Molecular genetics of the zona pellucida: implications for immunocontraceptive strategies

Successful immunocontraceptive agents must prevent fertilization without compromising the health of the individual exposed to immunization. The zona pellucida, which surrounds all mammalian eggs and is unique to the female gamete, represents a potential target for immunocontraception. Mouse and human zonae pellucidae are composed of three glycoproteins, designated ZP1, ZP2 and ZP3. The genes are conserved and the transcripts that encode the zona proteins have been characterized in both species. In mice, the expression of the zona genes is oocyte specific. The recent elucidation of the primary structure of the zona proteins in a number of species has provided critical information for the rational design of a contraceptive vaccine. We and others have demonstrated that both passive and active immunization strategies that target individual zona proteins can prevent fertilization. Although various contraceptive strategies have been tested in a laboratory setting, the applicability of these protocols to humans remains to be determined. The recent revolution in transgenesis coupled with the cloning of the human zona pellucida genes provide the means to produce animal models for testing immunocontraceptive strategies that target human zona proteins. These models could provide a system for the initial evaluation of vaccine candidates prior to trials in primates.