title: Effects of maternal antenatal glucocorticoid treatment on apoptosis in the ovine fetal cerebral cortex.
abstract: We examined the effects of single and multiple maternal glucocorticoid courses on apoptosis in the cerebral cortices of ovine fetuses (CC). Ewes received single dexamethasone or placebo courses at 104-106 or 133-135 days or multiple courses between 76-78 and 104-106 days gestation. In the single-course groups, ewes received four 6 mg dexamethasone or placebo injections every 12 hr for 48 hr. Multiple-course groups received the same treatment once per week for 5 weeks. Neuronal and nonneuronal apoptotic cell numbers per square millimeter were determined with TUNEL and NeuN staining and with caspase-3 enzyme activity on CC tissues harvested at 106-108 (70%) or 135-137 (90%) days of gestation. Apoptotic cell numbers and caspase-3 activity were 50% lower (P < 0.02) after single placebo courses at 90% than 70% gestation; 90% of apoptotic cells were (P < 0.01) nonneuronal at both ages. Nonneuronal apoptotic cells and caspase-3 activity were 40% and 20% lower (P < 0.02) after single dexamethasone than placebo courses at 70%, but not 90%, gestation. Caspase-3 activity was 20% lower (P < 0.01) after multiple dexamethasone than placebo courses, but apoptotic cell number did not differ. We conclude that nonneuronal apoptosis represents the major form of apoptosis in the CC at both 70% and 90% of gestation. Apoptosis in nonneuronal cells decreases with maturity and after a single course of dexamethasone at 70%, but not at 90%, gestation and not after multiple courses at 70% gestation. We speculate that a single course of glucocorticoids exerts maturational changes on the rate of apoptosis in the cerebral cortex of preterm ovine fetuses.
authors: The Warren Alpert Medical School of Brown University, Providence, Rhode Island 02905, USA.
authors: Shadi N
authors: SN
authors: Malaeb
authors: Virginia
authors: V
authors: Hovanesian
authors: Matthew D
authors: MD
authors: Sarasin
authors: Silvia M
authors: SM
authors: Hartmann
authors: Grazyna B
authors: GB
authors: Sadowska
authors: Barbara S
authors: BS
authors: Stonestreet
mesh_terms: D000367:Age Factors; D000704:Analysis of Variance; D000818:Animals; D000886:Anthropometry / Q000379:methods; D017209:Apoptosis / Q000187:drug effects*; D053148:Caspase 3 / Q000378:metabolism; D002452:Cell Count / Q000379:methods; D002540:Cerebral Cortex / Q000473:pathology*; D053938:DNA Fragmentation / Q000187:drug effects; D003907:Dexamethasone; D004622:Embryo, Mammalian; D005260:Female; D005938:Glucocorticoids; D020287:In Situ Nick-End Labeling / Q000379:methods; D008297:Male; D009474:Neurons / Q000187:drug effects*; D010751:Phosphopyruvate Hydratase / Q000378:metabolism; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects / Q000139:chemically induced / Q000473:pathology / Q000503:physiopathology; D011897:Random Allocation; D012756:Sheep
chemical_list: D005938:Glucocorticoids; D003907:Dexamethasone; D053148:Caspase 3; D010751:Phosphopyruvate Hydratase