双酚A通过PTEN通路致原始卵泡过度激活及其在卵巢早衰发生中的作用

项目名称： 双酚A通过PTEN通路致原始卵泡过度激活及其在卵巢早衰发生中的作用

项目编号： No.21507094

项目类型： 青年科学基金项目

立项/批准年度： 2016

项目学科： 化学工业

项目作者： 胡颖

作者单位： 四川大学

项目金额： 22万元

中文摘要： 我们前期流行病学研究结果提示双酚A(BPA)是卵巢早衰(POF)发生的危险因素之一。卵泡池中原始卵泡过度过早地激活致其过早耗竭是POF发生的重要因素之一。最新文献报道，BPA可促进原始卵泡的异常激活，但其机制尚不清楚。PTEN信号系统对卵泡激活具有负调控作用，又称卵泡激活的“刹车”。为进一步探索BPA在POF发生中的作用及其可能的病理机制，本研究拟首先比较POF患者和正常人群血清BPA含量的差异，同时以小鼠为实验模型，采用细胞生物学、免疫荧光和分子生物学等技术，通过体内、体外实验研究BPA对卵泡激活和发育的影响；在此基础上，进一步研究BPA是否通过PTEN-PI3K-AKT信号途径诱导卵泡的过度激活以及在POF发生中的作用。该研究一方面将揭示重要的环境因素双酚A在POF发病中的作用及其分子机制，另一方面也可为POF患者的治疗以及从源头上降低该病的患病风险提供新的思路。

中文关键词： 双酚A；PTEN通路；原始卵泡；卵巢早衰

英文摘要： Our previous work shows that bisphenol A(BPA) is probably one of the risk factors of premature ovarian failure (POF). The essence of POF is the premature exhaustion of primordial follicles in the follicle pool, which is caused by the excessive premature activation of primordial follicles after birth. According to the latest research reports, BPA exposure promotes the transition of primordial follicles to primary follicles, thus the number of primordial follicles in the primordial follicle pool decreases significantly, however, the molecular mechanisms underlying abnomal follicle activation are poorly understood. PTEN signal system is a negative regulator of follicle activation, which is called the brake of follicle activation. Besides, BPA induces MCF-7 breast cancer cell proliferation by the role of PTEN/AKT/p53 axis. For a more detailed exploration of the relationship between BPA exposure and POF, and the pathological mechanisms, we plan to detect the levels of human serum BPA by Gas Chromatography/Mass Spectrometry (GC-MS) in both POF group and normal group. Meanwhile, female mice will be used to study the effect of BPA on follicular activation and development in vitro and in vivo by cell biology,immunofluorescence and molecular biology technique,and then,we plan to find out the modulating effect of PTEN-PI3K-AKT axis in the premature activation of primordial follicles and in the occurrence of POF induced by BPA. The aim of the study is to explore the molecular mechanism controlling the initiation of primordial follicle pool, providing a new idea for the treatment of POF and theoretical basis for reducing the risk of POF.

英文关键词： bisphenol A(BPA);PTEN signal pathway;primordial follicle;premature ovarian failure (POF)