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

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