Placental oxidative response in normal and overweight pregnancies

Abstract

Oxidative stress results in the disturbance of the balance between the production of reactive oxygen species (ROS), and their elimination in enzymatic and non-enzymatic reactions of neutralization and sweeping-up, as well as through the effect of exogenous antioxidants supplied with food. ROS include free radicals, such as, superoxide (%O2−), hydroxyl radicals (%OH) and non-radical intermediates, like hydrogen peroxide (H2O2) and singlet oxygen.ROS excess can lead to cellular damage of deoxyribonucleic acids, lipids and proteins. Antioxidants protect cells from peroxidation reactions, limiting cellular damage and helping to maintain cellular membrane integrity.Oxidative stress is implicated in the pathophysiology of many reproductive complications including infertility, miscarriage, pre-eclampsia &etc.The placenta is a highly complex and fascinating organ and it has various tasks.The placenta also has major endocrine actions that modulate maternal physiology and metabolism and provides a safe and protective milieu in which the fetus can develop.Obesity is a global health concern that has increased in the last decades. Obesity is characterized by a low-state chronic inflammation and oxidative stress, among other pathological changes.Obesity in women during their reproductive age or during pregnancy has been associated with an impairment in fertility & fecundity as well as a higher incidence of miscarriage and pregnancy pathologies including gestational hypertension, preeclampsia & gestational diabetes.Getting pregnant in this situation involves that gestation will occur in an unhealthy environment, that can potentially jeopardize both maternal and fetal health.Pregnancy associated with maternal obesity is also related to maternal systemic inflammatory conditions and placental inflammation. Maternal obesity influences oxidative stress and metabolic adjustments during pregnancy, thus affecting the placenta and fetal growth, and may also influence immune system activation.If ROS levels are maintained under control, they regulate trophoblast proliferation, invasion and angiogenesis, required for a healthy pregnancy. Enzymatic (superoxide dismutase, catalase and glutathione peroxidase) and non-enzymatic (vitamin C and E, glutathione) antioxidants neutralize the effect of highly reactive ROS by transforming them into less reactive species and eliminating oxidation by-products, protecting cells from oxidative damage. The enzyme superoxide dismutase converts the superoxide anion radical to hydrogen peroxide and oxygen, and catalase eliminates hydrogen peroxide when its quantities in the cell are higher, Interestingly, H2O2 is sufficient to promote SOD1 nuclear localization, indicating that it is responding to general ROS rather than SOD1 substrate superoxide. Catalase is one of the crucial antioxidant enzymes that mitigates oxidative stress to a considerable extent by destroying cellular hydrogen peroxide to produce water and oxygen. Hydrogen peroxide is freely diffusible and is relatively long-lived. It acts as a weak oxidizing as well as reducing agent; however, it is not very reactive, but it is the progenitor of many other reactive oxygen species (ROS). Catalase is used against numerous oxidative stress-related diseases as a therapeutic agent. In this project we have examined whether enzymatic antioxidants (SOD and CAT) are expressing more in placental tissue of Overweight (OW) mothers (physiologic) vs. normal weight (NW) due to the inflammation. Our preliminary data reported there are no significant differences in protein expression of SOD & CAT in placenta of OW in comparison to NW mothers. one expectation of our team for future prospective based on our obtained data is to design a ligand targeted liposome based on olive oil and encapsulate our desired enzymes (CAT and SOD) in liposome this method could be helpful to enhance the concentration of CAT & SOD in placenta.