The overall goal of this project is to determine the effects of obstruction of the male reproductive tract on the structure and function of its components, with emphasis on the development of germ cells in the seminiferous tubules, induction of antisperm antibodies, and characterization of dominant post-obstruction sperm autoantigens. The studies are aimed at understanding basic responses to obstruction of the vas deferens, which can result from developmental defects, trauma, and vasectomy. The proposed work builds on observations of increased antibodies to specific sperm autoantigens after prepuberal or adult obstruction of the vas deferens and of testicular alterations following vasectomy.
The first aim i s to determine whether early reversal of vasal obstruction or later postpubertal repair is more consistent with normal development of the testis and epididymis in a rat model system.
The second aim i s to determine whether obstruction of the vas deferens results in changes in apoptosis in cells of the seminiferous tubules and the epididymal epithelium.
The third aim i s to identify, isolate, and clone cDNAs to characterize the dominant sperm autoantigens post-obstruction in the rat. Recently, the first post- obstruction sperm autoantigen in the rat model has been successfully cloned, sequenced and expressed. Plasma cells that are producing antibodies to specific sperm antigens also will be localized by a labeled antigen method.
The fourth aim i s to determine if immunization with a purified recombinant post- obstruction sperm autoantigen results in reproductive tract alterations such as orchitis and epididymitis and to assess how responses to specific autoantigens contribute to post-obstruction chances. The fifth aim is to extend studies of dominant sperm autoaintigens from the rat to humans. The focus will be on species conserved antigens under the principle that conservation of antigens between species reflects conservation of important functions.
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