A Single Course of Synthetic Glucocorticoids in Pregnant Guinea Pigs Programs Behaviour and Stress Response in Two Generations of Offspring

Abstract

Treatment with a single course of synthetic glucocorticoids (sGC) is the standard of care for pregnant women who are at risk for preterm delivery. Animal studies have demonstrated that multiple course sGC can program altered hypothalamic-pituitary-adrenal (HPA) axis response to stress in first- (F1) and second-generation (F2) offspring. This study sought to determine whether HPA axis activity and stress-associated behaviours (locomotor activity, attention) are altered following a single course of sGC in F1 and F2 female and male offspring. Pregnant guinea pigs (F0) received sGC (1 mg/kg) or saline on gestational days 50&51. HPA function and behaviour were assessed in juvenile and adult F1-F2 offspring of both sexes following maternal transmission. In F1, sGC increased the HPA stress response in females, but decreased responsiveness in males (P<0.05). sGC exposure (F0) produced the opposite effects in F2 (P<0.05). Reduced HPA responsiveness in F2 females was associated with reduced expression of proopiomelanocortin mRNA and increased expression of glucocorticoid receptor in the anterior pituitary (P<0.05). Locomotor activity and prepulse inhibition were reduced by sGC in adult F1 offspring. No behavioural changes were observed in F2 animals. These data indicate that effects of antenatal treatment with a single course of sGC are present in F2 following maternal transmission. However, there are fewer effects on HPA activity and behaviour in F1 and F2 offspring compared to treatment with multiple courses of sGC.