Morphological and Functional Alterations in the Aorta of the Chronically Hypoxic Fetal Rat

In human pregnancy, reduced placental perfusion has been associated with fetal aortic thickening. However, the relative contributions of fetal undernutrition versus fetal underoxygenation to triggering alterations in fetal cardiovascular development remain uncertain. Here, we isolate the effects of chronic fetal hypoxia on fetal cardiovascular development in a specific rodent model of chronic fetal hypoxia independent of changes in nutrition during pregnancy. Pregnant rats were housed under normoxic (21% O 2 ) or hypoxic (13% O 2 ) conditions from day 6 to day 20 of gestation. At day 20, pups and placentas were weighed. Fetal thoraces were fixed for quantitative histological analysis of the aorta. In a separate group, fetal aortic reactivity was assessed via in vitro wire myography. The experiments controlled for sex and within-litter variation. Placental weight was increased and fetal weight maintained in hypoxic pregnancy. Hypoxic pregnancy led to a 176% increment in wall thickness and a 170% increment in the wall-to-lumen area ratio of the fetal aorta. Fetal aortic vascular reactivity was markedly impaired, showing reduced constrictor and relaxant responsiveness in hypoxic pregnancy. Chronic developmental hypoxia independent of changes in nutrition has profound effects on the morphology and function of the fetal aorta in a mammalian species.