Shifts in ovine cardiopulmonary microRNA expression in late gestation and the perinatal period.

Abstract

BACKGROUND:MicroRNAs (miRNAs) have been identified as important contributors to the regulation of early fetal cardiopulmonary development. However, miRNA expression profiles during late gestation and the early neonatal period are not fully elaborated in large mammals such as sheep (ovis aries). The aim of this study was to sequence miRNA from cardiopulmonary tissues in late gestation and neonate sheep to identify changes in miRNA expression. METHODS:Illumina HiSeq next-generation deep sequencing (NGS) was performed on ovine tissues from the left (LV) and right ventricles (RV), lungs and pulmonary artery (PA) of preterm fetuses (128 days), near-term fetuses (140 days) (term = 148 days) and neonatal lambs (5 days). NGS reads were mapped to the sheep genome (OviAri) and published miRNA sequences. RESULTS:Of 1345 cardiopulmonary miRNAs that were sequenced, relatively few major shifts in miRNA expression were detected with increased age from near term to neonates, and were confirmed by quantitative real-time PCR: bta-miR-146a (lung), bta-miR-22-3p (lung, LV), hsa-miR-335* (lung, PA), and miR-210 (lung, PA, LV). CONCLUSIONS:Sequencing of miRNA led to identification of four predominant miRNA in ovine cardiopulmonary tissues which alter expression during late gestation and the early neonatal period, concurrent with important functional changes in heart and lungs.