Differential Sperm Motility Mediates the Sex Ratio Drive Shaping Mouse Sex Chromosome Evolution

Abstract

SummaryThe mouse sex chromosomes exhibit an extraordinary level of copy number amplification of postmeiotically expressed genes [1, 2], driven by an “arms race” (genomic conflict) between the X and Y chromosomes over the control of offspring sex ratio. The sex-linked ampliconic transcriptional regulators Slx and Sly [3, 4, 5, 6, 7] have opposing effects on global transcription levels of the sex chromosomes in haploid spermatids via regulation of postmeiotic sex chromatin (PMSC) [8, 9, 10, 11] and opposing effects on offspring sex ratio. Partial deletions of the Y chromosome (Yq) that reduce Sly copy number lead to global overexpression of sex-linked genes in spermatids and either a distorted sex ratio in favor of females (smaller deletions) or sterility (larger deletions) [12, 13, 14, 15, 16]. Despite a large body of work studying the role of the sex chromosomes in regulating spermatogenesis (recent reviews [17, 18, 19, 20]), most studies do not address differential fertility effects on X- and Y-bearing cells. Hence, in this study, we concentrate on identifying physiological differences between X- and Y-bearing sperm from Yq-deleted males that affect their relative fertilizing ability and consequently lead to sex ratio skewing. We show that X- and Y-bearing sperm in these males have differential motility and morphology but are equally able to penetrate the cumulus and fertilize the egg once at the site of fertilization. The altered motility is thus deduced to be the proximate cause of the skew. This represents the first demonstration of a specific difference in sperm function associated with sex ratio skewing.

Sex and suicide: The curious case of Toll-like receptors

“…These studies collectively show that mouse sex ratio is regulated by a competition between the ampliconic sex-linked transcriptional regulators Sycp3-like X-linked (Slx), Slx-like 1 (Slxl1), and Sycp3-like Y-linked (Sly) [12]. Loss or knockdown of Sly leads to up-regulation of X-linked genes and female-biased litters as a result of differential X/Y sperm motility [51], but the causal chain between Slx/Sly competition and sperm motility remains elusive. Could TLR7/8 be the missing link?…”

New Biological Insights on X and Y Chromosome-Bearing Spermatozoa

“…This procedure allows producing over 90% of the male embryos following in vitro fertilization using ligand-selected highly motile spermatozoa. In another study using knockout (KO) mice model, Rathje et al (2019) reported that partial deletions of the Y chromosome (Yqdel) in males produce an equal number of X and Y spermatozoa. Although both sperm types are equally capable of fertilizing oocytes once at the site of fertilization, they exhibit a functional (motility and morphology) difference from each other that potentially skewed offspring sex ratio.…”

“…In a recent study, Umehara et al (2019) reported that ligand activation of TLR7/8 significantly decreased the motility of X spermatozoa (by altering ATP production) than that of Y. In addition, using the KO mice model, Rathje et al (2019) reported that Yqdel males (XYRIIIqdel) produced less motile Y spermatozoa compared to X.…”

Within-ejaculate sperm competition

“…Although it is conceivable and intuitive that different phenotypes would have different chances of fertilizing ova, this connection is not always explicitly established. Empirical evidence for within-ejaculate competition with fitness consequences and thus evolutionary potential comes from some meiotic drivers [37,39,43]. Outside of these ( perhaps extreme) examples, indications that within-ejaculate competition has evolutionary potential comes from studies linking withinejaculate sperm selection to offspring fitness [44][45][46], though the underlying mechanisms remain somewhat elusive.…”