Role of oxidative stress and antioxidant supplementation in pregnancy disorders

Abstract

Oxidative stress is widely implicated in failed reproductive performance, including infertility, miscarriage, diabetes-related congenital malformations, and preeclampsia. Maternal obesity is a strong risk factor for preeclampsia, and in a recent study we observed oxidative stress in the oocytes of obese animals before pregnancy as well as in early-stage embryos. This adds to the growing evidence that investigators need to focus more on the preconceptual period in efforts to prevent pregnancy disorders, including those related to oxidative stress. Our research has also focused on the role of free radicals and antioxidant capacity in preeclampsia. By measuring markers of lipid peroxidation and antioxidant capacity, we obtained unequivocal evidence for oxidative stress in this disorder. Partial failure of the process of placentation has been implicated, and recent findings suggest that ischemia-reperfusion in the placenta may contribute to oxidative stress in trophoblasts. Endoplasmic reticulum stress in the placenta may also play a role. Randomized controlled trials have been conducted by our group as well as others to determine whether early supplementation with vitamins C and E in women at risk of preeclampsia is beneficial, but these trials have shown no evidence that these supplements can prevent preeclampsia. Whether this indicates that an inappropriate antioxidant strategy was used or supplementation was administered too late in gestation to be beneficial is not known. Other potential approaches for preventing preeclampsia through amelioration of oxidative stress include the use of supplements in the preconceptual period, selenium supplements, antiperoxynitrite strategies, and statins.

Oxidative stress in pregnancy and fertility pathologies

“…In the same study, an increase in oxidative stress biomarkers, such as MDA and lipid peroxides, was observed in placental tissue from early pregnancy losses compared with controls, despite upregulation of antioxidants such as catalase, glutathione peroxidase, and Cu/Zn and Mn superoxide dismutase. The authors suggested that increased ROS may result from a premature and abrupt establishment of maternal placental perfusion (Poston et al 2011). By contrast, other studies also suggested that the oxidative damage to the trophoblast induced by premature and widespread onset of the maternal placental circulation is a key factor in early pregnancy loss, but the premature oxidative stress increase was concluded to result from the lack of antioxidant levels to neutralize the increased levels of ROS (Burton and Jauniaux 2011;Jauniaux et al 2003;Myatt and Cui 2004).…”

“…So, evidence from this review does not support routine antioxidant supplementation during pregnancy to reduce the risk of PE and other complications in pregnancy (Poston et al 2011;Ruder et al 2008). …”

“…Still, no correlation between antioxidant therapy and IUGR prevention has been reported. Preeclampsia Preeclampsia (PE), which affects 2-14 % of all pregnancies and occurs primarily in nulliparous women in the third trimester, is a clinical syndrome of systemic inflammatory response, characterized by hypertension (blood pressure higher than 140/90 mmHg) and either proteinuria (>300 mg/24 h) or endorgan dysfunction (central nervous system dysfunction, hepatic abnormality, thrombocytopenia, renal abnormality, pulmonary edema) after 20 weeks of gestation in a previously normotensive woman (Agarwal et al 2012;Burton and Jauniaux 2011;Roberts et al 2013;Myatt and Cui 2004;Poston et al 2011). PE can have an early-onset development, when it is manifested before 34 weeks of gestation, or a late onset, if it develops after the 34th week of gestation (Agarwal et al 2012).…”

“…However, when in excess, ROS can induce cell injury and a chronic inflammatory state that can trigger a cascade of free-radical reactions, promoting secondary ROS generation and resulting in cellular modification and damage in DNA, carbohydrates, proteins, and polyunsaturated fatty acids. This oxidative injury follows a general pattern that involves free thiol oxidation and formation of disulfide proteins, depletion of the ATP pool, free cytosolic Ca 2+ increment, disintegration of cytoskeleton, increase in membrane lipid peroxidation, release of cytosolic compounds, and DNA damage (Aherne and O'Brien 2000;DalleDonne et al 2006;Poston et al 2011). Examples of human conditions associated with increased oxidative state include cellular aging, brain dysfunction and neurodegenerative diseases, cancer, diabetes, rheumatoid arthritis, and cardiovascular and renal diseases (Dröge 2002;Mitjavila and Moreno 2012;Silva and Soares-daSilva 2007;Valko et al 2007).…”

“…However, in a scenario where oxidative stress is abnormally increased, damage affecting both the mother and the fetus can be observed. Several studies have been conducted for the last two decades that relate increased oxidative stress levels to several pregnancy pathologies, including gestational diabetes mellitus, spontaneous abortion, idiopathic recurrent pregnancy loss, defective embryogenesis, drug-induced teratogenicity, preeclampsia, intrauterine growth restriction, and minor congenital abnormalities, as well as to future diseases in adulthood such as obesity, diabetes mellitus, and hypertension (Burton et al 2009(Burton et al , 2010Dröge 2002;Hempstock et al 2003;Myatt 2010;Poston et al 2011;Shibata et al 2010;Theuerkauf et al 2010;Tuuli et al 2011).…”