Sperm Function in Fertilization Events

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DESCRIPTION (provided by applicant): The epididymal epithelium produces a region-specific luminal environment that promotes the post-testicular development of sperm motility and fertilizing capacity and maintains sperm viability during storage in the cauda epididymidis. Substantial progress has been made on identifying epididymal contributions to sperm maturation, however the mechanisms by which it maintains sperm viability during storage is less well understood. We have identified a potentially unique secretory protein of hamster cauda epididymal principal cells which specifically binds to, and polymerizes into a "death cocoon" surrounding defective luminal spermatozoa and sperm fragments, thereby segregating them from the viable sperm population. This protein termed eFGL (for epididymal fibrinogen-like protein) is a disulfide-linked oligomer of three subunits. Two eFGL subunits have been sequenced and identified as fibrinogen-related proteins: fgl2 (fibrinogen-like protein-2) a 65 kDa serine-protease and fgll (fibrinogen-like protein-1) a 33 kDa polypeptide of unknown function. The third subunit dc45 (for death cocoon 45 kDa polypeptide) has not been identified. We hypothesize that eFGL represents a novel protective mechanism which specifically recognizes and masks defective spermatozoa preventing their release ofhydrolases or antigens which could exert deleterious effects on the viable sperm population or initiate inflammatory or immune responses if they escape the blood-epididymis barrier. The specific aims of this study are: 1: To determine whether eFGL is expressed and secreted by only epididymal principal cells. 2: To determine which organelles of defective spermatozoa bind the epididymal FGL oligomer. 3: To determine if eFGL binding to specific sperm ligands promotes sperm death and/or death cocoon polymerization.4: To define the function of eFGL by targeted disruption of the fgl2 gene in mice.