• Li-Le Jiang, Juan-Ke Xie, Jin-Quan Cui, Duo Wei, Bao-Li Yin, Ya-Nan Zhang, Yuan-Hui Chen, Xiao Han, Qian Wang, and Cui-Lian Zhang.
• aSecond Hospital Affiliated to Zhengzhou University, Zhengzhou, Henan Province bZhengzhou University, Zhengzhou, Henan Province cReproductive Medical Center, People's Hospital of Henan Province, Zhengzhou, Henan Province, P.R. China.
• Medicine (Baltimore). 2017 Jan 1; 96 (2): e5768.

BackgroundDNA methylation modification has been proved to influence the phenotype of polycystic ovary syndrome (PCOS). Genome-wide association studies (GWAS) demonstrate that yes-associated protein (YAP1) genetic sites are associated with PCOS. The study aims to detect the methylation status of YAP1 promoter in ovary granulosa cells (GCs) of PCOS patients and explore novel therapeutic targets for PCOS.MethodsRandomized controlled trial was applied and a total of 72 women were included in the study, including 36 cases of PCOS patients and 36 cases of health controls. Ovary GCs were extracted from in vitro fertilization embryo transfer. Methylation status of YAP1 promoter was detected by bisulfite sequencing PCR (BSP). Protein and mRNA expression of YAP1 were measured by western blotting and real-time quantitate PCR.ResultsOverall methylation level of YAP1 promoter region from PCOS group was significantly lower than that from control group. CpG sites analysis revealed that 12 sites (-443, -431, -403, -371, -331, -120, -49, -5, +1, +9, +15, +22) were significantly hypomethylated in women with PCOS (P < 0.05). A significant upregulation of YAP1 mRNA and protein expression levels was observed. Testosterone concentration could alleviate the methylation status and demonstrate obvious dose-dependent relation.ConclusionOur research achievements manifest that hypomethylation of YAP1 promoter promotes the YAP1 expression, which plays a key role in the pathogenesis and accelerate PCOS.

24 keywords...

hide…