Sperm–Zona Pellucida Interaction: Molecular Mechanisms and the Potential for Contraceptive Intervention Matthew D. Dun, Lisa A. Mitchell, R. John Aitken, and Brett Nixon Contents 1 Introduction ............................................................................... 140 2 Sperm–Zona Pellucida Interaction ........................................................ 140 2.1 The Zona Pellucida ................................................................. 140 2.2 Sperm Receptor Molecules Involved in Zona Pellucida Interaction ................ 151 2.3 Toward an Integrated Model of Sperm–Zona Interaction ........................... 157 3 Potential for Contraceptive Intervention .................................................. 162 3.1 Target Antigens of the Zona Pellucida .............................................. 163 3.2 Target Antigens of Spermatozoa .................................................... 164 4 Summary .................................................................................. 165 References .................................................................................... 165 Abstract At the moment of insemination, millions of mammalian sperm cells are released into the female reproductive tract with the single goal of finding the oocyte. The spermatozoa subsequently ignore the thousands of cells they make contact with during their journey to the site of fertilization, until they reach the surface of the oocyte. At this point, they bind tenaciously to the acellular coat, known as the zona pellucida, which surrounds the oocyte and orchestrate a cascade of cellular interac- tions that culminate in fertilization. These exquisitely cell- and species- specific recognition events are among the most strategically important cellular interactions in biology. Understanding the cellular and molecular mechanisms that underpin M.D. Dun, L.A. Mitchell, and R.J. Aitken Reproductive Science Group, School of Environmental & Life Sciences, University of Newcastle, Callaghan, NSW 2308, Australia ARC Centre of Excellence in Biotechnology & Development, University of Newcastle, Callaghan, NSW 2308, Australia B. Nixon (*) Reproductive Science Group, School of Environmental & Life Sciences, University of Newcastle, Callaghan, NSW 2308, Australia e-mail: Brett.Nixon@newcastle.edu.au U.-F. Habenicht and R.J. Aitken (eds.), Fertility Control, Handbook of Experimental Pharmacology 198, DOI 10.1007/978-3-642-02062-9_9, # Springer-Verlag Berlin Heidelberg 2010 139