Neonatal Selenium Deficiency Decreases Selenoproteins in the Lung and Impairs Pulmonary Alveolar Development

Abstract

Decreased selenium (Se) levels during childhood and infancy are associated with worse respiratory health. Se is biologically active after incorporation into Se-containing antioxidant enzymes (AOE) and proteins. It is unknown how decreased maternal Se during pregnancy and lactation impacts neonatal pulmonary selenoproteins, growth, and lung development. Using a model of neonatal Se deficiency that limits Se intake to the dam during pregnancy and lactation, we evaluated which neonatal pulmonary selenoproteins are decreased in both the saccular (postnatal day 0, P0) and early alveolar (postnatal day 7, P7) stages of lung development. We found that Se deficient (SeD) pups weigh less and exhibit impaired alveolar development compared to Se sufficient (SeS) pups at P7. The activity levels of glutathione peroxidase (GPx) and thioredoxin reductase (Txnrd) were decreased at P0 and P7 in SeD lungs compared to SeS lungs. Protein content of GPx1, GPx3 and Txnrd1 were decreased in SeD lungs at P0 and P7, whereas Txnrd2 content was unaltered compared to SeS controls. The expression of NRF-2 dependent genes and several non-Se containing AOE were similar between SeS and SeD lungs. SeD lungs exhibited a decrease in selenoprotein N, an endoplasmic reticulum protein implicated in alveolar development, at both time points. We conclude that exposure to Se deficiency during pregnancy and lactation impairs weight gain and lung growth in offspring. Our data identify multiple selenoproteins in the neonatal lung that are vulnerable to decreased Se intake, which may impact oxidative stress and cell signaling under physiologic conditions as well as after oxidative stressors.

Selenium Deficiency Exacerbates Hyperoxia-Induced Lung Injury in Newborn C3H/HeN Mice

“…In the present study, litter sizes and weights were not different at birth through to PN14 between C3H/HeN SeD and SeS pups. These data differ from our previously reported findings in the C57Bl/6J strain, in which we observed modestly lower weights in SeD pups, beginning at PN7 and persisting through adulthood [33]. Se-dependent deficits in lung development were similar in both strains of mice.…”

“…Hawker et al [31] characterized the effects of hyperoxia exposure in the same rat model and Kim et al demonstrated the beneficial effects of Se repletion on lung development in hyperoxia-exposed newborn rats [32]. Building upon our previous study in Se-deficient newborn C57Bl/6J mice, which demonstrated impaired lung development and alveolarization [33], the present investigation indicates that the effects of Se status are strain-independent. Our data further supports the finding that Se status independently modifies perinatal lung development and establishes an exaggerated phenotype under hyperoxia in C3H/HeN mice.…”

Oxidative Stress Induced by Selenium Deficiency Contributes to Inflammation, Apoptosis and Necroptosis in the Lungs of Calves

“…Lungs are important organs for respiration in mammals, and many studies have shown that Se contributes to lung development [ 17 , 18 ]. Se deficiency is associated with worse respiratory health in humans during childhood and infancy, while Se deficiency enhances the susceptibility of neonatal lungs to injury [ 19 ]. When the antioxidant capacity of the lungs is reduced, higher oxygen exposure compared with other organs is more likely to cause oxidative stress.…”