权益分类	功能权益	普通用户	{{item.name}}会员
{{category.name}}	{{benefitItem.name}}

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.

胎盘在维持妊娠中起着至关重要的作用，它将母体循环中的氧气和营养物质输送给胎儿，并将胎儿的代谢产物返回母体。胎盘还具有许多重要的内分泌功能，因此，这些胎盘功能可能会受到具有内分泌干扰作用的环境污染物的发育和生殖毒理学的高风险。在本研究中，为了扩展对有机锡化合物的人类性发育和生殖毒性的认识，这些化合物可诱导腹足类软体动物雌性生殖系统的性异常，我们评估了这些化合物对人类和啮齿动物胎盘内分泌功能的可能影响。三丁基锡（TBT）、三苯基锡（TPT）及其烷基衍生物可增加人绒毛膜癌细胞hCG分泌和芳香化酶活性。TBT和TPT还影响大鼠和人绒毛膜癌细胞中各种类固醇代谢酶的mRNA表达。接下来，我们在妊娠第16天通过腹腔注射TBT检查了TBT在妊娠大鼠中的毒性。24h后，TBT在胎盘中蓄积，而在母肝和胎儿中蓄积较少。此外，我们发现了几个差异表达的基因在TPT处理的人绒毛膜癌细胞使用改进的差异显示方法。本研究表明，有机锡化合物对人和啮齿类动物的胎盘内分泌功能有很强的干扰作用，胎盘是有机锡化合物的潜在靶器官。