A novel circRNA-mRNA-miRNA regulatory axis as a sexual biological variable in a mouse model of experimental bronchopulmonary dysplasia

Bronchopulmonary Dysplasia (BPD) is a neonatal respiratory condition commonly seen in extremely low birth weight preterm babies, characterized by impaired lung alveolarization and dysregulated pulmonary vascularization with the intervention of and/or hyperoxia-induced or mechanical ventilation. This is the most common complication of prematurity; males born before the age of 26 weeks have a higher incidence of BPD with higher neonatal and infant mortality rates than females. We have also reported that after oxygen exposure, females had less morphological injury with better preservation of the pulmonary phenotype. The biological reasons behind this sex-specific differences are unknown. Since circRNAs are currently emerging as the new family of non coding RNAs to be implicated in gene and protein regulation, we hypothesize that some circRNAs may be involved in the decision making of good prognosis in females over males, after hyperoxia treatment. By deep RNA sequencing, we identified 53 circRNAs that were differentially expressed in male and female neonatal mice pups mimicking experimental BPD. In the current study, we have identified a novel regulatory circRNA-miRNA-mRNA axis which we believe might be involved in the sexual dimorphism of this neonatal disease in premature infants.