Intratesticular Expression of mRNAs of Both Interferon γ and Tumor Necrosis Factor α is Significantly Increased in Experimental Autoimmune Orchitis in Mice

Experimental autoimmune orchitis (EAO) is one of the models of immunological male infertility. Murine EAO is CD4+T cell-dependent and classically induced by immunization with a testicular homogenate and adjuvants. We previously established that immunization with viable syngeneic testicular germ cells (TGC) can also induce murine EAO with no use of any adjuvant. Analyses of this EAO model have already revealed that cultured spleen cells of immunized mice secreted interferon (IFN)-gamma and that treatment of the immunized mice with anti-IFN-gamma monoclonal antibodies significantly suppressed the EAO. It is known that both IFN-gamma and tumor necrosis factor (TNF)-alpha are representative cytokines of Th1 cells and exhibit local toxicity toward the seminiferous epithelium in vivo. However, changes in these two cytokines in EAO-affected testes have not yet been investigated. Therefore, in the present study, we investigated the expression of intratesticular IFN-gamma and TNF-alpha mRNAs in TGC-induced EAO using real-time RT-PCR. The results demonstrated that the intratesticular mRNAs for both IFN-gamma and INF-alpha significantly increased, while other cytokines such as IL-1 alpha, IL-1 beta, IL-6 and TGF-beta did not show dramatic changes in the immunized mice. These results suggest that secretion of significant amounts of IFN-gamma and TNF-alpha in situ contributes to the spermatogenic disturbance in EAO.