Bisphenol A and Ovotoxicity

双酚A(BPA)是一种内分泌干扰物，广泛用于聚碳酸酯塑料，如 食品包装产品、牛奶容器、婴儿奶瓶、食品罐头衬里和牙科材料。这个 双酚A的广泛使用引起了人们的担忧，因为发育和出生后接触双酚A的情况一直是 在各种物种中与女性不孕不育有关。虽然接触双酚A会导致各种不育 BPA诱导的不孕症的原因尚不清楚。初步数据显示，双酚A可能会导致 通过抑制卵泡生长和导致死亡(闭锁)而导致的不孕不育。此外，初步数据 提示双酚A可能通过抑制卵巢产生雌二醇而导致不孕不育。小其他 关于双酚A对卵巢功能的影响的信息是可用的。这项研究是由国家中心计划的 毒理学研究/食品和药物管理局(NCTR/FDA)提供了一个完美的机会来检查 双酚A对卵巢的影响。NCTR/FDA的设计可以很容易地扩展到测量 双酚A对卵泡生长、闭锁、卵泡数量、雌二醇水平、不孕症和卵巢早衰的影响。 具体地说，拟议的工作将通过检验BPA的假设来扩展NCTR/FDA的研究 暴露抑制卵泡生长并导致闭锁，导致低E2水平，继而导致不孕不育和/或 卵巢早衰。为了验证这一假设，将完成以下具体目标：1) 确定BPA暴露是否通过抑制卵泡生长和/或导致大鼠闭锁来减少卵泡数量 卵巢，2)确定BPA暴露是否通过抑制E2合成和/或通过增加E2来降低E2水平 在大鼠卵巢中的代谢，以及3)决定双酚A暴露导致不孕和早产的能力 成年大鼠卵巢衰竭。拟议的工作将通过以下方式增加我们对这些机制的了解 双酚A会引起卵毒性。重要的是要了解双酚A损害的机制 卵巢，因为这可能导致开发新的靶点来治疗低E2水平，不孕不育， 以及双酚A所致的卵巢早衰。

Bisphenol A (BPA) is an endocrine disrupting chemical that is widely used in polycarbonate plastics such as food packaging products, milk containers, baby bottles, liners for food cans, and dental materials. The widespread use of BPA raises concerns because developmental and postnatal exposures to BPA have been linked to female infertility in a variety of species. While BPA exposure causes infertility in a variety of species, the reasons for BPA-induced infertility are unknown. Preliminary data suggest that BPA may cause infertility by inhibiting growth and inducing death (atresia) of ovarian follicles. Further, preliminary data indicate that BPA may cause infertility by inhibiting the production of estradiol (E2) by the ovary. Little other information is available on the effects of BPA on ovarian function. The study planned by the National Center for Toxicologic Research/Food and Drug Administration (NCTR/FDA) offers a perfect opportunity to examine the effects of BPA on the ovary. The NCTR/FDA design can easily be expanded to measure the effects of BPA on ovarian follicle growth, atresia, follicle numbers, E2 levels, infertility, and premature ovarian failure. Specifically, the proposed work will expand the NCTR/FDA study by testing the hypothesis that BPA exposure inhibits follicle growth and induces atresia, leading to low E2 levels followed by infertility and/or premature ovarian failure. To test this hypothesis, the following specific aims will be completed: 1) determine if BPA exposure reduces follicle numbers by inhibiting follicle growth and/or inducing atresia in rat ovaries, 2) determine if BPA exposure reduces E2 levels by inhibiting E2 synthesis and/or by increasing E2 metabolism in rat ovaries, and 3) determine the ability of BPA exposure to cause infertility and premature ovarian failure in the adult rat. The proposed work will increase our understanding ofthe mechanisms by which BPA causes ovotoxicity. It is important to understand the mechanisms by which BPA damages the ovary because this may lead to the development of novel targets for the treatment of low E2 levels, infertility, and premature ovarian failure induced by BPA.