Experimental model of autoimmune orchitis with abdominal placement of donor's testes, epididymides, and vasa deferentia in recipient mice

Abstract

Haploid germ cells (spermatids and spermatozoa) develop in the testis after immune tolerance has been established. Therefore, they contain various autoimmunogenic antigens, but the testis is known to be an immunologically privileged organ. In particular, the blood-testis barrier formed by Sertoli cells protects autoimmunogenic haploid germ cells from attack by the autoimmune system. Experimental autoimmune orchitis (EAO), a breakdown of the testicular immune privilege leading to immunological male infertility, has been ordinarily induced in mice by immunization twice with testicular antigens+complete Freund's adjuvant (CFA)+Bordetella pertussis (BP). We previously found that two subcutaneous injections of viable syngeneic testicular germ cells induced murine EAO without the use of CFA+BP. In both EAO models, the lesions are characterized by spermatogenic disturbance with lymphocytic inflammation, and a second immunization with testicular antigens is critical for the disease induction. In the present study, we found that only one placement of a syngeneic donor's testes, epididymides and vasa deferentia (TEV) into the abdominal cavity or subcutaneous space was sufficient to induce EAO on the recipient's testes in mice. It was also noted that the placement of TEV induced only orchitis without epididymo-vasitis, while the serum autoantibodies were reactive with haploid germ cells existing throughout the TEV. Furthermore, the TEV placed in the abdominal cavity rather than the subcutaneous space was effective in inducing severe EAO, and the A/J strain was most susceptible to the TEV-induced EAO among the three strains examined. The model of EAO induced by the placement of the donor's TEV into the abdominal cavity in A/J mice will be helpful for the further analyses of testicular autoimmunity.