Effect of Periconceptional Undernutrition in Sheep on Late Gestation Expression of mRNA and Protein From Genes Involved in Fetal Adrenal Steroidogenesis and Placental Prostaglandin Production

In sheep, maternal periconceptional undernutrition precociously activates fetal hypothalamic-pituitary-adrenal function in a high proportion of animals, resulting in preterm birth. We investigated whether the effects of periconceptional undernutrition were mediated through genes encoding enzymes involved in adrenal steroidogenesis and in placental production and metabolism of steroids and prostaglandins. Singleton-bearing ewes were fed ad libitum (control, N) throughout gestation or undernourished from 60 days before until 30 days after mating. Fetal adrenal and placentome tissues were collected on gestational day 131. Fetal adrenal P450C17 protein expression was significantly increased with undernutrition. Placental prostaglandin endoperoxide synthase-2 expression was not different between groups. In undernourished pregnancies, there were significant positive correlations between fetal plasma adrenocorticotrophic hormone and cortisol concentrations and between fetal plasma adrenocorticotrophic hormone concentrations and placental prostaglandin endoperoxide synthase-2 messenger RNA (mRNA) and protein. These studies suggest that periconceptional undernutrition affects fetal adrenal P450C17, consistent with an elevation in plasma cortisol, and this occurs prior to activation of placental prostaglandin endoperoxide synthase-2 expression at gestational day 131.