This research will determine the mechanisms by which the fungicides benomyl and carbendazim induce testicular atrophy. Benomyl is a systemic benzimidazole fungicide that is used widely on numerous food crops and ornamentals. Carbendazim, also a benzimidazole fungicide, is a metabolite and natural breakdown product of benomyl. Both of these chemicals are known male reproductive toxicants. Benzimidazole exposures induce focal and total testicular atrophy, which cause infertility in male rats. However, the mechanisms leading to infertility remain unknown. Preliminary studies indicate that occlusion of the efferent ductules of the testis may be a major factor in the development of testicular atrophy. The proposed experiments will determine: a. acute dose-dependent changes in the testis and efferent ductules after exposure to benomyl and carbendazim; b. whether carbendazim's acute effects on the testis and efferent ductules are independent; c. the effect of carbendazim on Sertoli cell morphology in the testis; d. whether carbendazim disrupts the structure and function of ciliated and nonciliated cells of the ductal epithelium; e. if the testicular injury is reversible, depending upon the extent of efferent ductule or seminiferous tubule damage; and f. the relationship of testicular and ductal damage multiple exposures to low dosages of carbendazim. The results of this research will provide valuable information regarding the mechanisms of male infertility produced by the benzimidazole class of compounds, which will allow for more informed decisions of occupational risk to males from the wide spread use of these fungicides.

Agency
National Institute of Health (NIH)
Institute
National Institute of Environmental Health Sciences (NIEHS)
Type
First Independent Research Support & Transition (FIRST) Awards (R29)
Project #
1R29ES005214-01
Application #
3465310
Study Section
Toxicology Study Section (TOX)
Project Start
1989-07-01
Project End
1994-06-30
Budget Start
1989-07-01
Budget End
1990-06-30
Support Year
1
Fiscal Year
1989
Total Cost
Indirect Cost
Name
University of Illinois Urbana-Champaign
Department
Type
Schools of Veterinary Medicine
DUNS #
041544081
City
Champaign
State
IL
Country
United States
Zip Code
61820
Hess, R A; Nakai, M (2000) Histopathology of the male reproductive system induced by the fungicide benomyl. Histol Histopathol 15:207-24
Nakai, M; Hess, R A (1994) Morphological changes in the rat Sertoli cell induced by the microtubule poison carbendazim. Tissue Cell 26:917-27
Ilio, K Y; Hess, R A (1994) Structure and function of the ductuli efferentes: a review. Microsc Res Tech 29:432-67
Hess, R A; Miller, L A; Kirby, J D et al. (1993) Immunoelectron microscopic localization of testicular and somatic cytochromes c in the seminiferous epithelium of the rat. Biol Reprod 48:1299-308
Nakai, M; Moore, B J; Hess, R A (1993) Epithelial reorganization and irregular growth following carbendazim-induced injury of the efferent ductules of the rat testis. Anat Rec 235:51-60
Nitta, H; Bunick, D; Hess, R A et al. (1993) Germ cells of the mouse testis express P450 aromatase. Endocrinology 132:1396-401
Hardy, M P; Kirby, J D; Hess, R A et al. (1993) Leydig cells increase their numbers but decline in steroidogenic function in the adult rat after neonatal hypothyroidism. Endocrinology 132:2417-20
Hess, R A; Cooke, P S; Bunick, D et al. (1993) Adult testicular enlargement induced by neonatal hypothyroidism is accompanied by increased Sertoli and germ cell numbers. Endocrinology 132:2607-13
Ilio, K Y; Hess, R A (1992) Localization and activity of Na+,K(+)-ATPase in the ductuli efferentes of the rat. Anat Rec 234:190-200
Hess, R A; Chen, P (1992) Computer tracking of germ cells in the cycle of the seminiferous epithelium and prediction of changes in cycle duration in animals commonly used in reproductive biology and toxicology. J Androl 13:185-90

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