Effects of sex, litter size and periconceptional ewe nutrition on offspring behavioural and physiological response to isolation.

Maternal periconceptional undernutrition alters fetal hypothalamic-pituitary-adrenal (HPA) axis development. However, the effects of this early nutritional insult on postnatal HPA axis function and stress-related behaviours are unknown. We investigated in sheep the effects of different periods of undernutrition, and of sex and litter size, on offspring behavioural and cortisol responses to isolation stress. We studied four nutritional groups: controls well nourished throughout pregnancy (n=39), or ewes undernourished (UN, 10-15% body weight reduction) before mating (-60 to 0d, n=26), after mating (-2 to +30d, n=20) or both (-60 to +30d, n=36). At 4 and 18months of age, offspring were isolated for 5min, their behaviour video recorded, and plasma cortisol concentrations measured. Offspring of all undernourished groups demonstrated 50% fewer escape attempts than controls at 4 months of age, and offspring of UN-60+30 ewes had 20% lower plasma cortisol area under the curve in response to isolation at 18months. Females had higher cortisol concentrations and vocalised more than males at 4 and 18months, and were more active at 18months. After isolation, UN-2+30 males had higher cortisol concentrations than UN-2+30 females whereas in all other groups males had lower concentrations than females. Singleton males made more escape attempts than females, whereas in twins females made more escape attempts than males. These findings suggest that maternal periconceptional undernutrition in sheep can suppress behavioural reactions and cortisol secretion in response to isolation stress in the offspring into adulthood, and that these effects differ between males and females.