PCOS患者颗粒细胞microRNA表达谱改变可能导致其细胞功能失调

发布时间：2018-09-10 07:13

【摘要】：多囊卵巢综合征是育龄期女性最为常见的一种内分泌疾病。它是一种异质性疾病,常合并其他内分泌疾病和内分泌功能紊乱表现。由于其广泛的患病率,以及对育龄女性造成的严重内分泌损害,成为了近年来女性不育的主要原因。卵巢功能的异常以及与之相关的内分泌代谢紊乱,是该病的主要病理机制。越来越多证据表明异常表达的nicroRNA与卵巢功能异常相关。我们通过microRNA芯片分析多囊卵巢综合征患者与正常管性不育患者的颗粒细胞发现52种异常表达的microRNA。其中38种上升,14种下调。我们对数据进行综合评价后,验证了其中的3个。其中miR-375表达上升明显,通过继续收集两类病人的样本用荧光实时定量分析,证实了芯片的结果。通过生物信息学分析,我们预测miR-375与表皮生长因子受体以及其作为信号通路的下游非受体酪氨酸激酶通路都存在序列互补关系,并且我们在不孕症患者原代颗粒细胞中和颗粒细胞系中分别加入miR-375过表达和抑制剂后都验证了这一分析结果。并且通过颗粒细胞瘤细胞系的信号通路抑制实验,我们还对该信号通道进行了抑制,观察到其与颗粒细胞中睾酮的产生与代谢所必须的关键酶密切相关,进而可能是造成多囊卵巢综合征患者的临床/血生化高雄表现的原因之一
[Abstract]:Polycystic ovary syndrome (PCOS) is one of the most common endocrine diseases in women of childbearing age. It is a heterogeneous disease, often accompanied by other endocrine diseases and endocrine dysfunction. Abnormal function and related endocrine and metabolic disorders are the main pathological mechanisms of the disease. Increasing evidence suggests that abnormal expression of nicroRNA is associated with abnormal ovarian function. Among them, 38 were up and 14 were down. Three of them were validated after comprehensive evaluation of the data. Among them, the expression of miR-375 increased significantly. The results were confirmed by real-time fluorescence quantitative analysis of the samples collected from two groups of patients. The downstream non-receptor tyrosine kinase pathway, as a signaling pathway, has a sequence complementarity relationship, which was confirmed by the addition of microRNA375 overexpression and inhibitors in primary granulosa cells and granulosa cell lines of infertility patients, respectively. They also inhibited this signaling pathway, and observed that it was closely related to the production of testosterone and the key enzymes necessary for metabolism in granulosa cells, which may be one of the reasons for the clinical / blood biochemical Kaohsiung manifestations of polycystic ovary syndrome
【学位授予单位】：浙江大学
【学位级别】：硕士
【学位授予年份】：2014
【分类号】：R711.75

【共引文献】