Effect of maternal nutrient restriction in early gestation on responses ofthe hypothalamic-pituitary-adrenal axis to acute isocapnic hypoxaemia in late gestation fetal sheep

Epidemiological and experimental evidence suggests that maternal undernutri tion during pregnancy may alter development of fetal organ systems. We have demonstrated previously that fetal hypothalamic-pituitary-adrenal (HPA) ax is responses to exogenous corticotropin-releasing hormone (CRH) + arginine vasopressin (AVP), or adrenocorticotrophin hormone (ACTH), are reduced in f etuses of mildly undernourished ewes. To examine these effects further we t ested HPA axis responses to acute isocapnic hypoxaemia in fetal sheep at 11 4-129 days gestation (dGA), following 15% reduction in maternal nutritional intake between 0 and 70 dGA. Fetuses from control (C) and nutrient-restric ted (R) ewes were chronically catheterised and plasma ACTH: and cortisol re sponses were determined at 114-115, 120-123 and 126-129 dGA during hypoxaem ia (1 h) induced by lowering the maternal inspired O-2 fraction (F-I,F-O2). Basal plasma cortisol concentrations and HPA axis responses at 114-115 and 120-123 dGA did not differ between C and R fetuses. At 126-129 dGA, both p lasma ACTH (P < 0.01) and cortisol (P < 0.05) responses were smaller in R f etuses compared to C fetuses. Fetal blood gas status, fetal body weight, bo dy proportions and organ weights did not differ between the groups. We conc lude that mild maternal undernutrition alters development of the fetal HPA axis producing a reduction in pituitary and adrenal responsiveness to endog enous stimuli.