Emerging Oxidative Stress Biomarkers and Mitochondrial Dysfunction in Preeclampsia from Pathogenesis to Precision Medicine: A Narrative Review

Preeclampsia continues to be a major cause of maternal and neonatal morbidity worldwide. Current diagnostic criteria are based on clinical signs that appear relatively late. Target organ damage is already in progress, and early disease progress often goes undetected at this time. Recent research has altered our perception of this condition and has confirmed that trophoblast mitochondria are actively involved in the etiology of hypertensive disease and not just responding to it. Mitochondrial dysfunction in the placenta results in increased production of free radicals, breakdown of the membrane, disruption in cellular iron balance, and poor organelle clearance, all of which affect the function of the placenta negatively. This review focuses on five important mitochondrial biomarkers that characterize this destructive process: 8-hydroxy-2'-deoxyguanosine indicates direct oxidative damage to mitochondrial DNA, and changes in copy numbers and cell-free DNA fragments in plasma indicate increased cell damage and systemic inflammation. Oxidized cardiolipin and malondialdehyde indicate membrane lipid degradation. Changes in levels of GPX4, mitochondrial ferritin, and transferrin receptor 1 indicate initiation of iron-dependent ferroptosis. Finally, reduced PINK1/Parkin signaling is a sign of the cell's cleanup system failing, allowing damaged mitochondria to accumulate and pushing trophoblasts into premature aging. These markers together depict the convergence of redox imbalance, structural membrane damage, iron dysregulation, and clearance defects driving placental breakdown and maternal disease.