The Joint Annual Scientific Meetings of the Endocrine Society of Australia and the Society for Reproductive Biology 2018

Mechanistic insights into epididymosome-sperm interactions (#35)

Wei Zhou 1 , Simone J Stanger 1 , Amanda L Anderson 1 , Geoffry N De Iuliis 1 , Adam McCluskey 2 , Eileen A McLaughlin 1 3 , Matthew D Dun 4 5 , Brett Nixon 1
  1. Priority Research Centre for Reproductive Science, The University of Newcastle, Newcastle, New South Wales, Australia
  2. Priority Research Centre for Chemical Biology, The University of Newcastle, Newcastle, New South Wales, Australia
  3. School of Biological Sciences, University of Auckland, Auckland , New Zealand
  4. School of Biomedical Sciences and Pharmacy, The University of Newcastle, Newcastle, New South Wales, Australia
  5. Cancer Research Program, Hunter Medical Research Institute, Newcastle, New South Wales, Australia

The mammalian epididymis is responsible for the provision of a highly specialized environment in which spermatozoa acquire functional maturity and are subsequently stored in preparation for ejaculation. Making important contributions to both processes are epididymosomes, small extracellular vesicles released from the epididymal soma via an apocrine secretory pathway. While considerable effort has been focused on defining the cargo transferred between epididymosomes and spermatozoa, comparatively less is known about the mechanistic basis of these interactions. To investigate this phenomenon, we have utilized an in vitro co-culture system to track the transfer of biotinylated protein cargo between mouse epididymosomes and recipient spermatozoa. Our data indicate that epididymosome-sperm interactions are initiated via tethering of the epididymosome to receptors restricted to the post-acrosomal domain of the sperm head. Thereafter, epididymosomes mediate the transfer of protein cargo to spermatozoa via a process that is dependent on dynamin, a family of mechanoenzymes that direct intercellular vesicle trafficking. Notably, upon co-culture of sperm with epididymosomes, dynamin 1 undergoes a pronounced relocation between the peri- and post-acrosomal domains of the sperm head. This repositioning of dynamin 1 is potentially mediated via its association with membrane rafts and ideally positions the enzyme to facilitate the uptake of epididymosome-borne proteins. Accordingly, disruption of membrane raft integrity or pharmacological inhibition of dynamin both potently suppress the transfer of biotinylated epididymosome proteins to spermatozoa. Together, these data provide new mechanistic insight into epididymosome-sperm interactions with potential implications extending to the manipulation of sperm maturation for the purpose of fertility regulation.