Essential role for SUN5 in anchoring sperm head to the tail

  • Elife. 2017 Sep 25;6:e28199. doi: 10.7554/eLife.28199.
Yongliang Shang  #  1  2 ,  Fuxi Zhu  #  3  4 ,  Lina Wang  1  2 ,  Ying-Chun Ouyang  1 ,  Ming-Zhe Dong  1 ,  Chao Liu  1 ,  Haichao Zhao  1  2 ,  Xiuhong Cui  1 ,  Dongyuan Ma  5 ,  Zhiguo Zhang  3  4 ,  Xiaoyu Yang  6 ,  Yueshuai Guo  7 ,  Feng Liu  2  5 ,  Li Yuan  8 ,  Fei Gao  1  2 ,  Xuejiang Guo  7 ,  Qing-Yuan Sun  1  2 ,  Yunxia Cao  3  4 ,  Wei Li  1  2
Affiliations
  • 1. State Key Laboratory of Stem Cell and Reproductive Biology, Institute of Zoology, Chinese Academy of Sciences, Beijing, China.
  • 2. University of Chinese Academy of Sciences, Beijing, China.
  • 3. Reproductive Medicine Center, Department of Obstetrics and Gynecology, The First Affiliated Hospital of Anhui Medical University, Hefei, China.
  • 4. Institute of Reproductive Genetics, Anhui Medical University, Hefei, China.
  • 5. State Key Laboratory of Membrane Biology, Institute of Zoology, Chinese Academy of Sciences, Beijing, China.
  • 6. Center of Clinical Reproductive Medicine, First Affiliated Hospital, Nanjing Medical University, Nanjing, China.
  • 7. State Key Laboratory of Reproductive Medicine, Collaborative Innovation Center of Genetics and Development, Department of Histology and Embryology, Nanjing Medical University, Nanjing, China.
  • 8. Savaid School of Medicine, University of Chinese Academy of Sciences, Beijing, China.
  • # Contributed equally.
PMID: 28945193 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.