Hypoxia downregulates the angiogenesis in human placenta via Notch1 signaling pathway

Abstract

Placentation, which is critical for maternal-fetal exchange of nutrients and gases, is a complicated process comprising stepwise vasculogenesis and angiogenesis. Hypoxia caused by impaired trophoblast invasion may cause various angiogenic abnormalities in human placenta. The Notch1 signaling pathway plays an important role in the regulation of angiogenesis. The angiogenesis of human umbilical vein endothelial cells (HUVECs) under normal/hypoxic conditions and the mRNA/protein level of Notch1/Dell4/Jagged1 were investigated in this study. The effects of DAPT/JAG-1 on the migration of HUVECs were also assessed by cell wound healing assay, so as to discover the possible role of notch1 signaling pathway in the angiogenesis of human placenta. The results showed that angiogenic ability of HUVECs was seriously reduced under hypoxic conditions. The mRNA and protein levels of Notch1/Dell4/Jagged1 were decreased in the hypoxic group compared to the control one. In addition, the migration capability of HUVECs was significantly obstructed when treated with DAPT and under hopoxic condition, but promoted when treated with JAG-1. The above results demonstrate that hypoxia downregulates the angiogenesis in human placenta via Notch1 signaling pathway.

The effects of flavonoids on human first trimester trophoblast spheroidal stem cell self-renewal, invasion and JNK/p38 MAPK activation: Understanding the cytoprotective effects of these phytonutrients against oxidative stress

“…A critical component for a successful pregnancy and healthy placental function is the proper development of angiogenic (adequate trophoblast invasion) and vascular (maternal spiral artery remodelling) networks [1,14]. Oxidative stress (such as hypoxia and/or hypoxia reoxygenation) during gestation results in impairment of trophoblast invasion and abnormalities in human placenta [14,49,51].…”

“…Interestingly, pregnancy can be considered as a state of oxidative stress due to the increased placental mitochondrial activity and production of ROS as low/moderate levels of oxidative stress is essential for the normal development of foetal growth [12,13]. Increased placental oxidative stress has been linked to the pathophysiology of pregnancy complications such as foetal growth restriction, pre-eclampsia (PE), maternal/foetal immune disturbance, and miscarriage [1,14]. PE is a major disease of human pregnancy, characterised by hypertension (160/110 mmHg) and proteinuria (>300 mg/24 h) mainly developing after 20 weeks of gestation [8].…”