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ORIGINAL RESEARCH article

Front. Physiol.
Sec. Developmental Physiology
Volume 15 - 2024 | doi: 10.3389/fphys.2024.1488152
This article is part of the Research Topic Hypoxia During Growth and Development View all articles

Chronic fetal hypoxia and antenatal Vitamin C exposure differentially regulate molecular signalling in the lung of female lambs in early adulthood

Provisionally accepted
Erin Victroria McGillick Erin Victroria McGillick 1*Sandra Orgeig Sandra Orgeig 1Beth J Allison Beth J Allison 2Kirsty L Brain Kirsty L Brain 2Melanie R Bertossa Melanie R Bertossa 1Stacey Holman Stacey Holman 1Ashley Meakin Ashley Meakin 1Michael D Wiese Michael D Wiese 1Youguo Niu Youguo Niu 2Nozomi Itani Nozomi Itani 2Katie L Skeffington Katie L Skeffington 2Christian Beck Christian Beck 2Kimberley Jae Botting Kimberley Jae Botting 2Janna L Morrison Janna L Morrison 1Dino Giussani Dino Giussani 2
  • 1 University of South Australia, Adelaide, Australia
  • 2 University of Cambridge, Cambridge, England, United Kingdom

The final, formatted version of the article will be published soon.

    Introduction: Chronic fetal hypoxia is commonly associated with fetal growth restriction and can predispose to respiratory disease at birth and in later life. Antenatal antioxidant treatment has been investigated to overcome the effects of oxidative stress in utero to improve respiratory outcomes. We aimed to determine if the effects of chronic fetal hypoxia and antenatal antioxidant administration persist in the lung in early adulthood. Methods: Chronically catheterised pregnant sheep were exposed to normoxia (N; n=20) or hypoxia (H; n=18; 10% O2) ± maternal daily i.v. saline (N=11; H=8) or Vitamin C (VC; NVC=9; HVC=10) from 105-138d (term, ~145d). Lungs were collected from female lambs 9 months after birth (early adulthood). Lung tissue expression of genes and proteins regulating oxidative stress, mitochondrial function, hypoxia signalling, glucocorticoid signalling, surfactant maturation, inflammation and airway remodelling were measured. Results: Chronic fetal hypoxia upregulated lung expression of markers of prooxidant, surfactant lipid transport and airway remodelling pathways in early adulthood. Antenatal Vitamin C normalized prooxidant and airway remodelling markers, increased endogenous antioxidant, vasodilator and inflammatory markers, and altered regulation of hypoxia signalling and glucocorticoid availability. Conclusion: There are differential effects of antenatal Vitamin C on molecular markers in the lungs of female lambs from normoxic and hypoxic pregnancy in early adulthood.

    Keywords: Chronic Fetal Hypoxia, antenatal antioxidant, vitamin C, postnatal, molecular, Lung

    Received: 29 Aug 2024; Accepted: 19 Nov 2024.

    Copyright: © 2024 McGillick, Orgeig, Allison, Brain, Bertossa, Holman, Meakin, Wiese, Niu, Itani, Skeffington, Beck, Botting, Morrison and Giussani. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

    * Correspondence: Erin Victroria McGillick, University of South Australia, Adelaide, Australia

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