# Environmental Pollution and Oxidative Stress: Health Effects During Pregnancy: A Review
## 5 Oxidative Stress and Adverse Obstetric Outcomes
The main pathophysiological disorder involves vasospasm and fluid transfer from intravascular to extravascular space. The exact causal factor of preeclampsia has not been fully determined. However, endogenous endothelial cell dysfunction, lipid peroxidation, and changes in immune responses are involved in the pathogenesis of the disease [97; 98]. Endothelial cell dysfunction [40] and vasoconstriction [99] can be caused by placental ischemia/hypoxia, which is considered to be a major causative agent of oxidative stress [100]. Preeclampsia is connected to notably augmented oxidative stress compared to normal pregnancies [101]. Oxidative stress has been viewed as one of the variables engaged with the pathogenesis of the disease [102; 103]. The mode of action of ROS during preeclampsia may vary from case to case. Studies have shown that augmented ROS levels in cases of preeclampsia leads to neutrophil activation. Activated neutrophils in turn are involved in the pathophysiology of preeclampsia, causing vascular endothelial damage and dysfunction [104]. In women with preeclampsia, an increase in endothelial NO is common. Increased xanthine oxidase (XO) activity is considered to be one of the causes of oxidative stress during preeclampsia. XO carries O2-, which reacts with NO and leads to the formation of ONOO- located in the vessels of the placenta after the onset of preeclampsia [105]. Inaddition, the increased NO synthase activity and the decreased SOD activity observed during preeclampsia lead to increased ONOO- formation. The reduced bioavailability of NO (from the endothelium) due to its oxidative damage is probably an element of the pathology of preeclampsia. As previously mentioned, preeclampsia involves endothelial cell dysfunction, lipid peroxidation, and changes in immune responses. The latter leads to activation of cellular immunity, which is probably involved in the pathogenesis of preeclampsia and release of endothelial ROS. Alternatively, oxidative stress is considered to cause vascular endothelial cell dysfunction [106]. Studies have shown that preeclampsia is characterized by increased production of advanced glycosylation (AGE) end products in the mother's serum. AGEs are molecules that bind to cell surface receptors (RAGES). During preeclampsia, there is also increased regulation of RAGE in the myometrium and placenta. The binding of AGEs to these receptors causes ROS genesis and consequently vascular dysfunction. Lipid peroxidation levels are higher than normal in placenta, serum, and plasma in women with preeclampsia [107]. As a typical pregnancy advances, the cell reinforcement limit of vitamin E and the vasodilatory impact of prostacyclins increase. In instances of preeclampsia, no comparable changes are recorded. Conversely, there is an expansion in the vasoconstratricity action of thromboxane and the poisonous impact of lipid peroxides [105]. Both lipid peroxidation and changes in the immune reaction engage with the endothelial cell brokenness seen in the disease. Poor perfusion of the placental tissues during preeclampsia activates the production of free radicals and lipid peroxidation [108]. The presence of lipid peroxides and the lack of oxidative balance in the blood are probably part of the cytotoxic mechanism that causes damage to endothelial cells [109]. Severe lipid peroxidation may result from ROS overproduction and neutrophil activation, as previously mentioned [110]. This has a compensatory response and a sharp increase in antioxidants in women with preeclampsia. In addition to the above, genetic factors may be involved in the genesis of ROS and consequently in the pathophysiology of preeclampsia. It is thought that women with preeclampsia may have a genetic predisposition to high levels of lipid peroxidation and therefore increased levels of oxidative stress [111]. Early onset of preeclampsia is associated with elevated levels of protein carbonyls, lipid peroxides, nitrotyrosine radicals, and DNA oxidation, which are signs of placental oxidative stress [40].