REPRODUCTIONREVIEW Focus on Fertilization The mechanism of sperm–oocyte fusion in mammals

Sperm–oocyte fusion is one of the most impressive events in sexual reproduction, and the elucidation of its molecular mech-anism has fascinated researchers for a long time. Because of the limitation of materials and difficulties in analyzing membrane protein–protein interactions, many attempts have failed to reach this goal. Recent studies involving gene targeting have clearly demonstrated the various molecules that are involved in sperm–oocyte binding and fusion. Sperm ADAMs (family of proteins with a disintegrin and metalloprotease domain), including fertilin a, fertilin b and cyritestin, have been investigated and found to be important for binding rather than for fusion and painstaking studies have raised suspicions that their putative receptors, oocyte integrins, are necessary for the sperm–oocyte interaction. Recently, several studies have focused the spot-light on CD9 and glycosylphosphatidylinositol (GPI)-anchored proteins on oocytes, and epididymal protein DE on sperm, as candidate molecules involved in sperm–oocyte fusion. Lack of, or interference with the function of, these proteins can disrupt the sperm–oocyte fusion without changing the binding. In this review we highlight the candidate molecules involved in the sperm–oocyte interaction suggested from the recent progress in this research field. Reproduction (2004) 127 423–42