To explore the specific methylation pattern changes based on the whole genome level of ovarian tissue in Uygur polycystic ovary syndrome (PCOS) patients.

From May 2014 to June 2016 in First People′s Hospital of Kashgar Prefecture, a total of 60 cases PCOS ovarian tissues of Uygur PCOS patients (into PCOS group) and 60 cases of normal ovarian tissues of Uygur ovarian cysts patients (into control group) were obtained as research materials. The cytosine-phosphate-guanine (CpG) islands and promoter regions of whole genome of ovarian tissues in two groups were taken methylation scanning by methylated DNA immunoprecipitation-chip (MeDIP-chip) technology. Regions of MeDIP-chip results of peak scores ≥2 were taken as positive methylation regions to screening the methylation genes. The functional relevances of organism in which participated by specific hypermethylation genes with peak scores ≥5 were investigated by analysis of gene ontology (GO) and Pathway. The statistical methods of paired t test and chi-square test were used to compare the differences of ovarian tissue methylation spectrum between two groups. This study was in line with World Medical Association Declaration of Helsinki revised in 2013, and all participants were voluntary to participate in this study and signed the informed consents.

①The results of MeDIP-chip showed that the methylation rates of CpG islands and gene promoters in PCOS group were 12.9% (3 633/28 226) and 3.8% (687/18 028), respectively, and were 13.3% (3 759/28 226) and 3.6% (643/18 028) in control group, respectively. There were no significant differences between two groups of ovarian tissues in whole genome methylation levels and distributions of methylation fragments in genome regions (P>0.05). ②There were no significant differences between two groups of ovarian tissues in methylation levels in upstream regulatory regions and core promoter regions of genomic transcriptional regulatory regions (P>0.05). The methylation level in gene coding regions of transcriptional regulatory regions of ovarian tissues in PCOS group was (3.14±0.21), which was lower than that in control group (3.96±0.23), and the difference was statistically significant (t=2.653, P=0.010). ③There was significant difference between two groups of ovarian tissues whole genome in distribution of 3 types of hypermethylation promoters including high CpG promoters (HCP), intermediate CpG promoters (ICP) and low CpG promoters (LCP) (χ²=3.208, P=0.002), which were the highest HCP proportion (40.1%) in PCOS group and the lowest HCP proportion (13.3%) in control group. The HCP methylation level of ovarian tissues whole genome in PCOS group was (0.68±0.08), which was lower than that in control group (0.71±0.09), while the methylation levels of ICP and LCP were (0.74±0.13) and (0.76±0.11), and they were both higher than those in control group, which were (0.61±0.07) and (0.32±0.03), and all the differences were statistically significant (t=1.686, P=0.049; t=1.992, P=0.028; t=3.361, P=0.002). ④The results of GO and Pathway analysis showed that the specific hypermethylation genes of Uygur PCOS patients′ ovarian tissues were mainly participated in the progress of receptor binding, protein binding, hormone activity, transcriptional regulatory activity, transcription factor activity and DNA binding.

Compare with the Uygur female normal ovarian tissue, the Uygur PCOS patients ovarian tissue′s methylation level in gene coding region was lower, the proportion of HCP was the highest with lower level of methylation, and the methylation level of ICP and LCP were both higher. All these specific methylation changes may response to the occurrence and development of PCOS in Uygur patients.