09月, 日本語, 鳥取市, 国内会議ラット小腸の粘膜上皮におけるToll-like receptorの発現に関する免疫組織化学的研究
口頭発表（一般）
- The 6th International Symposium on Electron Microscopy in Medicine and Biology, 2009年09月, 英語, 神戸市, 国際会議Immunohistochemical study on the Toll-like receptor expression in villous columnar epithelial cells of rat small intestine
ポスター発表
共同研究・競争的資金等の研究課題
- 日本学術振興会, 科学研究費助成事業 若手研究, 若手研究, 神戸大学, 2020年04月01日 - 2023年03月31日小腸粘膜内神経ネットワークの構造とその形成過程の解明
初年度は，ラットの腸管粘膜内神経ネットワーク構造について，以下の成果を得た。 ・serial block-face走査型電子顕微鏡（SBF-SEM）を用いて，ラット小腸粘膜において，神経線維が線維芽細胞様細胞（FBLC）やマクロファージ様細胞に接続しており，その接続部には複数パターンの接続構造が形成されることを明らかにした（Nakanishi et al., 2020, J. Vet. Med. Sci.）。 さらに，今後粘膜内神経ネットワークと粘膜内細胞ないし腸内細菌との関連を明らかにする研究につなげるために，以下の基盤的研究を実施した（②~④は第163回日本獣医学会学術集会で公表）。 ①小腸粘膜内マクロファージの多様性を免疫組織化学，SBF-SEMにより解析し，腸絨毛から腸陰窩にいたる領域ごとに特徴的なマクロファージが存在していることを明らかにした（Mantani et al., 2021, Cell Tissue Res.）。②小腸において神経線維の接続が多くみられたFBLCについてより広範な知見を得るため，大腸におけるFBLCのレパートリーについて免疫組織化学的解析およびSBF-SEM解析を実施し，盲腸と下行結腸では異なる性質のFBLCが存在していることを明らかにした。③腸管各部位の集合リンパ小節に存在する間葉系細胞である細網細胞の組織学特徴を調べ，下行結腸の細網細胞は回腸や盲腸とは異なる性質を示す可能性を示した。④消化管内における腸内細菌の定着程度の概日リズムを調べた結果，とくに胃の無腺部と回腸粘膜に定着する細菌量は1日の中で変動する可能性を明らかにした。
- 学術研究助成基金助成金／基盤研究(C), 2018年04月 - 2021年03月
競争的資金
- 学術研究助成基金助成金／若手研究(B), 2016年04月 - 2019年03月, 研究代表者
競争的資金
- 学術研究助成基金助成金／基盤研究(C), 2015年04月 - 2018年03月
競争的資金