
The X-linked miR-506 family miRNAs, which are predominantly expressed in spermatogenic cells and sperm, have rapidly evolved across mammals. Ablation of multiple miR-506 family clusters compromises sperm competitiveness and male reproductive fitness, suggesting these miRNAs function to finetune gene expression during spermatogenesis to enhance sperm competition and male reproductive success.


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Despite rapid evolution across eutherian mammals, the X-linked miR-506 family miRNAs are located in a region flanked by two highly conserved protein-coding genes ( Slitrk2 and Fmr1 ) 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 miR-506 family miRNAs were derived from the MER91C DNA transposons. Selective inactivation of individual miRNAs or clusters caused no discernable defects, but simultaneous ablation of five clusters containing nineteen members of the miR-506 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 miR-506 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 miR-506 family miRNAs function to enhance sperm competitiveness and reproductive fitness of the male by finetuning gene expression during spermatogenesis.

Significance Statement The X-linked miR-506 family has rapidly evolved in mammals, but their physiological significance remains elusive. Given their abundant and preferential expression in the testis and sperm, these X-linked miRNAs likely play a functional role in spermatogenesis and/or early embryonic development. However, the deletion of either individual miRNA genes or all of the five miRNA clusters encoding 38 mature miRNAs did not cause major fertility defects in mice. When these mutant males were subjected to conditions resembling polyandrous mating, the mutant sperm were much less competitive than the wild-type sperm, rendering the mutant males “functionally sub-fertile”. Our data suggest that the miR-506 family of miRNAs regulates sperm competition and the reproductive fitness of the male.

### Competing Interest Statement

The authors have declared no competing interest.

The Rapidly Evolving X-linked miR-506 Family Finetunes Spermatogenesis to Enhance Sperm Competition

rapid-evolution-of-the-x-linked-mir-506-family-enhances-sperm-competitiveness-and-male-reproductive-fitness


Rapid Evolution of the X-Linked miR-506 Family Enhances Sperm Competitiveness and Male Reproductive Fitness
