Retardation of spermiation following short-term treatment of rats with theobromine.

Groups of 4-6 Fü-albino rats were examined 24 h after 3 daily doses of 500 mg/kg bw of theobromine administered orally by gavage as well as 1, 2, 4, 6, and 10 weeks after 5 daily doses. Controls received the standard solvent vehicle (SSV) only. A variety of parameters were assessed including body and organ weights, serum clinical chemistry, hematological parameters, epididymal sperm motility and LDH-X fraction in seminal plasma, serum gonadotropins and testosterone, and the morphology of various organs. Testes were perfused with 5% glutaraldehyde and semi-thin sections were evaluated. The most striking morphological observation was a retarded release of late spermatids into the tubular lumen mainly 2 weeks post treatment. This partial disruption of the rigid spermatogenic synchronization was not followed by substantial germ cell death. The other parameters investigated remained relatively normal throughout the study. These observations suggest that theobromine at the dose tested rather selectively interferes with germ cell kinetics. Sertoli cell toxicity could account for these early and subtle effects as well as for the late and severe effects of subchronic exposure of rats to theobromine as reported in the literature.