Feto- and utero-placental vascular adaptations to chronic maternal hypoxia in the mouse.

KEY POINTS: Chronic fetal hypoxia is one of the most common complications of pregnancy and is known to cause fetal growth restriction. The structural adaptations of the placental vasculature responsible for growth restriction with chronic hypoxia are not well elucidated. Using a mouse model of chronic maternal hypoxia in combination with micro-computed tomography and scanning electron microscopy, we found several placental adaptations that were beneficial to fetal growth including capillary expansion, thinning of the interhaemal membrane and increased radial artery diameters, resulting in a large drop in total utero-placental vascular resistance. One of the mechanisms used to achieve the rapid increase in capillaries was intussusceptive angiogenesis, a strategy used in human placental development to form terminal gas-exchanging villi. These results contribute to our understanding of the structural mechanisms of the placental vasculature responsible for fetal growth restriction and provide a baseline for understanding adaptive physiological responses of the placenta to chronic hypoxia. ABSTRACT: The fetus and the placenta in eutherian mammals have a unique set of compensatory mechanisms to respond to several pregnancy complications including chronic maternal hypoxia. This study examined the structural adaptations of the feto- and utero-placental vasculature in an experimental mouse model of chronic maternal hypoxia (11% O2 from embryonic day (E) 14.5-E17.5). While placental weights were unaffected by exposure to chronic hypoxia, using micro-computed tomography, we found a 44% decrease in the absolute feto-placental arterial vascular volume and a 30% decrease in total vessel segments in the chronic hypoxia group compared to control group. Scanning electron microscopy imaging showed significant expansion of the capillary network; consequently, the interhaemal membrane was 11% thinner to facilitate maternal-fetal exchange in the chronic hypoxia placentas. One of the mechanisms for the rapid capillary expansion was intussusceptive angiogenesis. Analysis of the utero-placental arterial tree showed significant increases (24%) in the diameter of the radial arteries, resulting in a decrease in the total utero-placental resistance by 2.6-fold in the mice exposed to chronic maternal hypoxia. Together these adaptations acted to preserve placental weight whereas fetal weight was decreased.