Genetic Strain and Sex Differences in a Hyperoxia-Induced Mouse Model of Varying Severity of Bronchopulmonary Dysplasia

Bronchopulmonary dysplasia (BPD) is a disease prevalent in preterm babies with a need for supplemental oxygen resulting in impaired lung development and dysregulated vascularization. Epidemiological studies have shown that males are more prone to BPD and have a delayed recovery compared to females for reasons unknown. Here, we tried to recapitulate mild, moderate, and severe BPD, using two different strains of mice: CD1 (outbred) and C57BL/6 (inbred), in males and females. Aside from higher body weight in the CD1 strain, there were no other gross morphological differences with respect to alveolar development between the two strains. With respect to lung morphology after oxygen exposure, females had less injury with better preservation of alveolar chord length and decreased alveolar protein leak and inflammatory cells in the bronchoalveolar lavage fluid. In addition, housekeeping genes, which are routinely used as loading controls, were expressed differently in males and females. In the BPD mouse model, gonadotropin-releasing hormone was increased in females as compared to males. Specific microRNAs (miR146 and miR34a) were expressed differently in the sexes. In the severe BPD mouse model, administering miR146-mimic to males attenuated lung damage while administering miR-146 inhibitor to females increased pulmonary injury.