Research progress of ferroptosis in gynecological diseases

The concept of ferroptosis debuted as a newly defined programmed cell death in 2012. Among programmed cell death mechanisms, ferroptosis stands out as being fundamentally dependent on iron. At the heart of this mechanism lies the progressive accumulation of lipid peroxides - a chain reaction propelled by available iron, terminating when intracellular levels become fatally toxic. Inhibition of cystine transporters within cells (notably induced by compounds like Erastin) initiates a chain reaction: when intracellular levels of glutathione (GSH) become depleted, downstream suppression of glutathione peroxidase 4 (GPX4) activity impedes lipid peroxide clearance, whose accumulation drives the cell toward death upon exceeding a critical concentration.

Early-stage experimental models highlight ferroptosis's contribution to propelling high-impact gynecological disease progression, namely precancerous endometrial hyperplasia, endometrial cancer (EC), endometriosis (EMS), and ovarian cancer (OC). Hence, elucidating the intricate regulatory machinery behind ferroptosis in gynecological pathologies bears both theoretical importance and translational promise.

This review aimed to systematically synthesize current knowledge on ferroptosis in gynecological diseases and their associated regulatory mechanisms, offering insights relevant to both basic research and clinical application.