Ovarian fibrosis in polycystic ovary syndrome: Mechanisms, evidences, and clinical implications

Abstract

Polycystic ovary syndrome (PCOS) is a complex heterogeneous endocrine disorder characterized by hyperandrogenism, ovulatory dysfunction, and polycystic ovarian morphology. Emerging studies suggest that ovarian fibrosis, as an underrecognized pathological feature, may contribute to ovarian dysfunction and infertility in PCOS phenotypes. Available experimental and limited human studies indicate that hyperandrogenism, insulin resistance, chronic low-grade inflammation, oxidative and endoplasmic reticulum stress collectively promote extracellular matrix accumulation and stromal remodeling predominantly through transforming growth factor-β (TGF-β)-mediated signaling pathways. Additionally, fibrotic remodeling has been linked to other pathways, including the NLRP3 inflammasome, PI3K/Akt, Hippo/YAP, and epithelial-mesenchymal transition. Although standardised diagnostic criteria are currently lacking, new imaging modalities, such as shear-wave elastography, and circulating fibrosis-related biomarkers may offer non-invasive approaches to evaluating ovarian fibrotic alterations. Furthermore, several anti-fibrotic agents, metabolic modulators, phytochemicals, and stem cell-based therapies have been suggested to have potential therapeutic effects in ovarian fibrosis models of PCOS. Overall, ovarian fibrosis represents a developing aspect of PCOS pathophysiology that requires further clinical and translational investigation.

Keywords: Anti-fibrotic agents; Extracellular matrix; Fibrotic remodeling; Ovarian fibrosis; PCOS; TGF-β.