Evaluation of zona pellucida antigens as potential candidates for immunocontraception

Antibodies directed against the zona pellucida can interrupt sperm-egg recognition in vitro. However, the mechanisms by which anti-zona antibodies exert this contraceptive effect in vivo remain uncertain. There is an accumulating body of evidence to suggest that active immunity against zona antigens not only induces infertility via an antibody-mediated interruption of sperm--egg interaction but also disrupts normal ovarian function. We have evaluated the consequence of inducing active immunity against purified recombinant human ZP3 (rec.hZP3) and human ZP3 peptides, using the marmoset monkey, Callithrix jacchus, as an animal model. Although infertility was established in animals that received rec.hZP3, it was associated with ovarian dysfunction characterized by suppression of folliculogenesis and depletion of the primordial follicle pool. Immunization with continuous human ZP3 peptides, identified by epitope mapping studies, did not induce ovarian pathology but the antibody titres were insufficient to suppress fertility significantly and consistently. Clearly, further research is required to identify and segregate epitopes on the zona glycoproteins that are capable of inducing infertility without any side effects.