Caput epididymitis but not orchitis was induced by vasectomy in a murine model of experimental autoimmune orchitis

Abstract

Immunization of mice with viable syngeneic testicular germ cells (TGC) alone can induce autoimmune responses against autoantigens of both round and elongating spermatids, resulting in the development of experimental autoimmune orchitis (EAO). Histological lesions in this EAO model without an adjuvant are characterized by lymphocytic infiltration into the testes, spermatogenic disturbance, and a complete lack of epididymitis. In this study, we investigated the effects of vasectomy (Vx) on TGC-induced EAO expecting that Vx augments the severity of testicular inflammation in A/J mice. The results showed that mice receiving Vx alone exhibited no significant inflammatory cell response in either the testes or epididymides, and mice receiving shamVxCTGC immunization had EAO with no epididymitis. In sharp contrast, no EAO was found in the testes of any mice receiving VxCTGC immunization. Instead, caput epididymitis involving CD4CT cells, CD8CT cells, B cells, and macrophages were induced in them with striking elevation of the tissue levels of both IL6 and IL10 mRNA. Furthermore, serum autoantibodies induced by shamVxCTGC immunization were reactive with both round (immature) and elongating (mature) spermatids; however, those induced by VxCTGC immunization were specific to acrosomes of mature spermatids and spermatozoa. These unexpected results indicate that Vx may induce the mode by which autoreactive lymphocytes gain access to TGC autoantigens in the epididymides, leading to autoimmune responses against the autoantigens of mature rather than immature spermatids. Reproduction (2008) 135 859-866

The Origin of Lymphatic Capillaries in Murine Testes

“…In this EAO model, lymphocytic inflammation starts from the tubuli recti and then spreads to the peripheral testes; however, the epididymides and vasa deferentia are not involved (Itoh et al, 1995). It was recently found that vasectomy after immunization with testicular germ cells changed the histopathological mode of inflammation, significant lymphocytic infiltration being induced in the initial segment of the epididymis instead of by EAO (Qu et al, 2008). These phenomena suggest that the microenvironment of testis and the initial segment of epididymis are sensitive to inflammatory cell responses.…”

The Immunophysiology of Male Reproduction

“…874,922 Likewise, mice with a targeted deletion of the immunoregulatory AIRE transcription factor developed sperm antibodies and leukocytic infiltrates in the epididymis, without orchitis. 923 Vasectomized A/J mice that have been immunized with syngeneic testicular spermatogenic cells develop epididymitis independent of orchitis, 924,925 suggesting that the epididymis can be the primary site of immune reactions following vasectomy, as well. The epididymis is also more susceptible than the testis to spermatic granuloma formation in humans and in experimental mice.…”

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

“…Real-time RT-PCR (TaqMan) analysis for relative determination of the mRNA level was performed using the standard curve method [17]. The detection of cytokine mRNAs was performed using proprietary predeveloped TaqMan primers (IFN-γ (ID: Mm00801778-m1), TNF-α (ID: Mm00443258-m1), IL-1α (ID: Mm00443258-m1), IL-1β (ID: Mm00434228-m1), IL-6 (ID: Mm00446190-m1), TGF-β (ID: Mm0041724-m1) and β-actin (ID: Mm00607939-s1); PE Applied Biosystems, Foster City, CA, USA).…”