Inhibition of Sperm Binding and Fertilization of Human Ova by Antibody to Porcine Zona Pellucida and Human Sera

To assess the effect of antibodies to zona pellucida on fertilization in man, follicular oocytes were matured in vitro and preincubated in either control sera (rabbit preimmune or from a normal fertile woman), an antiserum to porcine zona, or one of two sera from women (one postmenopausal, the other infertile for unknown reasons) believed to have autoantibodies to zona. When these sera were tested by indirect immunofluorescence on porcine zonae, the control sera were negative and the other sera strongly positive for antizona antibodies. The sera-treated oocytes were inseminated in vitro with either 3 or 20 × 105 sperm/ml using methods known to result in high rates of fertilization under normal conditions. The porcine heteroantibody completely inhibited sperm binding to the zona in eight of nine oocytes and resulted in the formation of a distinct precipitate in the outer zona when examined by light or electron microscopy. Both human sera, positive for antizona antibodies, reduced the number of sperm attaching to zona. Serum from one woman (MENO) had an effect similar to heteroantibody, although complete inhibition of sperm binding and penetration was only observed in the more dilute sperm concentration used for insemination. However, sperm bound to and penetrated the outer zonae of all oocytes treated with the other zona antibody positive serum (WHO 73). It is concluded that the heteroantibody to porcine zona will completely inhibit human fertilization in vitro and that sera of some women may also inhibit or reduce the possibility of fertilization. The potential for a contraceptive vaccine is indicated and the results support the idea that autoantibodies to zona may contribute to human infertility.