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

Abstract

Epidemiological and experimental data support the hypothesis of 'fetal programming', which proposes that alterations in fetal nutrition and endocrine status lead to permanent adaptations in fetal homeostatic mechanisms, producing long-term changes in physiology and determine susceptibility to later disease. Altered hypothalamic-pituitaryadrenal (HPA) axis function has been proposed to play an important role in programming of disease risk. The aim of the present study was to examine the effects of maternal nutrient restriction imposed during different periods of gestation on the HPA axis function in sheep, at different ages postnatal. Pregnant ewes were fed a 50% nutrient-restricted diet from days 0-30 (group R1, nZ7), or from days 31-100 of gestation (group R2, nZ7) or a control 100% diet throughout pregnancy, (Control, nZ8). Blood samples were collected at 10-day intervals from day 40 of gestation to term. Lambs were born naturally and fed to appetite throughout the study period. At 2, 5 . 5, and 10 months of age lambs were given an i.v. injection of corticotrophin-releasing hormone (CRH) and blood samples were collected at K15, 0, 15, 30, 60, 120, and 180 min postinjection. Maternal cortisol levels were significantly higher (P!0 . 05) in group R1 compared with the other two groups, whereas maternal insulin levels were lower (P!0 . 05) in group R2 compared with control. Birth weight of lambs was not affected by the maternal nutritional manipulation. The area under the curve for ACTH and cortisol response to CRH challenge was greater (P!0 . 05) in lambs of group R1 at two months of age, whereas no difference was detected at the ages of 5 . 5 and 10 months. However, significantly higher (P!0 . 01) basal cortisol levels were observed in lambs of R1 group at 5 . 5 months of age.There was no interaction between treatment and sex for both pituitary and adrenal responses to the challenge. A significant sex effect was evident with females responding with higher ACTH and cortisol levels at the age of 5 . 5 months (P!0 . 01, P!0 . 001 respectively) and with higher cortisol levels (P!0 . 01) at 10 months of age than males. It is concluded that the HPA axis is programmable by altered nutrition in utero. The sensitivity of the axis to exogenous stimulation is enhanced during early postnatal life and attenuated with age, suggesting a role for the postnatal influences in resetting of the HPA axis and emphasizing the importance of identifying the impact of maternal undernutrition at several time points after birth.

Pathology of Runting in Farmed Saltwater Crocodiles (Crocodylus porosus) in Australia

“…It has been established in many animals, from fish to birds and mammals, that maternal stress may influence the hypothalamicpituitary-adrenal axis of the offspring, resulting in altered behavioral development and/or ill thrift in the offspring for several months after birth. 2,8,13,16,17,36,45 In lizards, treatment of reproductive females or eggs with corticosterone can affect hatchling body size, growth rate, behavior (eg, dispersal and antipredator responses), and even sex. 52,66,68 Likewise, in crocodilians, limited studies suggest that high plasma corticosterone in females may result in relatively poor egg quality and decreased hatchling survival.…”

Early postnatal alteration of body composition in preterm and small-for-gestational-age infants: implications of catch-up fat

“…Periconceptional undernutrition of sheep is reported to have only a minor influence on HPA axis function in their young adult offspring (15). In addition, the HPA axis can be reset by postnatal influences (16). A metaanalysis of human epidemiological studies reported an inverse association between birth weight and circulating cortisol level, although the majority of studies were underpowered.…”

Dietary restriction in the periconceptional period in normal-weight or obese ewes results in increased abundance of angiotensin-converting enzyme (ACE) and angiotensin type 1 receptor (AT1R) in the absence of changes in ACE or AT1R methylation in the adrenal of the offspring

“…Adversity in early life can result in long-term changes in the HPA axis as a consequence of epigenetic modifications of key regulatory genes in rodents, sheep and humans (Weaver et al 2004, Oberlander et al 2008, Murgatroyd et al 2009, Stevens et al 2010, Zhang et al 2010, Grace et al 2011. It has previously been demonstrated in sheep that exposure to maternal undernutrition during the periconceptional period and early gestation results in altered fetal adrenal development from as early as 55 days of gestation (termZ150G3 days of gestation; MacLaughlin et al 2007), an earlier prepartum activation of the fetal HPA axis (Edwards & McMillen 2002b, Bloomfield et al 2004, an increased risk of premature delivery (Bloomfield et al 2003) and increased plasma cortisol concentrations in the post-natal lamb (Gardner et al 2006, Chadio et al 2007. We have also recently reported that exposure to dietary restriction during the periconceptional period in either normal-weight or overweight ewes using the same animals in the current study results in increased adrenal growth, a greater cortisol response to stress and a decrease in the adrenal expression and methylation levels of the imprinted gene, insulin-like growth factor 2 (IGF2) in the offspring (Zhang et al 2010).…”