# Linking Oxidative Stress to Placental Dysfunction: The Key Role of Mitochondria in Trophoblast Function

## TL;DR

This review explores how oxidative stress disrupts mitochondrial function in trophoblast cells, contributing to placental dysfunction and complications like preeclampsia.

## Contribution

The paper systematically reviews how oxidative stress affects mitochondrial pathways in trophoblasts, linking these changes to placental dysfunction.

## Key findings

- Oxidative stress impairs mitochondrial function in trophoblasts, increasing ROS and triggering apoptosis.
- OS disrupts trophoblast proliferation, migration, and angiogenic balance, contributing to placental dysfunction.
- Mitochondrial DNA release and altered mitophagy are linked to reduced cell viability and pregnancy complications.

## Abstract

Oxidative stress (OS) is a critical regulator of placental development; however, its specific effects on trophoblast biology remain incompletely elucidated. This narrative review synthesizes evidence derived from studies using human placental tissues and trophoblast cell models to delineate how excessive reactive oxygen species (ROS) disrupt molecular and cellular pathways essential for normal placentation. The literature search was restricted to human-based and in vitro investigations. Across these studies, OS was consistently shown to impair mitochondrial function in trophoblasts, resulting in increased mitochondrial ROS generation, loss of mitochondrial membrane potential, and activation of apoptotic signaling cascades. These mitochondrial disturbances were associated with reduced trophoblast proliferation, migration, and invasion, as well as dysregulation of angiogenic balance. Furthermore, several studies reported alterations in mitophagy, involvement of redox-sensitive pathways such as CYP1A1 and KLF9, and the extracellular release of mitochondrial DNA, which was linked to reduced cell viability and increased necrotic cell death. Collectively, the available evidence indicates that OS interferes with key trophoblast-dependent developmental processes, providing mechanistic insight into the pathogenesis of placental dysfunction observed in pregnancy complications such as preeclampsia (PE) and intrauterine growth restriction (IUGR). Elucidation of these pathways may inform the development of targeted therapeutic strategies aimed at preserving placental function and improving adverse pregnancy outcomes.