Effects of organotin compounds on the endocrine functions of placenta.

有机锡化合物对胎盘内分泌功能的影响。

基本信息

批准号：
13470499
负责人：
TANAKA Keiichi
金额：
$ 9.41万
依托单位：
Osaka University
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (B)
财政年份：
2001
资助国家：
日本
起止时间：
2001 至 2002
项目状态：
已结题

项目摘要

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.

胎盘通过将氧气和养分从结emal循环传递到胎儿，并通过将胎儿代谢物归还母亲，在维持怀孕中起着至关重要的作用。胎盘还具有许多关键的内分泌，因此这些胎盘功能可能对具有内分泌干扰作用的环境污染物的发育和生殖毒理学具有很高的风险。在本研究中，为了扩展有机蛋白化合物的人性性发育和生殖毒性的知识，这些化合物在腹足动物软体动物中诱导性异常对FEMAIL生殖器系统诱导性异常，我们评估了这些化合物对人和啮齿动物中胎盘源自分泌功能的可能影响。 Tributyltin（TBT），Triphenyltin（TPT）及其各种烷基衍生物增加了人类绒毛膜细胞的HCG分泌和芳香酶活性。 TBT和TPT还会影响大鼠和人类绒毛膜瘤细胞中各种类固醇代谢的掺杂的mRNA表达。接下来，我们检查了妊娠16日对TBT注射TBT的TBT的毒性动物学。24H后，TBT积聚在胎盘中，而不是在Matemal肝脏和胎儿中。此外，我们使用改进的差分显示方法确定了在TPT处理的人类绒毛膜癌细胞中差异表达的几个基因。我们的造型表明，有机蛋白化合物是人和啮齿动物的胎盘内分泌功能的有效破坏者，胎盘代表了有机蛋白化合物的潜在靶向器官。