Recovery of glucocorticoid-related loss of synaptic density in the fetal sheep brain at 0.75 of gestation

Antenatal glucocorticoids routinely used to accelerate fetal lung maturation in human pregnancy at risk of preterm delivery decrease synaptic density and complex electrocortical activity in the fetal sheep brain at 0.87 gestation. We examined whether the effects of betamethasone on synaptic density depend on maturation of hypothalamo-pituitary-adrenal (HPA) axis and whether these effects are reversible. Betamethasone infusion to fetal sheep comparable to the dose used clinically (3.3 mug kg(-1) h(-1) over 48 h) at 0.75 gestation and, thus, before the prepartum increase of cortisol, reduced synaptophysin immunoreactivity (SY-IR) in the frontal neocortex, caudate putamen and hippocampus (P < 0.05). Loss of SY-IR exceeded that shown previously at 0.87 gestation (P < 0.05). It was not accompanied by neuronal damage and was reversible within 24 h. In conclusion, fetal betamethasone exposure induces a gestational age-dependent decrease of synaptic density that is transient and more severe in younger fetuses. (C) 2004 Elsevier Ireland Ltd. All rights reserved.