Selenium modulates perinatal pulmonary vascular responses to hyperoxia.

Mammalian lung development depends on growth and differentiation of both endothelial and epithelial subpopulations to allow for gas exchange. Premature infants are born with developmentally immature lungs and often require supplemental oxygen (O2) to survive. Excess O2 can lead to oxidative stress, which damages the pulmonary vasculature and contributes to bronchopulmonary dysplasia (BPD). Selenoproteins are critical for detoxifying reactive oxygen intermediates. Selenoprotein production is dependent upon adequate selenium (Se) levels. Using a model of perinatal Se deficiency in C3H/HeN mice, we assessed the impacts of Se status and postnatal O2 exposure on lung vascular development at P14. Furthermore, we compared the transcription of endothelial subpopulation and endothelial-to-mesenchymal transition markers in control and O2-exposed lungs using RNAseq from P3 mouse lungs. Transcriptional changes identified from RNAseq were validated using qRT-PCR. Se deficiency and O2 exposure independently decreased the number of pulmonary arterioles at P14. In addition, Se deficiency and O2 exposure decreased transcription of the general capillary endothelial cell markers Aplnr and Ptprb. These findings support the hypothesis that Se deficiency confers susceptibility to hyperoxic pulmonary vascular maldevelopment as is seen in BPD.NEW & NOTEWORTHY The data demonstrate a reduction in the number of pulmonary blood vessels in the setting of perinatal selenium deficiency that is exacerbated by postnatal O2 exposure. RNA analysis of peripheral lung tissue indicated that changes in vessel density were associated with alterations in the transcription of genes responsible for maintenance of endothelial phenotype and homeostasis in our experimental bronchopulmonary dysplasia model.