Colchicine Disrupts the Cytoskeleton of Rat Testis Seminiferous Epithelium in a Stage-Dependent Manner1

Sertoli cell microtubules play an important role in the process of spermatogenesis. We investigated the effects of colchicine, a microtubule-disrupting agent, on the seminiferous epithelium. Rats were injected intratesticularly with 0.004-40 micrograms colchicine/testis. Colchicine had a dose-related effect on seminiferous tubule fluid secretion and completely blocked secretion at a dose of 40 micrograms colchicine/testis. Colchicine also resulted in a dose-related decrease in testes weight 2 and 8 wk after injection. When 40 micrograms colchicine/testis was used, testis morphology showed a time-dependent increase in the incidence of sloughing over a time course of 1, 3, 6, and 16 h. Quantitative analysis demonstrated that stage IX-XIV seminiferous tubules were most sensitive to sloughing. Changes in the distribution of tubulin immunostaining within Sertoli cells occurred preferentially in stage VII-VIII seminiferous tubules, which were most resistant to sloughing. In addition, colchicine resulted in disruption of vimentin filaments in stage IX-XIV seminiferous tubules, which correlated with the stage-dependent sensitivity of sloughing. We propose that the stage dependence of colchicine-induced effects reflects the dynamic and stage-dependent role of microtubules in spermatogenesis. Furthermore, cellular structures other than microtubules, such as vimentin filaments, may be important for maintaining the structural integrity of the seminiferous epithelium.