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C. J. Henderson, M. J. Hulme and R. J. Aitken

Summary. The notion of a contraceptive vaccine based on gamete-specific surface antigens was first proposed over a decade ago, as the result of in-vitro and in-vivo studies, and in recent years has been the subject of intensive research. In particular, the zona pellucida has attracted much attention as a potential target for immunological intervention in the fertilization process. Such is the rapidly-expanding nature of research into the biochemical and biological characterization of this structure, that a review of the implications for the development of a contraceptive vaccine seems timely.

Keywords: zona pellucida; contraceptive vaccine; antibodies

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R. J. Aitken, E. Holme, D. W. Richardson and M. Hulme

Summary. Intact and univalent antibodies were prepared against mechanically isolated mouse zonae pellucidae solubilized in a variety of ways (heat, low pH, SDS, urea and trypsin). The antisera bound avidly and specifically to solubilized iodinated zona antigens and the intact zona structure.

When the concentrations of immunoreactive Fab material in the intact and univalent antibody preparations were equalized and compared for their ability to block the sperm-binding stage of fertilization, only the intact γ-globulin preparations possessed antifertility activity. These results indicate that antibodies raised against intact solubilized zonae pellucidae block fertilization by cross-linking antigens on the outer zona surface, thereby indirectly masking the sperm receptor sites. The integrity of these surface components did not appear to be affected by solubilization procedures that disrupt non-covalent bonds (heating, low pH, SDS and urea) although they did appear to be adversely affected by trypsin treatment.

None of the antisera tested contained antibodies directed against the sperm receptor site indicating that these critical components lack immunogenicity.

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R. J. Aitken, M. J. Hulme, C. J. Henderson, T. B. Hargreave and A. Ross

Summary. Washed ejaculated human spermatozoa were surface labelled with 125I, using solid phase (iodogen) or enzymic (lactoperoxidase) methods, while membrane components possessing terminal galactose or galactosamine residues were labelled with the galactose oxidase–sodium [3H]borohydride technique. All three procedures revealed the presence of 2 major labelled surface components. The first comprised a broad band of radioactivity migrating just behind the ion front on SDS-PAGE, which could be extracted with chloroform and methanol, suggesting a lipid-like composition. The second fraction exhibited properties consistent with a major glycoprotein component of the human sperm plasma membrane, giving a peak of radioactivity with M r = 20 000, within which a discrete doublet of bands (M r = 17 000 and 19 000) could be resolved by autoradiography. A more detailed analysis of the labelled protein fraction after TCA precipitation revealed a number of other surface components, the major ones of which exhibited M r values of 30 000, 45 000, 66 000, 115 000 000 and 160 000.

Western blot analysis was then used to determine whether any of the surface components described above interacted with the γ-globulin fraction of antisera obtained from patients exhibiting idiopathic autoimmunity against sperm antigens. Using a purified membrane preparation as the target, antibodies were detected against numerous high molecular weight bands with M r values similar to the major components of the human sperm surface (35 000, 45 000, 66 000, 90 000 and 150 000). The nature of the antigens targeted by these antisera did not correlate with the ability of the latter to stimulate or suppress sperm–oocyte fusion.

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D. H. Abbott, A. S. McNeilly, S. F. Lunn, M. J. Hulme and F. J. Burden

Summary. Plasma concentrations of progesterone, cortisol, LH and prolactin were measured in dominant and subordinate female marmosets in 10 well-established peer groups. Subordinate females never ovulated, had a reduced LH response to LH-RH and showed no positive feedback LH surge after oestrogen administration. There was no evidence of elevated plasma cortisol levels or hyperprolactinaemia in subordinates and all showed a similar prolactin response to TRH in comparison with dominants. However, subordinates showed a reduced prolactin response to metoclopramide. These results clearly indicate that high circulating levels of cortisol or prolactin are not responsible for the inhibition of ovulation in female marmosets.