The effect of placental hypoxia on endothelial damage in preeclampsia

Abstract

It is hypothesized that in response to hypoxia, the placenta releases placental secreted messengers (PSMs) in the maternal circulation, which initiate endothelial damage. Currently, there is a great interest in using dietary antioxidant interventions to prevent PE. Endothelial cells were cultured and incubated with conditioned medium (CM) of placentas which were exposed to 21% O2 (control) or 100% N2 (pHCM). In addition, quercetin was introduced prior to aeration. Additionally, endothelial cells were exposed to CM of trophoblasts, which were exposed to 21% O2 or 1% O2 (tHCM). Cell viability was assessed by MTT assay. ROS formation and antioxidant capacity were measured by DCFH-DA, glutathione, and TEAC assays. mRNA expression levels of antioxidants and inflammatory markers were measured by qPCR. ELISA detected proinflammatory factors and VEGF. Endothelial exposure to pHCM and tHCM decreased the cell viability and antioxidant capacity, and increased ROS formation. pHCM decreased endothelial VEGF secretion, while tHCM stimulated endothelial IL-6 and -8 secretion and decreased VEGF expression. The antioxidant intervention prevented pHCM-induced effects. Hypoxia in placental tissue and trophoblast cells leads to the release of factors, which induced endothelial cell death, ROS formation, inflammation, and reduced antioxidant capacity. These consequences may trigger endothelial damage. Results of quercetin protection indicate the potentials of a dietary intervention in PE.