Effect of prenatal hypoxia in transgenic mouse models of preeclampsia and fetal growth restriction.

Mice lacking endothelial nitric oxide synthase (eNOS(-)(/-)) or catechol-O-methyl transferase (COMT(-/-)) exhibit a preeclampsia-like phenotype and fetal growth restriction. We hypothesized that a hypoxic insult would result in a more severe phenotype. Pregnant eNOS(-/-), COMT(-/-) and control (C57BL/6J) mice were randomized to hypoxic (10.5% O(2)) or normal conditions (20.9% O(2)) from gestational day 10.5 to 18.5. Hypoxia increased the blood pressure in all genotypes and proteinuria in C57BL/6J and eNOS(-/-) mice. Fetal survival was significantly reduced following hypoxia, particularly in eNOS(-/-) mice. Birth weight was decreased in both C57BL/6J and COMT(-/-) mice. Placentas from COMT(-/-) mice demonstrated increased peroxynitrite. Despite similar hypoxia-induced effects on maternal blood pressure and proteinuria, eNOS(-/-) embryos have a decreased tolerance to hypoxia. Compared to C57BL/6J, COMT(-/-) mice exhibited less severe changes in proteinuria and fetal growth when exposed to prenatal hypoxia. This relative resistance to prenatal hypoxia was associated with a significant increase in placental levels of peroxynitrite.