Mitochondrial Dysfunction and Oxidative Stress in Pregnancy Complications

Pregnancy complications such as preeclampsia and fetal growth restriction frequently involve dysregulated mitochondrial function and elevated oxidative stress within the placenta. Under normal conditions, placental mitochondria supply ATP through oxidative phosphorylation, regulate redox signalling and buffer calcium flux to support trophoblast proliferation, invasion and endocrine function. In complicated pregnancies, impaired electron transport chain activity, altered mitochondrial dynamics (fusion–fission balance) and defective quality control lead to excessive production of reactive oxygen species (ROS). Accumulating ROS triggers lipid peroxidation, protein oxidation and DNA damage, promoting trophoblast apoptosis, aberrant angiogenic factor release and systemic endothelial dysfunction in the mother. Moreover, chronic oxidative stress activates hypoxia‐responsive pathways, exacerbating anti‐angiogenic signalling and further compromising placental perfusion. Adaptive mitochondrial responses—such as increased mitochondrial biogenesis, modifications of respiratory coupling efficiency and selective removal of damaged organelles (mitophagy)—can initially counterbalance stress, but prolonged or severe insults overwhelm these processes. The resultant trophoblastic senescence, inflammatory cytokine release and anti‐angiogenic factor production underpin the clinical manifestations of hypertensive and growth‐restricted pregnancies. A clearer understanding of how mitochondrial redox balance and organelle quality control intersect has highlighted novel biomarkers and therapeutic targets aimed at restoring mitochondrial homeostasis and alleviating pregnancy morbidity.

Research from Nature Portfolio

Recent studies have elucidated the central role of mitochondrial redox signalling in the pathogenesis of preeclampsia. One investigation demonstrated that plasma from preeclamptic pregnancies induces mitochondrial superoxide generation and impairs respiratory capacity in endothelial cells; targeting these changes with a mitochondria‐selective antioxidant restored mitochondrial membrane potential, reduced inflammatory marker expression and prevented oxidative‐stress-induced cell death. Another analysis of placental samples from early‐ and late‐onset preeclampsia patients revealed differential mitochondrial adaptations: early‐onset cases exhibited elevated mitochondrial DNA copy number, increased complex I-linked respiration and altered expression of fusion and biogenesis regulators, suggesting an adaptive response to maintain ATP production under hypoxic stress. Studies of trophoblast subtypes further showed that undifferentiated cytotrophoblasts possess higher rates of oxidative phosphorylation and glycolysis than their syncytiotrophoblast counterparts, emphasising the importance of cell‐type-specific mitochondrial capacity in placental resilience to oxidative challenges.

Mitochondrial Dysfunction and Oxidative Stress in Pregnancy Complications publication trend

The graph below shows the total number of articles in mitochondrial dysfunction and oxidative stress in pregnancy complications across all publications each year (not limited to Nature Index journals).

Technical terms

Oxidative stress: A state in which the generation of reactive oxygen species exceeds antioxidant defences, resulting in molecular damage.

Reactive oxygen species (ROS): Chemically reactive molecules containing oxygen, including superoxide and hydrogen peroxide, that can modulate cell signalling and induce oxidative damage.

Mitochondrial dysfunction: Impairment of normal mitochondrial processes such as oxidative phosphorylation, ion homeostasis or organelle dynamics, leading to energy deficits and redox imbalance.

Mitophagy: Selective autophagic removal of damaged or superfluous mitochondria to maintain cellular health and adaptive capacity.

Electron transport chain (ETC): A series of protein complexes in the inner mitochondrial membrane that transfer electrons and drive ATP synthesis through oxidative phosphorylation.

Trophoblast: Specialized placental epithelial cell lineage involved in nutrient exchange, hormone production and maternal-fetal immune tolerance.

References

1. Nitroxide—HMP—Protects Human Trophoblast HTR-8/SVneo Cells from H2O2-Induced Oxidative Stress by Reducing the HIF1A Signaling Pathway. Antioxidants (2023).
2. Placental Mitochondrial Function and Dysfunction in Preeclampsia. International Journal of Molecular Sciences (2023).
3. 6-Gingerol alleviates placental injury in preeclampsia by inhibiting oxidative stress via BNIP3/LC3 signaling-mediated trophoblast mitophagy. Frontiers in Pharmacology (2023).
4. Therapeutically targeting mitochondrial redox signalling alleviates endothelial dysfunction in preeclampsia. Scientific Reports (2016).
5. Mitochondrial role in adaptive response to stress conditions in preeclampsia. Scientific Reports (2016).
6. Cytotrophoblast, Not Syncytiotrophoblast, Dominates Glycolysis and Oxidative Phosphorylation in Human Term Placenta. Scientific Reports (2017).
7. Placental mitochondrial adaptations in preeclampsia associated with progression to term delivery. Cell Death & Disease (2018).