Placental ferroptosis in preeclampsia: An integrative and comprehensive review.

Ferroptosis, a regulated form of iron-dependent cell death driven by lipid peroxidation, has recently gained attention as a potential contributor to the pathophysiology of preeclampsia, a major cause of maternal and perinatal morbidity and mortality. This review synthesizes current evidence linking ferroptosis to placental dysfunction and explores its relevance to the pathogenesis of preeclampsia. We examine how disrupted iron metabolism, oxidative stress, and impaired antioxidant defenses create a permissive environment for ferroptotic damage in the syncytiotrophoblast. Key biochemical pathways, including redox phospholipid metabolism, glutathione-GPX4 activity, and mitochondrial function, are reviewed in detail. We also discuss emerging data connecting placental ferroptosis to systemic maternal manifestations via sFlt-1 release and extracellular vesicle-mediated endothelial injury. Finally, we highlight therapeutic implications, including pharmacological inhibition of ferroptosis and drug repurposing strategies. By integrating diverse mechanistic insights, ferroptosis emerges as a unifying paradigm that may reshape our understanding and treatment of preeclampsia.