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

Abstract

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 response profiles for ACTH and cortisol were determined at 113-116 and 125-127 dGA after administration of corticotrophin releasing hormone (CRH) and arginine 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+AVP was significantly smaller at 113-116 dGA (P<0·01), and cortisol responses were smaller at both 113-116 dGA (P<0·01) and 125-127 dGA (P<0·0001). Cortisol 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 gestation.

Prenatal Programming of Hypertension

“…In the sheep, both maternal calorie restriction and steroid administration may induce demonstrable changes in the offspring HPA. Calorie restriction in early pregnancy has been reported to suppress the HPA during fetal life (23, 86,87), to increase glucocorticoid receptor expression in several tissues of the newborn (70), and to result in augmented cortisol response in later life (23). Dodic and coworkers (32,33) examined the HPA in the sheep-steroid model.…”

Impact of maternal undernutrition on the hypothalamic–pituitary–adrenal axis responsiveness in sheep at different ages postnatal

“…It has been shown that maternal nutrient restriction, which has no effect on birth weight, can alter the function of the hypothalamic-pituitary-adrenal (HPA) axis (Hawkins et al 1999(Hawkins et al , 2000, which has been suggested to play a role in programming of the later disease (Seckl 1997). Studies examining the impact of maternal nutrient restriction on HPA axis have been mostly limited to the late-gestation fetus or young lambs (Hawkins et al 2000, Edwards & McMillen 2002, Bloomfield et al 2004 and only a few have been undertaken to establish the long-term effects of maternal undernutrition on HPA function in the adult sheep.…”

Dietary restriction in pregnant rats causes gender‐related hypertension and vascular dysfunction in offspring

“…In this study we have investigated the last of these, the responses to moderate restriction of all dietary constituents. In a recent investigation, lambs from ewes subjected to only 15% dietary restriction during gestation were hypertensive, and demonstrated perturbed activity of the HPA axis in the absence of growth retardation Hawkins et al 1999).…”