“…Whether physiologic mobilization is initiated by G i -protein mediated ligand-receptor interactions (Ward et al, 1994), extracellular Ca 2+ influxes (Jungnickel et al, 2001), activation of internal inositol 1,4,5-triphosphate receptors (Herrick et al, 2005) or other mechanisms remains unclear. Although multiple agonists induce the acrosome reaction two-to threefold over background in vitro (Florman and Storey, 1982;Bleil and Wassarman, 1983;Meizel, 1985;Roldan et al, 1994;Shi and Roldan, 1995;Murase and Roldan, 1995;Sato et al, 2000;Son and Meizel, 2003), only binding or penetration of the zona pellucida during fertilization is 100% effective in triggering acrosome exocytosis (Austin, 1975;Saling et al, 1979;Yanagimachi, 1994).…”