These heritable molecular alterations regulate gene expression patterns and influence key pathophysiological processes, including ovarian dysfunction, hormonal dysregulation, and insulin signaling impairment, without modifying the underlying DNA sequence ( Regarding DNA methylation, studies have demonstrated hypermethylation of the insulin receptor (INSR) promoter region in both ovarian and adipose tissues of PCOS patients, resulting in downregulated insulin receptor expression and aggravated insulin resistance ( Concerning histone modifications, granulosa cells from PCOS patients exhibit enhanced histone deacetylase (HDAC) activity, which decreases acetylation levels of pro-inflammatory cytokines ( e.g ., TNF-, IL-6) and suppresses their transcriptional activation
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Additionally, the infusion of native human GIP (142) into cardiac myocytes isolated from embryonic mouse hearts inhibited the increase in brain natriuretic peptide (BNP) and transforming growth factor- (TGF- 1) mRNA expression induced by angiotensin II (Ang II) [13]
