IFN-γ/JAK/STAT1 通路在PCOS卵泡发育障碍中的作用研究

Polycystic ovary syndrome (PCOS) is the most common endocrinopathy among women of reproductive age. Its etiology and pathophysiology are not known by us yet. Currently, it is well accepted that low-grade chronic inflammation is universally presented in PCOS; however, it is not yet elucidated weather low-grade chronic inflammation participate in the etiology of PCOS. Our preliminary experiment indicated that IFN-γ, its receptor and other inflammatory factors secreted by IFN-γ pathway is hyper-expressed in women with PCOS. As a result, we presume that IFN-γ pathway may function in the folliculogenesis dysfunction in PCOS. In order to elucidate the function of IFN-γ pathway in the process of fulliculogenesis dysfunction, the current project is planned to manipulate in vitro culture system of follicles, granulosa cells and thecal cells, and employ qRT-PCR, immunohistochemistry, western blotting, virus transfection, MTT, flowcytometrie et al. And through in vitro experiment, we expect to illuminate the mechanism of anti-inflammatory drugs in treatment of PCOS through IFN-γ pathway. Our current project is of paramount importance in elucidating ovarian inflammation in PCOS and mechanism of clinical treatment.

多囊卵巢综合征（PCOS）是育龄期妇女常见的内分泌代谢疾病，其确切病因和具体发病机制还尚未阐明。目前研究认为慢性低度炎症普遍存在于PCOS，但迄今为止PCOS处于慢性低度炎症的机制亦不清楚，是否影响了PCOS卵泡发育也未阐明。我们的预实验显示IFN-γ及其受体IFN-γR、IFN-γ通路调控分泌的炎症因子在PCOS患者颗粒细胞中高表达。因此我们推测IFN-γ通路在PCOS卵泡发育障碍中起作用。本项目拟通过体外卵泡、颗粒细胞及卵泡膜细胞培养体系，利用qRT-PCR、免疫组化、Western blotting、病毒转染、MTT法、流式细胞分析术等实验方法，研究IFN-γ通路在卵泡发育障碍中的作用，并通过体内外实验，阐明抗炎药物是否通过IFN-γ通路对PCOS卵巢局部的治疗作用。本项目对揭示PCOS卵巢局部炎症作用机制及临床治疗具有重要意义。

多囊卵巢综合征(polycystic ovary syndrome, PCOS)是一种临床表现复杂、以稀发/无排卵、高雄激素和卵巢多囊样改变为主要特征的内分泌及生殖功能障碍性疾病，已报道的病因有遗传因素、环境因素及免疫因素等。本项目对PCOS和对照外周血淋巴细胞亚群分析，发现PCOS 组IFN-γ所占百分比明显增加，有统计学意义。利用ELISA法也检测到PCOS患者的卵泡液中IFN-γ高于正常对照。通过体外颗粒细胞及卵泡膜细胞培养体系，利用 qRT-PCR、Western blotting、CCK8法、流式细胞分析术等实验方法，从蛋白质和mRNA水平，IFN-γ处理颗粒细胞及卵泡膜细胞后，细胞增殖加快，细胞凋亡减慢，雌激素分泌减少，孕激素分泌增加，雄激素分泌减少，cyp11a1、 star表达明显升高， cyp19a1表达降低，STAT1被磷酸化，证实了 IFN-γ通路在颗粒细胞及卵泡膜细胞细胞的增殖、凋亡及分泌激素过程中起重要作用。本项目初步研究了IFN-γ通路在卵泡发育中的作用，为阐明PCOS排卵障碍提供了新的线索，为PCOS发病机制的免疫因素提供新的理论依据。