A COMPARISON OF FETO-PLACENTAL VASCULARITY IN NORMAL AND GROWTH RESTRICTED PREGNANCIES

Abstract

In human pregnancy, the feto-placental vessels are crucial for efficient materno-fetal transfer; hence they play a pivotal role in the pathogenesis of fetal growth restriction (FGR). We, as well as other research groups, have observed abnormalities in the FGR feto-placental vasculature, which, though inconclusive, were suggestive of a state of panhypovascularity. The goal of the work presented in this thesis was to investigate this. We hypothesised that the placenta may be panhypovascular in FGR due to failed angiogenesis; and enhancing angiogenesis in the placenta may improve fetal growth.Custom-designed techniques including advanced imaging, computer-aided analyses and tube-forming experiments were employed to compare feto-placental vessels and endothelial cells in placentas from normal and FGR-complicated pregnancies while aiming to answer two main research questions: (i) is the FGR placenta panhypovascular? (ii) can angiogenesis be induced or enhanced to improve placental vascularity?Findings include: (i) shorter arterial [p = 0.03 and 0.009 when data adjusted for placental surface area (PA) and weight (PW) respectively] and longer venous path [p = 0.05 and 0.03, adjusted for PA and PW respectively] in FGR placentas though no difference in the total number of arterial or venous branches, diameter, and tortuosity of the vessels compared to normal; (ii) altered angiogenic behaviour/response of FGR placental endothelial cells following in vitro pharmacological manipulation of WNT signalling; (iii) human placental endothelial cells are capable of regaining their angiogenic potential following withdrawal of WNT inhibition.These findings discount the hypothesis of panhypovascularity in FGR placentas, but identify additional, previously unreported, feto-placental vascular abnormalities associated with FGR. Also, the findings provide evidence that impairment of WNT signalling may play a role in defective angiogenesis and consequent dysvascularity in the FGR placenta. The evidence suggests the WNT pathway should be explored as a potential new target for therapeutic interventions to correct placental dysvascularity in FGR.

Date of Award	31 Dec 2017
Original language	English
Awarding Institution	The University of Manchester
Supervisor	John Aplin (Supervisor) & Edward Johnstone (Supervisor)