Immunoinhibition of human fertilization in vitro by antibodies to the cumulus oophorus intercellular matrix.
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Rabbit polyvalent antiserum raised against the solubilized cumulus matrix was a powerful inhibitor of human fertilization in vitro, affecting sperm-zona pellucida interaction. Both sperm binding to, and penetration of, the zona pellucida were severely impaired by the anti-cumulus matrix antiserum, whereas no effects of this antiserum on cumulus matrix solubilization or penetration of zona-free human eggs were evident. Moreover, the anti-cumulus antiserum partly neutralized the acrosome reaction-inducing activity of the cumulus matrix. These results warrant further research into the functional specificity of different cumulus matrix components and into the effects of the respective antibodies on reproductive function as a possible lead to a new approach to contraceptive vaccine development. (+info)
Contraception in mares heteroimmunized with pig zonae pellucidae.
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Ten fertile feral mares and 6 domestic horses (4 fertile mares, 1 infertile mare, 1 gelding) were immunized with heat-solubilized pig zonae pellucidae by 4 injections equivalent to 2000 or 5000 zonae each at 2-4-week intervals and a booster injection of 20,000 zonae 6-10 months after the last of the initial inoculations. The immune response was reflected by high antibody levels as measured by an enzyme-linked immunosorbent assay (ELISA) using immobilized pig zona antigen. In-vivo inhibition of fertility occurred in 12 (86%) of the 14 fertile mares studied and persisted for a minimum of 7 months. Repeated mating of the fertile domestic mares resulted in conception when anti-pig zona antibody concentrations had decreased from initial peak absorbance ratios (greater than 1.0) to relatively lower levels (0.64 or less with one exception). An indirect immunofluorescence assay, revealed a considerably lower cross-reactive antibody titre with horse oocytes as compared to pig oocytes. Clinical, endocrinological and histological analyses of the ovaries and their function following regained fertility after immunization revealed no abnormalities. One mare remained infertile. (+info)
Immunological approaches to fertility regulation.(68/106)
Contraceptive potential of antibodies to the zona pellucida.
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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. (+info)
Ovaries remain functional in squirrel monkeys (Saimiri sciureus) immunized with porcine zona pellucida 55,000 macromolecule.
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Fifty female squirrel monkeys were each immunized with 200 micrograms of a purified preparation of the 55,000 macromolecule (ZP3) from porcine zona pellucida. The fertility status of these immunized monkeys, as well as the effect of ZP3 antibodies on ovarian function, was monitored. High anti-ZP3 titers were achieved (greater than 75% binding levels as determined by radioimmunoassay) and remained high (approximately 67% binding level) for the duration of this study. Hormonal evaluations indicated initial disturbances in normal ovarian steroid secretion and function that were confirmed by laparoscopic observation and oocyte production data. Histological examination of ovaries at 6-7 mo post-injection suggested an interference in folliculogenesis. No pregnancies were observed in the immunized monkeys during this period. By 10-15 mo post-immunization, hormonal and laparoscopic data indicated that ovarian function was recovering in injected monkeys despite the continued presence of high titers to ZP3. Collectively, these results demonstrate that although immunization with ZP3 initially produces disturbances in normal ovarian function that inhibit fertility, these effects are reversible. Such findings encourage the continued intensive investigation of purified porcine zona macromolecules for immunocontraceptive purposes. (+info)
Current trends in antifertility vaccine research.
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We review the major advances that have recently occurred in the area of antifertility vaccines by examining the immunogenic potential of gamete, embryonic and placental antigens. In human trials using beta-human chorionic gonadotropin coupled with tetanus toxoid as the immunogen, the major problems with antifertility vaccines relate to specificity and maintaining an adequate antibody titer to disrupt gestation. Possible complications include cross-reaction with other body tissues, immune complex deposition, cytotoxicity, impaired immunologic tumor surveillance and nonreversibility. (+info)
Fertility control in the bitch by active immunization with porcine zonae pellucidae: use of different adjuvants and patterns of estradiol and progesterone levels in estrous cycles.
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To determine the changes in patterns of 17 beta-estradiol and progesterone levels underlying abnormal cycles in bitches immunized with solubilized crude porcine zonae pellucidae (cPZP), to attempt to circumvent these problems by immunizing with a purified zona fraction (pPZP), and to test the effectiveness of different adjuvants, bitches were immunized with cPZP or pPZP 2-6 times with no adjuvant, Freund's adjuvant, alum adjuvant, or the adjuvant CP-20,961. The bitch immunized without adjuvant had a low titer with a normal cycle and fertility. Immunization with cPZP and adjuvant produced moderate to high titers of antizona antibodies and infertility. Bitches with high titers experienced abnormal estrous cycles. Estradiol rose during proestrus, but instead of falling sharply in early estrus as in controls, it remained elevated. Progesterone did not rise. The moderate-titered bitches had normal cycles and steroid patterns. Bitches immunized with pPZP had moderate titers. Cycles were normal after 3 injections, but after 6 injections one bitch had an abnormal cycle. One pPZP-immunized bitch remained fertile but the others were infertile. Alum was the mildest adjuvant, causing no injection site lesions, but the highest titers occurred with Freund's and CP-20,961 adjuvants. All three adjuvants induced titers sufficient to inhibit fertility. Infertility in bitches immunized with PZP may be due to prevention of zona penetration, because their antisera inhibited zona penetration of oocytes by spermatozoa in vitro. However, alterations in ovarian function preventing ovulation and luteinization could be involved in high-titered bitches. (+info)