A rat model for arrest of alveolarization induced by antenatal endotoxin administration

Pediatr Res. 2006 Mar;59(3):396-400. doi: 10.1203/01.pdr.0000200796.86858.ca.


A possible association between intrauterine inflammation and impairments of lung development has been suggested. The purpose of this study is to determine the influence of a potent proinflammatory agent, intra-amniotic lipopolysaccharide (LPS), on lung development. At 21 d gestation, an intra-amniotic injection of 1 microg LPS was administered to two subgroups of WKAH rats. One subgroup received only LPS and the other received LPS plus a fetal intraperitoneal dose of 0.25 microg granulocyte-colony stimulating factor (hrG-CSF) to produce peripheral blood neutrophilia. A third subgroup received hrG-CSF only, and a control group received maternal intraamniotic and fetal intraperitoneal normal saline. All pups were delivered by cesarean section at 22 d (term, 22.5 d) and maintained under identical conditions. Left upper lungs were obtained for morphometric analysis at 1, 3, 7, 14, 21, 45, and 60 d of age. Morphometric analysis indicated that changes in alveolar surface density (Sv), average alveolar radius (r), and numerical density of alveoli (nv) all showed that there were fewer and larger alveoli in rat lungs that had been exposed to LPS, but not to hrG-CSF alone or saline. LPS-exposed alveoli showed fewer secondary septa, suggesting an arrest of alveolarization. No destructive changes were observed in any alveoli. We concluded that these changes could be caused purely by intra-amniotic LPS. These abnormalities closely mimic those of new bronchopulmonary dysplasia. The LPS damage model may be applicable to further studies of the pathophysiology of new BPD.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Animals, Newborn
  • Disease Models, Animal
  • Endotoxins / immunology
  • Endotoxins / pharmacology*
  • Female
  • Fetus / drug effects*
  • Fetus / immunology
  • Gestational Age
  • Pregnancy
  • Pregnancy Outcome
  • Pulmonary Alveoli* / anatomy & histology
  • Pulmonary Alveoli* / drug effects
  • Pulmonary Alveoli* / embryology
  • Pulmonary Alveoli* / immunology
  • Rats


  • Endotoxins