Elucidation of membrane fusion machinery in fertilization

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Despite the biological importance of sperm-egg fusion in fertilization, the molecular mechanisms underlying this step remain largely unknown. We focused on elucidating the molecular mechanisms of sperm-egg fusion by using genetically manipulated mice. In this application, we reached to obtain two aspects about mammalian fertilization as follows. We identified an IZUMO1-interacting protein in spermatozoon. We produced an Ace3 disrupted mouse line, and found the localization of IZUMO1 spread in a little wider area on spermatozoa, but the elimination of ACE3 did not result in a loss of sperm fertilizing ability. Utilizing Izumo1-deficient spermatozoa, we found that the spermatozoa had the ability to pass through the ZP at least twice. Apparently, some spermatozoa that had undergone the acrosome reaction long before contact with the ZP remained capable of crossing the ZP and fertilizing eggs. The concept that acrosome-reacted spermatozoa are unable to bind to the ZP and have lost their fertilizing capacity must be reconsidered.