Epigenetic regulation of ovarian steroidogenesis in PCOS: HDAC inhibitors and short-chain fatty acids.

Authors

Tanwi Ghosh, Payal Mittal

Published in

Molecular biology reports. Volume 53. Issue 1. Aug 21, 2026. Epub Aug 21, 2026.

Abstract

Polycystic ovary syndrome (PCOS) is a complex endocrine-metabolic condition characterized by hyperandrogenism, ovulatory dysfunction and insulin resistance. Epigenetic regulation seems to play a role in the pathophysiology of PCOS, with an increasing number of studies showing such. Recent studies have proposed that the regulation of genes related to steroidogenesis in the ovary may be related to the dysregulation of the activity of the histone deacetylase (HDAC) and histone acetylation. This review is a narrative summary of the current experimental and preclinical evidence compiled to date supporting the role of epigenetic regulation, HDACs overactivity and short-chain fatty acids (SCFAs) signalling pathway in the contribution of ovarian steroidogenic dysfunction in PCOS. The literature search was carried out in the PubMed, Scopus and Google Scholar databases considering molecular pathways involved in the regulation of chromatin structure, gene expression and ovarian metabolism. The time searched was from 2000 to 2026. In vitro and animal model studies have shown that overexpression of HDAC and decreased histone H3/H4 acetylation at the promoter regions of key genes such as CYP19A1 (aromatase) and follicle-stimulating hormone receptor (FSHR) may contribute to decreased aromatase activity, follicular arrest, and hyperandrogenism in PCOS. SCFAs, especially sodium butyrate, appear to exert a natural HDAC inhibitory effect and in pre-clinical studies, have been found to restore histone acetylation, regulate inflammatory and oxidative stress pathways, and enhance steroidogenic balance. So far, there is only observational microbiome research on humans, and a few pilot clinical trials, and there is no causality yet established.

PMID:
42627443
Bibliographic data and abstract were imported from PubMed on 22 Aug 2026.

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