We have previously studied morphologic and physiologic alterations in the male reproductive tract after vasectomy in several species. In the proposed work we plan to determine whether vasectomy-induced changes are reversed by a subsequent vasovasostomy.
The first aim of the proposed work is to determine the extent of alterations in the microscopic structure of the testis, the integrity of the blood-testis barrier and structure and physiology of the epididymis and vas deferens in vasectomized animals and in animals subjected to vasectomy followed later by vasovasostomy.
The second aim i s to determine the extent to which the loss of fertility after vasectomy can be restored by vasovasostomy, and to relate the fertility status of individuals to the persistence or reversal of anatomic and physiologic changes in the reproductive tract.
The third aim i s to determine whether increases in serum antisperm antibodies generated after vasectomy are affected by vasovasostomy and whether restoration of fertility is correlated with a decline in antibody levels. The study will be carried out in the Lewis rat because these animals rapidly acquire testicular lesions and serum antisperm antibodies after vasectomy. Our studies combine morphological, physiological and immunological approaches. Young adult male rats will be subjected to bilateral extrascrotal vasectomy. Three months later a microsurgical vasovasostomy will be performed. Animals will be maintained for 1 or 4 months after vasovasostomy. One group of controls will receive sham operations, while a second group of controls will receive a vasectomy but no vasovasostomy. Methods include micropuncture light and electron microscopy, and measurement of intraluminal hydrostatic pressure. The blood-testis barrier will be studied by lanthanum tracer experiments, freeze-fracture, and transepithelial transport of 3H-inulin. Patency of the anastomosis after vasovasostomy will be investigated by microscopy and by measuring its resistance to fluid flow. Immunologic studies will employ three tests for serum antisperm antibodies: sperm agglutination, immunofluorescence, and a solid phase immunofiltration microtiter assay.

Agency
National Institute of Health (NIH)
Institute
Eunice Kennedy Shriver National Institute of Child Health & Human Development (NICHD)
Type
Research Project (R01)
Project #
5R01HD018825-03
Application #
3315982
Study Section
Reproductive Biology Study Section (REB)
Project Start
1984-09-01
Project End
1987-08-31
Budget Start
1986-09-01
Budget End
1987-08-31
Support Year
3
Fiscal Year
1986
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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