Retardation of Spermiation Following Short-Term Treatment of Rats with Theobromine

  • R. A. Ettlin
  • J. M. Armstrong
  • S. Buser
  • U. Hennes
Part of the Archives of Toxicology book series (TOXICOLOGY, volume 9)


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.

Key words

Testicular toxicity Spermatogenic desynchronization Sertoli cells LDH-X Theobromine Rats 





Sertoli cell


standard solvent vehicle (containing carboxy­methylcellulose and Tween 70)


lactate dehydrogenase


fraction X of LDH (different isoenzymes)


red blood cells count




mean corpuscular volume


packed cell volume


mean corpuscular hemoglobin


mean corpuscular hemoglobin con­centration


white blood cell count


GPT transaminases


alkaline phosphatase


acid phosphatase


luteinizing hormone


follicle stimulating hormone


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  1. Clermont Y (1972) Kinetics of spermatogenesis in mammals: Seminiferous epithelium cycle and spermatogonial renewal. Physiol Rev 52: 198–236PubMedGoogle Scholar
  2. Clermont Y, Harvey SC (1965) Duration of the cycle of the seminiferous epithelium of normal, hypo physectomized and hypophysectomized-hormone treated albino rats. Endocrinology 76: 80–89PubMedCrossRefGoogle Scholar
  3. Dahlbäck M, Heintz L, Ryrfeldt A, Stenberg K (1984) Toxic effects of some xanthine derivatives with special emphasis on adverse effects on rat testes. Toxicology 32: 23–35PubMedCrossRefGoogle Scholar
  4. Davis BJ (1964) Disc electrophoresis II. Method and application to human serum proteins. Ann NY Acad Sci 121: 404–427PubMedCrossRefGoogle Scholar
  5. Dym M (1977) The role of the Sertoli cell in spermatogenesis. In: Yates R, Gordon M (eds) Male reproductive system. Raven Press, New York, pp 155–169Google Scholar
  6. Ettlin RA, Bechter R, Dixon RL (1982) Assessment of testicular toxicity associated with anticancer agents. 1. Histopathology. Proc West Pharmacol Soc 25: 381–384PubMedGoogle Scholar
  7. Ettlin RA, Bechter R, Lee IP, Hodel C (1984) Aspects of testicular toxicity induced by anticancer drugs. Arch Toxicol Supp 17: 151–154CrossRefGoogle Scholar
  8. Gavella M, Cvitkovic P, Skrabalo Z (1982) Seminal plasma isoenzyme LDH-X in infertile men. Andrologia 14: 104–109PubMedCrossRefGoogle Scholar
  9. Heywood LH (1980) Testosterone levels in the male laboratory rat: Variations under experimental conditions. Int J Androl 3: 519–529PubMedCrossRefGoogle Scholar
  10. Jackson H, Fox BW, Craig AW (1961) Antifertility substances and their assessment in the male rodent. J Reprod Fertil 2: 447–465PubMedCrossRefGoogle Scholar
  11. Russell LD, Lee IP, Ettlin R, Malone JP (1983) Morphological pattern of response after administration of procarbazine: Alteration of specific cell associations during the cycle of the seminiferous epithelium of the rat. Tissue Cell 15: 391–404PubMedCrossRefGoogle Scholar
  12. Tarka SM, Zoumas BL, Gans JH (1979) Short-term effects of graded levels of theobromine in laboratory rodents. Toxicol appl Pharmacol 49: 127–149PubMedCrossRefGoogle Scholar

Copyright information

© Springer-Verlag 1986

Authors and Affiliations

  • R. A. Ettlin
    • 1
  • J. M. Armstrong
    • 2
  • S. Buser
    • 1
  • U. Hennes
    • 1
  1. 1.F. Hoffmann-La Roche & Co. Ltd.BaselSwitzerland
  2. 2.Hoffmann-La Roche Inc.NutleyUSA

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