Publications (8)17.43 Total impact
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Article: Postinflammation stage of autoimmune orchitis induced by immunization with syngeneic testicular germ cells alone in mice.
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ABSTRACT: We previously established an immunological infertility model, experimental autoimmune orchitis (EAO), which can be induced by two subcutaneous injections of viable syngeneic testicular germ cells on days 0 and 14 in mice without using any adjuvant. In this EAO model, CD4+ T-cell-dependent lymphocytic infiltration and immune deposits were found with spermatogenic disturbance on day 120. However, the late stage of EAO (= postactive inflammation stage on day 365) has not yet been investigated. Therefore, we investigated the histopathological characteristics of the late stage. The results revealed that the lymphocytic infiltration finally resolved; however, the seminiferous epithelium persistently showed maturation arrest and the Sertoli cell-only feature. In the seminiferous tubules showing maturation arrest, both proliferation and apoptosis of germ cells had occurred simultaneously. It was also noted that there were deposits of immunoglobulin G and the third component of complement on the thickened basement membrane of seminiferous tubules in the late stage of EAO. These results indicate that histopathology after active inflammation in EAO comprises persistent damage to the seminiferous epithelium and may resemble the histopathology of "idiopathic disturbance of spermatogenesis" in man.Medical Molecular Morphology 12/2012; 45(1):35-44. · 1.39 Impact Factor -
Article: Cadmium exposure increases susceptibility to testicular autoimmunity in mice.
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ABSTRACT: Cadmium, one of various environmental toxicants, is known to suppress systemic immunity and to injure the testicular capillary endothelia with resultant necrosis of testicular tissues in mice and rats treated with high doses. Recently, it also became evident that cadmium can affect the integrity of the blood-testis barrier (BTB), the endocrine function of Leydig cells, apoptosis of germ cells and systemic immunity, even on treatment with a low dose that does not induce spermatogenic disturbance. Experimental autoimmune orchitis (EAO), i.e., an organ-specific autoimmunity of the testis, can be induced by repeated immunization with testicular antigens, and its pathology is characterized by lymphocytic inflammation and spermatogenic disturbance. In the present study, we investigated the morphological and functional changes of testes in mice treated with a low dose of cadmium chloride (CdCl(2) ) and also examined its toxicity as to susceptibility to EAO. The results showed that exposure to 3 mg CdCl(2) kg(-1) body weight did not affect the spermatogenic state. However, the BTB at the tubuli recti and the rete testis, but not the seminiferous tubules, was slightly weakened, and intra-testicular mRNA expression of interleukin (IL)-6, tumor necrosis factor-α and IL-1β was significantly increased by the CdCl(2) treatment. Furthermore, immunization with testicular antigens after the CdCl(2) exposure significantly augmented the EAO severity. Therefore, exposure to a low dose of CdCl(2) induces no significant disturbance of spermatogenesis, however, it does change the immunological microcircumstances in the testis, resulting in increased susceptibility to testicular autoimmunity. Copyright © 2012 John Wiley & Sons, Ltd.Journal of Applied Toxicology 01/2012; · 2.48 Impact Factor -
Article: Intratesticular expression of mRNAs of both interferon γ and tumor necrosis factor α is significantly increased in experimental autoimmune orchitis in mice.
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ABSTRACT: 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)-γ and that treatment of the immunized mice with anti-IFN-γ monoclonal antibodies significantly suppressed the EAO. It is known that both IFN-γ and tumor necrosis factor (TNF)-α 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-γ and TNF- α mRNAs in TGC-induced EAO using real-time RT-PCR. The results demonstrated that the intratesticular mRNAs for both IFN-γ and TNF-α significantly increased, while other cytokines such as IL-1α, IL-1β, IL-6 and TGF-β did not show dramatic changes in the immunized mice. These results suggest that secretion of significant amounts of IFN-γ and TNF-α in situ contributes to the spermatogenic disturbance in EAO.Journal of Reproduction and Development 01/2011; 57(2):296-302. · 1.46 Impact Factor -
Article: Developmental ontogeny of autoantigens associated with localized autoimmunity in murine testis and epididymis.
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ABSTRACT: Experimental autoimmune orchitis (EAO) with experimental autoimmune epididymitis (EAE) can be induced in mice by immunization with testicular antigens emulsified in adjuvants. On immunization with syngeneic testicular germ cells (TGC) alone, EAO with no EAE is induced in mice. Recently, we found that EAE with no EAO can be induced in vasectomized mice by immunization with TGC. In the present study, we investigated the appearance of autoantigens relevant to EAO and EAE by reacting each immune serum sample with testes and epididymides extracts from normal mice of various ages by immunoblotting. The results showed that the antisera obtained from mice with EAO lesions specifically defined testicular antigens with molecular weights of 15 kDa, 40 kDa, 75 kDa and >200 kDa from 4 weeks of age, but the antisera obtained from mice with EAE strongly defined both testicular and epididymal antigens of 25 kDa from 5 and 8 weeks of ages, respectively. These results suggest that vasectomy changes the target autoantigens in TGC-induced autoimmunity.Journal of Reproductive Immunology 12/2010; 87(1-2):45-51. · 2.97 Impact Factor -
Article: Histological development of human testicular cords from 70 to 90 days of gestation.
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ABSTRACT: The development of the testicular cord structure was investigated in 4 human fetuses between 70 and 90 days of gestation, in which the testicular cords are differentiating into the seminiferous tubules. Histological examinations were performed using stains with haematoxylin-eosin (HE), Masson's trichrome (MT), periodic acid schiff (PAS), anti-proliferating cell nuclear antigen (PCNA) monoclonal antibodies, and TUNEL methods. It was found that the testicular cords structures were indefinitely observed in HE-stained sections of four fetuses. However, the basement membranes of the testicular cord were clearly stained with MT, showing the tubular structure. Furthermore, cells in the testicular cords were positive with PAS, but the interstitial tissues outside the testicular cords were negative. PCNA-positive cells were detected not only inside but also outside the testicular cords, however, TUNEL positive cells are not detected throughout all testicular tissues.Okajimas Folia Anatomica Japonica 11/2010; 87(3):103-8. -
Article: Caput epididymitis but not orchitis was induced by vasectomy in a murine model of experimental autoimmune orchitis.
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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 shamVx+TGC immunization had EAO with no epididymitis. In sharp contrast, no EAO was found in the testes of any mice receiving Vx+TGC immunization. Instead, caput epididymitis involving CD4+T cells, CD8+T 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 shamVx+TGC immunization were reactive with both round (immature) and elongating (mature) spermatids; however, those induced by Vx+TGC 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 07/2008; 135(6):859-66. · 2.58 Impact Factor -
Article: Splenic cytokines in mice immunized with testicular germ cells.
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ABSTRACT: We previously established that two subcutaneous injections of viable syngeneic testicular germ cells (TGC) alone can induce CD4+ T cell-dependent experimental autoimmune orchitis (EAO) in mice. This model is histologically characterized by lymphocytic infiltration into the testes and the following aspermatogenesis. In the present study, we investigated the dynamics of splenic cytokines in EAO, using specific enzyme-linked immunosorbent assay. We found that splenic production of both type 1 helper T cell (Th1) and type 2 helper T cell (Th2)-related cytokines increased after the second but not the first immunization with TGC, indicating that secondary immune responses are critical to the EAO induction. However, the production of Th1-related cytokines became predominant at the clinical stage of EAO. Additionally, serum FSH and inhibin-B increased and decreased, respectively, during EAO. On the other hand, LH did not significantly change and testosterone temporally increased during the same period. These results indicate that both Th1- and Th2-related cytokines are involved at the pre-clinical phase of EAO, but that Th1- rather than Th2-related cytokines are responsible for the clinical phase when spermatogenesis is disrupted but the Leydig cell function is well preserved.International Journal of Andrology 08/2007; 31(5):471-6. · 3.59 Impact Factor -
Article: Tissue microcircumstances for leukocytic infiltration into the testis and epididymis in mice.
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ABSTRACT: Spermatozoa do not appear in the seminiferous epithelium until puberty, when immune tolerance has already been established. Therefore, they contain various autoimmunogenic materials which are recognized as foreign by the self immune system. However, the testis and epididymis are known as immunologically privileged organs. In particular, the blood-testis barrier (BTB) formed by Sertoli cells and the blood-epididymal barrier formed by epididymal epithelial cells protect autoimmunogeneic spermatozoa from attack by the self immune system. The immune privileged circumstances in the testis and epididymis have been demonstrated by many studies to involve a local transplantation system. We review here the immune privileged status of these organs from the viewpoint of induction of inflammatory cell responses in mice. The testicular interstitium in mice is resistant to vasculitis, lymphangitis, spermatic granuloma and polymorphonuclear cell infiltration: however, the epididymal interstitium is vulnerable to them. Therefore, the testicular tissue outside BTB is also protected from inflammatory cell infiltration, although many resident macrophages are normally present in the testis. In sharp contrast, subcutaneous injection of viable syngeneic testicular germ cells (TGC) alone induces autoimmune orchitis with no involvement of the epididymitis in mice. In the testes of TGC-immunized animals, severe lymphocytic infiltration with aspermatogenesis was seen in spite of no use of adjuvants. Unexpectedly, injections of viable epididymal spermatozoa (ES) did not evoke any autoimmune inflammation in the epididymides. Therefore, the testis rather than the epididymis may easily become an unprivileged organ as to autoimmunity under some special conditions.Journal of Reproductive Immunology 11/2005; 67(1-2):57-67. · 2.97 Impact Factor
Top co-authors
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Institutions
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2012
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Chiba University
Chiba-shi, Chiba-ken, Japan
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2008–2012
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Tokyo Medical University
- Department of Anatomy
Tokyo, Tokyo-to, Japan
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