环境雌激素BPA会导致卵母细胞第一次减数分裂（MI）缺陷，产生非整倍体配子，但雌激素本身在此过程的作用未知。我们前期实验结果表明，雌二醇抑制MI前期，且下调与之相关的同源重组系统和黏连蛋白基因的表达。由此我们推断：雌激素可以调控包括同源重组在内的MI前期。为探索此机制，本课题通过小鼠胚胎卵巢体外培养模型，利用分子标记物，分析雌二醇对卵母细胞MI前期及同源重组的影响；利用雌激素受体拮抗剂和雌激素受体敲除小鼠，明确雌二醇的受体途径；运用定量PCR、免疫印迹、siRNA、慢病毒超表达等技术，明确关键基因在此过程的表达变化与功能，探明雌二醇抑制小鼠卵母细胞MI前期的分子机理。最后，分析具有雌激素样活性的DEHP、DES、BPA等环境污染物对卵母细胞早期发育的影响。研究结果有助于深入理解激素与生殖细胞发育的辩证关系，还有望为防治生殖危害、保护人类生殖能力和优生优育提供新的思路和研究靶点与方法。

BPA, an estrogen-like endocrine disrupting chemical, causes failures in meiosis I, resulting in aneuploid oocytes. However, the role of estrogen, per se, is unknown in the progression. Our preliminary work showed that, 17 β-estradiol (E2) inhibited meiotic prophase I progression of oocytes, and down-regulated the mRNA expression of genes responsible for homologous recombination and encoding subunits of cohesins. Therefore, we speculate that E2 regulates meiosis prophase I, as well as homologous recombination. In this study, we will employ fetal ovary culture system to investigate the underlying mechanism of E2 to regulate Meiotic Prophase I and homologous recombination. We will identify the involved receptors by specific antagonists and mutant mice, and explore the molecular mechanism by identifying and screening out the key downstream genes. Moreover, the effects of the environmental endocrines, such as DEHP, DES and BPA, on the MI prophase progression will be observed. The study will help better understanding the regulatory mechanism of Meiotic Prophase I, providing useful information in the hazard of the environmental endocrines. It may also provide new methods to protect and improve human reproductive quality.