Perinatal Inflammation and Decreases in miR29b‐1 Expression are Associated with Structural and Functional Pulmonary Deficits in Adult Mice

Abstract

BackgroundMaternal inflammation contributes to premature delivery. Premature infants routinely receive therapeutic oxygen and exhibit persistently diminished respiratory function into adulthood. The long term pulmonary consequences of perinatal inflammation are unclear.ObjectiveWe tested the hypothesis that a hostile perinatal environment induces fibrotic pathways resulting in pulmonary fibrosis.MethodsPregnant C3H/HeN mice were LPS or saline injected on embryonic day (E) 16. Offspring were placed in room air (RA) or 85% O2 for 14 d then returned to RA. PFTs, microCTs, molecular, and histological analyses were performed between E18 and 8 weeks of age.Main ResultsAlveolarization was most compromised in LPS/O2 exposed mice. Collagen staining and protein levels were increased and static‐compliance was decreased only in LPS/O2 exposed mice. 3‐D MicroCT reconstruction revealed increased tissue densies only in LPS/O2 mice. Development of fibrosis was associated with decreased miR29b‐1 expression and evidence of TGF‐β/Smad signaling during embryonic and early fetal lung development.ConclusionsSystemic maternal LPS administration induces a pro‐fibrotic response in fetal lung tissue that in combination with neonatal hyperoxia exposure depresses miR29b‐1 and activates of pro‐fibrotic pathways, resulting in impaired alveolarization, fibrosis, and compromised function in adulthood.