Cotyledon and binucleate cell nitric oxide synthase expression in an ovinemodel of fetal growth restriction

Heat exposure early in ovine pregnancy results in placental insufficiency a nd intrauterine growth restriction (PI-IUGR). We hypothesized that heat exp osure in this model disrupts placental structure and reduces placental endo thelial nitric oxide synthase (eNOS) protein expression. We measured eNOS p rotein content and performed immunohistochemistry for eNOS in placentas fro m thermoneutral (TN) and hyperthermic (HT) animals killed at midgestation ( 90 days). Placental histomorphometry was compared between groups. Compared with the TN controls, the HT group showed reduced delivery weights (457 +/- 49 vs. 631 +/- 21 g; P< 0.05) and a trend for reduced placentome weights ( 288 +/- 61 vs. 554 +/- 122 g; P = 0.09). Cotyledon eNOS protein content was reduced by 50% in the HT group (P< 0.03). eNOS localized similarly to the vascular endothelium and binucleated cells (BNCs) within the trophoblast of both experimental groups. HT cotyledons showed a reduction in the ratio of fetal to maternal stromal tissue (1.36 +/- 0.36 vs. 3.59 +/- 1.2; P less t han or equal to 0.03). We conclude that eNOS protein expression is reduced in this model of PI-IUGR and that eNOS localizes to both vascular endotheli um and the BNC. We speculate that disruption of normal vascular development and BNC eNOS production and function leads to abnormal placental vascular tone and blood flow in this model of PI-IUGR.