Preeclampsia (PE) is usually associated with the accumulation of reactive oxygen species (ROS) resulting from heightened oxidative stress (OS). Ferroptosis is a unique type of lipid peroxidation-induced iron-dependent cell death distinct from traditional apoptosis, necroptosis, and pyroptosis and most likely contributes considerable to PE pathogenesis. At approximately 10-12 weeks of gestation, trophoblasts create an environment rich in oxygen and iron. In patients with PE, ferroptosis-related genes such as HIF1 and MAPK8 are downregulated, whereas PLIN2 is upregulated. Furthermore, miR-30b-5p overexpression inhibits solute carrier family 11 member 2, resulting in a decrease in glutathione levels and an increase in the labile iron pool. At the maternal-fetal interface, physiological hypoxia/reperfusion and excessive iron result in lipid peroxidation and ROS production. Owing to the high expression of Fpn and polyunsaturated fatty acid-containing phospholipid-related enzymes, including acyl-CoA synthetase long-chain family member 4, lysophosphatidylcholine acyl-transferase 3, and spermidine/spermine N1-acetyltransferase 1, trophoblasts become more susceptible to OS and ROS damage. In stage 1, the injured trophoblasts exhibit poor invasion and incomplete uterine spiral artery remodeling caused by ferroptosis, leading to placental ischemia and hypoxia. Subsequently, ferroptosis marked by OS occurs in stage 2, eventually causing PE. We aimed to explore the new therapeutic target of PE through OS in ferroptosis.
Keywords: Ferroptosis; Lipid peroxidation; Oxidative stress; Pre-eclampsia; Reactive oxygen species.
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