Pregnancy Under Pressure: Oxidative Stress as a Common Thread in Maternal Disorders

Abstract

Oxidative stress, defined as the imbalance between reactive oxygen species (ROS) and antioxidant defenses, plays a pivotal role in the pathogenesis of several pregnancy complications, notably preeclampsia (PE), gestational diabetes mellitus (GDM), fetal growth restriction (FGR), and recurrent pregnancy loss (RPL). During normal pregnancy, low to moderate ROS levels support essential placental functions such as angiogenesis and trophoblast differentiation. However, excessive ROS production overwhelms antioxidant systems, leading to lipid peroxidation, protein and DNA damage, and impaired placental function. This review synthesizes current evidence linking oxidative stress to adverse pregnancy outcomes, highlighting key biomarkers such as malondialdehyde (MDA), 8-hydroxy-2'-deoxyguanosine (8-OHdG), and 8-iso-prostaglandin F2α (8-iso-PGF2α). While antioxidant therapies-particularly vitamins C and E, selenium, and folic acid-have shown promise in reducing oxidative markers, their impact on clinical outcomes remains inconsistent. The variability in results underscores the need for standardized biomarker protocols and personalized treatment strategies based on genetic predispositions and baseline oxidative status. Future research may better harness antioxidant interventions to improve maternal-fetal health by addressing these gaps.

Keywords: 8-OHdG; 8-iso-PGF2α; MDA; antioxidants; biomarker standardization; fetal growth restriction; gestational diabetes mellitus; oxidative stress; preeclampsia; pregnancy complications; recurrent pregnancy loss.

Figure 1

The mechanisms of oxidative stress and their effects on cellular components (Figure created in BioRender).

Figure 2

Search strategy, the PRISMA flow diagram [20].

Figure 3

Pregnancy Complications Linked to Oxidative Stress [25,59,72,79] (Figure created in BioRender). ↑ = increase; ↓ = decrease The diagram illustrates the role of oxidative stress as a central pathogenic mechanism contributing to four major pregnancy complications: preeclampsia (PE), gestational diabetes mellitus (GDM), fetal growth restriction (FGR), and recurrent pregnancy loss (RPL). Elevated levels of reactive oxygen species (ROS) and a decline in antioxidant defenses lead to cellular damage—manifesting in distinct patterns across complications. In PE, oxidative stress is associated with increased malondialdehyde (MDA), reduced vitamins C and E, and endothelial dysfunction. GDM involves elevated MDA levels, decreased antioxidant enzymes superoxide dismutase (SOD) and glutathione peroxidase (GPX), and beta cell damage. FGR is characterized by increased 8-hydroxy-2′-deoxyguanosine (8-OHdG), placental damage, and impaired oxygen/nutrient delivery. RPL is linked to heightened oxidative DNA damage and reduced antioxidant capacity.

Figure 4

Mind Map of Oxidative Stress in Pregnancy (Figure created in BioRender). The mind map outlines the core concepts and relationships discussed in the review. At the center is oxidative stress, driven primarily by increased reactive oxygen species (ROS) and reduced antioxidant defenses. These imbalances, often amplified by mitochondrial overactivity in pregnancy, lead to cellular damage—including lipid peroxidation (e.g., malondialdehyde (MDA); 8-iso-Prostaglandin F2α (8-iso-PGF2α)), protein oxidation, and DNA damage (e.g., 8-hydroxy-2′-deoxyguanosine (8-OHdG)). Such damage is implicated in multiple pregnancy complications, including preeclampsia (PE), gestational diabetes mellitus (GDM), fetal growth restriction (FGR), and recurrent pregnancy loss (RPL). To monitor and understand oxidative stress, biomarkers such as MDA, 8-OHdG, and 8-iso-PGF2α are critical. These indicators are central to both diagnosis and therapy assessment. Current therapeutic strategies involve antioxidant supplementation (e.g., vitamins C/E, selenium, folic acid) and lifestyle interventions such as improved diet and physical activity. Future directions emphasize the need for personalized treatment, standardized biomarker protocols, and large-scale randomized controlled trials (RCTs) to refine and validate these interventions.