Effect of periconceptional undernutrition and gender on hypothalamic–pituitary–adrenal axis function in young adult sheep

Abstract

Glucocorticoids are proposed to act as intermediary factors that transcribe the developmental programming sequelae of maternal nutrient restriction (NR). Periconceptional undernutrition of sheep markedly activates fetal hypothalamicpituitary-adrenal (HPA) axis activity leading to preterm birth, while transient undernutrition during late gestation in sheep programs adult HPA axis function. To date, no study has examined resting or stimulated HPA axis function in young adult offspring following a periconceptional nutritional challenge. In the present study, 20 ewes were either periconceptionally undernourished (50% metabolisable energy requirements from days 1 to 30 gestation; NR, nZ8) or fed to control levels (100% requirement; controls, nZ12) to term (147 days gestation). Ewes were blood sampled remotely at 2 and 30 days using automated blood sampling equipment. Thereafter, offspring (controls, nZ6/6 males/females; NR, nZ4/4 males/females) were reared to 1 year of age and on separate days received either an i.v. corticotrophin-releasing hormone (CRH; 0$5 mg/kg) and vasopressin (AVP; 0$1 mg/kg) challenge or a synthetic ACTH i.v. bolus (Synacthen; 1$25 mg/kg), and blood samples were taken (manually and remotely) at appropriate intervals for measurement of plasma ACTH and cortisol accordingly. Resting plasma cortisol, assessed remotely, was similar in ewes during undernutrition (control 18$3G1$4 vs NR 23$4G1$9 nmol/l) and in offspring at 4 months of age (control male 17$6G2$9; control female 17$2G0$4, NR male 16$5G3$1, NR female 21$7G4$0 nmol/l). At 12 months of age, however, resting plasma cortisol was significantly increased in NR females (control male 28$0G1$5, control female 32$9G9, NR male 32G7, NR female 53G10 nmol/l, F 5$7, PZ0$02) despite no difference in plasma ACTH concentration. There was an interaction between nutritional group and gender for both the pituitary and adrenal responses to CRH and AVP, i.e. for controls, females exhibited increased plasma ACTH or cortisol relative to males but for NR this trend was either not present or reversed. The adrenocortical response to synthetic ACTH was gender-dependent only, being greater in female offspring. Combined CRH and AVP provoked a transient hypertension and marked bradycardia in all animals, irrespective of dietary group or gender and could be effectively reproduced by an AVP bolus alone. In conclusion, the present study has shown that periconceptional undernutrition of sheep has only a minor influence on HPA axis function in their young adult offspring when considered alongside the effect of gender per se.

Epigenetics and developmental programming of welfare and production traits in farm animals

“…Responses are variable (due, in part, to inconsistency between studies in time at which the offspring were assessed), but do suggest some sex-specific variation, as seen in young adult sheep (e.g. Gardner et al 2006), and differences in responses when lambs are younger or older. Studies in cattle are very scarce, but Lay et al (1997) showed that repeated transportation of Brahman cows during gestation increased the cortisol response of the progeny to an acute restraint stress.…”

Nutritional regulation of fetal growth and implications for productive life in ruminants

“…As in the placenta (see above), this response is mediated by an increase in both gene expression for the glucocorticoid receptor and reduced action of the enzyme 11b-hydroxysteriod dehydrogenase type 2 which occurs in a range of newborn tissues including heart, kidney, liver and lungs (Whorwood et al, 2001). These changes would be predicted to enhance glucocorticoid action even in the absence of any change in plasma cortisol (Gardner et al, 2006). These have no immediate adverse effect on the offspring and persist in some tissues into juvenile life when offspring are raised in an outdoor-free living environment.…”

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

“…Brief undernutrition for 10 but not 20 days during late gestation altered the HPA function in adult offspring, further emphasizing the fact that the timing, type, and duration of fetal nutrient restriction are each important in determining the nature of the fetal adaptive responses and their pathophysiological sequelae in later life (Bloomfield et al 2003). More recently periconceptional undernutrition was shown to exert a minor influence on HPA axis function in young adult sheep (Gardner et al 2006).…”

“…In sheep, maternal cortisol changes are related to the timing when feed restriction is imposed. Late-gestation undernutrition resulted in elevated maternal cortisol concentrations , while early-to mid-gestation or periconceptional undernutrition resulted in reduced or unchanged cortisol levels respectively (Bispham et al 2003, Gardner et al 2006.…”