Essential role for SUN5 in anchoring sperm head to the tail

Elife. 2017 Sep 25;6:e28199. doi: 10.7554/eLife.28199.

Abstract

SUN (Sad1 and UNC84 domain containing)-domain proteins are reported to reside on the nuclear membrane playing distinct roles in nuclear dynamics. SUN5 is a new member of the SUN family, with little knowledge regarding its function. Here, we generated Sun5-/- mice and found that male mice were infertile. Most Sun5-null spermatozoa displayed a globozoospermia-like phenotype but they were actually acephalic spermatozoa. Additional studies revealed that SUN5 was located in the neck of the spermatozoa, anchoring sperm head to the tail, and without functional SUN5 the sperm head to tail coupling apparatus was detached from nucleus during spermatid elongation. Finally, we found that healthy heterozygous offspring could be obtained via intracytoplasmic injection of Sun5-mutated sperm heads for both male mice and patients. Our studies reveal the essential role of SUN5 in anchoring sperm head to the tail and provide a promising way to treat this kind of acephalic spermatozoa-associated male infertility.

Keywords: ICSI; SUN5; acephalic spermatozoa; developmental biology; mouse; pseudo-globozoospermia; sperm head-tail connection; stem cells.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Male
  • Membrane Proteins / deficiency
  • Membrane Proteins / metabolism*
  • Mice, Knockout
  • Nuclear Envelope / metabolism
  • Sperm Head / physiology*
  • Sperm Tail / physiology*
  • Spermatogenesis*

Substances

  • Membrane Proteins
  • SUN5 protein, mouse

Grant support

The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.