Molecular regulation of lung maturation in near-term fetal sheep by maternal daily vitamin C treatment in late gestation.
Authors
McGillick, Erin V
Orgeig, Sandra
Allison, Beth J
Brain, Kirsty L
Niu, Youguo
Itani, Nozomi
Skeffington, Katie L
Kane, Andrew D
Herrera, Emilio A
Morrison, Janna L
Giussani, Dino A
Publication Date
2022-03Journal Title
Pediatr Res
ISSN
0031-3998
Publisher
Springer Science and Business Media LLC
Volume
91
Issue
4
Pages
828-838
Language
en
Type
Article
This Version
VoR
Metadata
Show full item recordCitation
McGillick, E. V., Orgeig, S., Allison, B. J., Brain, K. L., Niu, Y., Itani, N., Skeffington, K. L., et al. (2022). Molecular regulation of lung maturation in near-term fetal sheep by maternal daily vitamin C treatment in late gestation.. Pediatr Res, 91 (4), 828-838. https://doi.org/10.1038/s41390-021-01489-4
Abstract
BACKGROUND: In the fetus, the appropriate balance of prooxidants and antioxidants is essential to negate the detrimental effects of oxidative stress on lung maturation. Antioxidants improve respiratory function in postnatal life and adulthood. However, the outcomes and biological mechanisms of antioxidant action in the fetal lung are unknown. METHODS: We investigated the effect of maternal daily vitamin C treatment (200 mg/kg, intravenously) for a month in late gestation (105-138 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. RESULTS: Maternal vitamin C treatment increased fetal lung gene expression of the antioxidant enzyme SOD-1, hypoxia signaling genes (HIF-2α, HIF-3α, ADM, and EGLN-3), genes regulating sodium movement (SCNN1-A, SCNN1-B, ATP1-A1, and ATP1-B1), surfactant maturation (SFTP-B and ABCA3), and airway remodeling (ELN). 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. CONCLUSIONS: 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. IMPACT: 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. 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. 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.
Keywords
Basic Science Article, basic-science-article
Sponsorship
National Health and Medical Research Council (NHMRC) of Australia
Funder references
British Heart Foundation (RG/17/8/32924)
British Heart Foundation (None)
Identifiers
s41390-021-01489-4, 1489
External DOI: https://doi.org/10.1038/s41390-021-01489-4
This record's URL: https://www.repository.cam.ac.uk/handle/1810/336830
Rights
Licence:
http://creativecommons.org/licenses/by/4.0/
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