The rapidly evolving X-linked <i>MIR-506</i> family fine-tunes spermatogenesis to enhance sperm competition.

Abstract

Despite rapid evolution across eutherian mammals, the X-linked <i>MIR-506</i> family miRNAs are located in a region flanked by two highly conserved protein-coding genes (<i>SLITRK2</i> and <i>FMR1</i>) on the X chromosome. Intriguingly, these miRNAs are predominantly expressed in the testis, suggesting a potential role in spermatogenesis and male fertility. Here, we report that the X-linked <i>MIR-506</i> family miRNAs were derived from the MER91C DNA transposons. Selective inactivation of individual miRNAs or clusters caused no discernible defects, but simultaneous ablation of five clusters containing 19 members of the <i>MIR-506</i> family led to reduced male fertility in mice. Despite normal sperm counts, motility, and morphology, the KO sperm were less competitive than wild-type sperm when subjected to a polyandrous mating scheme. Transcriptomic and bioinformatic analyses revealed that these X-linked <i>MIR-506</i> family miRNAs, in addition to targeting a set of conserved genes, have more targets that are critical for spermatogenesis and embryonic development during evolution. Our data suggest that the <i>MIR-506</i> family miRNAs function to enhance sperm competitiveness and reproductive fitness of the male by finetuning gene expression during spermatogenesis.