A single course of prenatal betamethasone in the rat alters postnatal brain cell proliferation but not apoptosis.
The aim of this study was to determine the effects of a clinically relevant single course of prenatal betamethasone in the rat on growth parameters with particular reference to brain cell proliferation and apoptosis. We report that administration of 170 microg kg-1 betamethasone twice within 4 h to E20 pregnant rats conveys moderate somatic growth retardation. Further, using a measure of brain cell proliferation independent of blood-brain barrier (BBB) permeability, we demonstrate for the first time that betamethasone is chronically anti-proliferative to brain cells without inducing caspase-3-mediated apoptosis. More importantly we show that there is a significant and sexually divergent rebound of neural proliferation which occurs earlier in males than in females and continues until at least 21 days of postnatal life. BBB permeability to [3H]thymidine was significantly increased by steroid treatment re-iterating the fact that tracer studies not correcting for BBB permeability, such as bromodeoxyuridine (BrdU), may be questionable in this type of study. Further, prenatal steroid treatment did not alter postnatal corticosterone levels. In summary we show that prenatal betamethasone conveys significant and long-lasting side effects and that its human clinical application in preterm labour needs more careful consideration as compared to the relative ease with which it is prescribed today.
Scheepens
Arjan
A
Department of Pediatrics, GROW Research Institute, University of Maastricht, 6202 AZ Maastricht, The Netherlands.
van de Waarenburg
Marjo
M
van den Hove
Daniël
D
Blanco
Carlos E
CE
D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D001623:Betamethasone / Q000494:pharmacology*; D001724:Birth Weight; D001812:Blood-Brain Barrier / Q000502:physiology; D001921:Brain / Q000166:cytology* / Q000187:drug effects* / Q000254:growth & development; D053148:Caspase 3; D020169:Caspases / Q000378:metabolism; D002455:Cell Division / Q000187:drug effects; D003345:Corticosterone / Q000097:blood; D005260:Female; D005938:Glucocorticoids / Q000494:pharmacology*; D006257:Head / Q000033:anatomy & histology / Q000254:growth & development; D006943:Hyperglycemia / Q000139:chemically induced; D008098:Litter Size; D009929:Organ Size; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects; D051381:Rats; D011916:Rats, Inbred F344; D015996:Survival Rate
D005938:Glucocorticoids; D001623:Betamethasone; C505407:CASP3 protein, human; C505410:Casp3 protein, rat; D053148:Caspase 3; D020169:Caspases; D003345:Corticosterone