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

Abstract

Preeclampsia is a pregnancy-specific syndrome with multisystem involvement which leads to foetal, neonatal, and maternal morbidity and mortality. This syndrome is characterized by the onset of clinical signs and symptoms and delivery before (early-onset preeclampsia, eoPE), or after (late-onset preeclampsia, loPE), the 34 weeks of gestation. Preeclampsia is a mitochondrial disorder where its differential involvement in eoPE and loPE is unclear. Mitochondria regulate cell metabolism and are a significant source of reactive oxygen species (ROS). The syncytiotrophoblast in eoPE and loPE show altered mitochondrial structure and function resulting in ROS overproduction, oxidative stress, and cell damage and death. Mitochondrial dysfunction in eoPE may result from altered expression of several molecules, including dynamin-related protein 1 and mitofusins, compared with loPE where these factors are either reduced or unaltered. Equally, mitochondrial fusion/fission dynamics seem differentially modulated in eoPE and loPE. It is unclear whether the electron transport chain and oxidative phosphorylation are differentially altered in these two subgroups of preeclampsia. However, the activity of complex IV (cytochrome c oxidase) and the expression of essential proteins involved in the electron transport chain are reduced, leading to lower oxidative phosphorylation and mitochondrial respiration in the preeclamptic placenta. Interventional studies in patients with preeclampsia using the coenzyme Q₁₀, a key molecule in the electron transport chain, suggest that agents that increase the antioxidative capacity of the placenta may be protective against preeclampsia development. In this review, the mitochondrial dysfunction in both eoPE and loPE is summarized. Therapeutic approaches are discussed in the context of contributing to the understanding of mitochondrial dysfunction in eoPE and loPE.

Keywords: Mitochondrial dysfunction; Placenta; Preeclampsia; ROS.