Research Progress on Mechanism and Intervention of Ferroptosis in Polycystic Ovary Syndrome

doi:10.12280/gjfckx.20260313

Abstract

Abstract:

Ferroptosis, an iron-dependent form of programmed cell death, has been recently implicated in the pathogenesis of ovarian dysfunction in polycystic ovary syndrome (PCOS). Studies have revealed that hyperandrogenism may induce granulosa cell ferroptosis via mechanisms such as the androgen receptor-nuclear receptor coactivator 4 (NCOA4)-ferritinophagy axis and the endoplasmic reticulum stress-acyl-CoA synthetase long-chain family member 4 (ACSL4)/activating transcription factor 4 (ATF4)-mediated lipid peroxidation pathway, etc. Non-coding RNAs are involved in regulating granulosa cell ferroptosis through competing endogenous RNA mechanisms. Impairment of the AMP-activated protein kinase (AMPK)/nuclear factor-erythroid 2-related factor 2 (Nrf2) signaling pathway increases susceptibility of granulosa cells to ferroptosis. Regarding intervention strategies, traditional Chinese medicine monomers, compound prescriptions, and chemical agents have demonstrated promising therapeutic potential by upregulating the glutathione peroxidase 4 (GPX4)/solute carrier family 7 member 11 (SLC7A11) axis, inhibiting ACSL4 and 5-lipoxygenase, activating the AMPK/Nrf2 pathway, or targeting iron metabolism and autophagy pathways. However, current studies are predominantly conducted in animal models and at the cellular level, with limited evidence for clinical translation. Further exploration is needed for the identification of ferroptosis-related biomarkers and the evaluation of the efficacy and safety of targeted intervention strategies.

Key words: Polycystic ovary syndrome, Ferroptosis, Granulosa cells, Signal transduction, Therapy

WANG Zi-wei, YANG Ying, WANG Jia-lai, CHEN Chen-chen, LIN Na-na, ZHANG Yan-li, CHANG Hui. Research Progress on Mechanism and Intervention of Ferroptosis in Polycystic Ovary Syndrome[J]. Journal of International Obstetrics and Gynecology, 2026, 53(5): 481-486.

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