2002 Fiscal Year Final Research Report Summary
Effects of organotin compounds on the endocrine functions of placenta.
| Project/Area Number |
13470499
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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 |
Environmental pharmacy
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| Research Institution | Osaka University |
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Principal Investigator |
TANAKA Keiichi Osaka University, Graduate School of Pharmaceutical Sciences, Professor, 薬学研究科, 教授 (90068247)
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| Co-Investigator(Kenkyū-buntansha) |
UTOGUCHI Naoki Teikyo University, School of Pharmaceutical Sciences, Associate Professor, 薬学部, 助教授 (80276633)
ITOH Norio Osaka University, Graduate School of Pharmaceutical Sciences, Lecturer, 薬学研究科, 講師 (60176352)
NAKANISHI Tsuyoshi Osaka University, Graduate School of Pharmaceutical Sciences, Research Associate, 薬学研究科, 助手 (50303988)
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| Project Period (FY) |
2001 – 2002
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| Keywords | placenta / organotin compound / aromatase / tributyltin / triphenyltin / endocrine disruptor / human chorionic gonadotropin |
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| Research Abstract |
The placenta plays a vital role in the maintenance of a pregnancy by delivering oxygen and nutrients from the matemal circulation to the fetus and by returning fetal metabolites to the mother. The placenta also has many crucial endocrine Thus these placental functions might be at high risk dus to the developmental and reproductive toxicology of environmental contaminants which have endocrine-disrupting effects. In the present study, to extend knowledge on the human sexual developmental and reproductive toxicity of organotin compounds, which induce sexual abnormalities onto femail genital system in gastropod mollusks, we assessed the possible effect of these compounds on placental enodocrine functions in human and rodents. Tributyltin (TBT), triphenyltin (TPT) and their various alkyl derivatives increase hCG secretion and aromatase activity of human choriocarcinoma cells. TBT and TPT also affect mRNA expression of various steroid metabolizing emzymes in rat and human choriocarcinoma cells. Next, we examined the toxicokinetics of TBT in pregnant rat with intraperitoneal injection of TBT at gestational days 16. After 24h, TBT accumulated in placenta rather than in matemal liver and fetus. Moreover, we identified several genes differentially expressed in TPT-treated human choriocarcinoma cells using improved differential display method. Our stydies suggest that organotin compounda are potent disruptors of placental endocrine functions of human and rodents, and the placenta represents a potential target organ for organotin compounds.
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