The goal of this project is to determine the effects of obstruction during development of the male reproductive tract on the structure and function of its components, with emphasis on differentiation of the seminiferous epithelium, the inflammatory reaction in the epididymis and testis, and the development of antisperm antibodies.
The first aim i s to determine whether obstruction of the vas deferens during prepubertal development results in alterations of germ cell development in testes of Lewis rats.
The second aim i s to define the inflammatory response to obstruction by identifying the types of leukocytes which migrate from the vascular system into the epididymis, efferent ducts, and testis with immunocytochemistry, using monoclonal antibody markers for different classes of leukocytes. The nature of interstitial and intraepithelial leukocytes at different times during normal postnatal development will be studied. Then the influence of obstruction of the vas deferens on the patterns of leukocytes will be determined.
The third aim i s: 1) to determine the time of initiation and the course of the antisperm antibody response to pre-pubertal obstruction of the reproductive tract; 2) to define the specific sperm antigens recognized after obstruction during development; and 3) to compare the antigens recognized after obstruction during development with the immunodominant sperm antigens arising as a result of vasectomy in adult animals.
The fourth aim i s to determine whether early reversal of vasal obstruction or later postpubertal repair is more conducive to normal development of the testis and epididymis. The fifth aim is to determine the effects of obstruction of the corpus epididymidis early in postnatal development on migration of leukocytes from the vascular system into the tract proximal and distal to the obstruction, antisperm antibodies, and testicular morphology. Methods include light and electron microscopy, immunocytochemistry, determination of serum antisperm antibodies with an ELISA, electrophoresis and immunoblotting for definition of sperm autoantibodies, and physiological measurements of the resistance of the vas deferens to fluid flow. The studies provide background in an animal model pertinent to understanding the effects of obstructions that occur congenitally or iatrogenically during infant herniorrhaphy or orchidopexy.
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