Effect of maternal nutrient restriction in early gestation development of the hypothalamic-pituitary-adrenal axis in fetal sheep at 0.8-0.9 of gestation

The fetal hypothalamic-pituitary-adrenal (HPA) axis has numerous key roles in development. Epidemiological data have linked adverse prenatal nutrition with altered organ development and increased incidence of disease in adult life. We studied HPA axis development in resting and stimulated states in late gestation fetal sheep, following 15% reduction in maternal nutritional intake over the first 70 days of gestation (dGA). Fetuses from control (C) and nutrient-restricted (R) ewes were chronically catheterised and respons e profiles for ACTH and cortisol were determined at 113-116 and 125-127 dGA after administration of corticotrophin releasing hormone (CRH) and arginin e vasopressin (AVP). At 126-128 dGA cortisol profiles were also determined following ACTH administration. Basal ACTH and cortisol concentrations were not different between C and R fetuses. In R fetuses, ACTH response to CRH+A VP was significantly smaller at 113-116 dGA (P<0.01), and cortisol response s were smaller at both 113-116 dGA (P<0.01) and 125-127 dGA (P<0.0001). Cor tisol response to ACTH was also smaller in R fetuses (P<0.001). We conclude that, in late gestation fetal sheep, pituitary and adrenal responsiveness is reduced following modest maternal nutrient restriction in early gestatio n.