Antenatal glucocorticoids blunt the functioning of the hypothalamic-pituitary-adrenal axis of neonates and disturb some behaviors in juveniles

Abstract: Antenatal glucocorticoids are highly effective in preventing respiratory distress of premature babies but can induce physiological and behavioral disturbances in young infants as well as in animals. Therefore, the hypothalamic-pituitary-adrenal (HPA) axis of rat neonates, and the consequences on behavioral development of offspring have been studied after five antenatal injections of dexamethasone (DEX) or vehicle. DEX decreased offspring body weight at birth, and significantly delayed the normal growth for the first 3 weeks of life. This paralleled diminished behavioral performances measured on postnatal day 3 (righting reflex) and postnatal day 10 (grasping test). Circulating levels of adrenocorticotrophin (ACTH) and corticosterone were significantly decreased on postnatal day 1 and this was related to a diminution of HPA axis activity shown by the decrease of central expression of corticotropin releasing hormone (CRH) mRNA, immunoreactive content in paraventricular neurons (PVN) and in the median eminence endings were significantly decreased. On the other hand, expression of another secretagogue of ACTH, arginine vasopressin (AVP), was differently affected in the PVN parvocellular neurons of offspring of the DEX group since AVP mRNA increased whereas immunoreactive content of the PVN parvocellular neurons was lowered. Simultaneously, the co-production of AVP and CRH in PVN neurons was stimulated. This can support the view that antenatal DEX reached the fetus and produced some damage which did not parallel that induced by prenatal stress of the pregnant females, especially the low body weight of offspring. The harmful consequence of antenatal DEX treatment was not restrictively due to the blunting of the HPA axis but also to the low body weight, which disturbed behavioral performances for the first weeks of life and could participate in other disorders in adult life. [Copyright &y& Elsevier]