title: Lung maturity in esophageal atresia: Experimental and clinical study.
abstract: BACKGROUND
  Esophageal atresia and tracheoesophageal fistula (EA-TEF) survivors suffer respiratory morbidity of unclear pathogenesis. Defective lung morphogenesis has been described in the rat model. This study examined fetal lung growth and maturity in rats and patients with EA-TEF.
  
  
  METHODS
  Pregnant rats received either adriamycin or vehicle. Control and adriamycin-exposed lungs, with and without EA-TEF, were weighed and processed for RT-PCR, DNA quantification, immunofluorescence and immunoblot analysis of TTF1, VEGF, Sp-B, and α-sma. Twenty human lungs were also processed for immunofluorescence and Alcian-blue staining.
  
  
  RESULTS
  Lungs from fetuses with EA-TEF (E21) showed decreased total DNA; FGF7 and TTF1 mRNA expressions were upregulated at E15 and E18, respectively. Protein expression and immunofluorescent distribution of maturity markers were similar. Lungs from stillborns with EA-TEF showed decreased epithelial expression of Sp-B and VEGF whereas those from newborns tended to have less Sp-B and more VEGF and mucous glands.
  
  
  CONCLUSIONS
  The lungs of rats with EA-TEF were hypoplastic but achieved near-normal maturity. Stillborns with EA-TEF exhibited an apparently disturbed differentiation of the airway epithelium. Newborns with EA-TEF demonstrated subtle differences in the expression of differentiation markers, and increased number of mucous glands that could influence postnatal respiratory adaptation and explain some respiratory symptoms of EA-TEF survivors.
authors.affiliation: Department of Pediatric Surgery, Hospital Universitario La Paz, Madrid, Spain; Department of Congenital Malformations, INGEMM and IdiPaz Research Laboratory, Madrid, Spain; Faculty of Medicine, University of Porto, Porto, Portugal. Electronic address: catarina.fragoso@gmail.com.
authors.forename: Ana Catarina
authors.initials: AC
authors.lastname: Fragoso
authors.affiliation: Department of Pediatric Surgery, Hospital Universitario La Paz, Madrid, Spain; Department of Congenital Malformations, INGEMM and IdiPaz Research Laboratory, Madrid, Spain.
authors.forename: Leopoldo
authors.initials: L
authors.lastname: Martinez
authors.affiliation: Faculty of Medicine, University of Porto, Porto, Portugal.
authors.forename: José
authors.initials: J
authors.lastname: Estevão-Costa
authors.affiliation: Department of Pediatric Surgery, Hospital Universitario La Paz, Madrid, Spain; Department of Congenital Malformations, INGEMM and IdiPaz Research Laboratory, Madrid, Spain.
authors.forename: Juan A
authors.initials: JA
authors.lastname: Tovar
mesh_terms: D000818:Animals; D015415:Biomarkers / Q000378:metabolism; D004317:Doxorubicin; D004933:Esophageal Atresia / Q000139:chemically induced / Q000196:embryology* / Q000378:metabolism; D005260:Female; D005325:Fetal Organ Maturity; D006801:Humans; D008168:Lung / Q000196:embryology* / Q000378:metabolism; D011247:Pregnancy; D051381:Rats; D017207:Rats, Sprague-Dawley; D014138:Tracheoesophageal Fistula / Q000139:chemically induced / Q000196:embryology* / Q000378:metabolism
chemical_list: D015415:Biomarkers; D004317:Doxorubicin
keywords: adriamycin rat model; esophageal atresia; lung hypoplasia; lung maturity; newborn; tracheoesophageal fistula