Author:
Wang Fangfang,Pan Jiexue,Liu Ye,Meng Qing,Lv Pingping,Qu Fan,Ding Guo-Lian,Klausen Christian,Leung Peter C. K.,Chan Hsiao Chang,Yao Weimiao,Zhou Cai-Yun,Shi Biwei,Zhang Junyu,Sheng Jianzhong,Huang Hefeng
Abstract
Polycystic ovary syndrome (PCOS) is one of the most common female endocrine disorders and a leading cause of female subfertility. The mechanism underlying the pathophysiology of PCOS remains to be illustrated. Here, we identify two alternative splice variants (ASVs) of the androgen receptor (AR), insertion and deletion isoforms, in granulosa cells (GCs) in ∼62% of patients with PCOS. AR ASVs are strongly associated with remarkable hyperandrogenism and abnormalities in folliculogenesis, and are absent from all control subjects without PCOS. Alternative splicing dramatically alters genome-wide AR recruitment and androgen-induced expression of genes related to androgen metabolism and folliculogenesis in human GCs. These findings establish alternative splicing of AR in GCs as the major pathogenic mechanism for hyperandrogenism and abnormal folliculogenesis in PCOS.
Funder
National Natural Science Foundation of China
Gouvernement du Canada | Canadian Institutes of Health Research
Publisher
Proceedings of the National Academy of Sciences
Cited by
81 articles.
订阅此论文施引文献
订阅此论文施引文献,注册后可以免费订阅5篇论文的施引文献,订阅后可以查看论文全部施引文献