Oxidative stress and mitochondrial dysfunction in early-onset and late-onset preeclampsia

Area of Science:

• Obstetrics and Gynecology
• Mitochondrial Biology
• Pathophysiology

Background:

• Preeclampsia is a serious pregnancy syndrome affecting multiple systems, leading to significant maternal and fetal morbidity and mortality.
• It is classified as early-onset preeclampsia (eoPE) or late-onset preeclampsia (loPE) based on gestational age at delivery (before or after 34 weeks).
• Preeclampsia is increasingly recognized as a mitochondrial disorder, but the specific roles of mitochondrial dysfunction in eoPE versus loPE remain unclear.

Purpose of the Study:

• To review and summarize the current understanding of mitochondrial dysfunction in both early-onset preeclampsia (eoPE) and late-onset preeclampsia (loPE).
• To explore the differential involvement of mitochondrial alterations in eoPE and loPE.
• To discuss potential therapeutic strategies targeting mitochondrial dysfunction in preeclampsia.

Main Methods:

• Review of existing literature on mitochondrial structure and function in preeclamptic placentas.
• Analysis of studies investigating molecular mechanisms, including protein expression and mitochondrial dynamics (fusion/fission).
• Examination of evidence related to the electron transport chain, oxidative phosphorylation, and reactive oxygen species (ROS) production.

Main Results:

• Altered mitochondrial structure and function, leading to increased ROS production, oxidative stress, and cell damage, are observed in the syncytiotrophoblast in both eoPE and loPE.
• Mitochondrial dysfunction in eoPE may involve differential expression of proteins like dynamin-related protein 1 and mitofusins compared to loPE.
• Reduced activity of Complex IV and essential electron transport chain proteins leads to impaired oxidative phosphorylation and mitochondrial respiration in preeclamptic placentas.

Conclusions:

• Mitochondrial dysfunction is a key feature of preeclampsia, with distinct molecular and dynamic alterations potentially differentiating eoPE and loPE.
• Impaired placental mitochondrial respiration and increased oxidative stress contribute to preeclampsia pathogenesis.
• Targeting mitochondrial function and enhancing antioxidative capacity, potentially with agents like coenzyme Q10, shows promise as a therapeutic strategy for preeclampsia.