Effects of Prenatal Dexamethasone Treatment on Postnatal Physical, Endocrine, and Social Development in the Common Marmoset Monkey

Abstract

The prophylactic treatment of diagnosed preterm delivery with synthetic glucocorticoids, such as dexamethasone (DEX), is commonplace. Long-term effects of such treatment are not well understood. In the present study, we exposed pregnant common marmosets (Callithrix jacchus), small-bodied monkeys that are therefore advantageous for long-term primate studies, to daily repeated DEX (5 mg/kg orally) either during early (d 42-48) or late (d 90-96) pregnancy (gestation period of 144 d). Relative to control, we investigated DEX effects in terms of maternal endocrinology (plasma cortisol and estrogen titers) and offspring physical growth, plasma and urinary ACTH and cortisol titers, and social and maintenance behaviors from birth to weaning. Both DEX treatments resulted in markedly reduced maternal plasma cortisol titers during treatment and reduced estimated gestation period. Both treatments were without effects on neonate morphometric measurements and basal hypothalamic-pituitary-adrenal axis activity. Early DEX treatment resulted in increased infant body weight at postnatal d 56 and 84, co-occurring at the behavioral level with increased time spent in eating solid food, a mobile state, solitary play, and exhibiting tail hair piloerection. The constellation of physical and behavioral effects of early DEX suggests interesting parallels with the human metabolic syndrome, providing primate support that the latter is causally associated with the fetal environment, including prenatal programming. This novel primate in vivo evidence for postnatal effects of prenatal synthetic glucocorticoid exposure indicates the importance of improved understanding of this acute clinical treatment in terms of its long-term effects on offspring well-being.