Dramatic Changes in 67 MicroRNAs During Initiation of First Wave of Spermatogenesis in Mus musculus Testis:Global Regulatory Insights Generated by MicroRNA-mRNA Network Analysis.
We mapped global changes in microRNA (miRNA) and mRNA profiles spanning the first wave of spermatogenesis using prepubertal (Postnatal Day 8, P8), pubertal (Postnatal Day 16, P16) and adolescent (Postnatal Day 24, P24) mouse testes and identified differential expression of 67 miRNAs and 8,226 mRNAs. These two datasets were integrated into miRNA-dependent regulatory networks based on miRWalk predictions. In network representing P8 to P16 transition, downregulation of 4 and upregulation of 19 miRNAs were linked with 81 upregulated and 228 downregulated target mRNAs respectively. Further, during P16 to P24 transition, 2 miRNAs were downregulated and 8 miRNAs were upregulated, which linked with 64 upregulated and 389 downregulated mRNAs respectively. Only three of the miRNAs present in the network, viz., miR-34b-5p, miR-34c and miR-449a, showed progressive increase from P8 through P16 to P24, while the remaining miRNAs in the network showed statistically significant changes in their levels either during P8 to P16 transition or during P16 to P24 transition. Analysis of the chromosomal location of these differentially expressed miRNAs showed that 14 out of 25 miRNAs upregulated from P8 to P16 and 18 out of 40 miRNAs upregulated from P8 to P24 were X-linked. This is suggestive of their escape from meiotic sex chromosome inactivation (MSCI) and post meiotic sex chromatin (PMSC). This integrated network of miRNA and mRNA level changes in mouse testis during the 1st wave of spermatogenesis is expected to build a base for evaluating the role of miRNA-mediated gene expression regulation in maturing mammalian testis.
AUTHORS: Sree S, Radhakrishnan K, Indu S, Kumar PG