Oxidative Stress in Pathogenesis of Preeclampsia: Mechanistic and Clinical Insights

Preeclampsia, affecting 3–8% of pregnancies worldwide, remains a leading cause of maternal and perinatal morbidity and mortality. This review synthesizes current molecular, immunological, and hemodynamic evidence to clarify the central role of oxidative stress in the pathogenesis of preeclampsia. Placental oxidative stress, resulting from an imbalance between reactive oxygen species (ROS) generation and antioxidant defenses, secondary to placental hypoxia due to various etiologies especially impaired spiral artery remodeling, drives mitochondrial dysfunction in trophoblasts, ischemia–reperfusion injury, inflammatory pathway activation, and disruption of angiogenic homeostasis, thereby promoting systemic inflammation. Key regulatory pathways, including Nrf2/HO-1, NF-κB, PI3K/Akt, and HIF-1α, together with biomarkers such as malondialdehyde, 8-isoprostane, and the sFlt-1/PlGF ratio, characterize this redox imbalance. Although experimental studies demonstrate promising effects of targeted antioxidants, mitochondria-directed agents, and pathway-specific modulators, clinical translation remains limited, as non-specific antioxidants such as vitamins C and E have failed to prevent preeclampsia. Future advances will likely depend on mechanism-based therapies initiated early in pregnancy and tailored to the disease subtype and biomarker profiles. Collectively, this review provides an integrated mechanistic framework and highlights critical knowledge gaps that must be addressed to enable the development of effective preventive and therapeutic interventions for preeclampsia.