MECHANISM OF INFERTILITY IN MALE GUINEA-PIGS IMMUNIZED WITH SPERM PH-20

PH-20, a testis-specific protein first expressed in haploid germ cells , is present on the posterior head plasma membrane and inner acrosomal membrane of mature guinea pig sperm. PH-20 is bifunctional, having a hyaluronidase activity that allows sperm to penetrate the cumulus laye r and a separate activity required for binding of acrosome-reacted spe rm to the zona pellucida. The immunization of male guinea pigs with PH -20 reproducibly results in infertility with a duration of 6-12 mo or longer. In this study, we analyzed the immunopathology in the reproduc tive tract of PH-20-immunized males to probe the mechanism(s) responsi ble for the induced infertility and found two separate effects. Remark ably, in almost all infertile, PH-20-immunized males, the caudae epidi dymides were empty (contained no sperm) or contained only abnormal spe rm. The complete loss of normal sperm in the epididymis apparently res ults in infertility. A second effect was the induction of experimental autoimmune orchitis (EAO), representing the first report of EAO induc ed by a purified testis/sperm molecule of known functions. PH-20-induc ed EAO differed from EAO induced by crude testis antigens in two respe cts: 1) an absence of epididymitis with abscess and granuloma and 2) t he presence of antibody on germ cells within seminiferous tubules and inside the cauda epididymidis. The former suggests that crude testis a ntigens other than PH-20 are responsible for epididymitis, and the lat ter suggests a possible role of antibody in EAO pathogenesis and infer tility induction. Return to fertility, after 6-12 mo, was accompanied by regression of EAO and reappearance of spermatozoa in the caudae epi didymides.