Introduction: Preeclampsia (PE) is a major disease of human pregnancy, marked by hypertension and proteinuria, appearing during the second or third trimester of gestation. Incidence differs depending on geographical region, time of year, nutrition, and race/ethnicity, but it affects roughly 3–8% of women worldwide. The mechanisms responsible for the pathogenesis of preeclampsia are unclear. It has been reported that preeclampsia is associated with endothelial dysfunction, systemic vasoconstriction, inflammation, oxidative stress, and intrauterine growth restriction, and multiorgan dysfunction. Reactive oxygen species (ROS) are highly reactive free radicals, including superoxide (O−2), hydrogen peroxide (H2O2), hydroxyl radical (OH), and peroxynitrite (ONOO−) that damage protein, DNA, and RNA within a cell causing cellular dysfunction and death. Oxidative stress is created by the imbalance between ROS and antioxidant defense of the cell. During normal gestation, ROS production is reported to be increased; however, excessive ROS production has been reported in pathological states, such as preeclampsia. In this article we will review studies evaluating the role of oxidative stress in terms of pathogenesis of preeclampsia.
Methods: In order to find relevant studies to the research question, an electronic search with time (recent five years, up to 2021) and language (English) restrictions was conducted using PubMed including “Preeclampsia”, “Oxidative stress” and “Reactive Oxygen Species” keywords. Most recent studies including case control studies, original research and review articles were selected. Analysis was done and data were synthesized and compiled in a sequential and presentable paradigm.
Results: Several studies relate the development of preeclampsia with the inadequate invasion of the trophoblast and uterine artery remodeling due to the abnormal regulation of cell–cell and cell–matrix interaction. In preeclamptic women, maternal circulating levels, placental tissue levels and production rate of lipid peroxides are increased, and several antioxidants are markedly decreased. One study suggested the role of SOD3 single nucleotide gene polymorphism in the increased oxidative stress in preeclampsia. A significant decrease in tissue levels of vitamin E, and in the activities of superoxide dismutase and glutathione peroxidase are found in the placenta of these women. Another source of oxidative stress in preeclamptic women is the activation of leukocytes in their circulation which has been reported by several articles. It has been also stablished that in preeclampsia, maternal circulating neutrophils and monocytes are activated, which generate superoxides (O2) by the activity of NADPH oxidase and hence cause oxidative stress. Plasma thrombomodulin, an anticoagulation factor, is also significantly elevated in women with preeclampsia, with elevations detected as early as 24 weeks into the pregnancy.
Conclusion: The available literature reveals that Preeclampsia is characterized by increased oxidative stress due to the imbalance between lipid peroxidation and antioxidant defense mechanisms, leading to endothelial dysfunction and free radical mediated cell injury. A comprehensive understanding and the detailed knowledge of the pathogenesis of the preeclampsia will enable us to identify the responsible contributing bio- molecules for this disease. Measurement of these contributing biomolecules can help us in predicting the disease earlier. It is hoped that we can identify the biomarkers of preeclampsia with high predictive, preventive, and prognostic value and incorporate with current clinical practice to improve the care for pregnant women.