Transcriptomic profiling of the preterm,hyperoxia exposed, rabbit's lung

Bronchopulmonary dysplasia (BPD) is a multifactorial chronic lung disease of premature neonates. The development of BPD depends on several prenatal and postnatal factors that induce inflammation, altering alveolar growth and pulmonary vascular development. Animal models are essential to investigating the precise molecular pathways leading to BPD. The preterm rabbit combines many advantages of both small (e.g., rodents) and large BPD models (i.e., preterm lambs and baboons). For instance, preterm rabbits display mild-to-moderate respiratory distress at delivery, which, along with ongoing exposure to high oxygen concentration (95% O2), leads to functional and morphological lung changes that resemble the phenotype of human BPD. Nevertheless, the molecular pathways leading to the development of the BPD-like phenotype in this model remain largely ununderstood. We, therefore, aimed to characterize the longitudinal gene expression in the lungs of preterm rabbits continuously exposed to 95% O2 on postnatal days 3, 5, and 7. The longitudinal transcriptomic analysis revealed different expression patterns for several genes and pathways. Over time, extracellular matrix organization and angiogenesis were increasingly downregulated, while apoptosis, RNA processing, and inflammation showed the opposite trend. On the 28th day of gestation (term 31 days), does (3.8±0.3 kg of body weight) were initially sedated with intramuscular (i.m.) medetomidine 2 mg/kg (Domitor®, Orion Pharma, Finland). Ten minutes later, the animals received 25 mg/kg of ketamine (Imalgene®, Merial, France) and 5 mg/kg of xylazine (Rompun®, Bayer, Germany) i.m. When adequate sedation was reached, does were placed in the supine position, shaved on the abdomen, and euthanized with an overdose of 100 mg/kg of pentothal sodium (50 mg/kg MSD Animal Health, USA). Pups were then extracted through hysterectomy. After one hour, surviving pups were weighed and placed into incubators (Okolab, Naples, Italy) under normoxia (21% O2) or hyperoxia (95 % or 70 % O2) conditions for up to 7 days. Before lung harvesting, pups were euthanized with a pentothal sodium overdose.