Immunosuppression of Fertility by LDH-C4

  • Erwin Goldberg
  • Joyce A. Shelton
Part of the Reproductive Biology book series (RBIO)


The natural response of the immune system to foreign proteins can be exploited in the development of a vaccine for control of fertility. Potential target antigens for such a vaccine include those that are found specifically on the surface of sperm and are absent from somatic tissues (reviewed by Aitken, 1982, Goldberg, 1983, Anderson and Alexander, 1983). Such antigens are uniquely suited to incorporation into a vaccine that may be applicable to both male and female use. They do not appear in the male until spermatogenesis begins, which is after the immune system has already become tolerant to “self-antigens”. Even after they appear, they are isolated from the male immune system by the blood-testes barrier. They are not found at all in female tissues. Thus these antigens can provoke antibody formation in either males or females. Furthermore, a vaccine would have the advantage over currently available contraceptive methodologies of not interfering with hormonal and metabolic functions.


Reproductive Tract Human Sperm Diphtheria Toxoid Muramyl Dipeptide Mouse Sperm 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. Aitken, R. J., 1982, The contraceptive potential of antisperm antibodies, in: “Progress Towards a Male Contraceptive,” S.J. Jeffcoate and M. Sandler, eds., John Wiley and Sons, Ltd., London, pp. 109–134.Google Scholar
  2. Alvarez, J. G. and Storey, B. T., 1984, Assessment of cell damage caused by spontaneous lipid peroxidation in rabbit sperm, Biol. Reprod., 30: 323–331.PubMedCrossRefGoogle Scholar
  3. Anderson, D.J. and Alexander, N. J., 1983, A new look at antifertility vaccines, Fertil. Steril., 40: 557–571.PubMedGoogle Scholar
  4. Beer, A. E. and Neaves, W. B., 1979, Antigenic status of semen from the viewpoints of the female and male, Fertil. Steril., 29: 3–22.Google Scholar
  5. Beyler, S. A., Wheat, T. E. and Goldberg, E., 1985, Binding of antibodies against antigenic domains of murine lactate dehydrogenase-C4 to human and mouse spermatozoa, Bio1. Reprod., 32: 1201–1210.CrossRefGoogle Scholar
  6. Eventoff, W., Rossmann, M. G., Taylor, S. S., Torff, H. J., Meyer, H., Keil, W., and Kiltz, H. H., 1977, Structural adaptations of lactate dehydrogenase isozymes, Proc. Nat. Acad. Sci. U.S.A., 74: 2677–2681.CrossRefGoogle Scholar
  7. Goldberg, E., 1971, Immunochemical specificity of lactate dehydrogenase-X, Proc. Nat. Acad. Sci. U.S.A., 68: 349–352.CrossRefGoogle Scholar
  8. Goldberg, E., 1977, Isozymes in testes and spermatozoa, in: “Isozymes: Current Topics in Biological and Medical Research,” M. S. Rattazzi, J.G. Scandelios, G. S. Whitt, eds., Alan R. Liss, Inc., New York, Vol. 1, pp. 79–124.Google Scholar
  9. Goldberg, E., 1983, Current status of research on sperm antigens: potential applications as contraceptive vaccines, in: “Research Frontiers in Fertility Regulation,” G. I. Zatuchni, ed., Program for Applied Research on Fertility Regulation, Chicago, Vol. 2, pp. 6–11.Google Scholar
  10. Goldberg, E., Gonzales-Prevatt, V., and Wheat, T.E., 1981, Immunosuppression of fertility in females by injection of spermspecific LDH-C4 (LDH-X): prospects for development of a contraceptive vaccine, in: “Human Reproduction,” Proceedings of the IIIrd World Congress, K. Semm and L. Mettler, eds., Excerpta Medica, Amsterdam, pp. 360–363.Google Scholar
  11. Goldberg, E., Wheat, T.E., 1976, Induction of infertility in male rabbits by immunization with LDH-X, in: “Regulatory Mechanisms of Male Reproductive Physiology,” C. H. Spilman, T. J. Lobl, K. T. Kirton, eds., American Elsevier Publ. Co., New York, pp. 133–138.Google Scholar
  12. Goldberg, E., Wheat, T. E., Powell, J. E., Stevens, V. C., 1981, Reduction of fertility in female baboons immunized with lactate dehydrogenase C4, Fertil. Steril., 35: 214–217.PubMedGoogle Scholar
  13. Jones, W. R., 1980, Immunological factors in male and female infertility, in: “Immunological Aspects of Reproduction and Fertility Control,” J. P. Hearn, ed., Univ. Park Press, Baltimore, pp. 105–140.CrossRefGoogle Scholar
  14. Jones, W.R., 1982, Immunization against spermatozoal antigens, in: “Immunological Aspects of Reproduction and Fertility Regulation,” Blackwell Scientific Publications, Oxford, pp. 91–146.Google Scholar
  15. Kille, J. W., Goldberg, E., 1979, Female reproductive tract immunoglobulin responses to a purified sperm-specific antigen (LDH-C4), Biol. Reprod. 20: 863–871.PubMedGoogle Scholar
  16. Lerum, J. E., and Goldberg, E., 1974, Immunological impairment of pregnancy in mice by lactate dehydrogenase-X, Biol. Reprod., 11: 108–115.PubMedCrossRefGoogle Scholar
  17. Li, S. S.-L., Feldman, R. J., Okabe, M., and Pan, Y.-C. E., 1983a, Molecular features and immunological properties of lactate dehydrogenase C4 isozymes from mouse and rat testes, J. Bio1. Chem., 258: 7017–7032.Google Scholar
  18. Li, S. S.-L., Fitch, W. M., Pan, Y.-C. E., and Sharief, F. S., 1983b, Evolutionaly relationships of vertebrate lactate dehydrogenase isozymes, A4 (muscle), B4 (heart), and C4 (testis), J. Bio1. Chem., 258: 7029–7032.Google Scholar
  19. Montgomery, P. C., Lemaitre-Coelho, I. M., and Vaer, J.-P., 1980, A common mucosal immune system. Antibody expression in secretions following gastro-intestinal stimulation, Immunol. Commun., 9: 705–713.PubMedGoogle Scholar
  20. Musick, W. D. L., and Rossmann, M. G., 1979a, The structure of mouse testicular lactate dehydrogenase isoenzyme C4 at 2.9Å resolution, J. Biol. Chem., 254: 7611–7620.PubMedGoogle Scholar
  21. Musick, W. D. L., and Rossmann, M. G., 1979b, The tentative amino acid sequencing of lactate dehydrogenase C4 by X-ray diffraction analysis, J. Biol. Chem., 254: 7621–7623.PubMedGoogle Scholar
  22. Naz, R., Alexander, N., Isahakia, M., 1984, Monoclonal antibody to a human germ cell membrane glycoprotein that inhibits fertilization, Science, 225: 342–344.PubMedCrossRefGoogle Scholar
  23. O’Rand, M. G., 1981, Inhibition of fertility and sperm-zona binding by antiserum to the rabbit sperm membrane autoantigen RSA-1, Biol. Reprod., 25: 621–628.PubMedCrossRefGoogle Scholar
  24. O’Rand, M. G., and Irons, G. P., 1984, Monoclonal antibodies to rabbit sperm autoantigens. II. Inhibition of human sperm penetration of zona-free hamster eggs, Biol. Reprod., 30: 731–736.PubMedCrossRefGoogle Scholar
  25. O’Rand, M. G., Irons, G. P., and Porter, J. P., 1984, Monoclonal antibodies to rabbit sperm autoantigens. I. Inhibition of in vitro fertilization and localization on the egg, Bio1. Reprod., 30: 721–729.CrossRefGoogle Scholar
  26. O’Rand, M. G., and Porter, J. P., 1982, Purifications of rabbit sperm autoantigens by preparative SDS gel electrophoresis: amino acid and carbohydrate content of RSA-1, Biol. Reprod., 27: 713–721.PubMedCrossRefGoogle Scholar
  27. O’Rand, M. G., and Romrell, L. J., 1981, Localization of a single sperm membrane autoantigen (RSA-1) on spermatogenic cells and spermatogonia, Dev. Biol., 84: 322–331.PubMedCrossRefGoogle Scholar
  28. Saling, P. M., Raines, L. M., and O’Rand, M. G., 1983, Monoclonal antibody against mouse sperm blocks a specific event in the fertilization process, J. Exp. Zool., 227: 481–486.PubMedCrossRefGoogle Scholar
  29. Shelton, J. A., Abe, M., and Goldberg, E., 1983, Cellular and local immunity to sperm-specific lactate dehydrogenase-C4, J. Reprod. Immunol. (suppl. July), p. 26.Google Scholar
  30. Shelton, J. A., Alexander, N. J., and Goldberg, E., 1984, Local secretory immunity to sperm-specific lactate dehydrogenase C4 in the reproductive tract of the female rhesus macaque, Biol. Reprod., (suppl. #1), 30: 74.CrossRefGoogle Scholar
  31. Shelton, J. A., and Goldberg, E., 1985, Induction of cell-mediated cytotoxic immunity to sperm-specific lactate dehydrogenase-C4 in SJL/J female mice, Biol. Reprod., 32: 556–560.PubMedCrossRefGoogle Scholar
  32. Stevens, V. C., Cinader, B., Powell, J. E., Lee, A. C., and Koh, S. W., 1981a, Preparation and formulation of a human chorionic gonadotropin anti-fertility vaccine: selection of adjuvant and vehicle, Amer. J. Reprod. Immunol., 1: 315–321.Google Scholar
  33. Stevens, V. C., Cinader, B., Powell, J. E., Lee, A. C., and Koh, S. W., 1981b, Preparation and formulation of a human chorionic gonadotropin anti-fertility vaccine: selection of a peptide immunogen, Amer. J. Reprod. Immunol., 1: 307–314.Google Scholar
  34. Tomasi, T. B., 1980, The secretory immune system, in: “Immunological Aspects of Infertility and Fertility Regulation”, D. S. Dhindsa, and G. F. B. Schumacher, eds., Elsevier-N. Holland, Inc., New York, pp. 23–31.Google Scholar
  35. Tomasi, T. B., and Bienenstock, J., 1968, Secretory immunoglobulins, in: “Advances in Immunology”, F. J. Dixon, Jr. and H. G. Kunkel, eds., Academic Press, New York, Vol. 9, pp. 1–96.Google Scholar
  36. Tung, K. S. K., 1983, Experimental models of autoimmunity and isoimmunity to sperm, in: “Immunology of Reproduction,” T. G. Wegmann and T. J. Gall, eds., Oxford University Press, New York, pp. 404–423.Google Scholar
  37. Wheat, T. E., and Goldberg, E., 1977, Isolation of the sperm-specific lactate dehydrogenase from mouse, rabbit and human testes and human spermatozoa, in: “Immunological Influences on Human Fertility”, B. Boettcher, ed., Harcourt Brace Jovanovich, Australia, pp. 221–227.Google Scholar
  38. Wheat, T. E., and Goldberg, E., 1983, Sperm-specific lactate dehydrogenase C4: antigenic structure and immunosuppression of fertility, in: “Isozymes: Current Topics in Biological and Medical Research”, M. C. Rattazzi, J. G. Scandelios, and G. S. Whitt, Alan R. Liss, Inc., New York, Vol. 7, pp. 113–130.Google Scholar
  39. Wheat, T. E., and Goldberg, E., 1985, Antigenic domains of the spermspecific lactate dehydrogenase, Molec. Immunol., in press.Google Scholar
  40. Wheat, T. E., and Goldberg, E., 1985, Immunochemical dissection of the testes-specific isozyme, lactate dehydrogenase, Ann. NY Acad. Sci., 438: 156–159.CrossRefGoogle Scholar
  41. Wheat, T. E., Shelton, J. A., Gonzales-Prevatt, V., and Goldberg, E., 1985, The antigenicity of synthetic peptide fragments of LDH-C4, Molec. Immunol., in press.Google Scholar
  42. Wolf, D. P., Tokoloski, J. E., Dandekar, P., and Bechtol, K. B., 1983, Characterization of human sperm surface antigens with monoclonal antibodies, Biol. Reprod., 29: 713–723.PubMedCrossRefGoogle Scholar

Copyright information

© Plenum Press, New York 1986

Authors and Affiliations

  • Erwin Goldberg
    • 1
  • Joyce A. Shelton
    • 1
  1. 1.Dept of Biochemistry, Molecular Biology & Cell BiologyNorthwestern UniversityEvanstonUSA

Personalised recommendations