Administration of antenatal glucocorticoids and postnatal surfactant ameliorates respiratory distress syndrome-associated neonatal lethality in Erk3(-/-) mouse pups

Pediatr Res. 2014 Jul;76(1):24-32. doi: 10.1038/pr.2014.54. Epub 2014 Apr 14.


Background: Respiratory distress syndrome (RDS) persists as a prevalent cause of infant morbidity and mortality. We have previously demonstrated that deletion of Erk3 results in pulmonary immaturity and neonatal lethality. Using RNA sequencing, we identified corticotrophin releasing hormone (CRH) and surfactant protein B (SFTPB) as potential molecular mediators of Erk3-dependent lung maturation. In this study, we characterized the impact of antenatal glucocorticoids and postnatal surfactant on neonatal survival of Erk3 null mice.

Methods: In a double crossover design, we administered dexamethasone (dex) or saline to pregnant dams during the saccular stage of lung development, followed by postnatal surfactant or saline via inhalation intubation. Survival was recorded, and detailed lung histological analysis and staining for CRH and SFTPB protein expression were performed.

Results: Without treatment, Erk3 null pups die within 6 h of birth with reduced aerated space, impaired thinning of the alveolar septa, and abundant glycogen stores, as described in human RDS. The administration of dex and surfactant improved RDS-associated lethality of Erk3(-/-) pups and partially restored functional fetal lung maturation by accelerating the downregulation of pulmonary CRH and partially rescuing the production of SFTPB.

Conclusion: These findings emphasize that Erk3 is integral to terminal differentiation of type II cells, SFTPB production, and fetal pulmonary maturity.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Differentiation
  • Corticotropin-Releasing Hormone / metabolism
  • Cross-Over Studies
  • Dexamethasone / administration & dosage
  • Dexamethasone / chemistry
  • Disease Models, Animal
  • Female
  • Glucocorticoids / administration & dosage*
  • Glucocorticoids / chemistry
  • Lung / embryology*
  • Lung / growth & development*
  • Lung / pathology
  • Male
  • Maternal Exposure
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Mitogen-Activated Protein Kinase 6 / genetics
  • Pregnancy
  • Pregnancy, Animal
  • Pulmonary Surfactant-Associated Protein B / metabolism
  • Pulmonary Surfactants / administration & dosage*
  • Respiratory Distress Syndrome, Newborn / drug therapy*
  • Respiratory Distress Syndrome, Newborn / genetics
  • Time Factors


  • Glucocorticoids
  • Pulmonary Surfactant-Associated Protein B
  • Pulmonary Surfactants
  • Dexamethasone
  • Corticotropin-Releasing Hormone
  • Mapk6 protein, mouse
  • Mitogen-Activated Protein Kinase 6