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Antioxidants improve respiratory function in postnatal life and adulthood. However, the outcomes and biological mechanisms of antioxidant action in the fetal lung are unknown.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>We investigated the effect of maternal daily vitamin C treatment (200\u2009mg\/kg, intravenously) for a month in late gestation (105\u2013138 days gestation, term ~145 days) on molecular regulation of fetal lung maturation in sheep. Expression of genes and proteins regulating lung development was quantified in fetal lung tissue. The number of surfactant-producing cells was determined by immunohistochemistry.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Maternal vitamin C treatment increased fetal lung gene expression of the antioxidant enzyme<jats:italic>SOD-1<\/jats:italic>, hypoxia signaling genes (<jats:italic>HIF-2\u03b1<\/jats:italic>,<jats:italic>HIF-3\u03b1<\/jats:italic>,<jats:italic>ADM<\/jats:italic>, and<jats:italic>EGLN-3<\/jats:italic>), genes regulating sodium movement (<jats:italic>SCNN1-A<\/jats:italic>,<jats:italic>SCNN1-B<\/jats:italic>,<jats:italic>ATP1-A1<\/jats:italic>, and<jats:italic>ATP1-B1<\/jats:italic>), surfactant maturation (<jats:italic>SFTP-B<\/jats:italic>and<jats:italic>ABCA3<\/jats:italic>), and airway remodeling (<jats:italic>ELN<\/jats:italic>). There was no effect of maternal vitamin C treatment on the expression of protein markers evaluated or on the number of surfactant protein-producing cells in fetal lung tissue.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>Maternal vitamin C treatment in the last third of pregnancy in sheep acts at the molecular level to increase the expression of genes that are important for fetal lung maturation in a healthy pregnancy.<\/jats:p><\/jats:sec><jats:sec><jats:title>Impact<\/jats:title><jats:p><jats:list list-type=\"bullet\"><jats:list-item><jats:p>Maternal daily vitamin C treatment for a month in late gestation in sheep increases the expression of gene-regulating pathways that are essential for normal fetal lung development.<\/jats:p><\/jats:list-item><jats:list-item><jats:p>Following late gestation vitamin C exposure in a healthy pregnancy, an increase in lung gene but not protein expression may act as a mechanism to aid in the preparation for exposure to the air-breathing environment after birth.<\/jats:p><\/jats:list-item><jats:list-item><jats:p>In the future, the availability\/development of compounds with greater antioxidant properties than vitamin C or more specific targets at the site of oxidative stress in vivo may translate clinically to improve respiratory outcomes in complicated pregnancies at birth.<\/jats:p><\/jats:list-item><\/jats:list><\/jats:p><\/jats:sec>","DOI":"10.1038\/s41390-021-01489-4","type":"journal-article","created":{"date-parts":[[2021,4,15]],"date-time":"2021-04-15T14:11:34Z","timestamp":1618495894000},"page":"828-838","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":15,"title":["Molecular regulation of lung maturation in near-term fetal sheep by maternal daily vitamin C treatment in late gestation"],"prefix":"10.1038","volume":"91","author":[{"given":"Erin V.","family":"McGillick","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sandra","family":"Orgeig","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Beth J.","family":"Allison","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kirsty L.","family":"Brain","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Youguo","family":"Niu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Nozomi","family":"Itani","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Katie L.","family":"Skeffington","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Andrew D.","family":"Kane","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Emilio A.","family":"Herrera","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Janna L.","family":"Morrison","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Dino A.","family":"Giussani","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","published-online":{"date-parts":[[2021,4,15]]},"reference":[{"key":"1489_CR1","doi-asserted-by":"publisher","first-page":"191","DOI":"10.1016\/j.siny.2010.04.001","volume":"15","author":"JM Davis","year":"2010","unstructured":"Davis, J. 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