Role of genomic DNA methylation in PCOS pathogenesis: a systematic review and meta-analysis involving case-controlled clinical studies

Abstract

PCOS is often associated with aberrant DNA methylation. Despite the advances in diagnostics and treatment of PCOS, the pathophysiological mechanism remain unknown. Several genes are epigenetically dysregulated in PCOS and associated with pathological consequences of PCOS and metabolic comorbidities, however the methylation status of specific genes and to what extent the genes are deregulated in terms of methylation pattern are unknown. This review aimed to analyse the existing data for specific genes and find conclusive evidence of their involvement in PCOS and associated risks. A comprehensive literature search was conducted in five electronic databases. The case-controlled clinical studies using both PCOS and healthy women and evaluating the methylation pattern without any treatment or intervention were included in the study. A random-effect model was used to extract the data for meta-analysis, and outcomes were expressed as standardized mean difference with a 95% CI. From 541 screened records, 41 studies were included in the review and 21 of them were used for meta-analysis of 20 genes. Meta-analysis revealed a significant global DNA hypomethylation in different tissues and peripheral blood of patients with PCOS compared to healthy controls. Specific gene methylation assessment revealed that genes associated with several functions were significantly hypomethylated and hypermethylated in patients with PCOS. This review provides conclusive evidence of epigenetic deregulation of specific genes in PCOS. These genes can potentially be used to develop diagnostic biomarkers or as targets for personalised therapy.

Effects of Mindfulness-Based Therapy on Clinical Symptoms and DNA Methylation in Patients with Polycystic Ovary Syndrome and High Metabolic Risk

“…DNA methylation appears to play an important role in the pathogenesis of PCOS. Studies have reported alterations in DNA methylation in ovarian [ 18 ] and adipose tissue [ 19 ], skeletal muscle [ 20 ], as well as in peripheral blood [ 21 ] and umbilical cord blood [ 22 ]. These DNA methylation changes likely participate in the deregulation of genes involved in inflammation, hormone synthesis and signaling, and glucose and lipid metabolism [ 18 ].…”

Alteration of the N6-methyladenosine methylation landscape in a mouse model of polycystic ovary syndrome

“…Given the continuously increasing incidence of PCOS in recent years, it is important to explore the mechanisms of PCOS development and to develop effective treatments for patients with PCOS. PCOS is commonly associated with aberrant DNA methylation, and several genes are epigenetically dysregulated, and are associated with the pathological consequences of PCOS and metabolic comorbidities [ 27 ]. However, the methylation status of specific genes and the extent to which genes are dysregulated in terms of methylation patterns are unknown.Due to the reversibility of epigenetic modifications, "druable" regions can be screened to target or correct abnormalities in gene expression, so PCOS methylation promises the development of novel chromatin methylation therapies targeting PCOS [ 28 ].Herein, we used epitranscriptomic microarray for the first time to investigate the altered m 6 A modification of mRNAs and preliminarily explore the potential molecular mechanisms of m 6 A modification in the mouse model of PCOS induced by hyperandrogenism, and to screen new molecular targets and develop effective targets for treating PCOS or inhibiting its progression.…”

Effects of TCM on polycystic ovary syndrome and its cellular endocrine mechanism

“…Emotional factors can affect the changes of the hypothalamic–pituitary–ovarian axis (HPOA) and cause neuroendocrine changes, resulting in irregular ovarian ovulation and PCOS. Some studies have suggested that the occurrence of PCOS is related to DNA methylation, X chromosome inactivation, and histone modification ( 7 ). Some scholars have found that the anti-Müllerian hormone (AMH) is associated with the etiology of PCOS, and the concentration of AMH can predict the ovarian response in ovulation induction ( 8 ).…”