【摘要】 目的:全基因组范围内探索高雄激素调控卵巢颗粒细胞的直接效应基因及通路，为高雄激素参与多囊卵巢综合征（PCOS）的发病机理提供数据支持。方法:以人卵巢颗粒细胞系KGN为研究对象，用高浓度睾酮(10^-5mol/L)处理，应用雄激素受体的抗体进行染色质免疫共沉淀，构建DNA文库，进行高通量测序及生物信息学分析。结果:高浓度睾酮处理后，KGN细胞中雄激素受体结合的Peak区域与对照组明显不同。高雄激素诱导其受体结合的Peak为1823个，大部分集中于基因间区与内含子。Peak关联靶基因富集到细胞凋亡、铁死亡、细胞黏附分子、磷脂酶D信号途径、cAMP信号通路、磷脂酰肌醇信号系统、磷酸肌醇代谢、神经活性配体-受体相互作用8个信号通路，涉及基因43个。结论:研究揭示了高雄激素诱导的卵巢颗粒细胞发生改变的重要信号通路，有助于从源头上阐明雄激素参与PCOS发病机理的机制，并为PCOS的治疗提供潜在的靶点。更多还原

【Abstract】 Objective:To explore the direct effect genes and pathways of ovarian granulosa cells regulated by hyperandrogen in the whole genome, so as to provide data support for the pathogenesis of PCOS.Methods:Human ovarian granulosa cell line KGN cells were treated with high concentration of testosterone(10^-5mol/L),and the antibody of androgen receptor was used for chromatin immunoprecipitation.Construct DNA library and carry out high-throughput sequencing and bioinformatics analysis.Results:After treatment with high concentration of testosterone, the peak region of androgen receptor binding in KGN cells was significantly different from that in the control group.There were 1823 peaks induced by hyperandrogen, most of which were located in intergenic regions and introns.Peak related target genes were enriched in 8 signaling pathways, including apoptosis, ferroptosis, cell adhesion molecules, phospholipase D signaling pathway, cAMP signaling pathway, phosphatidylinositol signaling system, Inositol phosphate metabolism and neuroactive ligand-receptor interaction, involving 43 genes.Conclusion:This study reveals the important signal pathway of ovarian granulosa cells changes induced by hyperandrogen.The results help to clarify the mechanism of androgen involved in the pathogenesis of PCOS from the source, and provide potential targets for the treatment of PCOS.更多还原