Comprehensive analysis of genome-wide DNA methylation across human polycystic ovary syndrome ovary granulosa cell

// Jiawei Xu 1, * , Xiao Bao 1, * , Zhaofeng Peng 1 , Linlin Wang 1 , Linqing Du 1 , Wenbin Niu 1 , Yingpu Sun 1 1 Center for Reproductive Medicine, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan 450000, China * These authors have contributed equally to this work Correspondence to: Yingpu Sun, e-mail: [email protected] Keywords: polycystic ovary syndrome, granulosa cell, DNA methylation, global DNA methylation and hydroxymethylation Received: February 04, 2016      Accepted: March 28, 2016      Published: April 1, 2016 ABSTRACT Polycystic ovary syndrome (PCOS) affects approximately 7% of the reproductive-age women. A growing body of evidence indicated that epigenetic mechanisms contributed to the development of PCOS. The role of DNA modification in human PCOS ovary granulosa cell is still unknown in PCOS progression. Global DNA methylation and hydroxymethylation were detected between PCOS’ and controls’ granulosa cell. Genome-wide DNA methylation was profiled to investigate the putative function of DNA methylaiton. Selected genes expressions were analyzed between PCOS’ and controls’ granulosa cell. Our results showed that the granulosa cell global DNA methylation of PCOS patients was significant higher than the controls’. The global DNA hydroxymethylation showed low level and no statistical difference between PCOS and control. 6936 differentially methylated CpG sites were identified between control and PCOS-obesity. 12245 differential methylated CpG sites were detected between control and PCOS-nonobesity group. 5202 methylated CpG sites were significantly differential between PCOS-obesity and PCOS-nonobesity group. Our results showed that DNA methylation not hydroxymethylation altered genome-wide in PCOS granulosa cell. The different methylation genes were enriched in development protein, transcription factor activity, alternative splicing, sequence-specific DNA binding and embryonic morphogenesis. YWHAQ, NCF2, DHRS9 and SCNA were up-regulation in PCOS-obesity patients with no significance different between control and PCOS-nonobesity patients, which may be activated by lower DNA methylaiton. Global and genome-wide DNA methylation alteration may contribute to different genes expression and PCOS clinical pathology.