Skip to main content
SpringerLink
Log in

Ultrastructural, Biochemical, and Endocrine Studies on the Effects of Gossypol and its Isomeric Derivatives on The Male Reproductive Tract

  • Chapter
Gossypol

Part of the book series: Reproductive Biology ((RBIO))

Abstract

Chinese scientists have reported that in clinical trials involving more than 8000 men tested over a four-year period gossypol was found to be a 99.89% effective, safe, and reversible contraceptive [1]. Treatment for eight weeks with 20 mg of gossypol daily decreases sperm counts to well below 4 x 106/ml; a maintenance dose of 40 mg of gossypol/wk thereafter sustains infertility. Gossypol does not appear to affect plasma testosterone levels in human subjects [2, 3] or in monkeys [4, 5], and the drug is without adverse effects on sexual function. A few minor side effects occur but they are transient and disappear spontaneously within the first few weeks of treatment. Hypokalemic paralysis, a potentially serious side effect reported by Chinese investigators in 66/8806 cases (0.75%) [6], was not observed in Brazilian men treated with gossypol [7] and it has since been suggested that the incidence of hypokalemia in China may be related more to regional differences in dietary intake than to effects of gossypol on serum potassium [8]. More recently, double-blind studies in gossypol-treated men in China have failed to confirm a causal relationship between gossypol and hypokalemia [9]. Interestingly, there is a high incidence of spontaneously occurring periodic hypokalemic paralysis in Oriental men [10].

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Log in via an institution
Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 39.99
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 54.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. National Coordinating Group on Male Antifertility Agents, Gossypol — A New Antifertility Agent for Males, Chinese Med. J., 4: 417 (1978).

    Google Scholar 

  2. Ibid.

    Google Scholar 

  3. F. Coutinho, J. F. Melo, I. Barbosa, and S. J. Segal, Biphasic action of gossypol in men, Fertil. Steril., in press (1984).

    Google Scholar 

  4. W. Bardin, Plasma testosterone in monkeys, in: “Gossypol- A possible male antifertility agent: Report of a Workshop, Vol. 1” ( G. Zaruchni and K. Osborne, eds.), Research Frontiers in Fertility Regulation, PARFR, Chicago (1981).

    Google Scholar 

  5. L. Shandilya, T. B. Clarkson, M. R. Adams, and J. C. Lewis, Effects of gossypol on reproductive and endocrine functions of male cynomolgus monkeys (Macaca fascicularis), Biol. Reprod., 27: 241 (1982).

    Article  PubMed  CAS  Google Scholar 

  6. National Coordinating Group on Male Antifertility Agents, 1978, op. cit. (see Ref. 1).

    Google Scholar 

  7. E. Coutinho, et al., 1983, op. cit. (see Ref. 3).

    Google Scholar 

  8. M. R. N. Prasad and E. Diczfalusy, Gossypol, in: “Proceedings of Second International Congress of Andrology,” Int. J. Androl. Suppl. 5:53 (1981).

    Article  Google Scholar 

  9. Z. Liu, 1981, personal communication.

    Google Scholar 

  10. A. McFadzean and R. Yeung, Periodic paralysis complicating thyrotoxicosis in Chinese, Brit. Med. J., 1: 45 (1967).

    Article  Google Scholar 

  11. M. B. Abou-Donia, Physiological effects and metabolism of gossypol, Residue Rev., 61: 125 (1978).

    Google Scholar 

  12. L. C. Berardi and L. A. Goldblatt, Gossypol, in: “Toxic Con- situents of Plant Foodstuffs” ( I. E. Liener, ed.), Academic Press, New York (1980).

    Google Scholar 

  13. X. S. Pu, Studies on the antifertility effect of gossypol, a new contraceptive for males, in: “Recent Advances in Fertility Regulation” ( C. F. Chang, D. Griffin, and A. Woolman, eds.), Atar S.A., Geneva (1980).

    Google Scholar 

  14. G. I. Zatuchni and K. Osborne, Gossypol — “A possible male anti- fertility agent, Report of a Workshop, Vol. 1,” Research frontiers in fertility, Chicago (1981).

    Google Scholar 

  15. M. R. Prasad and E. Diczfalusy, 1982, op. cit. (see Ref. 8).

    Article  CAS  Google Scholar 

  16. H. Jackson, “Gossypol. In Progress Towards a Male Contraceptive II, Vol. 8: ( S. L. Jeffcoate and M. Sandler, eds.), John Wiley and Sons, New York (1982).

    Google Scholar 

  17. S. P. Xue, Z. H. Zhou, Y. Liu, Y. W. Wu, and S. D. Zong, The pharmacokinetics of 14C-gossypol acetic acid in rats. I. Whole body and micro-autoradiographic studies on the distribution and fate of 14C-gossypol in the rat body, Doc. 4th Natl. Conf. Male Antifertil. Agents, Suzhou (1975), Acta Biol. Exp. Symp., 12: 179 (1979).

    Google Scholar 

  18. S. P. Xue, Y. Zhou, Y. Lin, Y. W. Liu, Y. W. Wu, and S. D. Zong, The pharmacokinetics of distribution, excretion and metabolism of studies on the kinetics of distribution, excretion and metabolism of 14C-gossypol acetic acid in the rat body, Doc. 4th Natl. Conf. Male Antifertil. Agents, Suzhou (1975), Acta Biol. Exp. Sin., 12: 275 (1979).

    Google Scholar 

  19. S. P. Xue, Y. Zhou, Y. Lin, Y. W. Liu, Y. W. Wu, and S. D. Zong, The pharmacokinetics of distribution, excretion and metabolism of studies on the kinetics of distribution, excretion and metabolism of 14C-gossypol acetic acid in the rat body, Doc. 4th Natl. Conf. Male Antifertil. Agents, Suzhou (1975), Acta Biol. Exp. Sin., 12: 275 (1979).

    Google Scholar 

  20. P. B. Coulson, R. Snell, and C. Parise,In vitroeffects of the antifertility agent, gossypol, on the reproductive organs in male mice, Int. J. Androl., 3: 507 (1980).

    Article  PubMed  CAS  Google Scholar 

  21. L. Zhou, C. Chen, N. Wang, and H. Lai, Observations on long- term administration of gossypol acetic acid to rats, Doc. 4th Natl. Conf. Male Antifertil. Agents, Suzhou (1975), Natl. Med. J. Chin., 60: 343 (1980).

    CAS  Google Scholar 

  22. S. A. Bozek, D. R. Jensen, and J. N. Tone, Scanning electron microscope study of spermatozoa from gossypol-treated rats, Cell Tissue Res., 219: 659 (1981).

    Article  PubMed  CAS  Google Scholar 

  23. M. A. Hadley and M. H. Burgos, Inhibition of rat epididymal sperm by gossypol, paper presented at the New York Academy of Sciences meeting on the Cell Biology of the Testis, April, 1981.

    Google Scholar 

  24. H. Jackson, Comparative effects of some antispermatogenic chemicals, in: “The Regulation of Mammalian Reproduction” ( S. Segal, R. Crozier, P. Carfman, and P. Candliffe, eds.), Thomas, Sprinfield, Illinois (1973).

    Google Scholar 

  25. P. B. Coulson, et al., 1980, op. cit. (see Ref. 20).

    Article  PubMed  CAS  Google Scholar 

  26. M. A. Hadley and M. H. Burgos, 1981, op. cit. (see Ref. 23).

    Google Scholar 

  27. A. Bozek, et al., 1981, op. cit. (see Ref. 22).

    Article  PubMed  CAS  Google Scholar 

  28. A. P. Hoffer, Ultrastructural studies of spermatozoa and the epithelial lining of the epididymis and vas deferens in rats treated with gossypol, Archives Androl., 8: 233 (1982).

    Article  CAS  Google Scholar 

  29. Z. P. Gu, S. D. Tsong, and C. C. Chang, Effect of gossypol on the testis and epididymis of rat and hamster, Contracept. Deliv. Systems 3 (3/4):279 abstract (1982).

    Google Scholar 

  30. Z. P. Gu, S. D. Tsong, and C. C. Chang, Effect of gossypol on the testis and epididymis of rat and hamster, Contracept. Deliv. Systems 3 (3/4):279 abstract (1982).

    Google Scholar 

  31. P. Wong, W. Lee, A. Tsang, W. Fu, and Q. Chen, Lack of an effect of gossypol on the epididymis of the rat, Contraception, 27: 391 (1983).

    Article  PubMed  CAS  Google Scholar 

  32. A. P. Hoffer, 1984, unpublished results.

    Google Scholar 

  33. M. C. Chang, Z. Gu, and S. K. Saksena, Effects of gossypol on the fertility of male rats, hamsters, and rabbits, Contraception, 21 (5): 451 (1980).

    Article  Google Scholar 

  34. D. W. Hahn, C. Rusticus, A. Probst, R. Homm, and A. N. Johnson, Antifertility and endocrine activities of gossypol in rodents, Contraception, 24: 97 (1981).

    Article  PubMed  CAS  Google Scholar 

  35. D. P. Waller, H. H. S. Fong, G. A. Cordel, and D. D. Soejarto, Antifertility effects of gossypol and its impurities on male hamsters, Contraception, 23: 653 (1981).

    Article  PubMed  CAS  Google Scholar 

  36. A. P. Hoffer, Effects of gossypol on the seminiferous epithelium in the rat: A light and electron microscope study, Biol. Reprod., 28: 1007 (1983).

    Article  CAS  Google Scholar 

  37. A. P. Hoffer, 1984, unpublished results.

    Google Scholar 

  38. R. Oko and F. Hrudka, Segmental aplasia of the mitochondrial sheath and sequelae induced by gossypol in rat spermatozoa, Biol. Reprod., 26: 183 (1982).

    Article  PubMed  CAS  Google Scholar 

  39. M. Flores and D. W. Fawcett, Ultrastructural effects of the antispermatogenic compound, WIN 18446 (bis dichloroacetyl diamine), Anat. Record., 172: 310 (1972).

    Google Scholar 

  40. A. H. ElJack and F. Hrudka, Pattern and dynamics of teratospermia induced in rams by parental treatment with ethylene dibromide, J. Ultrastruct. Res., 67: 124 (1979).

    Article  PubMed  CAS  Google Scholar 

  41. T. J. Lobl and J. Mathews, Effect of l-(2,4-dichlorobenzyl)- indazole-3-carboxylic acid on sperm tails in rhesus monkeys, J. Reprod. Fertil., 52: 275 (1978).

    Article  PubMed  CAS  Google Scholar 

  42. A. P. Hoffer, 1983, op. cit. (see Ref. 35).

    Article  PubMed  CAS  Google Scholar 

  43. I. H. Chen and R. D. Yates, Effects of simulated high altitude on hamster testes (Abstract), Anat. Rec., 178: 326 (1974).

    Google Scholar 

  44. P. M. Krueger, G. D. Hodgens, and R. J. Sherins, New evidence for the role of the Sertoli cell and spermatogonia in feedback control of FSH secretion in male rats, Endocrin., 95: 995 (1974)

    Article  Google Scholar 

  45. C. J. Flickinger, Regional differences in synthesis, intracellu lar transport, and secretion of protein in the mouse epididymis Biol. Reprod., 25: 871 (1981).

    Article  PubMed  CAS  Google Scholar 

  46. J. B. Kerr, K. A. Rich, and D. M. deKretser, Effects of exper- mental cryptorchidism on the ultrastructure and function of the Sertoli cell and peritubular tissue of the rat testis, Biol. Reprod., 21: 823 (1979).

    Article  PubMed  CAS  Google Scholar 

  47. M. Flores and D. W. Fawcett, 1972, op. cit. (see Ref. 38).

    Google Scholar 

  48. D. Waller, N. Bunyapraphatsara, A. Martin, C. Vournazos, M. Ahmed, D. Soejarto, G. Cordell, L. Russell, and J. Malone, Effect of (+)-gossypol on fertility in male hamsters, J. Androl 4: 276 (1983).

    PubMed  CAS  Google Scholar 

  49. A. P. Hoffer, 1984, unpublished results.

    Google Scholar 

  50. L. Zhuang, D. Phillips, G. Gunsalus, C. W. Bardin, and J. P. Mather, Effects of gossypol on rat Sertoli and Leydig cells in primary culture and established cell lines, J. Androl., 4: 336 (1983).

    PubMed  CAS  Google Scholar 

  51. A. P. Hoffer and R. Todd, 1984, unpublished results.

    Google Scholar 

  52. National Coordinating Group on Male Antifertility Agents, 1978, op. cit. (see Ref. 1).

    Google Scholar 

  53. S. P. Xue, Studies on the antifertility effect of gossypol, a new contraceptive for males, in: “Recent Advances in Fertility Regulation” ( C. F. Chang, D. Griffin, and A. Woolman, eds.), Atar S.A., Geneva (1981).

    Google Scholar 

  54. W. Bardin, 1980, op. cit. (see Ref. 4).

    Google Scholar 

  55. Z. Liu, G. Liu, L. Hei, R. Zhang, and C. Yu, Clinical trial of gossypol as a male antifertility agent, in: “Recent Advances in Fertility Regulation” ( C. F. Chang, D. Griffin, and A. Woolman, eds.), Atar S.A., Geneva (1981).

    Google Scholar 

  56. E. Coutinho, et al., 1983, op. cit. (see Ref. 3).

    Google Scholar 

  57. L. Shandilya, et al., 1982, op. cit. (see Ref. 5).

    Article  PubMed  CAS  Google Scholar 

  58. M. Hadley, T. Lin, and M. Dym, Effects of gossypol on the reproductive system of male rats, J. Androl., 2: 190 (1981).

    CAS  Google Scholar 

  59. M. C. Chang, et al., 1980, op. cit. (see Ref. 32).

    Article  Google Scholar 

  60. A. P. Hoffer, S. J. Klein, S. Weston, and J. A. Canick, Direct effects of gossypol on steroidogenic enzymes in rat and human testis microsomes, Endocrin., 112: 104 (1983).

    Article  Google Scholar 

  61. A. P. Hoffer and B. Hinton, Morphological evidence for a blood- epididymis barrier and the effects of gossypol on its integrity, Biol. Reprod., 30: 991 (1984).

    Article  PubMed  CAS  Google Scholar 

  62. L. F. Zhou and H. P. Lei, Recovery of fertility in rats after gossypol treatment, in: “Recent Advances in Fertility Regulation” (C. F. Chang, D. Griffin, and A. Woolman, eds.), Atar S.A., Geneva (1980), pp. 147 - 151.

    Google Scholar 

  63. L. F. Zhou and H. P. Lei, Recovery of fertility in rats after gossypol treatment, in: “Recent Advances in Fertility Regulation” (C. F. Chang, D. Griffin, and A. Woolman, eds.), Atar S.A., Geneva (1980), pp. 147 - 151.

    Google Scholar 

  64. A. P. Hoffer and R. Todd, 1984, op. cit. (see Ref. 50).

    Google Scholar 

  65. S. Wallenstein, C. L. Zucker, and J. L. Fleiss, Some statistical methods useful in circulation research, Circul. Res., 47 (1): 1 (1980).

    CAS  Google Scholar 

  66. C. C. Chang, Z. Gu, and Y. Y. Tsong, Studies on gossypol. I. Toxicity, antifertility, and endocrine analyses in male rats, Int. J. Fertil., 27: 213 (1982).

    PubMed  CAS  Google Scholar 

  67. Ibid.

    Google Scholar 

  68. Ibid. Hadley et al. (1981).

    Google Scholar 

  69. Ibid. Chang et al. (1982).

    Google Scholar 

  70. National Coordinating Group on Male Infertility Agents, 1978, op. cit. (see Ref. 1).

    Google Scholar 

  71. C. C. Chang, et al., 1982, op. cit. (see Ref. 65).

    PubMed  CAS  Google Scholar 

  72. A. P. Hoffer, 1983, op. cit. (see Ref. 35).

    Article  CAS  Google Scholar 

  73. Y. B. Ko, X. K. Lin, Y. H. Chang, Y. Z. Mar, S. E. Yu, and Y. Din, Studies on the antifertility effect of gossypol III. The determination of the quantities of gossypol in blood and related internal organs after administration of the drug in rats, Acta. Biol. Exp. Sinica, 12: 69 (1979).

    CAS  Google Scholar 

  74. Y. E. Wang, T. G. Lou, and X. C. Tang, Studies on the antifertility actions of cottonseed meal and gossypol, Acta Pharmacol. Sinic., 14: 663 (1979).

    CAS  Google Scholar 

  75. W. W. Tso and C. S.Lee, Effect of gossypol on boar spermatozoain vitro, Arch. Androl., 7: 85 (1981).

    Article  PubMed  CAS  Google Scholar 

  76. A. Blanco, On the functional significance of LDHX, John Hopkins Med. J., 146: 231 (1980).

    CAS  Google Scholar 

  77. Chi-Yu Lee and H. V. Mailing, Selective inhibition of sperm- specific lactate dehydrogenase-x by an antifertility agent, gossypol, Fed. Proc., 40 (3): 718 (1981).

    Google Scholar 

  78. K. Olgiati, A. P. Hoffer, and W. A. Toscano, Jr., Gossypol modulation of nucleotide metabolizing enzymes in the male reproductive tract, Biol. Reprod., 28 (Suppl): 159 (1983).

    Google Scholar 

  79. K. Olgiati, A. P. Hoffer, and W. A. Toscano, Effects of gossypol on nucleotide metabolism in the reproductive system of male rats, submitted.

    Google Scholar 

  80. Chi-Yu Lee, Y. S. Moon, J. H. Yan, and A. F. Chen, Enzyme inactivation and inhibition by gossypol, Molec. Cell Biochem., 47: 65 (1982).

    Article  PubMed  CAS  Google Scholar 

  81. A. Yoshida and E. Freese, Lactate dehydrogenase fromBacillusSubtilis, Meth. Enzymol., 41: 304 (1975).

    Article  PubMed  CAS  Google Scholar 

  82. C. Y. Lee and H. V. Mailing, 1981, op. cit. (see Ref. 76).

    Google Scholar 

  83. K. Olgiati, et al., 1983, op. cit. (see Ref. 79).

    Google Scholar 

  84. K. Olgiati, et al., 1984, op. cit. (see Ref. 80).

    Google Scholar 

  85. T. Braun and R. Dods, Development of a Mh2+-sensitive, “soluble” adenylate cyclase in rat testis, Proc. Natl. Acad. Sci. (USA), 72: 1097 (1975).

    Article  CAS  Google Scholar 

  86. A. R. Kornblihtt, M. M. Flawia, and H. M. Torres, Manganese ion dependent adenylate cyclase activity in rat testis: Purification and properties, Biochem., 20: 1262 (1981).

    Article  CAS  Google Scholar 

  87. Ibid.

    Google Scholar 

  88. Y. Salomon, G. Landos, and M. Rodbell, A highly sensitive adenylate cyclase assay, Anal. Biochem., 58: 541 (1974).

    Article  PubMed  CAS  Google Scholar 

  89. P. Margalith, Inhibitory effect of gossypol on microorganisms, Appl. Microbiol., 15: 952 (1967).

    PubMed  CAS  Google Scholar 

  90. P. H. Dorsett and E. E. Kerstine, Antiviral activity of gossypol and apogossypol, J. Pharm. Sci., 64: 1073 (1975).

    Article  PubMed  CAS  Google Scholar 

  91. E. M. Vermel, The search of antitumor substances of plant origin, Acta Uni. Int. Cancrum., 20: 211 (1964).

    CAS  Google Scholar 

  92. K. Wichmann, A. Vaheri, and T. Luukkainen, Inhibiting herpes simplex virus type 2 infection in human epithelial cells by gossypol, a potent spermicidal and contraceptive agent, Am. J. Obstet. Gynecol., 142 (5): 593 (1982).

    PubMed  CAS  Google Scholar 

  93. P. H. Dorsett and E. E. Kerstine, 1975, op. cit. (see Ref. 91).

    Google Scholar 

  94. Y. E. Wang, et al., 1979, op. cit. (see Ref. 73).

    CAS  Google Scholar 

  95. M. R. N. Prasad and E. Diczfalusy, 1981, op. cit. (see Ref. 8).

    Article  Google Scholar 

  96. A. Manmade, P. Herlihy, J. Quick, R. P. Duffley, M. Burgos, and A. P. Hoffer, Gossypol: Synthesis andin vitrospermicidal activity of isomeric hemigossypol derivatives, Ex- perientia, 39: 1276 (1983).

    CAS  Google Scholar 

  97. H. Jackson, 1973, op. cit. (see Ref. 24).

    Google Scholar 

  98. N. K. Kalla, Gossypol — the male antiffertility agent, IRCS-Med. Sci., 10: 766 (1982).

    CAS  Google Scholar 

  99. M. B. Abou-Donia, 1976, op. cit. (see Ref. 11).

    PubMed  CAS  Google Scholar 

  100. L. C. Berardi and L. A. Goldblatt, 1980, op. cit. (see Ref. 12).

    Google Scholar 

  101. Z. Liu, et al., 1981, op. cit. (see Ref. 54).

    Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Harvard Program in Urology (Longwood Area), 02115, Boston, Massachusetts, USA

    Anita P. Hoffer

  2. The Department of Anatomy, Harvard Medical School Brigham and Women’s Hospital, 02115, Boston, Massachusetts, USA

    Anita P. Hoffer

Authors
  1. Anita P. Hoffer
    View author publications

    You can also search for this author in PubMed Google Scholar

Editor information

Editors and Affiliations

  1. The Rockeller Foundation, New York, New York, USA

    Sheldon J. Segal

Rights and permissions

Reprints and permissions

Copyright information

© 1985 Plenum Press, New York

About this chapter

Cite this chapter

Hoffer, A.P. (1985). Ultrastructural, Biochemical, and Endocrine Studies on the Effects of Gossypol and its Isomeric Derivatives on The Male Reproductive Tract. In: Segal, S.J. (eds) Gossypol. Reproductive Biology. Springer, Boston, MA. https://doi.org/10.1007/978-1-4613-2809-4_13

Download citation

  • DOI: https://doi.org/10.1007/978-1-4613-2809-4_13

  • Publisher Name: Springer, Boston, MA

  • Print ISBN: 978-1-4612-9729-1

  • Online ISBN: 978-1-4613-2809-4

  • eBook Packages: Springer Book Archive

Publish with us

Policies and ethics

Search

Navigation