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Sex-related differences in long-term pulmonary outcomes of neonatal hyperoxia in mice
Fumihiko Namba1, Ryo Ogawa1, Masato Ito1
1a Department of Pediatrics, Saitama Medical Center , Saitama Medical University , Kawagoe , Saitama , Japan.
Insights
Neonatal hyperoxia exposure differentially impacts adult male and female mouse lungs. Males showed increased respiratory resistance, while females experienced delayed alveolarization, highlighting sex-specific long-term pulmonary outcomes.
Area of Science:
- Pulmonary Medicine
- Neonatal Research
- Sex Differences in Disease
Background:
- Premature infants often require hyperoxia, increasing risk for bronchopulmonary dysplasia (BPD).
- BPD exhibits sex-specific variations in development and severity.
- Mechanisms underlying sex-related BPD differences remain underexplored.
Purpose of the Study:
- To investigate the long-term, sex-specific pulmonary effects of neonatal hyperoxia in adult mice.
- To understand how early-life oxygen exposure influences lung function and structure differently in males and females.
Main Methods:
- Newborn mice were exposed to 95% oxygen (hyperoxia) for 96 hours, followed by recovery to adulthood (8 weeks).
- Lung tissues were analyzed at various time points (4 days, 14 days, 8 weeks).
- Pulmonary function, airway hyper-responsiveness, and lung structure were assessed in adult mice.
Main Results:
- Neonatal hyperoxia did not affect body weight, muscarinic receptor gene expression, or bronchiolar thickness in adult mice.
- Male mice exposed to neonatal hyperoxia exhibited increased respiratory resistance and decreased methacholine sensitivity.
- Female mice exposed to neonatal hyperoxia showed delayed alveolarization.
Conclusions:
- Neonatal hyperoxia has distinct long-term effects on pulmonary outcomes in adult female and male mice.
- These findings underscore the importance of considering sex as a biological variable in BPD research and treatment.
Aim:
Premature infants are often exposed to hyperoxia to maintain adequate oxygenation, which may lead to the development of bronchopulmonary dysplasia (BPD). Sex-specific differences exist in the development and severity of BPD. Only a few studies have examined the mechanisms underlying these sex-related differences. The aim of the present study is to examine the sex-related long-term effects of neonatal hyperoxia on the lungs of adult mice.
Materials And Methods:
Newborn mice were exposed to 95% oxygen (hyperoxia) for 96 hours and were allowed to recover in room air to adulthood (8 weeks of age). Lung tissues were excised at 4 days, 14 days, or 8 weeks of age. Short-term effects of neonatal hyperoxia on the mouse lung and sex-related differences in pulmonary function, airway hyper-responsiveness, and lung structure in adult mice were assessed.
Results:
Neonatal hyperoxia was found to have no differential effect on body weight, muscarinic acetylcholine receptor gene expression, or bronchiolar epithelial thickness in adult mice. Respiratory resistance was increased and sensitivity to methacholine was decreased in male adult mice following exposure to neonatal hyperoxia, whereas delayed alveolarization was observed in female adult mice following exposure to neonatal hyperoxia.
Conclusions:
The findings of the present study demonstrate that neonatal hyperoxia differentially affects pulmonary outcome in female and male adult mice.
