Maternal undernutrition during late gestation induces fetal overexposure to glucocorticoids and intrauterine growth retardation, and disturbs the hypothalamopituitary adrenal axis in the newborn rat

As fetal overexposure to glucocorticoids has been postulated to induce intr auterine growth retardation (IUGR) in humans, we investigated the effects o f maternal 50% food restriction (FR50) in rats during the last week of gest ation on the hypothalamo-pituitary adrenal (HPA) axis activity in both moth ers and their fetuses. In mothers, FR50 increased both the plasma corticost erone (B) level from embryonic days 19-21 and the relative adrenal weight a t term. FR50 decreased at term both the maternal plasma corticosteroid-bind ing globulin level and placental 11 beta -hydroxysteroid dehydrogenase type 2 expression. In newborns, maternal FR50 reduced body and adrenal weights, glucocorticoid and mineralocorticoid receptor expressions in the hippocamp us, corticoliberin expression in the hypothalamic paraventricular nucleus, and plasma ACTH. In FR50 newborns, the plasma B level was increased at birt h and decreased 2 h later. When maternal circulating B was maintained at th e basal level by adrenalectomy and B supply, FR50 induced IUGR in pups and decreased placental 11 beta- hydroxysteroid dehydrogenase type 2 expression at term, but did not disturb the offspring's HPA axis. These results sugge st that maternal undernutrition during late gestation induces both IUGR and an overexposure of fetuses to maternal B, which disturb the development of the HPA axis.