Mammalian fertilization is a multistep process that culminates in the fusion of the sperm and oocyte plasma membranes (reviewed by Primakoff and Myles, 2002). Mature gametes meet in the oviduct and the sperm penetrates two oocyte barriers – the cumulus cell layer and the zona pellucida (ZP), which is the oocyte extracellular matrix. Binding to the ZP signals the sperm to exocytose its single giant secretory vesicle, the acrosome (Bleil and Wassarman, 1983), and this exocytosis must occur for sperm to become fusion competent. The exocytosis of the acrosome (called the acrosome reaction) results in significant remodeling of the sperm surface. The outer acrosomal and anterior head plasma membranes vesiculate and are lost from the sperm, exposing a new surface membrane (the inner acrosomal membrane) and changing the morphology of the cell. Additionally, the contents of the acrosome contain hydrolytic enzymes, which might modify proteins on the entire sperm surface and prime the sperm for cell-cell attachment and fusion.
Fusion is topologically confined to a specific region of each gamete, which might reflect a unique protein population, lipid organization or composition, or membrane morphology of that region. The sperm plasma membrane overlying the acrosome that does not participate in the acrosome reaction is termed the equatorial region, and the fusion process is apparently initiated in this region of the sperm (Yanagimachi, 1988). The oocyte plasma membrane can be divided into two surface domains: the microvillar-free region, which overlies the meiotic spindle; and the microvillar-rich region, which covers the rest of the oocyte surface. Sperm-oocyte fusion occurs predominantly (Johnson et al., 1975) or exclusively (Ebensperger and Barros, 1984) in the microvillar-rich region. Shortly after fusion, a global exocytic event occurs in the oocyte and the contents of cortical secretory granules are released into the extracellular milieu. Included in these granules are enzymes that modify the ZP in a way that prevents further sperm penetration through this matrix. The oocyte plasma membrane rapidly becomes refractory to a second fusion event, which indicates that the fusion machinery is tightly regulated. How the membrane block to polyspermy is established is not known, but this depends upon incorporation of the sperm membrane into the oocyte plasma membrane, a post-fusion increase in intracellular calcium concentration, and actin polymerization (Maleszewski et al., 1996; McAvey et al., 2002). Fusion competence might be disabled by removal or inactivation of key proteins, or by a chemical or physical block that renders another fusion event less probable.