Oxidative Stress and Placental Pathogenesis: A Contemporary Overview of Potential Biomarkers and Emerging Therapeutics

Abstract

Oxidative stress (OS) plays a crucial role in placental pathogenesis and pregnancy-related complications. This review explores OS's impact on placental development and function, focusing on novel biomarkers for the early detection of at-risk pregnancies and emerging therapeutic strategies. We analyzed recent research on OS in placental pathophysiology, examining its sources, mechanisms, and effects. While trophoblast invasion under low-oxygen conditions and hypoxia-induced OS regulate physiological placental development, excessive OS can lead to complications like miscarriage, preeclampsia, and intrauterine growth restriction. Promising OS biomarkers, including malondialdehyde, 8-isoprostane, and the sFlt-1/PlGF ratio, show potential for the early detection of pregnancy complications. Therapeutic strategies targeting OS, such as mitochondria-targeted antioxidants, Nrf2 activators, and gasotransmitter therapies, demonstrate encouraging preclinical results. However, clinical translation remains challenging. Future research should focus on validating these biomarkers in large-scale studies and developing personalized therapies to modulate placental OS. Emerging approaches like extracellular vesicle-based therapies and nanomedicine warrant further investigation for both diagnostic and therapeutic applications in pregnancy-related complications. Integrating OS biomarkers with other molecular and cellular markers offers improved potential for the early identification of at-risk pregnancies.

Keywords: DNA damage; intrauterine fetal growth restriction; maternal–placental–fetal interactions; novel therapeutic approaches; oxidative stress biomarkers; placental molecular pathology; pre-eclampsia; pregnancy complications; pregnancy loss/miscarriage; trophoblast.

Figure 1

First-trimester chorionic villi (200×), in hematoxylin-eosin (HE) staining.

Figure 2

Third-trimester mature chorionic villi (200×), in hematoxylin-eosin (HE) staining.

Figure 3

First-trimester chorionic villi (200×), in hematoxylin-eosin (HE) staining, demonstrating enlargement, chorangiosis and accelerated villous maturation.