Mitochondrial Oxidative Phosphorylation Alterations in Placental Tissues from Early- and Late-Onset Preeclampsia

Preeclampsia (PE), a pregnancy complication characterized by high blood pressure and organ damage, has been suggested to be associated with mitochondrial dysfunction, although evidence remains limited. This study aimed to investigate the activity of oxidative phosphorylation (OXPHOS) enzymes and the expression of related proteins in placental tissues from women diagnosed with early-onset preeclampsia (eoPE, <34 weeks of gestation), late-onset preeclampsia (loPE, ≥34 weeks of gestation), and normotensive controls. Placental samples were analyzed using immunohistochemistry, western blotting, and enzymatic activity assays to assess the activity and expression of OXPHOS complexes. Complex I activity was increased by 80% in eoPE and 56% in loPE, with positive correlations between normalized complex I expression, gestational age at delivery (r = 0.85, <i>p</i> = 0.01), and birth weight (r = 0.88, <i>p</i> = 0.004) in loPE. Relative complex II expression in loPE showed positive correlations with pregnancy duration (r = 0.76, <i>p</i> = 0.03) and birth weight (r = 0.77, <i>p</i> = 0.03), while in controls, complex II expression correlated with pregnancy duration (r = 0.64, <i>p</i> = 0.03). Additionally, complex IV enzyme activity in eoPE was negatively correlated with maternal age at birth (r = -0.69, <i>p</i> = 0.03). The observed correlations highlight mitochondrial metabolism as a promising biomarker for predicting disease progression and guiding therapeutic interventions in preeclampsia. Unraveling its precise role in PE pathogenesis is critical to advancing diagnostic precision and improving maternal-fetal outcomes.