Toxicant-induced acceleration of epididymal sperm transit: Androgen-dependent proteins may be involved

Previously we established that a 4-d exposure to chloroethylmethanesulphonate (GEMS), a chemical that significantly reduces serum testosterone (T) levels, resulted in a significant decrease in cauda epididymal sperm reserves in adult male rats while homogenization-resistant testicular spermatid numbers were unaffected, This epididymis-specific alteration occurred whether or not circulating T Levels were maintained using T-filled Silastic implants, To determine whether this epididymis-specific decrease in sperm number was the result of decreased epididymal transit time, the vas deferens was ligated at its midpoint just prior to the first of 4 d of exposure to CEMS with and without T implantation, If epididymal sperm transit was accelerated due to treatment, there would be fewer sperm in the caput/corpus and more sperm in the cauda/vas of the treated animals compared to control, The number of sperm in the caput/corpus decreased significantly (P < 0.05) while the number of sperm in the cauda/vas increased significantly in both the GEMS and GEMS + T animals, Daily sperm production was unaffected, but transit time through the caput/corpus epididymidis was decreased significantly in both treatment groups, To determine if testicular fluid played a role in the epididymis-specific decline in sperm numbers, the efferent ducts were ligated at the same time the vas deferens was ligated, Again, the number of sperm in the caput/corpus decreased significantly with treatment while there was a reciprocal increase in the number of cauda/vas sperm relative to controls, Finally, to determine whether an androgen-mediated process might be involved, the known antiandrogen hydroxyflutamide (HFLUT) was given to castrated, T-implanted animals in which the fertilizing ability of epididymidal sperm is maintained over 4 days, Once again, the number of sperm in the caput/corpus decreased significantly while there was a reciprocal increase in cauda/vas sperm, A quantitative evaluation of the protein profile in homogenates of the caput/corpus epididymidis revealed treatment-related diminutions in two proteins CC9 (Mr = 42 kDa, pI = 4.2) and CC34 (Mr = 35 kDa, pI = 5.5), and the level of each of these proteins in the caput/corpus was significantly correlated with the decrease in caput/corpus sperm number, Thus, both CER/IS and HFLUT accelerate sperm transit through the proximal segment of the epididymis; and, while this effect is not dependent on the testis, it may involve a lesion in androgen-dependent epididymal function. (C) 1997 Elsevier Science Inc.