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Updated: Sep 25, 2026
Instrumentation of Near-term Fetal Sheep for Multivariate Chronic Non-anesthetized Recordings
Published on: October 25, 2015
Brief undernutrition in late-gestation sheep programs the hypothalamic-pituitary-adrenal axis in adult offspring
Frank H Bloomfield1, Mark H Oliver, C Diana Giannoulias
1Department of Physiology, University of Toronto, Toronto, Ontario, Canada M5S 1A8.
Insights
Maternal undernutrition for 10 days in late gestation alters adult offspring’s hypothalamic-pituitary-adrenal (HPA) axis function. This effect was independent of birth weight, suggesting distinct programming mechanisms for physiological axes.
Area of Science:
- Endocrinology
- Developmental Biology
- Neuroendocrinology
Background:
- Reduced birth size is linked to altered hypothalamic-pituitary-adrenal (HPA) axis function in humans and animals.
- Maternal undernutrition during gestation can impact fetal HPA development.
- The precise relationship between birth size, fetal nutrition, and adult HPA pathophysiology remains unclear.
Purpose of the Study:
- To investigate the long-term effects of maternal undernutrition during late gestation on adult offspring's HPA axis function in sheep.
- To determine if these effects are associated with birth weight or current body weight.
Main Methods:
- Pregnant ewes were subjected to severe undernutrition for 10 days (UN10) or 20 days (UN20) in late gestation, or were fed ad libitum (controls).
- Adult female offspring (30 months old) underwent an insulin tolerance test and a corticotropin-releasing hormone (CRH) plus arginine vasopressin (AVP) challenge.
- Hormonal responses (ACTH, cortisol, 11-deoxycortisol, progesterone) and protein levels (P450c17, P45011β1) were analyzed.
Main Results:
- UN10 ewes exhibited an increased ACTH response to CRH+AVP and insulin challenges, with elevated 11-deoxycortisol and lower progesterone levels.
- No significant differences in HPA axis responses were observed in UN20 ewes compared to controls.
- Birth weight was lower in UN20 lambs, but adult weights and key protein levels did not differ significantly among groups.
Conclusions:
- Brief maternal undernutrition (10 days) in late gestation can alter adult offspring's HPA axis function.
- These HPA axis alterations appear independent of birth weight and current weight, suggesting specific programming mechanisms.
- Prolonged undernutrition (20 days) did not result in detectable long-term HPA axis dysfunction in this model.
Abstract:
Reduced size at birth in humans has been associated with altered function of the hypothalamic-pituitary-adrenal (HPA) axis in childhood and adult life. Experimentally, maternal undernutrition has also been associated with altered fetal HPA function. However, the relationship between birth size, fetal nutrition, and adult pathophysiology is not clear. We recently have reported that glucose tolerance, blood pressure, and IGF-I levels in adult sheep were more closely associated with birth weight than with nutritional insult in late gestation or with current weight. Here, we report adult HPA function in the same group of animals. Pregnant ewes were severely undernourished for 10 d (UN10) or 20 d (UN20) from 105 d gestation (term, 146 d), or were ad libitum-fed controls. At 30 months, female offspring were subjected to an insulin tolerance test and a CRH plus arginine vasopressin (AVP) challenge. UN20 lambs were lighter at birth, but there were no significant differences in weight at 30 months. Adult UN10 ewes had an increased ACTH response to both CRH+AVP challenge and insulin tolerance test, but no differences in cortisol response. UN10 ewes also demonstrated elevated 11-deoxycortisol concentrations, but lower progesterone concentrations, in response to CRH+AVP challenge. In contrast, the responses of UN20 ewes to these challenges were not different from ad libitum controls. Protein levels of P450(c17) and P450(11beta1) were not significantly different among groups. We conclude that brief maternal undernutrition for 10 d, but not 20 d, in late gestation alters HPA function in adult offspring. In contrast to our previous findings, these HPA effects are independent of birth weight and current weight, suggesting that different mechanisms may be involved in programming different physiological axes.
