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Bronchiolar remodeling in adult mice following neonatal exposure to hyperoxia: relation to growth
Megan O'Reilly1, Philip M Hansbro, Jay C Horvat
1Department of Anatomy and Developmental Biology, Monash University, Melbourne, Victoria, 3800, Australia.
Insights
Neonatal hyperoxia alters developing bronchioles, impacting adult lung function. Growth restriction modifies these effects, potentially explaining poor lung health in ex-preterm individuals.
Area of Science:
- Pulmonary Medicine
- Neonatology
- Developmental Biology
Background:
- Prolonged supplemental oxygen in preterm infants is linked to later-life impaired lung function.
- Neonatal hyperoxia is suspected to cause persistent changes in developing bronchioles, though effects on alveolarization are better understood.
- The impact of neonatal hyperoxia on bronchiolar development requires further investigation.
Purpose of the Study:
- To investigate the hypothesis that neonatal hyperoxia remodels bronchiolar walls, leading to altered adult lung function.
- To examine the specific effects of hyperoxia on bronchiolar structure and cellular composition.
- To determine how concomitant growth restriction influences hyperoxia-induced lung changes.
Main Methods:
- C57BL/6J mice were exposed to 65% oxygen from birth to postnatal day 7 (P7), with one group experiencing growth restriction (HE+GR) and another without (HE).
- A control group inhaled room air.
- Lung function testing and histological analysis of bronchiolar walls were performed at postnatal day 56 (P56).
Main Results:
- At P56, HE mice showed fewer Clara cells and more ciliated cells, with ~25% less collagen in bronchiolar walls compared to controls.
- HE+GR mice had ~13% more collagen in bronchiolar walls than controls.
- Male HE and HE+GR mice exhibited thicker bronchiolar epithelium and altered lung function (increased dynamic compliance in HE, decreased in HE+GR).
Conclusions:
- Neonatal hyperoxia induces significant remodeling of the bronchiolar wall.
- These structural changes affect lung function in adult male mice, with effects modulated by growth restriction.
- Findings offer a potential explanation for the observed poor lung function in ex-preterm children and adults.
Abstract:
Preterm infants who receive supplemental oxygen for prolonged periods are at increased risk of impaired lung function later in life. This suggests that neonatal hyperoxia induces persistent changes in small conducting airways (bronchioles). Although the effects of neonatal hyperoxia on alveolarization are well documented, little is known about its effects on developing bronchioles. We hypothesized that neonatal hyperoxia would remodel the bronchiolar walls, contributing to altered lung function in adulthood. We studied three groups of mice (C57BL/6J) to postnatal day 56 (P56; adulthood) when they either underwent lung function testing or necropsy for histological analysis of the bronchiolar wall. One group inhaled 65% O2 from birth until P7, after which they breathed room air; this group experienced growth restriction (HE+GR group). We also used a group in which hyperoxia-induced GR was prevented by dam rotation (HE group). A control group inhaled room air from birth. At P56, the bronchiolar epithelium of HE mice contained fewer Clara cells and more ciliated cells, and the bronchiolar wall contained ∼25% less collagen than controls; in HE+GR mice the bronchiolar walls had ∼13% more collagen than controls. Male HE and HE+GR mice had significantly thicker bronchiolar epithelium than control males and altered lung function (HE males: greater dynamic compliance; HE+GR males: lower dynamic compliance). We conclude that neonatal hyperoxia remodels the bronchiolar wall and, in adult males, affects lung function, but effects are altered by concomitant growth restriction. Our findings may partly explain the reports of poor lung function in ex-preterm children and adults.
