Maternal Betamethasone and Chorioamnionitis Induce Different Collagenases during Lung Maturation in Fetal Sheep

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.