The overall goal of this project is to determine the extent to which morphologic, physiologic and immunologic alterations after vasectomy are reversed by a subsequent vasovasostomy, and to correlate specific alterations with post-vasovasostomy infertility. During the current grant period, we studied Lewis rats which received either a bilateral vasectomy and a later vasovasostomy, a vasectomy alone, or sham operations. Some vasectomy-induced alterations were not reversed by a subsequent vasovasostomy.
The first aim of the proposed work is to determine the nature and sequence of the initial alterations after vasectomy in the Lewis rat and to determine whether the lesions and infertility are reversible by vasovasostomy, provided it is performed early enough.
The second aim i s to define autoantigens and the role of antisperm antibodies in development of testicular alterations after vasectomy in Lewis rats. Comparisons, with respect to autoantigens recognized, will be made between sera from animals showing elevated antisperm antibodies with and without testicular alterations, and between sera obtained before and after vasovasostomy.
The third aim i s to determine whether the reversal of reproductive tract alterations, antisperm antibody levels, and fertility after vasovasostomy in Lewis rats can be modified by treatment with immunosuppressive drugs (glucocorticoids and cyclosporin).
The fourth aim i s to determine the extent to which alterations after vasectomy are reversed by vasovasostomy in Sprague-Dawley rats, and, most importantly, to determine the basis for the differences in fertility after vasovasostomy which we have observed in preliminary studies on this strain. Young adult male rats will be subjected to bilateral extrascrotal vasectomy and, at a later time, a microsurgical vasovasostomy will be performed. A second group of animals will receive a vasectomy but no vasovasostomy, and a third group will receive sham operations. The animals will be studied at several intervals after the operations. Methods include light and electron microscopy, measurement of intraluminal hydrostatic pressure by micropuncture, probing of the blood-testis barrier with tracers and freeze-fracture, intratesticular testosterone determinations, measurement of the resistance of the vas deferens to fluid flow, determination of serum antisperm antibody levels with an ELISA, and fertility testing. Post-vasectomy autoantigens will be studied by gel electrophoresis, western blotting, and vectorial labeling techniques.

Agency
National Institute of Health (NIH)
Institute
Eunice Kennedy Shriver National Institute of Child Health & Human Development (NICHD)
Type
Research Project (R01)
Project #
2R01HD018825-04
Application #
3315978
Study Section
Reproductive Biology Study Section (REB)
Project Start
1984-09-01
Project End
1990-08-31
Budget Start
1987-09-01
Budget End
1988-08-31
Support Year
4
Fiscal Year
1987
Total Cost
Indirect Cost
Name
University of Virginia
Department
Type
Schools of Medicine
DUNS #
001910777
City
Charlottesville
State
VA
Country
United States
Zip Code
22904
Flickinger, C J; Bush, L A; Howards, S S et al. (1997) Distribution of leukocytes in the epithelium and interstitium of four regions of the Lewis rat epididymis. Anat Rec 248:380-90
Flickinger, C J; Howards, S S; Baran, M L et al. (1997) Appearance of 'natural' antisperm autoantibodies after sexual maturation of normal Lewis rats. J Reprod Immunol 33:127-45
Flickinger, C J; Baran, M L; Howards, S S et al. (1996) Sperm autoantigens recognized by autoantibodies in developing rats following prepubertal obstruction of the vas deferens. J Androl 17:433-42
Flickinger, C J; Herr, J C; Baran, M L et al. (1995) Temporal appearance of antisperm antibodies during sexual maturation of rats after obstruction of the vas deferens. J Androl 16:75-9
Flickinger, C J; Herr, J C; Baran, M L et al. (1995) Testicular development and the formation of spermatic granulomas of the epididymis after obstruction of the vas deferens in immature rats. J Urol 154:1539-44
Flickinger, C J; Howards, S S; Herr, J C (1995) Effects of vasectomy on the epididymis. Microsc Res Tech 30:82-100
Flickinger, C J; Howards, S S; Bush, L A et al. (1995) Antisperm autoantibody responses to vasectomy and vasovasostomy in Fischer and Lewis rats. J Reprod Immunol 28:137-57
Flickinger, C J; Harris, M; Herr, J C et al. (1994) Early antibody response following vasectomy is related to fertility after vasovasostomy in glucocorticoid-treated and untreated Lewis rats. J Urol 151:791-6
Flickinger, C J; Howards, S S; Bush, L A et al. (1994) Temporal recognition of sperm autoantigens by IgM and IgG autoantibodies after vasectomy and vasovasostomy. J Reprod Immunol 27:135-50
Flickinger, C J; Herr, J C; Sisak, J R et al. (1993) Ultrastructure of epididymal interstitial reactions following vasectomy and vasovasostomy. Anat Rec 235:61-73

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