The heat stressinduced IUGR placenta is characterized by reduced size and impaired function. Mechanisms responsible for early uterineplacental angiogenic development are poorly understood. However, it has been proposed that changing concentrations of the two steroids P4 and E2, regulate circulating growth factors involved in this development. This study investigates maternal P4 and E2 changes during early gestation in normothermic(NT) and hyperthermic (HT) ewes. Ten singleton ewes were examined at 4070 days post coitus (dpc). Four days following maternal arterial and uterine venous catheterization, and temperature transmitter placement (35 ± 2 dpc), ewes were moved to a HT environment (n=5; 40°C 12 h/d, 35°C 12 h/d; 30% relative humidity [RH]) or remained in a NT environment (n=5; 17± 2°C 24 h; 30% RH). Maternal core body temperature (CBT) was recorded every 15 minutes. Blood samples were collected on ice and plasma stored at 80°C until assay. Mean data were analyzed using Student's ttest. Ewes subjected to hyperthermia displayed a significantly elevated CBT (39.79± 0.02 vs. 39.17 ± 0.01 °C; p≤0.001). Hyperthermic ewe arterial P4 concentrations were significantly reduced (23.6 ± 1.1 vs. 29.4 ± 1.7 nmol/L; p≤0.02). Furthermore, HT uterine venous P4 concentrations were significantly lower than NT ewes (221.1 ± 111.9 vs. 1674.9 ± 348.8 nmol/L; p≤0.02). Venous E2 was not detected. Pregnant ewes exposed to chronic hyperthermia during early placental development display significantly reduced P4 concentrations. Elevated P4 concentrations have been reported to stimulate the in vitro secretion of the cytokine, vascular endothelial growth factor (VEGF). We postulate that reduced P4 concentrations in HT ewes could impair VEGF secretion. The reduced VEGF output by the developing placental microvasculature endothelial cells, during early gestation, could result in impaired placental development, reducing placental mass and impairing function in the later stages of gestation. This study potentially highlights a new pathophysiological mechanism of IUGR placental development.
