Repeated Intrauterine Exposures to Inflammatory Stimuli Attenuated Transforming Growth Factor-beta Signaling in the Ovine Fetal Lung

Jennifer J. P. Collins, Suhas G. Kallapur, Christine L. Knox, Matthew W. Kemp, Elke Kuypers, Luc J. I. Zimmermann, John P. Newnham, Alan H. Jobe, Boris W. Kramer*

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review


Background: Bronchopulmonary dysplasia (BPD) is one of the most common complications after preterm birth and is associated with intrauterine exposure to bacteria. Transforming growth factor-beta (TGF beta) is implicated in the development of BPD. Objectives: We hypothesized that different and/or multiple bacterial signals could elicit divergent TGF beta signaling responses in the developing lung. Methods: Time-mated pregnant Merino ewes received an intra-amniotic injection of lipopolysaccharide (LPS) and/or Ureaplasma parvum serovar 3 (UP) at 117 days' and/or 121/122 days' gestational age (GA). Controls received an equivalent injection of saline and or media. Lambs were euthanized at 124 days' GA (term = 150 days' GA). TGF beta 1, TGF beta 2, TGF beta 3, TGF beta receptor (R) 1 and TGF beta R2 protein levels, Smad2 phosphorylation and elastin deposition were evaluated in lung tissue. Results: Total TGF beta 1 and TGF beta 2 decreased by 24 and 51% after combined UP+LPS exposure, whereas total TGF beta 1 increased by 31% after 7 days' LPS exposure but not after double exposures. Alveolar expression of TGF beta R2 decreased 75% after UP, but remained unaltered after double exposures. Decreased focal elastin deposition after single LPS exposure was prevented by double exposures. Conclusions: TGF beta signaling components and elastin responded differently to intrauterine LPS and UP exposure. Multiple bacterial exposures attenuated TGF beta signaling and normalized elastin deposition.
Original languageEnglish
Pages (from-to)49-55
Issue number1
Publication statusPublished - 2013


  • Neonatal outcome
  • Lung development
  • Intrauterine infection
  • Chorioamnionitis
  • Bronchopulmonary dysplasia

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