Prenatal maternal lipopolysaccharide and mild newborn hyperoxia increase intrapulmonary airway but not vessel reactivity in a mouse model

Margaret E. Kuper-Sassé, Peter M. Macfarlane, Catherine A. Mayer, Richard J. Martin, Y. S. Prakash, Christina M. Pabelick, Thomas M. Raffay

Research output: Contribution to journalArticlepeer-review

Abstract

Maternal infection is a risk for preterm delivery. Preterm newborns often require supplemental oxygen to treat neonatal respiratory distress. Newborn hyperoxia exposure is associated with airway and vascular hyperreactivity, while the complications of maternal infection are variable. In a mouse model of prenatal maternal intraperitoneal lipopolysaccharide (LPS, embryonic day 18) with subsequent newborn hyperoxia (40% oxygen × 7 days) precision-cut living lung slices were used to measure intrapulmonary airway and vascular reactivity at 21 days of age. Hyperoxia increased airway reactivity to methacholine compared to room air controls. Prenatal maternal LPS did not alter airway reactivity in room air. Combined maternal LPS and hyperoxia exposures increased airway reactivity vs. controls, although maximal responses were diminished compared to hyperoxia alone. Vessel reactivity to serotonin did not significantly differ in hyperoxia or room air; however, prenatal maternal LPS appeared to attenuate vessel reactivity in room air. Following room air recovery, LPS with hyperoxia lungs displayed upregulated inflammatory and fibrosis genes compared to room air saline controls (TNFαR1, iNOS, and TGFβ). In this model, mild newborn hyperoxia increases airway but not vessel reactivity. Prenatal maternal LPS did not further increase hyperoxic airway reactivity. However, inflammatory genes remain upregulated weeks after recovery from maternal LPS and newborn hyperoxia exposures.

Original languageEnglish (US)
Article number195
JournalChildren
Volume8
Issue number3
DOIs
StatePublished - Mar 2021

Keywords

  • Airway hyperreactivity
  • Hyperoxia
  • Inflammation
  • Precision-cut lung slice
  • Vessel hyperreactivity

ASJC Scopus subject areas

  • Pediatrics, Perinatology, and Child Health

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