Maternally administered dexamethasone transiently increases apoptosis in lungs of fetal rats.
In late gestation, morphological maturation of fetal lung includes septal thinning of potential airspaces, a process accelerated by exogenous glucocorticoids. Apoptosis occurs in normal fetal lung. Glucocorticoids increase apoptosis in several tissues. The authors hypothesized that exogenous glucocorticoids would increase apoptosis in fetal lung, primarily in the interstitium. They administered dexamethasone (DEX), 1 mg/kg, or vehicle (Control) to pregnant rats at 19 days of gestation. Fetuses were delivered at 3, 7, 12, or 24 hours post injection. DEX decreased fetal body weight and lung weight, DNA, and protein 12 hours post injection. Using the terminal deoxynucleotide transferase-mediated dUTP nick-end labeling (TUNEL) reaction to label apoptotic cells in lung, they calculated an apoptotic index (AI, apoptotic cells/1000 total cells) for each fetus. Average DEX AI (3.6+/-2.6, mean+/-SD) was greater than Control (1.7+/-0.5) (P<.02). All DEX AIs were greater than Control AIs at 3, 7, and 12 hours, but were similar to Controls at 24 hours post injection. Apoptotic cells appeared to be interstitial, based on colocalization with vimentin staining. Presence of apoptotic cells was confirmed by electron microscopy and detection of the nucleosomal ladder pattern on DNA electrophoresis. The authors conclude that maternal administration of dexamethasone increases apoptosis in fetal lung, primarily in the interstitium. They speculate that apoptosis may contribute to morphological fetal lung maturation induced by endogenous glucocorticoids.
Cardiovascular Research Institute and Department of Pediatrics, University of California, San Francisco, USA. LouisS@intra.niddk.nih.gov
Louis M
LM
Scavo
Valerie
V
Newman
Robert
R
Ertsey
Cheryl J
CJ
Chapin
Joseph A
JA
Kitterman
D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D002452:Cell Count; D004247:DNA / Q000032:analysis; D003907:Dexamethasone / Q000008:administration & dosage / Q000633:toxicity*; D005260:Female; D020567:Fetal Weight / Q000187:drug effects; D005333:Fetus / Q000187:drug effects* / Q000473:pathology; D005865:Gestational Age; D005938:Glucocorticoids / Q000008:administration & dosage / Q000633:toxicity*; D020287:In Situ Nick-End Labeling; D007273:Injections, Intramuscular; D008168:Lung / Q000187:drug effects* / Q000196:embryology / Q000473:pathology; D018811:Maternal Exposure; D009929:Organ Size / Q000187:drug effects; D038081:Organogenesis / Q000187:drug effects*; D011247:Pregnancy; D051381:Rats
D005938:Glucocorticoids; D003907:Dexamethasone; D004247:DNA