RESEARCH FOR MCP IN SEMEN AND SPERM-EGG INTERACTION

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1.Membrane cofactor protein (MCP), CD46, whose primary function is to protect host cells from homologous complement, has been presumed to serve as a sperm adhesion molecule for oocytes. The purpose of this study was to clarify the relationship between the properties of MCP expressed on epididymal sperm and their fertilizing ability in a recently developed strategy for assisted reproduction. We collected ejaculated sperm from normal subjects and epididvmal sperm from vasectomized subjects and patients with congenital absence of the vas deferens. Westent blotting and cofactor activity assay were performed to investigated the structural and functional properties of MCP.Epididymal spermatozoa which showed a reduced fertilizing ability tended to react poorly with antibodies against MCP and also showed low cofactor activity, indicating weak complement regulatory activity compared to that of ejaculated spermatozoa. MCP is sufficiently expressed in ejaculated sperm in men with a normally developed epididymis but is diminished in epididymal sperm from men with congenital or acquired obstruction of the vas deferens.2.Three infertile subjects fulfillling normal or subnormal criteria on routine semen analysis showed abnormal sperm CD46 (membrane cofactor protein of complement) by SDS-PAGE/immunoblotting analysis using a panel of monoclonal antibodies. The sperm CD46 isoform has been reported to be associated with sperm-egg interaction. These 3 patients expressed normal CD46 isoforms on their lymphocytes and granulocytes. Thus, sperm-specific abnormalities in these proteins parallels male infertility, suggesting a new category of infertility, probably due to aberrations in the molecules related to sperm-egg interaction.