Proteomic analysis of sex differences in hyperoxic lung injury in neonatal mice

Sex-specific differences in the severity of bronchopulmonary dysplasia (BPD) are due to different susceptibility to hyperoxic lung injury, but the mechanism is unclear. In this study, neonatal male and female mouse pups (C57BL/6J) were exposed to hyperoxia and lung tissues were excised on postnatal day 7 for histological analysis and tandem mass tags proteomic analysis. We found that the lung sections from the male mice following postnatal hyperoxia exposure had increased alveolar simplification, significant aberrant pulmonary vascularization and arrest in angiogenesis compared with females. Comparison of differentially expressed proteins revealed 377 proteins unique to female and 425 unique to male as well as 750 proteins in both male and female. Bioinformatics analysis suggested that several differentially expressed proteins could contribute to the differences in sex-specific susceptibility to hyperoxic lung injury. Our results may help identify sex-specific biomarkers and therapeutic targets of BPD.