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

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 p...

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Main Authors: Laura G. Sherlock, William C. McCarthy, Maya R. Grayck, Mack Solar, Andres Hernandez, Lijun Zheng, Cassidy Delaney, Trent E. Tipple, Clyde J. Wright, Eva S. Nozik
Format: Article
Language:English
Published: MDPI AG 2022-12-01
Series:Antioxidants
Subjects:
Online Access:https://www.mdpi.com/2076-3921/11/12/2417
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author Laura G. Sherlock
William C. McCarthy
Maya R. Grayck
Mack Solar
Andres Hernandez
Lijun Zheng
Cassidy Delaney
Trent E. Tipple
Clyde J. Wright
Eva S. Nozik
author_facet Laura G. Sherlock
William C. McCarthy
Maya R. Grayck
Mack Solar
Andres Hernandez
Lijun Zheng
Cassidy Delaney
Trent E. Tipple
Clyde J. Wright
Eva S. Nozik
author_sort Laura G. Sherlock
collection DOAJ
description 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.
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spelling doaj.art-e83c1785e9a34dd0b1b4a53e485f58c72023-11-24T12:57:44ZengMDPI AGAntioxidants2076-39212022-12-011112241710.3390/antiox11122417Neonatal Selenium Deficiency Decreases Selenoproteins in the Lung and Impairs Pulmonary Alveolar DevelopmentLaura G. Sherlock0William C. McCarthy1Maya R. Grayck2Mack Solar3Andres Hernandez4Lijun Zheng5Cassidy Delaney6Trent E. Tipple7Clyde J. Wright8Eva S. Nozik9Perinatal Research Center, Department of Pediatrics, University of Colorado Anschutz Medical Campus, Aurora, CO 80045, USAPerinatal Research Center, Department of Pediatrics, University of Colorado Anschutz Medical Campus, Aurora, CO 80045, USAPerinatal Research Center, Department of Pediatrics, University of Colorado Anschutz Medical Campus, Aurora, CO 80045, USAPerinatal Research Center, Department of Pediatrics, University of Colorado Anschutz Medical Campus, Aurora, CO 80045, USAPerinatal Research Center, Department of Pediatrics, University of Colorado Anschutz Medical Campus, Aurora, CO 80045, USAPerinatal Research Center, Department of Pediatrics, University of Colorado Anschutz Medical Campus, Aurora, CO 80045, USAPerinatal Research Center, Department of Pediatrics, University of Colorado Anschutz Medical Campus, Aurora, CO 80045, USADepartment of Pediatrics, University of Oklahoma College of Medicine, Oklahoma City, OK 73104, USAPerinatal Research Center, Department of Pediatrics, University of Colorado Anschutz Medical Campus, Aurora, CO 80045, USACardiovascular Pulmonary Research Laboratories, Departments of Pediatrics and Medicine, University of Colorado Anschutz Medical Campus, Aurora, CO 80045, USADecreased 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.https://www.mdpi.com/2076-3921/11/12/2417seleniumlungbronchopulmonary dysplasiapulmonary developmentantenatal nutritionglutathione peroxidase
spellingShingle Laura G. Sherlock
William C. McCarthy
Maya R. Grayck
Mack Solar
Andres Hernandez
Lijun Zheng
Cassidy Delaney
Trent E. Tipple
Clyde J. Wright
Eva S. Nozik
Neonatal Selenium Deficiency Decreases Selenoproteins in the Lung and Impairs Pulmonary Alveolar Development
Antioxidants
selenium
lung
bronchopulmonary dysplasia
pulmonary development
antenatal nutrition
glutathione peroxidase
title Neonatal Selenium Deficiency Decreases Selenoproteins in the Lung and Impairs Pulmonary Alveolar Development
title_full Neonatal Selenium Deficiency Decreases Selenoproteins in the Lung and Impairs Pulmonary Alveolar Development
title_fullStr Neonatal Selenium Deficiency Decreases Selenoproteins in the Lung and Impairs Pulmonary Alveolar Development
title_full_unstemmed Neonatal Selenium Deficiency Decreases Selenoproteins in the Lung and Impairs Pulmonary Alveolar Development
title_short Neonatal Selenium Deficiency Decreases Selenoproteins in the Lung and Impairs Pulmonary Alveolar Development
title_sort neonatal selenium deficiency decreases selenoproteins in the lung and impairs pulmonary alveolar development
topic selenium
lung
bronchopulmonary dysplasia
pulmonary development
antenatal nutrition
glutathione peroxidase
url https://www.mdpi.com/2076-3921/11/12/2417
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