Bisphenol A and Ovotoxicity

双酚A（BPA）是一种内分泌干扰化学品，广泛用于聚碳酸酯塑料， 食品包装产品、牛奶容器、婴儿奶瓶、食品罐内衬和牙科材料。的 BPA的广泛使用引起了人们的关注，因为发育和出生后暴露于BPA已经 与多种物种的雌性不育有关虽然BPA暴露会导致各种不孕症， 然而，BPA引起的不育原因尚不清楚。初步数据显示，BPA可能会导致 通过抑制卵泡的生长和诱导死亡（闭锁）而导致不育。此外，初步数据 表明BPA可能通过抑制卵巢产生雌二醇（E2）而导致不育。小其他 关于BPA对卵巢功能的影响的信息是可用的。国家中心计划的这项研究 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， BPA对卵巢的影响NCTR/FDA的设计可以很容易地扩展到测量的影响， BPA对卵泡生长、闭锁、卵泡数量、E2水平、不孕和卵巢早衰的影响。 具体来说，拟议的工作将通过检验BPA 暴露抑制卵泡生长并诱导闭锁，导致低E2水平，随后不孕和/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暴露是否通过抑制大鼠卵泡生长和/或诱导闭锁而减少卵泡数量 卵巢，2）确定BPA暴露是否通过抑制E2合成和/或通过增加E2 大鼠卵巢中的代谢，以及3）确定BPA暴露导致不孕和早产的能力 成年大鼠卵巢衰竭。拟议的工作将增加我们对机制的理解， BPA会导致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，用于治疗低E2水平，不孕症， 以及BPA引起的卵巢早衰。

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.