Disillusions and Hopes About Zona Pellucida Glycoproteins

  • Shobha Sehgal
  • S. K. Gupta
Part of the Progress in Vaccinology book series (VACCINOLOGY, volume 1)


Today there are serious concerns about the doubling time of the world’s population, which is getting progressively shorter (64). On the Indian scene, the continent has only 2.4% of world’s land area to support 14% of the population. The physical quality of life index is barely 40, which is far below the rest of the developed world (95 for the United States, 96 for Japan), and despite desperate efforts, the birth rate stands at 33 per 1,000. It is estimated that as many as 108 million couples are in the reproductive age group. There are 63,000 births against 25,000 deaths every day, and 13 million newborns added each year. The department of Science and Technology, Ministry of Health has rightly identified contraception as a thrust area. Over the last two decades several products have been floated for temporary control of fertility. These have largely been synthetic hormones but major drawbacks are that they have to be administered frequently over prolonged periods and have unacceptable side effects. It is apparent that the conventional modes of antifertility measures have been inadequate and impractical, Since vaccination has been an accepted mode for prevention of infectious diseases, it was deemed logical to devise vaccines for birth control as well. Theoretically it is possible to intercept pregnancy right from the hypothalamus to pituitary, gonads, and gametes (63). Contraceptive vaccines using β-subunit of human chorionic gonadotropins (HCG) and C-terminal peptide have already entered phase-I clinical trials (59,65). There are indications that gametes may also offer suitable modalities for birth control.


Zona Pellucida Passive Immunization Fertility Control Ovarian Weight Immunological Approach 
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. 1.
    Aitkin RJ, Richardson DW: Immunization against zona pellucida antigen, in Heap JP (ed):Immunological Aspects of Reproduction and Fertility Control. Lancaster, UK, MTP Press Ltd, 1980, pp 173–201.Google Scholar
  2. 2.
    Aitkin RJ, Richardson DW: Mechanism of sperm binding inhibition by antizona antisera. Gamete Res 1981;4:41–47.CrossRefGoogle Scholar
  3. Bamezai A, Tal war GP: Personal communication, 1986.Google Scholar
  4. 4.
    Bedford JM: Sperm/egg interaction: The specificity of human spermatozoa. Anat Ree 1977;188:477–488.CrossRefGoogle Scholar
  5. 5.
    Dean J, Ringuette M, Sobieski DA, et al; Molecular genetics of the mouse zona pellucida: Implications for fertilization and early development, in Talwar GP (ed): Immunological Approaches to Contraception and Promotion of Fertility. New York, Plenum Press, 1986, pp 241–249.Google Scholar
  6. 6a.
    Drell DW, Wood DM, Bundman D, et al: Immunological comparison of antibodies to zonae pellucidae in rats and rabbits. Biol Reprod 1984;30:435–444.PubMedCrossRefGoogle Scholar
  7. 6b.
    Drell DW, Dunbar BS: Monoclonal antibodies to rabbit and pig zonae pellucidae distinguish species specific as well as shared antigenic determinants. Biol Reprod 1984;30:445–457.PubMedCrossRefGoogle Scholar
  8. 7.
    Dudkiewicz AB, Noske IG, Shivers CA: Inhibition of implantation in the golden hamster by zona precipitating antibody. Fertil Steril 1975;26:686.PubMedGoogle Scholar
  9. 8.
    Dunbar BS, Raynor BD: Characterization of porcine zonae pellucida antigen. Biol Reprod 1980;22:941–954.PubMedCrossRefGoogle Scholar
  10. 9.
    Dunbar BS, Wardip MD, Hedrick JL: Isolation, physiochemical properties and macromolecular composition of zona pellucida from porcine oocytes. Biochem 1980;2:356–365.Google Scholar
  11. 10.
    Dunbar BS, Liu C, Sammons DW: Identification of the three major proteins of porcine and rabbit zonae pellucida by high resolution two dimensional gel electrophoresis: Comparison with serum, follicular fluid and ovarian cell proteins. Biol Reprod 1981;24:1111–1124.PubMedGoogle Scholar
  12. 11.
    Dunbar BS: Morphological, biochemical and immunochemical characterization of the mammalian zona pellucida, in Hartman J (ed): Mechanism and Control of Animal Fertilization. New York, Academic Press, 1983, p 139.Google Scholar
  13. 12.
    Dunbar BS, Wolgemuth DJ: Structure and function of the mammalian zona pellucida: a unique extra cellular matrix. Mod Cell Biol 1984;3:77–111.Google Scholar
  14. 13.
    Garavagno A, Rosada J, Barros C, et al: Some characteristics of the zona pellucida antigen in the hamster. J Exp Zool 1974; 189:37.PubMedCrossRefGoogle Scholar
  15. 14.
    Gerrity M, Niu E, Dunbar BS: A specific radioimmunoassay for evaluation of serum antibodies to zona pellucida antigens. J Reprod Immunol 1981;3:59–70.PubMedCrossRefGoogle Scholar
  16. 15.
    Gulyas BJ, Gwatkin RBL, Yuan LC: Active immunization of cynomolgus monkeys (Macaca fascicularis) with porcine zona pellucida. Gamete Res 1983;7(4): 299–307.CrossRefGoogle Scholar
  17. 16.
    Gupta SK, Sehgal S; Immunocontraception in rabbits using porcine zona pellucida antigens. Bull Post-Graduate Institute, Chandigarh, India, 1985;19,2. 54–58.Google Scholar
  18. 17.
    Gupta SK, Bhatnagar P, Dunbar BS, et al: Immunohistological studies during immunization with porcine zona pellucida, in Talwar GP (ed): Immunological Approaches to Contraception and Promotion of Fertility. New York, Plenum Press, 1986, pp 269–275.Google Scholar
  19. 18.
    Gwatkin RBL, Williams DT: Receptor activity of the hamster and mouse solubilized zona pellucida before and after the zona reaction. J Reprod Fertil 1977;49:55–59.PubMedCrossRefGoogle Scholar
  20. 19.
    Gwatkin RBL, Williams DT, Carlos DJ: Immunization of mice with heat-solubilized hamster zonae: Production of anti-zona antibody and inhibition of fertility. Fertil Steril 1977;28:871–877.PubMedGoogle Scholar
  21. 20.
    Gwatkin RBL, Williams DT: Immunization of female rabbits with heat-solubilized bovine zonae: Production of anti-zona antibody and inhibition of fertility. Gamete Res 1978;1:19–26.CrossRefGoogle Scholar
  22. 21.
    Gwatkin RBL, Anderson OF, Williams DT: Large scale isolation of bovine and pig zonae pellucidae: Chemical, immunological, and receptor properties. Gamete Res 1980;3:217.CrossRefGoogle Scholar
  23. Isojima S, Koyama K, Hasegawa A, et al: Monoclonal antibodies to porcine zona pellucida antigens and their inhibitory effects on fertilization. J Reprod Immunol 1984;6(2):77.PubMedCrossRefGoogle Scholar
  24. 23.
    Jilek F, Pavlok A: Antibodies against mouse ovaries and their effect on fertilization in vitro and in vivo in the mouse. J Reprod Fertil 1975;42:377–380.PubMedCrossRefGoogle Scholar
  25. 24.
    Jones WR: Immunization against the oocyte, in: Immunological Fertility Regulation. London, Blackwell Scientific Publication, 1982, pp 147–173.Google Scholar
  26. 25.
    Mahi CA, Yanagimachi R: Prevention of in vitro fertilization of canine oocytes by anti-ovary anti-sera: A potential approach to fertility control in the bitch. J Exp Zool 1979;210:129–135.PubMedCrossRefGoogle Scholar
  27. 26.
    Mahi CA, Huang TF, Yanagimachi R: Infertility in bitches induced by active immunization with porcine zonae pellucida. J Exp Zool 1982;222:89–95.CrossRefGoogle Scholar
  28. 27.
    Mahi-Brown CA, Yanagimachi R, Hoffman JC, et al: Fertility control in the bitch by active immunization with porcine zona pellucidae. Use of different adjuvants and patterns of oestradiol and progesteron levels in estrous cycles. Biol Reprod 1985;32:761–777.PubMedCrossRefGoogle Scholar
  29. 28.
    Mahi-Brown CA: Prospects for control of fertility in the female dog by active immunization with porcine zona pellucida proteins, in Talwar GP (ed): Immunological Approaches to Contraception and Promotion of Fertility. New York, Plenum Press, 1986, pp 301–309.Google Scholar
  30. 29.
    Nicolson GL, Yanagimachi R, Yanagimachi H: Ultrastructural localization of lectin binding sites on the zonae pellucidae and plasma membranes of mammalian eggs. J Cell Biol 1975;66:263–274.PubMedCrossRefGoogle Scholar
  31. 30.
    Oikawa T, Yanagimachi R, Nicolson GL: Species differences in the lectin-binding sites on the zona pellucida. J Reprod Fertil 1975;43:137.PubMedCrossRefGoogle Scholar
  32. 31.
    Oikawa T: A simple method for the isolation of a large number of ova from pig ovaries. Gamete Res 1978; 1:265.CrossRefGoogle Scholar
  33. 32.
    Ownby CL, Shivers CA: Antigens of the hamster ovary and effects of anti-ovary serum on eggs. Biol Reprod 1972;6:310–318.PubMedGoogle Scholar
  34. 33.
    Palm VS, Sacco AG, Syner FN, et al: Tissue specificity of porcine zona pellucida antigenis) tested by radio immunoassay, Biol Reprod 1979;21:709–713.PubMedCrossRefGoogle Scholar
  35. 34.
    Peterson RN, Russell LD, Bundman D, et al: Sperm egg interaction: Evidence for boar sperm plasma membrane receptor for porcine zona pellucida. Science 1980;207:73–74.PubMedCrossRefGoogle Scholar
  36. 35.
    Sacco AG, Shivers CA: Localization of tissue-specific antigens in rabbit ovary, oviduct and uterus by the fluorescent antibody technique. J Reprod Fertil 1973;32:415.PubMedCrossRefGoogle Scholar
  37. 36.
    Sacco AG, Palm VS: Heteroimmunization with isolated pig zonae pellucidae. J Reprod Fertil 1977;51:165–168.PubMedCrossRefGoogle Scholar
  38. Sacco AG: Antigenicity of the human zona pellucida. Biol Reprod 1977; 16:158PubMedCrossRefGoogle Scholar
  39. 38.
    Sacco AG: Antigenic cross reactivity between human and pig zonae pellucidae. Biol Reprod 1977;16:164–173.PubMedCrossRefGoogle Scholar
  40. 39.
    Sacco AG: Immunological specificity of anti-zona binding to zona pellucida. J Exp Zool 1978;204:181–198.PubMedCrossRefGoogle Scholar
  41. Sacco AG, Shivers CA: Immunologic inhibition of development, in:Methods in Mammalian Reproduction, vol 9. New York, Academic Press, 1978, pp 203–228.Google Scholar
  42. 41.
    Sacco AG: Inhibition of fertility in mice by passive immunization with antibodies to isolated zonae pellucidae. J Reprod Fertil 1979;56:533–537.PubMedCrossRefGoogle Scholar
  43. 42.
    Sacco AG, Subramanian MG, Yurewicz EC: Application of a radioimmunoassay (RIA) for monitoring immune response to porcine zonae pellucidae (41172). Proc Soe Exp Biol Med 1981;1967:318–326.Google Scholar
  44. 43.
    Sacco AG, Subramanian MG, Yurewicz EC: Active immunization of mice with porcine zona pellucida: Immune response and effect on fertility. J Exp Zool 1981;218:405–418.PubMedCrossRefGoogle Scholar
  45. 44.
    Sacco AG, Subramanian MG, Yurewicz EC: Passage of zona antibodies via placenta and milk following active immunization of female mice with porcine zona pellucida. J Reprod Immunol 1981;3:313–322.PubMedCrossRefGoogle Scholar
  46. 45.
    Sacco AG, Yurewicz EC, Subramanian MG, et al: Zona pellucida composition: species cross reactivity and contraceptive potential of antiserum to a purified pig zona antigen (PPZA). Biol Reprod 1981;25:997–1008.PubMedCrossRefGoogle Scholar
  47. Sacco AG, Subramanian MG, Yurewicz EC, et al: Heteroimmunization of squirrel monkeys (Saimiri Sciureous) with a purified porcine zonae antigen (PPZA): Immune response and biologic activity of antiserum. Fertil Steril 1983;39(3):350–358.PubMedGoogle Scholar
  48. 47.
    Sacco AG, Yurewicz EC, Zhang S: Immunoelectrophoretic analysis of the porcine zone pellucida. J Reprod Fertil 1983;68:21–31.PubMedCrossRefGoogle Scholar
  49. 48.
    Sacco AG, Subramanian MG, Yurewicz EC: Association of sperm receptor activity with a purified pig zona antigen (PPZA). J Reprod Immunol 1984;6:89–103.PubMedCrossRefGoogle Scholar
  50. 49.
    Sacco AG, Subramanian MG, Yurewicz EC, et al: Antigenic profile and impact of immunization with zonae pellucida antigens in primates, in Talwar GP (ed): Immunological Approaches to Contraception and Promotion of Fertility. New York, Plenum Press, 1986, pp 277–290.Google Scholar
  51. 51.
    Sacco A: 1986, Personal communicationGoogle Scholar
  52. 51a.
    Sehgal S, Gupta SK: Long term effects of immunization with porcine zona pellucida in rabbits, 1987, in press.Google Scholar
  53. 51b.
    Sehgal S, Bhatnagar P, Vasishta RKV, et al: Immunization of rhesus monkeys with porcine zona antigen: Effect on cyclicity. (Manuscript in preparation.)Google Scholar
  54. 52.
    Shivers CA, Dudkiewicz AB, Franklin LE, et al: Inhibition of sperm egg interaction by specific antibody. Science 1972;178:1211–1213PubMedCrossRefGoogle Scholar
  55. 53.
    Shivers CA: Immunological interference with fertilization, in Diczfalusy E (ed): Immunological Approaches to Fertility Control. Stockholm, Karolinska Institute!, 1974,p 223.Google Scholar
  56. 54.
    Shivers CA, Dunbar BS: Autoantibodies to zona pellucida. A possible cause for infertility in women. Science 1977;197:1087–1090.CrossRefGoogle Scholar
  57. 55.
    Shivers CA, Gengozian N, Franklin S, et al: Antigenic cross reactivity between human and marmoset zonae pellucidae, a potential target for immuno countraception. J Med Primatol 1978;7:242.PubMedGoogle Scholar
  58. 56.
    Shivers CA, Sieg PM, Kitchen H: Pregnancy prevention in the dog: Potential for an immunological approach. J Am Anim Hasp Assoc 1981;17:823–828.Google Scholar
  59. Skinner SM, Mills T, Kirchick HJ, et al: Immunization with zona pellucida proteins result in abnormal ovarian follicular differentiation and inhibition of gonadotropin induced steroid secretion. Endocrinology 1984;115(6):2418–2432.PubMedCrossRefGoogle Scholar
  60. 58.
    Skinner SM, Dunbar BS: Species variation in the zona pellucida, in Talwar GP (ed): Immunological Approaches to Contraception and Promotion of Fertility. New York, Plenum Press, 1986, pp 251–268.Google Scholar
  61. 59.
    Stevens VC: Current status of ant fertility vaccines using gonadotropin immunogens. Immunol Today 1986;7(12):369–374.CrossRefGoogle Scholar
  62. 60.
    Subramanian MG, Yurewicz EC, Sacco AG: Specific radioimmunoassay for the detection of a purified porcine zona pellucida antigen (PPZA). Biol Reprod 1981;24:933–943.PubMedCrossRefGoogle Scholar
  63. 61.
    Subramanian MG, Yurewicz EC, Sacco AG: Studies on the stability of 1251 -purified porcine zonae antigen (PPZA) obtained by chloramine-T Glucose oxidase with lactoperoxidase and N-bromosuccinimide iodination procedures. Gamete Res 1985;11:283–288.CrossRefGoogle Scholar
  64. 62.
    Suman Bamezai AK, Das C, Tal war GP: Effect of immunization of primates against porcine zonae on fertility and hormone profiles, in Talwar GP (ed): Immunological Approaches to Contraception and Promotion of Fertility. New York, Plenum Press, 1986, pp 291–299.Google Scholar
  65. 63.
    Talwar GP: Immunology in reproduction. J Reprod Med 1979;22(2):61–76.PubMedGoogle Scholar
  66. 64.
    Talwar GP: Immunological approaches to contraception: The need, basic promise and overview, in: Immunological Approaches to Contraception and Promotion of Fertility. New York & London, Plenum Press, 1986, pp 17–24.Google Scholar
  67. 67.
    Talwar GP: Phase I clinical trials using ß-HCG vaccine, 1986, personal communication.Google Scholar
  68. 66.
    Tsunoda Y, Chang MC: Effect of anti-rat ovary anti-serum on the fertilization of rat, mouse, and hamster eggs in vivo and in vitro. Biol Reprod 1976;14:354–361.PubMedCrossRefGoogle Scholar
  69. 67.
    Tsunoda Y, Chang MC: In vivo and in vitro fertilization of hamster, rat and mouse eggs after treatment with anti-hamster ovary antiserum, J Exp Zool 1976; 195: 409–416.PubMedCrossRefGoogle Scholar
  70. 68.
    Tsunoda Y, Sugie T: Inhibition of fertilization in mice by antizona pellucida serum. Jpn J Zool Sci 1977;48:784.Google Scholar
  71. 69.
    Tsunoda Y, Chang MC: Effect of anti-sera against eggs and zonae pellucidae on fertilization and development of mouse eggs in vivo and in culture. J Reprod Fertil 1978;54:233–237.PubMedCrossRefGoogle Scholar
  72. 70.
    Tsunoda Y, Chang MC: The suppressive effect of sera from old female mice on in vitro fertilization and blastocyst development. Biol Reprod 1979;20:355–361.PubMedCrossRefGoogle Scholar
  73. 71.
    Tsunoda Y, Sugie T, Mori J: Quantitative determination of litres of antizona serum. J ExpZool 1979:207:315.PubMedCrossRefGoogle Scholar
  74. 72.
    Tsunoda Y, SomaT, Sugie T: Inhibition of fertilization in cattle by passive immunization with anti-zona pellucida serum. Gamete Res 1981;4:133–138.CrossRefGoogle Scholar
  75. 73.
    Wolgemuth DJ, Celenza J, Bund man DS, et al: Formation of the rabbit zona pellucida and its relationship to ovarian follicular development. Dev Biol 1984;106:1–14.PubMedCrossRefGoogle Scholar
  76. 74.
    Watanabe M, Muramatsu T, Shirne H, et al: Discrete distribution of binding sites for dolichos biflorus agglutinin (DBA) and for peanut agglutinin (PNA) in mouse organ tissues. J Histochem Cytochem 1981;29:779–790.PubMedCrossRefGoogle Scholar
  77. 75.
    Wood DM, Dunbar BS: Direct detection of two cross reactive antigens between porcine and rabbit zona pellucida by radioimmunoassay and Immunoelectrophoresis. J ExpZool 1981;217:423–433.PubMedCrossRefGoogle Scholar
  78. 76.
    Wood DM, Celilia L, Dunbar BS: Effect of alloimmunization and heteroimmunization with zonae pellucidae on fertility in rabbits. Biol Reprod 1981;25:439–450.PubMedCrossRefGoogle Scholar
  79. 77.
    Yanagimachi R: Specificity of sperm-egg interaction, in Edidin M, Johnson MH (eds): Immunobiology of Gametes. London and New York, Cambridge Univ Press, 1977, pp 187–207.Google Scholar
  80. 78.
    Yurewicz EC, Sacco AG, Subramanian MG: Isolation and preliminary characterization of a purified pig zona antigen (PPZA) from porcine oocytes. Biol Reprod 1983;29:511–523.PubMedCrossRefGoogle Scholar

Copyright information

© Springer-Verlag New York Inc. 1988

Authors and Affiliations

  • Shobha Sehgal
  • S. K. Gupta

There are no affiliations available

Personalised recommendations