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A maternal hypoxia mouse model to study the effect of late gestational hypoxia on offspring lung outcomes
Thi-Tina N Nguyen1,2, Caitlin V Lewis1,2, Daniel Colon Hidalgo1,3
1Cardiovascular Pulmonary Research Laboratories, Department of Pediatrics and Department of Medicine, University of Colorado Anschutz Medical Campus, Aurora, CO, United States.
Insights
Late gestational hypoxia in mice disrupts offspring lung and pulmonary vascular development, leading to persistent problems and pulmonary hypertension (PH) in adulthood. This model aids research into maternal hypoxia
Area of Science:
- Perinatal Medicine
- Developmental Biology
- Pulmonary Medicine
Background:
- Extremely preterm birth is linked to bronchopulmonary dysplasia and pulmonary hypertension (PH).
- Maternal high-altitude exposure can negatively impact infant lung and vascular outcomes.
- Existing animal models for maternal hypoxia's long-term effects on offspring are limited.
Purpose of the Study:
- To develop and validate a mouse model for investigating the impact of late gestational hypoxia on lung and pulmonary vascular development.
- To test the hypothesis that maternal hypoxia disrupts fetal lung development, causing lasting pulmonary issues and PH in offspring.
Main Methods:
- Pregnant wild-type mice were exposed to hypobaric hypoxia (505 mmHg) from day 16.5 of gestation until birth.
- Lung and pulmonary vascular development were assessed in juvenile and adult offspring.
Main Results:
- Late gestational hypoxia caused abrupted alveolar and pulmonary vascular development in juvenile offspring.
- Adult offspring exhibited persistent abrupted alveolar development and developed pulmonary hypertension (PH).
Conclusions:
- Late gestational hypoxia in mice leads to significant, lasting deficits in lung and pulmonary vascular development, including PH.
- This novel animal model provides a platform for mechanistic studies on maternal hypoxia's role in adverse perinatal outcomes and adult disease susceptibility.
Abstract:
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.
