Repeated prenatal corticosteroid administration delays astrocyte and capillary tight junction maturation in fetal sheep.

Glucocorticoids are powerful regulators of cell differentiation and maturation. Their synthetic counterparts, the corticosteroids, are used widely in obstetric practice to enhance fetal lung maturation in cases of threatened preterm birth. Here we examined the effects of repeated corticosteroid administration on astrocyte and capillary tight junction development in the fetal sheep brain, selecting the corpus callosum for analysis. Pregnant ewes were given saline or betamethasone (0.5 mg/kg) at 104, 111, 118 and 124 days gestation. Lambs were delivered at term, terminally anaesthetized and transcardially perfused. Transverse semi-thin sections of the corpus callosum were cut and immuno-stained with antibody against glial fibrillary acidic protein (GFAP). Ultra-thin sections were examined in the electron microscope. The percentage area of GFAP staining was reduced in the corticosteroid-treated group compared to control (5.2 vs. 8.7%, P<0.05). The expression of GFAP in peri-capillary and parenchymal astrocytes was also reduced compared to control (peri-capillary: 3.0 vs. 9.5 microm2; parenchymal: 14.6 vs. 29.4 microm2, P<0.05). Furthermore, capillary tight junction maturation was delayed compared to control. Immature 'type II' junctions were more common in the corticosteroid-treated group (63 vs. 22%, P<0.05), whereas more mature 'type III' junctions were less common (27 vs. 65%, P<0.05). Our data suggest that repeated corticosteroids delay both astrocyte and capillary tight junction maturation. The implications for clinical practice are as yet unknown.