The contribution of placental oxidative stress to early pregnancy failure

Diminished survival of human cytotrophoblast cells exposed to hypoxia/reoxygenation injury and associated reduction of heparin-binding epidermal growth factor-like growth factor

“…Our findings, using a first trimester cytotrophoblast cell line, reveal that the protective activity of endogenous HBEGF is lost when O 2 levels are abruptly increased. The resulting cell death requires caspase activity and is accompanied by phosphatidylserine randomization, while cells remain intact and retain cytoplasmic LDH activity; all indicative of apoptosis (14) It has been suggested that excessive oxidative stress in the first trimester can compromise trophoblast function or survival (1)(2)(3)(4)(5)9). Trophoblast survival and extravillous differentiation required for remodeling of the uterine spiral arteries are deficient in both missed abortion and preeclampsia (1), perhaps due to elevated levels of oxidative stress.…”

“…A role for H/R injury in early pregnancy loss has been advanced by several lines of molecular evidence, including morphological evidence of increased apoptosis and markers of cellular stress, expression of heat shock protein 70, protein nitrosylation and lipid peroxidation in tissues obtained from missed abortions with early onset placental perfusion (1)(2)(3)(4)(5). Xanthine dehydrogenase, which normally utilizes NAD as an electron acceptor, is converted under the conditions of ischemia/reperfusion into xanthine oxidase.…”

“…The possible role of H/R in early pregnancy loss has been advanced by several lines of evidence. These include premature onset of the maternal circulation to the placenta, determined by Doppler ultrasonography and correlated to fragmented trophoblastic shell, limited EVT invasion of the placental bed and terminal spiral arteries (1)(2)(3)(4)(5). The effect is greatest in pregnancies less than 10 weeks gestation with recent fetal demise suggesting that early gestations are more susceptible to this damage.…”

Polymorphisms of glutathione peroxidase 1 (GPX1 Pro198Leu) and catalase (CAT C-262T) in women with spontaneous abortion

“…The elevated oxidative stress along with inefficient antioxidant status in placenta impairs its function and may result in fetal abnormalities or miscarriage [Jauniaux et al 2000]. In spite of considerable progress in identifying the causes of spontaneous abortion, the etiology remains unclear in about 40% of the cases [Hempstock et al 2003]. In recent years, there has been an increasing interest in gene polymorphisms as a susceptibility factor.…”

Oxidative stress in pregnancy and fertility pathologies

“…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).…”