Affiliation:
1. Department of Physiology and Cell Biology, University of Nevada, Reno School of Medicine
2. The Lundquist Institute for Biomedical Innovation at Harbor-UCLA Medical Center
3. Department of Developmental Biology, Memorial Sloan-Kettering Institute
4. Department of Biology, University of Texas at San Antonio
5. Department of Medicine, David Geffen School of Medicine at UCLA
Abstract
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 and their sequences diverged
via
LINE1-mediated retrotransposition during evolution. 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 gained 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.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 infertile”. Our data suggest that the
miR-506
family of miRNAs regulates sperm competition and the reproductive fitness of the male.
Publisher
eLife Sciences Publications, Ltd
Reference80 articles.
1. Duration of spermatogenesis in the mouse;Nature,1957
2. Novel stage classification of human spermatogenesis based on acrosome development;Biol Reprod,2013
3. Comparative analysis of mammalian sperm ultrastructure reveals relationships between sperm morphology, mitochondrial functions and motility;Reprod Biol Endocrinol,2019
4. Surfing the wave, cycle, life history, and genes/proteins expressed by testicular germ cells. Part 1: background to spermatogenesis, spermatogonia, and spermatocytes;Microsc Res Tech,2010
5. Evolution of primate gene expression;Nat Rev Genet,2006