Effects of gossypol on the seminiferous epithelium in the rat: a light and electron microscope study

This study was undertaken to determine the effects of 10, 20 and 30 mg/kg per day of gossypol for 2-11 weeks on the rat testis. At the light microscope level, the most striking effect of gossypol treatment is the presence of severely damaged and entirely normal seminiferous tubules adjacent to one another in the same section. Affected tubules exhibit intraepithelial vacuoles of varying size, exfoliation, and atrophy. With the electron microscope, the intraepithelial vacuoles are found to consist of intercellular spaces and intracellular vacuoles occurring primarily, though not exclusively, in the Sertoli cells. Severely affected Sertoli cells exhibit many large vacuoles as well as an overall decrease in cytoplasmic ground substance, rough and smooth endoplasmic reticulum and Golgi apparatus. There is an overall increase in the frequency of occurrences of vacuolated tubules with time and dose but in no group of animals were more than 46% of the tubules affected. At the electron microscope level, the most striking specific effect of gossypol treatment is the production of ultrastructural defects exclusively in the mitochondrial sheath of Stage 18 and 19 spermatids; these changes are evident in small numbers as early as 2 weeks after 20 mg/kg per day of gossypol and increase with dose and time. No other significant differences between germ cells or Leydig cells of control and gossypol-treated rats are observed under the experimental conditions employed. The significance of these observations is discussed in relation to the possible mechanisms of action of this new experimental male contraceptive.