Evaluating the Contribution of Chorioamnionitis to the Lung Phenotype of the Premature Rabbit Model of Bronchopulmonary Dysplasia

Chorioamnionitis (CA) is an inflammation of fetal membranes caused by intrauterine bacterial infections, underlying up to 70% of premature births and predisposing infants to bronchopulmonary dysplasia (BPD). This study aimed to establish a novel preterm rabbit BPD multi-hit model, including prematurity, hyperoxia, and CA. Pregnant rabbits received an intra-amniotic injection of lipopolysaccharide (LPS 1, 2.5, or 5 μg/sac) or saline (control) three days before delivery. Preterm rabbits delivered at 28 days of gestation were exposed to 50% O2 until postnatal day (PND) 7. Body weight, survival, pulmonary function, histology, and biomolecular outcomes were assessed. The 5 µg/sac LPS dose resulted in high mortality at birth and a low survival rate at PND7. Preterm rabbits injected with 1 and 2.5 µg/sac LPS showed a partial reduction in body weight at birth, which did not persist at PND7. Both the 1 and 2.5 μg/sac LPS doses slightly improved inspiratory capacity and reduced tissue damping in preterm rabbits compared to controls at PND7 (P<0.01). However, both doses worsened lung morphology at PND7, as evidenced by the higher mean wall transection length in LPS groups (P<0.05). LPS (2.5 μg/sac) significantly increased TGF-β and TNF-α mRNA levels (P<0.01) but did not affect VEGFA mRNA expression levels. The antenatal LPS dose of 2.5 µg/sac seems the most promising for establishing a model of CA in preterm rabbits, as evidenced by increased alveolar septa width and persistent inflammation. However, preliminary results suggest a paradoxical effect with this dose, as indicated by improved lung function parameters, requiring further confirmation.