Oxidative Stress in Preeclampsia and Placental Diseases

Abstract

Preeclampsia is a persistent hypertensive gestational disease characterized by high blood pressure and proteinuria, which presents from the second trimester of pregnancy. At the cellular level, preeclampsia has largely been associated with the release of free radicals by the placenta. Placenta-borne oxidative and nitrosative stresses are even sometimes considered as the major molecular determinants of the maternal disease. In this review, we present the recent literature evaluating free radical production in both normal and pathological placentas (including preeclampsia and other major pregnancy diseases), in humans and animal models. We then assess the putative effects of these free radicals on the placenta and maternal endothelium. This analysis was conducted with regard to recent papers and possible therapeutic avenues.

Role of aspirin‐triggered lipoxin A4, aspirin, and salicylic acid in the modulation of the oxidative and inflammatory responses induced by plasma from women with pre‐eclampsia

“…5,[48][49][50] In preeclampsia, increased reactive oxygen species generation, as well as decreased activity of the principal anti-oxidant enzyme, produces oxidative stress factors in placental tissue, which pass to maternal circulation leading to its characteristic alterations. Impaired remodeling of the spiral artery leads to hypoxia or re-oxygenation episodes, that could generate reactive oxygen species and also oxidized lipids, leading to placental oxidative stress and endothelial dysfunction.…”

“…1,2 Pre-eclampsia and eclampsia were the direct cause of 20% of the maternal deaths of women with severe maternal outcome, according to the WHO multicountry survey on maternal and newborn health. 4,5 Although the exact cause of this disorder is not clear, it is widely accepted that the onset of pre-eclampsia is associated with deficient trophoblast invasion leading to generalized endothelial dysfunction, leukocyte activation, and an exaggerated oxidative and inflammatory response. 4,5 Although the exact cause of this disorder is not clear, it is widely accepted that the onset of pre-eclampsia is associated with deficient trophoblast invasion leading to generalized endothelial dysfunction, leukocyte activation, and an exaggerated oxidative and inflammatory response.…”

“…6 The defective trophoblast invasion seen in pre-eclampsia drives to an incomplete maternal spiraled arteries remodeling, leading to relative hypoxia in the villous placenta or an ischemia/reperfusion type injury 7,8 and giving rise to a state of oxidative and nitrative stress. 5 On the other hand, Sacks et al 12 proposed that healthy human pregnancy is characterized by systemic activation of some of the cellular components of the innate immune system, specifically granulocytes, and monocytes. However, this is heightened in pregnancies complicated by pre-eclampsia as measured by increased markers of production of reactive oxygen species and decreases in anti-oxidant defenses.…”

The role of α2‐adrenergic receptors in hypertensive preeclampsia: A hypothesis

“…It is defined by the presence of de novo maternal hypertension (>140/90 mm Hg systolic/diastolic blood pressure) with proteinuria (>300 mg/24 h) or new‐onset thrombocytopenia, impaired liver function, renal insufficiency, pulmonary edema, or visual or cerebral disturbances . In severe cases, the mother may also develop comorbidities such as hepatic alterations, cerebral edema, disseminated vascular coagulation, and eclampsia . For the fetus, the main complications associated with PE include intrauterine growth restriction leading to low birthweight, prematurity, and fetal death.…”

“…During the first trimester of gestation in humans, the intervillous space remains physiologically hypoxic because extravillous trophoblast cells plug maternal spiral arteries preventing maternal red blood cells from passing into this space. Twelve to fourteen weeks into normal gestation, placental extravillous trophoblasts colonize the maternal spiral arteries as far as the proximal third of the myometrium leading to vasodilation increasing blood flow and raising oxygen supply, thus reversing the previous hypoxic environment . This requires extensive angiogenesis involving the differentiation of cytotrophoblasts from an epithelial phenotype to an endothelial phenotype with an ability to invade the uterus and engraft maternal blood vessels .…”