title: Prenatal glucocorticoids improve lung morphology and partially restores surfactant mRNA expression in lambs with diaphragmatic hernia undergoing fetal tracheal occlusion.
abstract: In fetal sheep with surgically created diaphragmatic hernia (DH), tracheal occlusion (TO) can restore lung growth but does not ameliorate the increase in inter-alveolar wall thickness (T(W)). We determined whether prenatal exposure to glucocorticoids (GC) could reduce T(w) in fetuses with DH undergoing TO. At 65 days of gestation, DH was created in 12 fetal sheep, and TO subsequently performed at 110 days (DH/TO). Six of these fetuses were exposed to betamethasone (DH/TO + GC; 0.5 mg/kg; maternal, IM) 48 hr before delivery; Sham operated fetuses (n = 7) served as controls. At 139 days, we measured alveolar surface density (S(V)), parenchymal tissue fraction, T(W), alveolar type 2 (AE2) cell density and lung surfactant protein (SP) mRNA expression. Prenatal GC decreased T(W) and S(V) by 33% and 27% respectively, and increased fixed lung volume (by 55%), AE2 cell density and partially restored SPmRNA expression. Our data indicate that prenatal exposure to GC can reverse some of the negative effects of prolonged fetal TO. We hypothesize that a GC-induced reduction in lung liquid volume during TO contributes, in part, to the observed increase in AE2 cell density and SPmRNA expression.
authors.affiliation: The Children's Institute for Surgical Science and the Center for Fetal Diagnosis and Treatment, The Children's Hospital of Philadelphia, Philadelphia, Pennsylvania, USA. daveym@email.chop.edu
authors.forename: Marcus G
authors.initials: MG
authors.lastname: Davey
authors.forename: Enrico
authors.initials: E
authors.lastname: Danzer
authors.forename: Uwe
authors.initials: U
authors.lastname: Schwarz
authors.forename: Lauren
authors.initials: L
authors.lastname: Robinson
authors.forename: Shincy
authors.initials: S
authors.lastname: Shegu
authors.forename: N Scott
authors.initials: NS
authors.lastname: Adzick
authors.forename: Alan W
authors.initials: AW
authors.lastname: Flake
authors.forename: Holly L
authors.initials: HL
authors.lastname: Hedrick
mesh_terms: D000818:Animals; D015153:Blotting, Western; D002452:Cell Count; D004195:Disease Models, Animal; D005260:Female; D018507:Gene Expression Regulation, Developmental / Q000187:drug effects*; D005865:Gestational Age; D005938:Glucocorticoids / Q000627:therapeutic use*; D006548:Hernia, Diaphragmatic / Q000378:metabolism* / Q000473:pathology; D007150:Immunohistochemistry; D008168:Lung / Q000187:drug effects / Q000196:embryology / Q000378:metabolism; D008171:Lung Diseases / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control; D011247:Pregnancy; D011295:Prenatal Care; D011663:Pulmonary Surfactants / Q000378:metabolism*; D012333:RNA, Messenger / Q000235:genetics*; D012756:Sheep; D014135:Tracheal Stenosis / Q000378:metabolism*
chemical_list: D005938:Glucocorticoids; D011663:Pulmonary Surfactants; D012333:RNA, Messenger