Treatments with supplemental oxygen in premature infants can impair lung development, leading to bronchopulmonary dysplasia (BPD). Although a stage-specific alteration of lung lipidome occurs during postnatal lung development, whether neonatal hyperoxia, a known mediator of BPD in rodent models, changes lipid profiles in mouse lungs is still to be elucidated. To answer this question, newborn mice were exposed to hyperoxia for 3 days and allowed to recover in normoxia until postnatal day (pnd) 7 and pnd14, time-points spanning the peak stage of alveologenesis. A total of 2263 lung lipid species were detected by liquid chromatography-mass spectrometry, covering 5 lipid categories and 18 lipid subclasses. The most commonly identified lipid species were glycerophospholipids, followed by sphingolipids and glycerolipids. In normoxic conditions, certain glycerophospholipid and glycerolipid species augmented at pnd14 compared to pnd7. At pnd7, hyperoxia generally increased glycerophospholipid, sphingolipid, and glycerolipid species. Hyperoxia increased NADPH, acetyl CoA, and citrate acid but reduced carnitine and acyl carnitine. Hyperoxia increased oxidized glutathione but reduced catalase. These changes were not apparent at pnd14. Hyperoxia reduced docosahexaenoic acid and arachidonic acid at pnd14 but not at pnd7. Altogether, the lung lipidome changes throughout alveolarization. Neonatal hyperoxia alters the lung lipidome, which may contribute to alveolar simplification and dysregulated vascular development.
Keywords: bronchopulmonary dysplasia; lipidomics; lung alveolarization; metabolomics; oxidative stress.