Ontogeny of endothelial nitric oxide synthase mRNA in an ovine model of fetal and placental growth restriction.

OBJECTIVE To determine: 1) placental eNOS mRNA concentration across gestation in normal ovine pregnancy and in an ovine model of intrauterine growth restriction (IUGR), and 2) placental eNOS protein concentration in early ovine pregnancy. STUDY DESIGN A total of 24 sheep were studied with 12 ewes placed in hyperthermic (HT) conditions to induce IUGR and 12 were kept in control conditions. HT and control animals underwent euthanasia at 3 developmental time points (55, 95, & 130 days gestational age; dGA) in ovine placental & fetal development. RESULTS Compared to controls, HT pregnancies showed 1) no differences in fetal weights at 55 dGA and 95dGA with significant reductions at 130 dGA, 2) significantly smaller placentae at 95 and 130 dGA with a trend for a reduction at 55 dGA, 3) significant decreases in cotyledon eNOS mRNA at 95 and 130 dGA, 4) a significant increase in caruncle eNOS mRNA expression at 130 dGA, 5) significant increase in eNOS protein in the caruncle, but not in the cotyledon at 55 dGA. CONCLUSION Placental eNOS concentration is transcriptionally regulated at mid-gestation, while additional post-transcriptional regulation is also involved during early and late gestation in this model of placental and fetal growth restriction.