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Updated: Aug 6, 2025
Isolated Lung Perfusion System in the Rabbit Model
Published on: July 15, 2021
Time-resolved transcriptomic profiling of the developing rabbit's lungs: impact of premature birth and implications
Matteo Storti1, Maria Laura Faietti2, Xabier Murgia3
1Department of Experimental Pharmacology and Translational Science, R&D, Chiesi Farmaceutici S.P.A., 43122, Parma, Italy.
Insights
The premature rabbit model effectively mimics human lung development and bronchopulmonary dysplasia (BPD) progression. This model reveals significant inflammatory and developmental pathway dysregulation following preterm birth, aiding BPD research.
Area of Science:
- Pulmonary Medicine
- Developmental Biology
- Animal Models
Background:
- Bronchopulmonary dysplasia (BPD) is linked to premature birth, inflammation, and therapies like oxygen and ventilation.
- Rodent models of BPD have limitations in fully recapitulating human lung development and disease.
- Understanding BPD pathogenesis requires robust models that mirror human developmental trajectories.
Purpose of the Study:
- To establish and validate a premature rabbit model for studying bronchopulmonary dysplasia (BPD).
- To investigate the impact of premature birth on lung development pathways in rabbits.
- To provide a cost-effective alternative to rodent models for BPD research.
Main Methods:
- Characterized normal rabbit lung development across key stages (pseudoglandular, canalicular, saccular, alveolar) using histology, transcriptomics, and proteomics.
- Developed a premature rabbit model at 28 days gestation, mirroring the early saccular phase.
- Compared transcriptomic profiles of preterm rabbits with age-matched term littermates during the first postnatal week.
Main Results:
- Histological analysis confirmed stage-specific lung development and validated time points for transcriptomic analysis.
- Premature birth significantly dysregulated inflammatory pathways, including TNF-responsive and NF-κB regulated genes, leading to sustained inflammation.
- Key developmental pathways, such as blood vessel morphogenesis and epithelial-mesenchymal transition, were disrupted in preterm rabbits.
Conclusions:
- The 28-day gestation premature rabbit is a suitable and cost-effective model for BPD research.
- This model allows for mechanistic and pharmacological investigations into BPD pathogenesis.
- The rabbit model offers advantages over rodent models for studying human-like lung development and disease.
Background:
Premature birth, perinatal inflammation, and life-saving therapies such as postnatal oxygen and mechanical ventilation are strongly associated with the development of bronchopulmonary dysplasia (BPD); these risk factors, alone or combined, cause lung inflammation and alter programmed molecular patterns of normal lung development. The current knowledge on the molecular regulation of lung development mainly derives from mechanistic studies conducted in newborn rodents exposed to postnatal hyperoxia, which have been proven useful but have some limitations.
Methods:
Here, we used the rabbit model of BPD as a cost-effective alternative model that mirrors human lung development and, in addition, enables investigating the impact of premature birth per se on the pathophysiology of BPD without further perinatal insults (e.g., hyperoxia, LPS-induced inflammation). First, we characterized the rabbit's normal lung development along the distinct stages (i.e., pseudoglandular, canalicular, saccular, and alveolar phases) using histological, transcriptomic and proteomic analyses. Then, the impact of premature birth was investigated, comparing the sequential transcriptomic profiles of preterm rabbits obtained at different time intervals during their first week of postnatal life with those from age-matched term pups.
Results:
Histological findings showed stage-specific morphological features of the developing rabbit's lung and validated the selected time intervals for the transcriptomic profiling. Cell cycle and embryo development, oxidative phosphorylation, and WNT signaling, among others, showed high gene expression in the pseudoglandular phase. Autophagy, epithelial morphogenesis, response to transforming growth factor β, angiogenesis, epithelium/endothelial cells development, and epithelium/endothelial cells migration pathways appeared upregulated from the 28th day of gestation (early saccular phase), which represents the starting point of the premature rabbit model. Premature birth caused a significant dysregulation of the inflammatory response. TNF-responsive, NF-κB regulated genes were significantly upregulated at premature delivery and triggered downstream inflammatory pathways such as leukocyte activation and cytokine signaling, which persisted upregulated during the first week of life. Preterm birth also dysregulated relevant pathways for normal lung development, such as blood vessel morphogenesis and epithelial-mesenchymal transition.
Conclusion:
These findings establish the 28-day gestation premature rabbit as a suitable model for mechanistic and pharmacological studies in the context of BPD.
