Maternal betamethasone and chorioamnionitis induce different collagenases during lung maturation in fetal sheep

Neonatology. 2008;94(2):79-86. doi: 10.1159/000115949. Epub 2008 Feb 11.

Abstract

Background: Fetal lung maturation occurs after both maternal corticosteroid administration and chorioamnionitis. The effectors of this antenatally-induced lung maturation are not understood. Matrix metalloproteinases (MMPs) 2 and 9 are type-IV collagenases that can degrade alveolar basement membranes.

Objectives: We hypothesized that the structural changes of lung maturation by both antenatal corticosteroid treatment and chorioamnionitis would be associated with increases in these MMPs.

Methods: 64 pregnant ewes were randomly assigned to one of four treatment groups: intra-amniotic injection of 10 mg endotoxin, maternal intramuscular injection of 0.5 mg/kg betamethasone, both treatments combined or saline-treated controls. We quantified MMP-2 which is derived from connective tissue and MMP-9 which is predominantly derived from neutrophils in fetal lung fluid of lambs after maternal corticosteroid therapy and induction of chorioamnionitis and the combination of both therapies given at 109-111 days' gestational age with delivery 1, 5 or 15 days later.

Results: Betamethasone, endotoxin and the combined treatments increased both surfactant pool size, lung gas volume and reduced alveolar wall thickness at 15 days. MMP-2 concentration was increased after betamethasone. MMP-9 concentration increased after endotoxin-induced chorioamnionitis but decreased by the combined treatments.

Conclusion: Lung maturation via different pathways may use different forms of collagenases for remodelling lung structure.

MeSH terms

  • Amnion / drug effects
  • Animals
  • Animals, Newborn
  • Betamethasone / pharmacology*
  • Chorioamnionitis / chemically induced
  • Chorioamnionitis / enzymology*
  • Chorioamnionitis / pathology
  • Disease Models, Animal
  • Drug Interactions
  • Endotoxins / pharmacology
  • Enzyme Induction
  • Escherichia coli / immunology
  • Female
  • Fetus / abnormalities
  • Fetus / drug effects*
  • Fetus / enzymology
  • Glucocorticoids / pharmacology*
  • Injections, Intramuscular
  • Maternal Exposure
  • Matrix Metalloproteinase 2 / biosynthesis*
  • Matrix Metalloproteinase 9 / biosynthesis*
  • Pregnancy
  • Pulmonary Alveoli / abnormalities
  • Pulmonary Alveoli / drug effects
  • Pulmonary Alveoli / enzymology
  • Pulmonary Surfactants / metabolism
  • Sheep

Substances

  • Endotoxins
  • Glucocorticoids
  • Pulmonary Surfactants
  • Betamethasone
  • Matrix Metalloproteinase 2
  • Matrix Metalloproteinase 9