Abstract
BackgroundPolycystic ovary syndrome (PCOS), whose etiology remains uncertain, is a highly heterogenous and genetically complex endocrine disorder. The aim of this study was to identify differentially expressed genes (DEGs) in granulosa cells (GCs) from PCOS patients and make epigenetic insights into the pathogenesis of PCOS.ResultsIncluded in this study were 110 women with PCOS and 119 women with normal ovulatory cycles undergoing in vitro fertilization acting as the control group. RNA-seq identified 92 DEGs unique to PCOS GCs in comparison with the control group. Bioinformatic analysis indicated that synthesis of lipids and steroids was activated in PCOS GCs. 5-Methylcytosine analysis demonstrated that there was an approximate 25% reduction in global DNA methylation of GCs in PCOS women (4.44 ± 0.65%) compared with the controls (6.07 ± 0.72%; P < 0.05). Using MassArray EpiTYPER quantitative DNA methylation analysis, we also found hypomethylation of several gene promoters related to lipid and steroid synthesis, which might result in the aberrant expression of these genes.ConclusionsOur results suggest that hypomethylated genes related to the synthesis of lipid and steroid may dysregulate expression of these genes and promote synthesis of steroid hormones including androgen, which could partially explain mechanisms of hyperandrogenism in PCOS.
Highlights
Polycystic ovary syndrome (PCOS), whose etiology remains uncertain, is a highly heterogenous and genetically complex endocrine disorder
There is evidence indicating that epigenetic alterations, including aberrant DNA methylation might contribute to the development of PCOS [7]
Our previous work has indicated that epigenetic alterations of several important transcription factors are involved in the follicular development in granulosa cells (GCs) that contribute to PCOS [7]
Summary
Polycystic ovary syndrome (PCOS), whose etiology remains uncertain, is a highly heterogenous and genetically complex endocrine disorder. DNA methylation is a highly tissue-specific phenomenon that varies with time on the basis of environmental fluctuations [8] It is involved in the stability of gene expression during organismal development [9, 10]. Specific genes such as LHR [11], EPHX1 [12], and CYP19A1 [13] have been demonstrated to be associated with PCOS with aberrant DNA methylation in distinct tissues. Our previous work has indicated that epigenetic alterations of several important transcription factors are involved in the follicular development in granulosa cells (GCs) that contribute to PCOS [7]
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