Genome wide screen of ovary specific DNA methylation in polycystic ovary syndrome

Capsule:
Methylation patterns in tissue from polycystic ovary syndrome were distinguishable from control samples and were associated with promoter class, genomic location, and specific biological networks.

Authors:
Ying-Ying Yu, Ph.D., Cui-Xiang Sun, Ph.D., Yin-Kun Liu, Ph.D., Yan Li, Ph.D., Li Wang, Ph.D., Wei Zhang, Ph.D.

Volume 104, Issue 1, Pages 145–153

Abstract:

Objective:
To compare genome-wide DNA methylation profiles in ovary tissue from women with polycystic ovary syndrome (PCOS) and healthy controls.

Design:
Case-control study matched for age and body mass index.

Setting:
University-affiliated hospital.

Patient(s):
Ten women with PCOS who underwent ovarian drilling to induce ovulation and 10 healthy women who were undergoing laparoscopic sterilization, hysterectomy for benign conditions, diagnostic laparoscopy for pelvic pain, or oophorectomy for nonovarian indications.

Intervention(s):
None.

Main Outcome Measure(s):
Genome-wide DNA methylation patterns determined by immunoprecipitation and microarray (MeDIP-chip) analysis.

Result(s):
The methylation levels were statistically significantly higher in CpG island shores (CGI shores), which lie outside of core promoter regions, and lower within gene bodies in women with PCOS relative to the controls. In addition, high CpG content promoters were the most frequently hypermethylated promoters in PCOS ovaries but were more often hypomethylated in controls. Second, 872 CGIs, specifically methylated in PCOS, represented 342 genes that could be associated with various molecular functions, including protein binding, hormone activity, and transcription regulator activity. Finally, methylation differences were validated in seven genes by methylation-specific polymerase chain reaction. These genes correlated to several functional families related to the pathogenesis of PCOS and may be potential biomarkers for this disease.

Conclusion(s):
Our results demonstrated that epigenetic modification differs between PCOS and normal ovaries, which may help to further understand the pathophysiology of this disease.

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