The Inhibition of Trophoblast Apoptosis by Shear Stress

In the first trimester of pregnancy trophoblast migrate along the uterine spiral arteries and replace the endothelial cells lining these vessels by mechanisms involving endothelial cell apoptosis. Inadequacies in this process of spiral artery remodelling have been associated with pre-eclampsia and IUGR. Until 10-12 weeks of gestation trophoblast also form plugs in the spiral arteries, preventing maternal blood flow into the intervillous space. The complete occlusion of the spiral arteries by trophoblast plugs is unique to human pregnancy and significantly affects spiral arterial resistance, blood flow and shear stress [1, 2]. Flow rate and shear stress are known to affect endothelial cell apoptosis, with higher levels of apoptosis occurring at lower flow rates in vitro [3, 4]. The inhibition of endothelial cell apoptosis by shear stress has been reported to involve many mechanisms including Fas/FasL interactions, eNOS upregulation, induction of inhibitors of apoptosis protein (IAP) 1 and 2 expression, and activation of the PI3k-Akt survival pathway [3, 4, 5, 6]. Therefore, we hypothesise that low rates of blood flow in the plugged spiral arteries during the first 10-12 weeks of pregnancy may reduce the resistance of endothelial cells to trophoblast-induced apoptosis.