94% of researchers rate our articles as excellent or good
Learn more about the work of our research integrity team to safeguard the quality of each article we publish.
Find out more
BRIEF RESEARCH REPORT article
Front. Physiol.
Sec. Respiratory Physiology and Pathophysiology
Volume 16 - 2025 | doi: 10.3389/fphys.2025.1513703
A maternal hypoxia mouse model to study the effect of late gestational hypoxia on offspring lung outcomes
Provisionally accepted
Thi-Tina N Nguyen 1
Caitlin V Lewis 1 Daniel Colon Hidalgo 2
Janelle N Posey 3 Mariah Jordan 3
Timothy E Porfilio 1 Maya R Grayck 4
Clyde J Wright 4
Cassidy Delaney 4
Eva S Nozik 1*- 1 Cardiovascular Pulmonary Research Laboratories and Pediatrics - Critical Care Medicine, University of Colorado Anschutz Medical Campus, Aurora, United States
- 2 Cardiovascular Pulmonary Research Laboratories and Medicine - Pulmonary and Critical Care, University of Colorado Anschutz Medical Campus, Aurora, United States
- 3 Cardiovascular Pulmonary Research Laboratories and Pediatrics - Neonatology, University of Colorado Anschutz Medical Campus, Aurora, United States
- 4 Pediatrics - Neonatology, University of Colorado Anschutz Medical Campus, Aurora, United States
Extremely preterm birth predisposes infants to bronchopulmonary dysplasia and associated pulmonary hypertension (PH). High altitude exposure during pregnancy has also been shown to worsen infant lung and pulmonary vascular outcomes. Animal models addressing the mechanisms for how maternal hypoxia impacts postnatal and adult lung and pulmonary vascular outcomes are lacking and development of a model to address this gap would enable new mechanistic studies. We hypothesize that late gestational hypoxia disrupts lung and pulmonary vascular development in the offspring, leading to abrupted lung development and PH in adulthood. Pregnant wild-type mice were exposed to hypobaric hypoxia at 505 mmHg, from day 16.5 of gestation until birth. Lung and pulmonary vascular outcomes were measured in juvenile and mature offspring. We found that late gestational hypoxia resulted in abrupted alveolar and pulmonary vascular development in juvenile offspring and that adult offspring showed persistent abrupted alveolar development as well as PH. This striking model will provide a new opportunity to determine mechanisms responsible for poor outcomes secondary to maternal hypoxia and assess important factors that increase susceptibility to adult diseases in former preterm infants.
Keywords: prenatal hypoxia, late gestation, lung development, Neonatal outcomes, pulmonary hypertension
Received: 18 Oct 2024; Accepted: 10 Feb 2025.
Copyright: © 2025 Nguyen, Lewis, Colon Hidalgo, Posey, Jordan, Porfilio, Grayck, Wright, Delaney and Nozik. 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:
Eva S Nozik, Cardiovascular Pulmonary Research Laboratories and Pediatrics - Critical Care Medicine, University of Colorado Anschutz Medical Campus, Aurora, United States
Disclaimer: All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article or claim that may be made by its manufacturer is not guaranteed or endorsed by the publisher.