Antenatal dexamethasone administration increases fetal lung DNA synthesis and RNA and protein content in nitrofen-induced congenital diaphragmatic hernia in rats.
Antenatal glucocorticoids treatment has been shown to correct pulmonary immaturity. The thymidine analog bromodeoxyuridine (BrdU) is incorporated into S-phase cells and used as a marker of DNA synthesis. In this study, we investigated the effect of antenatal glucocorticoid administration on DNA synthesis and RNA and protein content in nitrofen-induced congenital diaphragmatic hernia (CDH) in rats to better understand the effect of antenatal glucocorticoids on CDH lung. The CDH model was induced in pregnant rats using nitrofen. Dexamethasone (0.25 mg/kg) was given on d 18.5 and 19.5 of gestation (term = 22 d). BrdU was administered 1 h before fetuses were killed on d 21, and detected by immunohistochemistry. DNA synthesis was evaluated by percentage of BrdU-incorporated nuclei (BrdU labeling index). Total RNA and soluble protein were extracted from another set of left lungs to measure RNA and protein content. BrdU labeling index and total RNA content were significantly decreased in CDH lung compared with control rats. Antenatal dexamethasone treatment significantly increased BrdU labeling index and RNA and protein content in the left CDH lung. Our findings of decreased DNA synthesis and decreased RNA and protein content in CDH lung suggest that lung growth and development are suppressed in hypoplastic CDH lung. Increased DNA synthesis and increased RNA and protein content in dexamethasone-treated CDH lung suggest that antenatal glucocorticoids may accelerate fetal lung growth and development in CDH.
Oue
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Children's Research Centre, Our Lady's Hospital for Sick Children, Dublin, Ireland.
Shima
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H
Guarino
N
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Puri
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P
D000818:Animals; D001973:Bromodeoxyuridine / Q000032:analysis; D004261:DNA Replication / Q000187:drug effects*; D003907:Dexamethasone / Q000494:pharmacology / Q000627:therapeutic use*; D005260:Female; D005325:Fetal Organ Maturity / Q000187:drug effects*; D006548:Hernia, Diaphragmatic / Q000139:chemically induced; D065630:Hernias, Diaphragmatic, Congenital; D008168:Lung / Q000002:abnormalities / Q000187:drug effects / Q000196:embryology* / Q000378:metabolism; D010647:Phenyl Ethers / Q000633:toxicity*; D011247:Pregnancy; D014176:Protein Biosynthesis; D012313:RNA / Q000096:biosynthesis*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013268:Stimulation, Chemical
D010647:Phenyl Ethers; D012313:RNA; D003907:Dexamethasone; D001973:Bromodeoxyuridine; C007350:nitrofen