FTO基因在PCOS大鼠卵巢胰岛素抵抗及卵泡发育障碍中的作用机制研究

项目名称： FTO基因在PCOS大鼠卵巢胰岛素抵抗及卵泡发育障碍中的作用机制研究

项目编号： No.81501223

项目类型： 青年科学基金项目

立项/批准年度： 2016

项目学科： 医药、卫生

项目作者： 崔琳琳

作者单位： 山东大学

项目金额： 16万元

中文摘要： 多囊卵巢综合征（PCOS）是一种复杂的内分泌代谢性疾病，患者主要表现为卵泡发育及排卵障碍、高雄激素、卵巢多囊样变，其病因尚不明确。课题组前期GWAS研究提示FTO基因为PCOS的易感基因，结果在大样本汉族患者中得到证实。但FTO基因在PCOS发病机制中的作用尚不明确。既往研究表示FTO基因与胰岛素抵抗相关。胰岛素抵抗是PCOS重要的病理生理基础，卵巢局部胰岛素抵抗可能导致卵泡发育及排卵功能障碍。因此推测FTO基因可能通过影响卵巢局部胰岛素信号通路进而导致卵泡发育的异常。本项目拟利用PCOS大鼠模型和体外卵泡及卵巢细胞培养模型，通过RT-PCR、Western blot、原位杂交、免疫组化、病毒感染等分子生物学手段明确FTO基因对PCOS大鼠卵巢胰岛素信号通路以及卵泡发育的影响和作用机制，为PCOS临床治疗提供干预靶点。

中文关键词： 多囊卵巢综合征；FTO；胰岛素抵抗

英文摘要： Polycystic ovary syndrome(PCOS) characterized by ovulatory dysfunction, hyperandrogenism, and polycystic ovary, is a complex endocrine and metabolic disorder. Its etiology is unknown until now. In the previous genome wide association study, our group found fat mass- and obesity-associated gene (FTO) conferred to PCOS risk. It has been validated in PCOS of Han Chinese in a large-scale. However etiological mechanism of FTO in the occurrence of the syndrome is hardly known. It is previously demonstrated that FTO is related to insulin resistance(IR), which is considered as the key pathophysiological basis of PCOS. IR in ovary may cause the disturbance of follicle development and ovulation. Therefore, it is logically to hypothesis that FTO may disrupt the insulin signaling pathway and then lead to ovulatory dysfunction. In the present study, we will use RT-PCR, Western blot, in situ hybridization, and immunohistochemistry to investigate the expression of FTO in the ovary of PCOS rat, and use viral infection to study the role and mechanism of FTO in ovary IR and ovulatory dysfunction in vivo and in vitro. This study will demonstrated the possible etiological mechanism of FTO in PCOS and provide a potential target for clinical therapy.

英文关键词： polycystic ovary syndrome;FTO;insulin resistance