2010 Fiscal Year Final Research Report
Analysis for the mechanisms affecting neural of development by endocrine disrupting chemicals using non-human primates
| Project/Area Number |
20310034
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| Research Category |
Grant-in-Aid for Scientific Research (B)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Risk sciences of radiation/Chemicals
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| Research Institution | The University of Tokyo |
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Principal Investigator |
YOSHIKAWA Yasuhiro The University of Tokyo, 大学院・農学生命科学研究科, 教授 (80109975)
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| Co-Investigator(Renkei-kenkyūsha) |
HAMASAKI Yuko 東京大学, 大学院・農学生命科学研究科 (10422370)
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| Project Period (FY) |
2008 – 2010
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| Keywords | 霊長類 / カニクイザル / 胎児脳 / ビスフェノール / 免疫染色 / プロテオーム / メチマゾール / 甲状腺 |
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| Research Abstract |
Consideration of species differences in conducting risk assessments of endocrine disrupting chemicals to humans, closely related non-human primates were used in experiments. Bisphenol A was used as an estrogenic agents from the results of previous studies, and methimazole was conducted as an alternative of the PCB or TCDD which have the effect of inhibiting thyroid hormones. Bisphenol A treated groups consisting of male and female offspring were done in proteome analysis for sexually dimorphic nucleus of the brain. Exposure group of male exhibited female patterns, and exposed females tended to show neutral patterns. Peptide spots showing significant differences from the control group were targeted, and sex differences in the exposed group were studied. Several proteins covering the targeted spots were examined by immunohistochemical methos in both exposure and control groups for sex differences, however, to find the difference between the control sex difference or exposure effects were
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difficult morphologically. The quantitative analysis should be carried, including hormone receptors in the future. Methimazole administration experiments were found to affect severely both fetal thyroid hormone production and brain development in non-human primates. The experiments to elucidate the mechanisms of methimazole were proceeded. During different stages of pregnancy (early pregnancy, mid, late, and end stages) mothers were administered methimazole and the offspring fetal brain obtained from individuals were analyzed precisely. Terminal phase (doses from the 130 to 150 days in gestation) treatments influenced the strongest effect. Thus, new experiment was proceeded to add four more individuals to obtain reproducible results based on this. Quantitative analysis of changes in the expression of candidate proteins by Western blot analysis. Thyroid enlargement and dysfunction were observed in the exposed group with a clear reproducibility, however, as for neuronal development, individual differences in protein expression level were strong. A tendency of retardation in large neural cell projections in the exposed group was observed but there was no significant difference. A correlation between thyroid hormone concentrations with enlarging thyroid glands and neural developmental retardations in individuals did not reveal a clear relationship. Purkinje cells in the cerebellar and pyramidal cells in the cerebral cortex showed a strong impact by exposure compared to other neural cells. An experiment targeted to these cells was considered necessary by quantitative analysis of individual in the future. Less
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[Journal Article] Comparative proteomic analysis of macular and peripheral retina of cynomolgus monkeys (Macaca fascicularis)2010
Author(s)
Okamoto, H., Umeda, S., Nozawa, T., Suzuki, M., Yoshikawa Y., Matsuura, E., Iwata, T
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Journal Title
Exp.Anim. 59巻
Pages: 171-182
Peer Reviewed
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[Journal Article] Validation of salivary cortisol and testosterone assays in chimpanzees by liquid chromatography-tandem mass spectrometry.2009
Author(s)
Kutsukake N, Ikeda K, Honma S, Teramoto M, Mori Y, Hayasaka I, Yamamoto R, Ishida T, Yoshikawa Y, Hasegawa T.
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Journal Title
American Journal of Primatology 71巻,in press
Peer Reviewed
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[Journal Article] Alterations in male infant behaviors towards its mother by prenatal exposure to bisphenol A in cynomolgus monkeys (Macaca fascicularis) during early suckling period2009
Author(s)
Nakagami, A., Negishi, T., Kawasaki, K., Imai, N., Nishida, Y., Ihara, T., Kuroda, Y., Yoshikawa Y., Koyama, T.
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Journal Title
Psychoneuroendocrinology 34巻
Pages: 1189-1197
Peer Reviewed
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