Oral Presentation ESA-SRB-APEG-NZSE 2022

Novel insights into mouse sperm membrane proteins and surface remodelling during capacitation (#121)

Hanah M Hart 1 2 , David A Skerrett-Byrne 1 2 , Brett Nixon 1 2 , Geoffry N De Iuliis 1 2
  1. Infertility and Reproduction Research Program, Hunter Medical Research Institute, New Lambton Heights, NSW, Australia
  2. Priority Research Centre for Reproductive Science, School of Environmental and Life Sciences, The University of Newcastle, Callaghan, NSW, Australia

A critical stage of sperm maturation, termed ‘capacitation’, occurs while spermatozoa transit the female reproductive tract, and consists of a series of physiological and biochemical changes that ultimately afford spermatozoa the ability to recognise and fertilise an oocyte. Given the translationally quiescent nature of mature sperm cells, capacitation is largely supported by protein remodelling and post-translational modifications, with these events also driving the remodelling of the sperm surface architecture necessary for oocyte adhesion. Despite decades of research, the extent of sperm surface remodelling and the identification of the entities responsible for sperm-oocyte binding are yet to be fully elucidated. In this study, we have utilised a combination of comparative proteomic profiling and in silico analysis to identify membrane proteins in mouse spermatozoa immediately upon retrieval from the epididymis (non-capacitated), and after in vitro capacitation (capacitated). Using label-free quantification via high-resolution LC-MS/MS, we identified 1,745 and 1,562 insoluble proteins from non-capacitated and capacitated spermatozoa, respectively. Of the 684 membrane proteins identified, subsequent in silico analysis revealed a subset of 64 proteins from non-capacitated-, and 58 from capacitated spermatozoa that are universally characterised as ‘membrane’ proteins, with several not previously described or annotated in the sperm membrane, including carbohydrate binding proteins, such as malectin. These proteins may therefore represent new candidate receptors for binding of the glycoprotein rich zona pellucida matrix that surrounds the oocyte. Notably, we also identified a small number of proteins unique to either non-capacitated or capacitated spermatozoa that offer new insights into the surface changes that precede successful fertilisation. Such changes are of considerable interest in terms of informing rational avenues towards distinguishing fully functional sperm for use in assisted reproductive technologies.