MOLECULAR-GENETICS OF THE ZONA-PELLUCIDA - IMPLICATIONS FOR IMMUNOCONTRACEPTIVE STRATEGIES

Successful immunocontraceptive agents must prevent fertilization witho ut compromising the health of the individual exposed to immunization. The zona pellucida, which surrounds all mammalian eggs and is unique t o the female gamete, represents a potential target for immunocontracep tion. Mouse and human zonae pellucidae are composed of three glycoprot eins, designated ZP1, ZP2 and ZP3. The genes are conserved and the tra nscripts 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 rati onal design of a contraceptive vaccine. We and others have demonstrate d that both passive and active immunization strategies that target ind ividual zona proteins can prevent fertilization. Although various cont raceptive strategies have been tested in a laboratory setting, the app licability of these protocols to humans remains to be determined. The recent revolution in transgenesis coupled with the cloning of the huma n 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 va ccine candidates prior to trials in primates.