As the spermatozoa of eutherian mammals migrate from the testis through the epididymis they undergo a dramatic metamorphosis from nonmotile and infertile cells to fully functional gametes capable of sustaining progressive motility and of fertilizing eggs. Described collectively as epididymal maturation these physiologic changes in spermatozoa are associated termporally with alterations in sperm metabolism, sperm protein and phospholipid constituents, and sperm sulfhydryl content. However, the nature of these associations and the influence of the epididymal environment on the functional maturation of spermatozoa are not clearly understood. The studies proposed in this application seek to increase our knowledge regarding sperm epididymal maturation; specifically, how immature sperm acquire motility and fertility during epididymal maturation and how these vital sperm functions are maintained in mature spermatozoa. We plan to accomplish these goals by determining the conditions required in vitro to induce immature spermatozoa from the caput epididymidis to acquire rates and patterns of motility and fertility characteristic of mature spermatozoa from the cauda epididymidis. In addition, using radioactive isotopes and fluorescent dyes we will identify the internal and external sulfhydryl and disulfide proteins involved in the induction of motility in immature spermatozoa and in the maintenance of motility in mature spermatozoa. Finally, we will attempt to induce and enhance in vitro and in vivo fertility, as well as motility, in immature epididymal spermatozoa by treatment of the spermatozoa with proteins extracted from the epididymis or from mature caudal epididymal spermatozoa. In the long ter,m the information acquired in these studies can be applied directly to the development of new therapies for male infertility based on the enhancement of sperm motility and fertility in vitro, or, to the development of sperm-targeting contraceptive agents directed against the sperm sulfhydryl and disulfide proteins involved in motility and ultimately fertility.
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