Fertilization is a complicated process involving many molecules. In mammals, ovulated oocytes are surrounded by two substantial layers; the cumulus cell barrier and the zona pellucida (Fig. 1). Normally, only one sperm penetrates these two layers, and reaches and interacts with the oocyte plasma membrane, resulting in fusion and subsequent formation of a zygote. This process of penetrating these layers is important for sperm not only to reach the oolemma, but also to acquire fusibility. During this process, sperm undergo cellular exocytosis, called the acrosome reaction (Fig. 1). The acrosome is a large, Golgi-derived lysosome-like organelle that overlies the nucleus in the apical region of the sperm head. This organelle secretes enzymes such as the serine protease, acrosin, which helps sperm penetration into the zona pellucida (Abou-Haila & Tulsiani 2000). In addition to the secretion of enzymes, the acrosome reaction brings exposure of the inner acrosomal membrane to the outside by breaking the organelle. This process is necessary for the sperm to acquire fusibility with the oocyte plasma membrane. Sperm–oocyte fusion begins from the equatorial segment located between the inner acrosomal membrane and the plasma membrane overlying the nucleus in the posterior region of the sperm head (Yanagimachi & Noda 1970, Bedford et al. 1979).
Oocytes have a unique structure on their surface (Longo & Chen 1984
). The surface of oocytes is covered with microvilli with the exception of the region overlying the meiotic spindle. Oocyte microvilli surround the sperm head preceding the sperm–oocyte fusion. It has been observed that sperm rarely fuse with oocytes at the region lacking microvilli. Therefore, oocyte microvilli, together with the sperm equatorial segment, are thought to be rich in molecules involved in sperm–oocyte fusion.
For a long time, many efforts have been made to find molecules involved in the process of sperm–oocyte fusion. Pioneering studies using anti-sperm mAbs that inhibited fertilization suggested candidate molecules involved in the sperm–oocyte fusion process. Following such antibody studies came gene targeting, which has proved to be a powerful tool to reveal the function of candidate molecules involved in sperm–oocyte binding and fusion (Table 1). Although the detailed molecular mechanisms of this process have not yet been clarified, recent studies have elucidated certain molecules involved in the fusion or binding reaction (Cuasnicu et al. 2001, Evans 2002). In this review we highlight molecules participating in the sperm–oocyte interaction, acting at either the binding or the fusion stage (Fig. 2).