GSE118438
Next-generation sequencing of rhesus macaques lung after treatment with a low-dose or clinical antenatal corticosteroid treatment
Purpose: Evaluate fetal lung maturation and transcriptome after clinical treatment with antenatal corticosteroids compared to an alternative treatment with a slow release low-dose formulation. Methods: Lung mRNA profiles of rhesus macaques were generated by RNA sequencing. Reads that met quality thresholds were aligned to the rhesus macaque genome and number of reads per gene was counted. RNA-sequencing of the hippocampus was done. Differential expression analysis was done using read counts. Results: A relatively low dose of Beta-Ac increased lung compliance, surfactant concentration and relative airspace of the fetal lung equivalent to the clinical drug. By transcriptome analyses, the early suppression of genes associated with immune responses and the downregulation of genes associated with developmental pathways were less changed by Beta-Ac than the clinical drug. There were no significant differences between Beta-Ac and control while the clinical drug suppressed maturational pathways including genes involved in neurogenesis, neuronal differentiation and stem cell fate commitment. Conclusions: We report that low-dose betamethasone-acetate has decreased impact on lung transcriptome compared to the clinical treatment. Overall design: Time-pregnant rhesus macaques were treated with [1] antenatal corticosteroids or placebo prior to delivery at 4-6h or 5 days after treatments [2] corticsteroid treatments or placebo 5 days prior to delivery.