Skip to main content
SpringerLink
Log in

Testicular Autoimmunity by the Systemic Treatment with Immuno-Potentiating Agents in Experimental Animals

  • Chapter
  • First Online:
Testicular Autoimmunity

  • 385 Accesses

Abstract

Experimental autoimmune orchitis (EAO) can be induced by testicular antigens’ immunization with simultaneous treatments with adjuvants such as complete Freund’s adjuvant (CFA), Bordetella pertussis (BP), other microbial agents, and some immune-stimulating chemical (Fig. 5.1). These immuno-potentiating agents may easily overcome the testicular immune privilege systemically and/or locally.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Log in via an institution

Institutional subscriptions

References

  • Adekunle AO, Hickey WF, Smith SM, Tung KSK, Teuscher C. Experimental allergic orchitis in mice IV. Preliminary characterization of the major murine testis specific aspermatogenic autoantigen(s). J Reprod Immunol. 1987;12:49–62.

    Google Scholar 

  • Aslani F, Schuppe HC, Guazzone VA, Bhushan S, Wahle E, Lochnit G, Lustig L, Meinhardt A, Fijak M. Targeting high mobility group box protein 1 ameliorates testicular inflammation in experimental autoimmune orchitis. Hum Reprod. 2014.; pii: deu320

    Google Scholar 

  • Audia S, Nicolas A, Cathelin D, Larmonier N, Ferrand C, Foucher P, Fanton A, Bergoin E, Maynadie M, Arnould L, Bateman A, Lorcerie B, Solary E, Chauffert B, Bonnotte B. Increase of CD4+CD25+ regulatory T cells in the peripheral blood of patients with metastatic carcinoma: a Phase I clinical trial using cyclophosphamide and immunotherapy to eliminate CD4+CD25+ T lymphocytes. Clin Exp Immunol. 2007;150:523–30.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Bassi N, Luisetto R, Del Prete D, Ghirardello A, Ceol M, Rizzo S, Laccarino L, Gatto M, Valente ML, Punzi L, Doria A. Induction of ‘ASIA’ syndrome in NZB/NZWF1 mice after injection of complete Freund’s adjuvant (CFA). Lupus. 2012;21:203–9.

    Article  CAS  PubMed  Google Scholar 

  • Ben K, Alexander NJ, Huso N. In vitro cell-mediated and complement-mediated cytotoxicity to murine testicular cells. Am J Reprod Immunol. 1986;12:33–7.

    Article  CAS  Google Scholar 

  • Bernard CC, Toulett F, Lamoireux G. Inhibition by serum of autoimmune aspermatogenic orchitis. Aust J Exp Biol Med Sci. 1975;53:245–50.

    Article  CAS  PubMed  Google Scholar 

  • Bernard CCA, Mitchell GF, Leydon J, Bargerbos A. Experimental autoimmune orchitis in T-cell-deficient mice. Int Arch Allergy appl Immunol. 1978;56:256–63.

    Article  CAS  PubMed  Google Scholar 

  • Billiau A, Matthys P. Models of action of Freund’s adjuvants in experimental models of autoimmune disease. J Leukoc Biol. 2001;70:849–60.

    CAS  PubMed  Google Scholar 

  • Brode S, Raine T, Zaccone P, Coole A. Cyclophosphamide-induced type-1 diabetes in the NOD mouse is associated with a reduction of CD4+CD25+Foxp3+ regulatory T cells. J Immunol. 2006;177:6603–12.

    Article  CAS  PubMed  Google Scholar 

  • Carlo DJ, Hagopian A, Jackson JJ, Limjuco GA, Eylar EH. Experimental allergic orchitis and aspermatogenesis. VI. Transfer of allegic orchitis with immune cells. J Immunol. 1976;116:619–22.

    Google Scholar 

  • Cao Y, Zhao J, Yang Z, Cai Z, Zhang B, Zhou Y, Shen GX, Chen X, Li S, Huang B. CD4+Foxp3+ regulatory T cell depletion by low-dose cyclophosphamide prevents recurrence in patients wirh large condylomata acuminate after laser therapy. Clin Immunol. 2010;136:21–9.

    Article  CAS  PubMed  Google Scholar 

  • Chattopadhyay U. Immunological induction of aspermatogenesis. J Steroid Biochem. 1979;11:687–93.

    Article  CAS  PubMed  Google Scholar 

  • Chuang YH, Chiang BL, Chou CC, Hsieh KH. Immune effector cells induced by complete Freund’s adjuvant exert an inhibitory effect on antigen-specific type 2 T helper responses. Clin Exp Allergy. 1997;27:315–24.

    Article  CAS  PubMed  Google Scholar 

  • Chutna J, Rychlikova M. Prevention and suppression of experimental autoimmune aspermatogenesis in adult guinea pigs. Folia Biol. 1964;10:177–87.

    CAS  Google Scholar 

  • Clemens JW, Bruot BC. Testicular dysfunction in the adjuvant-induced arthritic rat. J Androl. 1989;10:419–24.

    Article  CAS  PubMed  Google Scholar 

  • Colafrancesco S, Perricone C, Priori R, Valesini G, Shoenfeld Y. Sjogren’s syndrome: another facet of the autoimmune/inflammatory syndrome induced by adjuvants (ASIA). J Autoimmun. 2014;51:10–6.

    Article  CAS  PubMed  Google Scholar 

  • Cruz-Tapias P, Agmon-Levin N, Israeli E, Anaya JM, Shoenfeld Y. Autoimmune (auto-inflammatory) syndrome induced by adjuvants (ASIA)—animal models as a proof of concept. Curr Med Chem. 2013;20:4030–6.

    Article  CAS  PubMed  Google Scholar 

  • Del Rio R, Sun Y, Alard P, Tung KSK, Teuscher C. H2 control of natural T regulatory cell frequency in the lymph node correlates with susceptibility to day 3 thymectomy-induced autoimmune disease. J Immunol. 2011;186:382–9.

    Article  PubMed  CAS  Google Scholar 

  • Del Rio R, McAllister RD, Meeker ND, Wall EH, Bond JP, Kyttaris VC, Tsokos GC, Tung KSK, Teuscher C. Identification of Orch3, a locus controlling dominant resistance to autoimmune orchitis, as kinesin family member 1C. PLoS Genet. 2012;8:1–9.

    Google Scholar 

  • Denduchis B, Lustig L, Gonzalez NN, Mancini RE. Studies of the nature of extracellular components of rat seminiferous tubular wall. I. Isolation and chemical characterization of basement membrane. Biol Reprod. 1975;13:274–81.

    Google Scholar 

  • Denduchis B, Lustig L, Gonzalez N, Puig RP. Isolation and immunological reactivity of soluble fractions from rat seminiferous tubule basement membrane. Arch Androl. 1979;2:233–40.

    Article  CAS  PubMed  Google Scholar 

  • Denduchis B, Satz ML, Sztein MB, Puig RP, Doncel G, Lustig L. Multifocal damage of the testis induced in rats by passive transfer of antibodies prepared against non-collagenous fraction of basement membrane. J Reprod Immunol. 1985;7:59–75.

    Article  CAS  PubMed  Google Scholar 

  • Deng T, Chen Q, Han D. The role of TAM receptor tyrosine kinases in the mammalian testis and immunoprivileged sites. Front Biosci. 2016;21:316–27.

    Article  Google Scholar 

  • Diehl SA, McElvany B, Noubade R, Seeberger N, Harding B, Spach K, Teuscher C. G proteins G-alpha-i1/3 are critical targets for Bordetella pertussis toxin-induced vasoactive amine sensitization. Infect Immun. 2014;82:773–82.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Doncel GF, Di Paola JA, Lustig L. Sequential study of the histopathology and cellular and humoral immune response during the development of an autoimmune in Wistar rats. Am J Reprod Immunol. 1989;20:44–51.

    Article  CAS  PubMed  Google Scholar 

  • Doncel GF, Denduchis B, Lustig L. Testicular lesions and lymphocyte subpopulations in rats immunized with a soluble fraction of testicular homogenate. Int J Androl. 1991;14:468–78.

    Article  CAS  PubMed  Google Scholar 

  • Doncel GF, Lustig L. Lymphocyte subsets in the lymph nodes of rats with autoimmune orchitis. Am J Reprod Immunol. 1991;25:35–40.

    Article  CAS  PubMed  Google Scholar 

  • Drumond AL, Weng CC, Wang G, Chiarini-Garcia H, Eras-Garcia L, Meistrich ML. Effects of multiple doses of cyclophosphamide on mouse testes: accessing the germ cells lost, and the functional damage of stem cells. Reprod Toxicol. 2011;32:395–406.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Eyquem A, Krieg H. Experimental autosensitization of the testis. Ann N Y Acad Sci. 1965;124:270–8.

    Article  CAS  PubMed  Google Scholar 

  • Fainboim L, Sztein MB, Serrate S, Mancini RE. Transfer of experimental allergic orchitis with immune RNA. Studies in vivo. Clin Exp Immunol. 1978;34:92–9.

    Google Scholar 

  • Fainboim L, Sztein MB, Serrate S, Satz L. In vitro transfer of cellular immunity in experimental allergic orchitis by means of immune RNA. Immunology. 1979;38:311–6.

    CAS  PubMed  PubMed Central  Google Scholar 

  • Falase EA, Adekunle AO, Neblett H, Teuscher C. Guinea pig testicular proacrosin-acrosin system: preliminary immunological characterization. J Reprod Immunol. 1989;15:241–56.

    Article  CAS  PubMed  Google Scholar 

  • Feng ZY, Ming W, Li LD, Louis J, Fei WY. Adoptive transfer of murine autoimmune orchitis with sperm-specific T lymphoblast. Arch Androl. 1990;24:51–9.

    Article  CAS  PubMed  Google Scholar 

  • Fijak M, Losub R, Schneider E, Linder M, Respondek K, Klug J, Meinhardt A. Identification of immunodominant autoantigens in rat autoimmune orchitis. J Pathol. 2005;207:127–38.

    Article  CAS  PubMed  Google Scholar 

  • Fijak M, Schneider E, Klug J, Bhushan S, Hackstein H, Schuler G, Wygrecka M, Gromoll J, Meinhardt A. Testosterone replacement effectively inhibits the development of experimental autoimmune orchitis in rats: Evidence for a direct role of testosterone on regulatory T cell expansion. J Immunol. 2011;186:5162–72.

    Article  CAS  PubMed  Google Scholar 

  • Fijak M, Damm LJ, Wenzel JP, Aslani F, Walecki M, Wahle E, Eisel F, Bhushan S, Hackstein H, Baal N, Shuler G, Konrad L, Rafiq A, O’Hara L, Smith LB, Meinhardt A. Influence of testosterone on inflammatory response in testicular cells and expression of transcription factor Foxp3 in T cells. Am J Reprod Immunol. 2015;10:1111.

    Google Scholar 

  • Fountain S, Holland MK, Hinds LA, Janssens PA, Kerr PJ. Interstitial orchitis with impaired steroidogenesis and spermatogenesis in the testes of rabbits infected with an attenuated strain of myxoma virus. J Reprod Fertil. 1997;110:161–9.

    Article  CAS  PubMed  Google Scholar 

  • Freund J, Lipton MM, Thompson GE. Aspermatogenesis in the guinea pig induced by testicular tissue and adjuvant. J Exp Med. 1953;97:711–26.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Fujii Y, Yokochi T, Nakashima I, Asai J, Kato N. A new mouse model for autoimmune orchitis. Med Microbiol Immunol. 1991;180:1–14.

    Article  CAS  PubMed  Google Scholar 

  • Gao JF, Call SB, Fillmore PD, Watanabe T, Meeker ND, Teuscher C. Analysis of the role of Bphs/Hrh1 in the genetic control of responsiveness to pertussis toxin. Infect Immun. 2003:1281–7.

    Google Scholar 

  • Gonzalez JL, Gallego E, Castano M, Rueda A. Testicular amyloidosis in hamsters experimentally infected with Leishmania donovani. Br J Exp Pathol. 1983;64:518–23.

    CAS  PubMed  PubMed Central  Google Scholar 

  • Guazzone VA, Rival C, Denduchis B, Lustig L. Monocyte chemoattractant protein-1 (MCP-1/CCL2) in experimental autoimmune orchitis. J Reprod Immunol. 2003;60:143–57.

    Article  CAS  PubMed  Google Scholar 

  • Guazzone VA, Denduchis B, Lustig L. Involvement of CD44 in leukocyte recruitment to the rat testis in experimental autoimmune orchitis. Reproduction. 2005;129:603–9.

    Google Scholar 

  • Guazzone VA, Jacob P, Theas MS, Lustig L. Cytokines and chemokines in testicular inflammation: a brief review. Microsc Res Tech. 2009;72:620–8.

    Article  CAS  PubMed  Google Scholar 

  • Guazzone VA, Hollwegs S, Mardirosian M, Jacob P, Hackstein H, Wygrecka M, Schneider E, Meinhardt A, Lustig L, FIjak M. Characterization of dendritic cells in testicular draining lymph nodes in a rat model of experimental autoimmune orchitis. Int J Androl. 2011a;34:276–89.

    Article  CAS  PubMed  Google Scholar 

  • Guazzone VA, Guerrieri D, Jacobo P, Glisoni RJ, Chiappetta D, Lustig L, Chuluyan HE. Micro-encapsulated secretory leukocyte protease inhibitor decreases cell-mediated immune response in autoimmune orchitis. Life Sci. 2011b;89:100–6.

    Article  CAS  PubMed  Google Scholar 

  • Guazzone VA, Jacobo P, Denduchis B, Lustig L. Expression of cell adhesion molecules, chemokines and chemokine receptors involved in leukocyte traffic in rats undergoing autoimmune orchitis. Reproduction. 2012;143:651–62.

    Article  CAS  PubMed  Google Scholar 

  • Hagopian A, Jackson JJ, Carlo DJ, Limjuco GA, Eylar EH. Experimental allergic aspermatogenic orchitis. III. Isolation of spermatozoal glycoproteins and their role in allergic aspermatogenic orchitis. J Immunol. 1975;115:1731–43.

    Google Scholar 

  • Hagopian A, Limjuco GA, Jackson JJ, Carlo DJ, Eylar EH. Experimental allergic aspermatogenic orchitis. IV. Chemical properties of sperm glycoproteins isolated from guinea pig testes. Biochim Biophys Acta. 1976;434:354–64.

    Google Scholar 

  • Hardy DM, Garbers DL. A sperm membrane protein that binds in a species-specific manner to the egg extracellular matrix is homologous to von Willebrand factor. J Biol Chem. 1995;270:26025–8.

    Article  CAS  PubMed  Google Scholar 

  • Hargis BT, Malkiel S, Berkelhammer J. Immunologically induced aspermatogenesis in the white mouse. J Immunol. 1968;101:374–5.

    CAS  PubMed  Google Scholar 

  • Hirai S, Naito M, Kuramasu M, Yuki O, Qu N, Terayama H, Hatayama N, Itoh M. Low-dose di(2-ethylhexyl) phthalate (DEHP) exposure increases susceptibility to testicular autoimmunity in mice. Reprod Biol. 2015;15:163–71.

    Article  PubMed  Google Scholar 

  • Hiramine C, Hojo K. Adoptive transfer of suppression of experimental allergic orchitis with lymphoid cells from antigen-pretreated guinea pig. Clin Immunol Immunopathol. 1984a;30:202–13.

    Article  CAS  PubMed  Google Scholar 

  • Hiramine C, Hojo K. Requirement of B lymphocytes in local adoptive transfer of experimental allergic orchitis by lymph node cells. Am J Reprod Immunol. 1984b;6:85–91.

    Google Scholar 

  • Hojo K, Hiramine C, Ishitaki M. Lymphocytes proliferative response in vitro and its cellular dependency in guinea pigs with experimental autoimmune orchitis. J Reprod Fertil. 1980;59:113–23.

    Google Scholar 

  • Hojo K, Hiramine C. Suppression of experimental allergic orchitis and cellular immune responses in guinea pig by pretreatment with testis antigen in incomplete Freund’s adjuvant. Int Arch Allergy Appl Immunol. 1982;69:40–9.

    Article  CAS  PubMed  Google Scholar 

  • Hojo K, Hiramine C. In vivo effects of cyclosporine A: abrogation of the induction of experimental allergic orchitis and sparing of the generation of suppressor cells. Int Arch Allergy Appl Immunol. 1985;78:63–70.

    Article  CAS  PubMed  Google Scholar 

  • Hong F, Wang Y, Zhou Y, Zhang Q, Ge Y, Chen M, Hong J, Wang L. Exposure to TiO2 nanoparticles induces immunological dysfunction in mouse testis. J Agric Food Chem. 2016;64:346–55.

    Article  CAS  PubMed  Google Scholar 

  • Ichinohasama R, Hirokawa K, Hatakeyama S. Spermatogenic disturbance induced in mice by combined local injection of monoclonal antibodies to Sertoli cell and to basal lamina of seminiferous tubules. Am J Reprod Immunol Microbiol. 1986;10:158–65.

    Article  CAS  PubMed  Google Scholar 

  • Iosub R, Klug J, Fijak M, Schneider E, Frohlich S, Blumbach K, Wennemuth G, Sommerhoff CP, Steinhoff M, Meinhardt A. Development of testicular inflammation in the rat involves activation of proteinase-activated receptor-2. J Pathol. 2006;208:686–98.

    Article  CAS  PubMed  Google Scholar 

  • Itoh M, Hiramine C, Hojo K. A new murine model of autoimmune orchitis induced by immunization with viable syngeneic testicular germ cells alone. I. Immunological and histological studies. Clin Exp Immunol. 1991a;83:137–42.

    Google Scholar 

  • Itoh M, Hiramine C, Tokunaga Y, Mukasa A, Hojo K. A new murine model of autoimmune orchitis induced by immunization with viable syngeneic testicular germ cells alone. II. Immunohistochemical findings of fully-developed lesion. Autoimmunity. 1991b;10:89–97.

    Google Scholar 

  • Itoh M, Mukasa A, Tokunaga Y, Hiramine C, Hojo K. New experimental model for adoptive transfer of murine autoimmune orchitis. Andrologia. 1991c;23:415–20.

    Article  CAS  PubMed  Google Scholar 

  • Itoh M, Chen XA, Takeuchi Y, Miki T. Morphological demonstration of the immune privilege in the testis using adjuvants: tissue responses of male reproductive organs in mice injected with Bordetella pertussigens. Arch Histol Cytol. 1995;58:575–9.

    Article  CAS  PubMed  Google Scholar 

  • Jackson JJ, Hagopian A, Carlo DJ, Limjuco GA, Eylar EH. Experimental allergic aspermatogenic orchitis. I. Isolation of a spermatozoal protein (AP1) which induces allergic aspermatogenic orchitis. J Biol Chem. 1975;250:6141–50.

    Google Scholar 

  • Jackson JJ, Hagopian A, Carlo DJ, Limjuco GA, Eylar EH. Experimental allergic aspermatogenic orchitis. II. Some chemical properties of the AP1 protein of the sperm acrosome. Biochim Biophys Acta. 1976;427:251–61.

    Google Scholar 

  • Jacobo P, Guazzone VA, Jarazo-Dietrich S, Theas MS, Lustig L. Differential changes in CD4+ and CD8+ effector and regulatory T lymphocyte subsets in the testis of rats undergoing autoimmune orchitis. J Reprod Immunol. 2009;81:44–54.

    Google Scholar 

  • Jacobo PV, Perez CV, Theas MS, Guazzone VA, Lustig L. CD4+ and CD8+ T cells producing Th1 and Th17 cytokines are involved in the pathogenesis of autoimmune orchitis. Reproduction. 2011a;141:249–58.

    Article  CAS  PubMed  Google Scholar 

  • Jacobo P, Guazzone VA, Theas MS, Lustig L. Testicular autoimmunity. Autoimmun Rev. 2011b;10:201–4.

    Article  CAS  PubMed  Google Scholar 

  • Jacobo PV, Fass M, Perez CV, Jarazo-Dietrich S, Lustig L, Theas MS. Involvement of soluble Fas ligand in germ cell apoptosis in testis of rats undergoing autoimmune orchitis. Cytokine. 2012;60:385–92.

    Article  CAS  PubMed  Google Scholar 

  • Jacobo P, Guazzone VA, Perez CV, Lustig L. CD4+ Foxp3+ regulatory T cells in autoimmune orchitis: phenotypic and functional characterization. Am J Reprod Immunol. 2015;73:109–25.

    Article  CAS  PubMed  Google Scholar 

  • Jarazo-Dietrich S, Jacobo P, Perez CV, Guazzone VA, Lustig L, Theas MS. Up regulation of nitric oxide synthase-nitric oxide system in the testis of rats undergoing autoimmune orchitis. Immunobiology. 2012;217:778–87.

    Article  CAS  PubMed  Google Scholar 

  • Jarazo-Dietrich S, Fass MI, Jacobo PV, Sobarzo CM, Lustig L, Theas MS. Inhibition of NOS-NO system prevents autoimmune orchitis development in rats: relevance of NO released by testicular macrophages in germ cell apoptosis and testosterone secretion. PLoS One. 2015;10:e0128709.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Katsh S. Adjuvants and aspermatogenesis in the guinea pig. Int Arch Allergy Appl Immunol. 1964;24:319–31.

    Article  CAS  PubMed  Google Scholar 

  • Kitaoka M, Hirai S, Terayama H, Naito M, Qu N, Hatayama N, Miyaso H, Matsuno Y, Komiyama M, Itoh M, Mori C. Effects on the local immunity in the testis by exposure to di-(2-ethylhexyl) phthalate (DEHP) in mice. J Reprod Dev. 2013;59:485–90.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Kohno S, Munoz JA, Williams TM, Teuscher C, Bernard CC, Tung KS. Immunopathology of murine experimental allergic orchitis. J Immunol. 1983;130:2675–82.

    CAS  PubMed  Google Scholar 

  • Kyewski B, Wekerle H. Increase of T lymphocyte self-reactivity in aging inbred rats: in vitro studies with a model of experimental autoimmune orchitis. J Immunol. 1978;120:1249–55.

    Google Scholar 

  • Lapchak PH, Guilbert LJ, Rabinovitch A. Tumor necrosis factor production is deficient in diabetes-prone BB rats and can be corrected by complete Freund’s adjuvant: a possible immunoregulatory role of tumor necrosis factor in the prevention of diabetes. Clin Immunol Immunolathol. 1992;65:129–34.

    Article  CAS  Google Scholar 

  • Li N, Liu Z, Zhang Y, Cheng Q, Liu P, Cheng CY, Lee WM, Chen Y, Han D. Mice lacking Axl and Mer tyrosine kinase receptors are susceptible to experimental autoimmune orchitis induction. Immunol Cell Biol. 2014; doi:10.1038/icb.2014.97.

  • Lipscomb HL, Gardner PJ, Sharp JG. The effect of neonatal thymectomy on the induction of autoimmune orchitis in rats. J Reprod Immunol. 1979;1:209–17.

    Article  CAS  PubMed  Google Scholar 

  • Liu Z, Zhao S, Chen Q, Yan K, Liu P, Li N, Cheng CY, Lee WM, Han D. Roles of Toll-like receptors 2 and 4 in mediating experimental autoimmune orchitis induction in mice. Biol Reprod. 2015;92:63. doi:10.1095/biolreprod.114.123901.

  • Loyo E, Jara LJ, Lopez PD, Puig AC. Autoimmunity in connection with a metal implant: a case of autoimmune/autoinflammatory syndrome induced by adjuvants. Autoimmun Highlights. 2012;4:33–8.

    Article  Google Scholar 

  • Lujan L, Perez M, Salazar E, Alvarez N, GImeno M, Pincrowski P, Irusta S, Santamaria J, Insausti N, Cortes Y, Figueras L, Cuartielles I, Vila M, Fantova E, Chapulle JL. Autoimmune/autoinflammatory syndrome induced by adjuvants (ASIA syndrome) in commercial sheep. Immunol Res. 2013;56:317–24.

    Article  CAS  PubMed  Google Scholar 

  • Lustig L, Denduchis B, Mancini RE. Studies of the nature of extracellular components of rat seminiferous tubular wall. II. Immunological characterization of basement membrane antigen. Int J Fertil. 1977;22:16–23.

    Google Scholar 

  • Lustig L, Denduchis B, Gonzalez NN, Puig RP. Experimental orchitis induced in rats by passive transfer of an antiserum to seminiferous tubule basement membrane. Arch Androl. 1978;1:333–43.

    Article  CAS  PubMed  Google Scholar 

  • Lustig L, Satz ML, Sztein MB, Denduchis B. Antigens of the basement membrane of the seminiferous tubules induce autoimmunity in Wistar rats. J Reprod Immunol. 1982;4:79–90.

    Article  CAS  PubMed  Google Scholar 

  • Lustig L, Satz ML, Denduchis B. Induction of multifocal leisons of the testis by passive transfer of immune cells. J Reprod Immunol. 1986;9:195–204.

    Article  CAS  PubMed  Google Scholar 

  • Lustig L, Doncel GF, Berensztein Denduchis B. Testis lesions and cellular and humoral immune responses induced in rats by immunization with laminin. Am J Reprod Immunol. 1987;14:123–8.

    Article  CAS  Google Scholar 

  • Lustig L, Doncel GF, Berensztein E, Puig RP, Denduchis B. Experimental autoimmune orchitis. Medicina (B Aires). 1989;49:225–31.

    CAS  Google Scholar 

  • Lustig L, Lourtau L, Perez R, Doncel GF. Phenotypic characterization of lymphocytic cell infiltrates into the testes of rats undergoing autoimmune orchitis. Int J Androl. 1993;16:279–84.

    Article  CAS  PubMed  Google Scholar 

  • Lustig L, Denduchis B, Ponzio R, Lauzon M, Pelletier RM. Passive immunization with anti-laminin immunoglobulin G modifies the integrity of the seminiferous epithelium and induces arrest of spermatogenesis in the guinea pig. Biol Reprod. 2000;62:1505–14.

    Article  CAS  PubMed  Google Scholar 

  • Ma RZ, Gao J, Meeker ND, Fillmore PD, Yung KSK, Watanabe T, Zachary JF, Offner H, Blankenhorn EP, Teuscher C. Identification of Bphs, an autoimmune disease locus, as histamine receptor H1. Science. 2002;297:620–3.

    Article  CAS  PubMed  Google Scholar 

  • Mahi-Brown CA, Yule TD, Tung KSK. Adoptive transfer of murine autoimmune orchitis to naive recipients with immune lymphocytes. Cell Immunol. 1987;106:408–19.

    Article  CAS  PubMed  Google Scholar 

  • Mahi-Brown CA, Yule TD, Tung KS. Evidence for active immunological regulation in prevention of testicular autoimmune disease independent of the blood-testis barrier. Am J Reprod Immunol Microbiol. 1988;16:165–70.

    Article  CAS  PubMed  Google Scholar 

  • Mahi-Brown CA, Tung KSK. Activation requirements of donor T cells and host T cell recruitment in adoptive transfer of murine experimental autoimmune orchitis (EAO). Cell Immunol. 1989;124:368–79.

    Article  CAS  PubMed  Google Scholar 

  • Mahi-Brown CA, Tung KSK. Transfer of susceptibility to experimental autoimmune orchitis from responder to non-responder substrains of BALB/c mice. J Reprod Immunol. 1990;18:247–57.

    Article  CAS  PubMed  Google Scholar 

  • Mancini RE, Fainboim L, Alonso A. Effect of intratesticular injection of antisperm serum. Allergy. Clin Immunol. 1974;53:69–76.

    Google Scholar 

  • Mealy K, Robinson B, Millette CF, Majzoub J, Wilmore DW. The testicular effects of tumor necrosis factor. Ann Surg. 1990;211:470–5.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Meeker ND, Hickey WF, Korngold R, Hansen WK, Sudweeks JD, Wardell BB, Griffith JS, Teuscher C. Multiple loci govern the bone marrow-derived immunoregulatory mechanism controlling dominant resistance to autoimmune orchitis. Proc Natl Acad Sci U S A. 1995;92:5684–8.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Meeker ND, Stafford AN, Lunceford JK, Avner P, Ma RZ, Teuscher C. Physical mapping of the autoimmune disease susceptibility locus, Bphs:co-localization with a cluster of genes from the TNF receptor superfamily on mouse chromosome 6. Mamm Genome. 1999;10:858–63.

    Article  CAS  PubMed  Google Scholar 

  • Meng AL, Tung KS. Cell-mediated and humoral immune responses to aspermatogenic antigen in experimental allergic orchitis in the guinea-pig. J Reprod Fertil. 1983;69:279–88.

    Article  CAS  PubMed  Google Scholar 

  • Mielcarek N, Hornquist EH, Johansson BR, Locht C, Abraham SN, Holmgren J. Interaction of Bordetella pertussis with mast cells, modulation of cytokine secretion by pertussis toxin. Cell Microbiol. 2001;3:181–8.

    Article  CAS  PubMed  Google Scholar 

  • Millar DG, Garza KM, Odermatt B, Elford AR, Ono N, Li Z, Ohashi PS. Hsp70 promotes antigen-presenting cell function and converts T-cell tolerance to autoimmunity in vivo. Nat Med. 2003;9:1469–79.

    Google Scholar 

  • Murphy CJ, Stermer AR, Richburg JH. Age- and species-dependent infiltration of macrophages into the testis of rats and mice exposed to mono-(2-ethylhexyl) phthalate (MEHP). Biol Reprod. 2014;91:18. doi:10.1095/biolreprod.113.115527.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Musha M, Hirai S, Naito M, Terayama H, Qu N, Hatayama N, Itoh M. The effects of adjuvants on autoimmune responses against testicular antigens in mice. J Reprod Develop. 2013;59:139–44.

    Article  CAS  Google Scholar 

  • Naito M, Hirai S, Terayama H, Qu N, Kuerban M, Musha M, Kitaoka M, Ogawa Y, Itoh M. Post-inflammation stage of autoimmune orchitis induced by immunization with syngeneic testicular germ cells alone in mice. Med Mol Morphol. 2012;45:35–44.

    Article  CAS  PubMed  Google Scholar 

  • Noubade R, Milligan G, Zachary JF, Blankenhorn EP, del Rio R, Rincon M, Teuscher C. Histamine receptor H1 is required for TCR-mediated p38 MAPK activation and optimal IFN-gamma production in mice. J Clin Invest. 2007;117:3507–18.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Pelletier RM, Nemirovsky RC, Hugon JS. Effects of immunization with Freund’s complete adjuvant and isologous spermatozoaon the seminiferous epithelium and blood-testis barrier in guinea pigs. Anat Rec. 1981;199:197–211.

    Article  CAS  PubMed  Google Scholar 

  • Perez C, Sobarzo C, Jacobo P, Jarazo Dietrich S, Theas M, Denduchis B, Lustig L. Impaired expression and distribution of adherens and gap junction proteins in the seminiferous tubules of rats undergoing autoimmune orchitis. Int J Androl. 2011;34:e566–77.

    Article  CAS  PubMed  Google Scholar 

  • Perez CV, Sobarzo CM, Jacobo PV, Pellizzari EH, Cigorraga SB, Denduchis B, Lustig L. Loss of occludin expression and impairment of blood-testis barrier permeability in rats with autoimmune orchitis: effect of interleukin-6 on Sertoli cell tight junctions. Biol Reprod. 2012;87:122. doi:10.1095/biolreprod.112.101709.

    Article  PubMed  CAS  Google Scholar 

  • Perez CV, Theas MS, Jacobo PV, Jarazo-Dietrich S, Guazzone VA, Lustig L. Dual role of immune cells in the testis: Protective or pathogenic for germ cells? Spermatogenesis. 2013;3:e23870.

    Article  PubMed  PubMed Central  Google Scholar 

  • Perez CV, Pellizzari EH, Cigorrage SB, Galardo MN, Naito M, Lustig L, Jacob PV. IL17A impairs blood-testis barrier integrity and induces testicular inflammation. Cell Tissue Res. 2014;358:885–98.

    Article  CAS  PubMed  Google Scholar 

  • Perez CV, Gomez LG, Gualdoni GS, Lustig L, Rabinovich GA, Guazzone VA. Dual roles of endogenous and exogenous galectin-1 in the control of testicular immunopathology. Sci Rep. 2015;5:12259. doi:10.1038/srep12259.

  • Person PL, Snoek M, Demant P, Woodward SR, Teuscher C. The immunogenetics of susceptibility and resistance to murine experimental allergic orchitis. Reg Immunol. 1992a;4:284–97.

    CAS  PubMed  Google Scholar 

  • Person PL, Korngold R, Teuscher C. Pertussis toxin-induced lymphocytosis is associated with alterations in thymocyte subpopulations. J Immunol. 1992b;148:1506–11.

    CAS  PubMed  Google Scholar 

  • Pokorna Z. Induction of autoimmune aspermatogenesis by noncellular cytophilic material. Folia Biol. 1969;15:173–80.

    CAS  Google Scholar 

  • Pokorna Z, Vojtiskova M, Draber P. Induction of autoimmune damage to spermatogenesis in guinea pigs by passive transfer of anti-F9 mouse tetatocarcinoma stem cell serum fraction. Folia Biol. 1984;30:50–6.

    CAS  Google Scholar 

  • Qu N, Terayama H, Naito M, Ogawa Y, Hirai S, Kitaoka M, Yi SQ, Itoh M. Caput epididymitis but not orchitis was induced by vasectomy in a murine model of experimental autoimmune orchitis. Reproduction. 2008;135:859–66.

    Article  CAS  PubMed  Google Scholar 

  • Qu N, Hirayanagi Y, Kuramasu M, Nagahori K, Hayashi S, Hirai S, Hatayama N, Ogawa Y, Itoh M. Goshajinkigan completely recover the severe aspermatogenesis after busulfan treatment in mice. 2017 (in preparation).

    Google Scholar 

  • Raghavendra V, Tanga FY, DeLeo JA. Complete Freund’s adjuvant-induced peripheral inflammation evokes glial activation and proinflammatory cytokine expression in the CNS. Eur J Neurosci. 2004;20:467–73.

    Article  PubMed  Google Scholar 

  • Rezvangfar M, Sadrkhanloy R, Ahmadi A, Shojaei-Sadee H, Rezvanfar M, Mohammadirad A, Salehnia A, Abdollahi M. Protection of cyclophosphamide-induced toxicity in reproductive tract histology, sperm characteristics, and DNA damage by an herbal source; evidence for role of free-radical toxic stress. Hum Exp Toxicol. 2008;27:901–10.

    Article  Google Scholar 

  • Rival C, Theas MS, Guazzone VA, Lustig L. Interleukin-6 and IL-6 receptor cell expression in testis of rats with autoimmune orchitis. J Reprod Immunol. 2006a;70:43–58.

    Article  CAS  PubMed  Google Scholar 

  • Rival C, Lustig L, Iosub R, Guazzone VA, Schneider E, Meinhardt A, Fijak M. Identification of a dendritic cell population in normal testis and in chronically inflamed testis of rats with autoimmune orchitis. Cell Tissue Res. 2006b;324:311–8.

    Article  PubMed  Google Scholar 

  • Rival C, Guazzone VA, von Wulffen W, Hackstein H, Schneider E, Lustig L, Fijiak M. Expression of co-stimulatory molecules, chemokine receptors and proinflammatory cytokines in dendritic cells from normal and chronically inflamed rat testis. Mol Hum Reprod. 2007;13:853–61.

    Article  CAS  PubMed  Google Scholar 

  • Rival C, Theas MS, Suescun MO, Jacobo P, Guazzone V, Van Rooijen N, Lustig L. Functional and phenotypic characteristics of testicular macrophages in experimental autoimmune orchitis. J Pathol. 2008;215:108–17.

    Article  CAS  PubMed  Google Scholar 

  • Roper RJ, Doerge RW, Call SB, Tung SK, Hickey EF, Teuscher C. Autoimmune orchitis, epididymitis, and vasitis are immunogenetically distinct lesions. Am J Pathol. 1998;152:1337–45.

    CAS  PubMed  PubMed Central  Google Scholar 

  • Sakamoto Y, Himeno K, Sanui H, Yoshida S, Nomoto K. Experimental allergic orchitis in mice. I. A new model induced by immunization without adjuvants. Clin Immunol Immunopathol. 1985;37:360–8.

    Google Scholar 

  • Sakamoto Y, Nomoto K. Suppression of delayed-type hypersensitivity to syngeneic testicular cells in mice: involvement of suppressor T cells which act at the induction stage. Cell Immunol. 1986;102:168–76.

    Article  CAS  PubMed  Google Scholar 

  • Sakamoto Y, Matsumoto T, Kumazawa J. Suppressive effect of cyclosporine A on delayed-type hypersensitivity to syngeneic testicular cells. J Antibiot. 1994;47:708–14.

    Article  CAS  PubMed  Google Scholar 

  • Sato K, Hirokawa K, Hatakeyama S. Experimental allergic orchitis in mice. Histopathological and immunological studies. VIrchows Arch [Pathol Anat]. 1981;392:147–58.

    Article  CAS  Google Scholar 

  • Sewell WA, Moerloose PA, McKimm-Breschkin JL, Vadas MA. Pertussigen enhances antigen-driven interferon-r production by sensitized lymphoid cells. Cell Immunol. 1986;97:238.

    Article  CAS  PubMed  Google Scholar 

  • Shoenfeld Y, Agmon-Levin N. ‘ASIA’-Autoimmune/inflammatory syndrome induced by adjuvants. J Autoimmun. 2011;36:4–8.

    Article  CAS  PubMed  Google Scholar 

  • Sliwa L, Macura B, Majewska M, Szczepanik M. Histological changes in seminiferous epithelium in testis of male mice induced by injection of lipopolysaccharide. Folia Med Cracov. 2009;50:107–17.

    PubMed  Google Scholar 

  • Sliwa L, Macura B, Majewska-Szczepanik M, Szczepanik M. Lack of TCRalphanbeta+ CD8+ and TCRgammadelta+ lymphocytes ameliorates LPS induced orchitis in mice –preliminary histological observations. Folia Biol. 2014;62:67–71.

    Article  CAS  Google Scholar 

  • Sonoda KH, Matsuzaki G, Nomura A, Yamada H, Hamano S, Nakamura T, Mukasa A, Nomoto K. Macrophages activated by Listeria monocytogenes induce organ-specific autoimmunity. Immunology. 1997;92:274–83.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Steenstra R, Neblett H, Teuscher C. Serum testosterone levels in Balb/cByJ and Balb/cJ substrain mice: potential relationship with differential susceptibility to experimental autoimmune orchitis (EAO). Autoimmunity. 1989;2:285–9.

    Article  CAS  PubMed  Google Scholar 

  • Sudweeks JD, Todd JA, Blankenhorn EP, Wardell BB, Woodward SR, Meeker ND, Estes SS, Teuscher C. Locus controlling Bordetella pertussis-induced histamine sensitization (Bphs), an autoimmune disease-susceptibility gene, maps distal to T-cell receptor beta-chain gene on mouse chromosome 6. Proc Natl Acad Sci U S A. 1993;90:3700–4.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Suescun MO, Calandra RS, Lustig L. Alteration of testicular function after induced autoimmune orchitis in rats. J Androl. 1994;15:442–8.

    CAS  PubMed  Google Scholar 

  • Suescun MO, Calandra RS, Lustig L. Increased testosterone production in vitro by Leydig cells from rats with severe autoimmune orchitis. Int J Androl. 1997;20:339–46.

    Google Scholar 

  • Suescun MO, Calandra RS, Lustig L. Effect of testicular macrophage conditioned media from rats with autoimmune orchitis on Leydig cell function. Am J Reprod Immunol. 2000;43:116–23.

    Article  CAS  PubMed  Google Scholar 

  • Suescun MO, Lustig L, Calandra RS, Groome NP, Campo S. Correlation between inhibin secretion and damage of seminiferous tubules in a model of experimental autoimmune orchitis. J Endocrinol. 2001;170:113–20.

    Article  CAS  PubMed  Google Scholar 

  • Suescun MO, Rival C, Theas MS, Calandra RS, Lustig L. Involvement of tumor necrosis factor-alpha in the pathogenesis of autoimmune orchitis in rats. Biol Reprod. 2003;68:2114–21.

    Article  CAS  PubMed  Google Scholar 

  • Sun B, Qi N, Shang T, Wu H, Deng T, Han D. Sertoli cell-initiated testicular innate immune response through toll-like receptor-3 activation is negatively regulated by Tyro3, Axl, and Mer receptors. Endocrinology. 2010;151:2886–97.

    Article  CAS  PubMed  Google Scholar 

  • Sztein MB, Satz ML, Serrate SA. Transfer of cell migration inhibition in vitro with xenogeneic RNA in experimental autoimmune orchitis. J Clin Lab Immunol. 1980;3:39–43.

    Google Scholar 

  • Tainosho S, Naito M, Hirai S, Terayama H, Qu N, Itoh M. Multilayered structure of the basal lamina of tubuli recti in normal mice. Med Mol Morphol. 2011;44:34–8.

    Article  PubMed  Google Scholar 

  • Tardif S, Wilson MD, Wagner R, Hunt P, Gertsenstein M, Nagy A, Lobe C, Koop BF, Hardy DM. Zonadhesin is essential for species specificity of sperm adhesion to the egg zona pellucida. J Biol Chem. 2010;285:24863–70.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Teuscher C, Wild GC, Tung KSK. Experimental allergic orchitis: the isolation and partial characterization of an aspermatogenic polypeptide (AP3) with an apparent sequential disease-inducing determinants. J Immunol. 1983a;130:2683–8.

    CAS  PubMed  Google Scholar 

  • Teuscher C, Wild GC, Tung KS. Acrosomal autoantigens of guinea pig sperm. I. The purification of an aspermatogenic protein, AP2. J Immunol. 1983b;130:317–22.

    Google Scholar 

  • Teuscher C, Smith SM, Goldberg EH, Shearer GM, Tung KSK. Experimental allergic orchitis in mice. I. Genetic control of susceptibility and resistance to induction of autoimmune orchitis. Immunogenetics. 1985a;22:323–33.

    Google Scholar 

  • Teuscher C, Potter M, Tung KS. Differential susceptibility to experimental autoimmune orchitis in Balb/c substrains. Curr Top Microbiol Immunol. 1985b;122:181–8.

    CAS  PubMed  Google Scholar 

  • Teuscher C. Experimental allergic orchitis in mice, II: association of disease susceptibility with the locus controlling Bordetella pertussis-induced sensitivity to histamine. Immunogenetics. 1985;22:417–25.

    Article  CAS  PubMed  Google Scholar 

  • Teuscher C. Association of Bordetella pertussis-induced hypersensitivity to serotonin with the H-2 gene complex. J Immunogeneti. 1986;13:51–5.

    Article  CAS  Google Scholar 

  • Teuscher C, Smith SM, Tung KSK. Experimental allergic orchitis in mice. III. Differential susceptibility in Balb/c sublines. J Reprod Immunol. 1987a;10:219–30.

    Google Scholar 

  • Teuscher C, Blankenhorn EP, Hickey WF. Differential susceptibility to actively induced experimental allergic encephalomyelitis (EAE) and experimental allergic orchitis (EAO) among Balb/c substrains. Cell Immunol. 1987b;110:294–304.

    Article  CAS  PubMed  Google Scholar 

  • Teuscher C, Blankenhorn EP, Hickey WF. Genetic analysis of Balb/cJ subline resistance to actively induced experimental allergic orchitis (EAO) and experimental allergic encephalomyelitis (EAE). Curr Top Microbiol Immunol. 1988;137:233–9.

    CAS  PubMed  Google Scholar 

  • Teuscher C, Zhou ZZ, Hickey WF. Actively induced experimental allergic orchitis in Lewis-resistant rats: reversibility of disease resistance by immunization with Bordetella pertussis. Cell Immunol. 1989;119:233–8.

    Article  CAS  PubMed  Google Scholar 

  • Teuscher C, Hickey WF, Korngold R. Experimental allergic orchitis in mice. V. Resistance to actively induced disease in Balb/cJ substrain mice is mediated by CD4+ T cells. Immunogenetics. 1990a;32:34–40.

    Google Scholar 

  • Teuscher C, Gasser DL, Woodward SR, Hickey WF. Experimental allergic orchitis in mice. VI: Recombinations within the H-2S/H-2 interval define the map position of the H-2-associated locus controlling disease susceptibility. Immunogenetics. 1990b;32:337–44.

    CAS  PubMed  Google Scholar 

  • Teuscher C, Hickey WF, Korngold R. An analysis of the role of tumor necrosis factor in the phenotypic expression of actively induced experimental allergic orchitis and experimental allergic encephalomyelitis. Clin Immunol Immunopathol. 1990c;54:442–53.

    Article  CAS  PubMed  Google Scholar 

  • Teuscher C, Meeker ND, Livingstone KD, Sudweeks JD, Griffith JS, Wardell BB, Hickey WF. Experimental allergic orchitis in mice. VII. Preliminary characterization of the aspermatogenic autoantigens responsible for eliciting actively and passively induced disease. J Reprod Immunol. 1994;26:233–49.

    Google Scholar 

  • Teuscher C, Hickey WF, Grafer CM, Tung KS. A common immunoregulatory locus controls susceptibility to actively induced experimental allergic encephalomyelitis and experimental allergic orchitis in BALB/c mice. J Immunol. 1998;160:2751–7.

    CAS  PubMed  Google Scholar 

  • Theas MS, Rival C, Lustig L. Germ cell apoptosis in autoimmune orchitis: involvement of the Fas-FasL system. Am J Reprod Immunol. 2003;50:166–76.

    Article  PubMed  Google Scholar 

  • Theas MS, Rival C, Dietrich SJ, Guazzone VA, Lustig L. Death receptor and mitochondrial pathways are involved in germ cell apoptosis in an experimental model of autoimmune orchitis. Hum Reprod. 2006;21:1734–42.

    Article  CAS  PubMed  Google Scholar 

  • Theas MS, Rival C, Jarazo-Dietrich S, Jacobo P, Guazzone VA, Lustig L. Tumor necrosis factor-alpha released by testicular macrophages induces apoptosis of germ cells in autoimmune orchitis. Hum Reprod. 2008;23:1865–72.

    Article  CAS  PubMed  Google Scholar 

  • Tonon S, Goriely S, Aksoy E, Pradier O, Del Giudice G, Trannoy E, Willems F, Goldman M, De Wit D. Bordetella pertussis toxin induces the release of inflammatory cytokines and dendritic cell activation in whole blood: impaired responses in human newborns. Eur J Immunol. 2002;32:3118–31125.

    Article  CAS  PubMed  Google Scholar 

  • Toullet F, Voisin GA, Nemirovsky M. Histoimmunochemical localization of three guinea-pig spermatozoal autoantigens. Immunology. 1973;24:635–53.

    CAS  PubMed  PubMed Central  Google Scholar 

  • Toullet F, Voisin GA. Passive transfer of autoimmune aspermatogenic orchiepididymitis (AIAO) by antispermatozoa sera. Influence of the type of autoantigen and of the class of antibody. Clin Exp Immunol. 1976;26:549–62.

    CAS  PubMed  PubMed Central  Google Scholar 

  • Tung KS, Unanue ER, Dixon FJ. Pathogenesis of experimental allergic orchitis. I. Transfer with immune lymph node cells. J Immunol. 1971a;106:1453–62.

    Google Scholar 

  • Tung KS, Unanue ER, Dixon FJ. Pathogenesis of experimental allergic orchitis. II. The role of antibody. J Immunol. 1971b;106:1463–72.

    Google Scholar 

  • Tung KS, Unanue ER, Dixon FJ. Immunological events associated with immunization by sperm in incomplete Freund’s adjuvant. Int Arch Allergy Appl Immunol. 1971c;41:565–74.

    Article  CAS  PubMed  Google Scholar 

  • Tung KS, Leong C, McCarty T. Pathogenesis of experimental allergic orchitis. III. T lymphocyte requirement in local adoptive transfer by peritoneal exudate cells. J Immunol. 1977;118:1774–9.

    Google Scholar 

  • Tung KS, Yule TD, Mahi-Brown CA, Listrom MB. Distribution of histopathology and Ia positive cells in actively induced and passively transferred experimental autoimmune orchitis. J Immunol. 1987;138:752–9.

    CAS  PubMed  Google Scholar 

  • Tung KS, Mahi-Brown CA, Yule TD. Immunologic mechanisms and target antigens in testicular autoimmunity. Ann N Y Acad Sci. 1989;564:267–80.

    Article  CAS  PubMed  Google Scholar 

  • Tung KS, Teuscher C. Mechanisms of autoimmune disease in the testis and ovary. Hum Reprod Update. 1995;1:35–50.

    Article  CAS  PubMed  Google Scholar 

  • Tung KS, Primakoff P, Woolman-Gamer L, Myles DG. Mechanism of infertility in male guinea pigs immunized with sperm PH-20. Biol Reprod. 1997;56:1133–41.

    Article  CAS  PubMed  Google Scholar 

  • Tung KS. Autoimmune disease of the testis and the ovary. The autoimmune diseases. 3rd ed. Amsterdam: Academic Press; 1998. p. 687–704.

    Google Scholar 

  • Tung PS, Fritz IB. Autoimmune orchitis can be induced by thymic lymphocytes autosensitized against syngeneic Sertoli cells in vitro. Biol Reprod. 1984;30:979–90.

    Google Scholar 

  • Tung PS, Fritz IB. Histopathological changes in testes of adult inbred rats immunized against pachytene spermatocytes or Sertoli cells. Int J Androl Suppl. 1987;2:459–81.

    Google Scholar 

  • Ueno A, Takeda M, Hirasawa K, Itagaki S, Doi K. Relation-ship between distribution of viral RNA and development of histopathological changes in encephalomyocarditis virus-induced orchitis in mice. Int J Exp Pathol. 1996;77:25–30.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Ueno A, Takeda M, Hirasawa K, Itagaki S, Doi K. Detection of viral RNA by electron microscopic in situ hybridization (ISH-EM) in the germinal epithelium of mice infected with encephalomyocarditis (EMC) virus. Exp Anim. 1997;46:79–81.

    Article  CAS  PubMed  Google Scholar 

  • Vojtiskova M, Pokorna Z. Prevention of experimental allergic aspermatogenesis by thymectomy in adult mice. Lancet. 1964;1:644–5.

    Article  CAS  PubMed  Google Scholar 

  • Vojtiskova M, Pokorna Z, Draber P. Autoimmune damage to spermatogenesis in rodents immunized with mouse F9 embryonic carcinoma cells. Proc Natl Acad Sci U S A. 1983;80:459–61.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Vojtiskova M, Pokorna Z, Draber P. Immunological tolerance to spermatogenic cell antigens induced by teratocarcinoma stem cell antigens. Folia Biol. 1984;30:290–5.

    CAS  Google Scholar 

  • Vulchanov VH. Testicular damage and autoantibody formation in guinea-pigs immunized with homologous seminal vesicular fluid. In: Immunology and reproduction. London: International Planned Parenthood Federation; 1969. p. 136–47.

    Google Scholar 

  • Wagner H, Starzinsk-Powitz A, Rollinghoff M, Golstein P, Jakob H. T-cell-mediated cytotoxic immune responses to F9 teratocarcinoma cells: cytolytic effector T cells lyse H-2-negative F9 cells and syngeneic spermatozoa. J Exp Med. 1978;147:251–64.

    Article  CAS  PubMed  Google Scholar 

  • Wakabayashi A, Eishi Y, Nakamura K. Regulation of experimental autoimmune orchitis by the presence or absence of testicular antigens during immunological development in SCID mice reconstituted with fetal liver cells. Immunology. 1997;92:84–90.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Wardlaw AC. Inheritance of responsiveness to pertussis HSF in mice. Int Arch Allergy Appl Immunol. 1970;38:573–89.

    Article  CAS  PubMed  Google Scholar 

  • Wekerle H, Begemann M. Experimental autoimmune orchitis: in vitro induction of an autoimmune disease. J Immunol. 1976;116:159–61.

    Google Scholar 

  • Wekerle H, Begemann M. In vitro induction of experimental autoimmune orchitis:role of serum factors. Transplant Proc. 1977;9:775–8.

    CAS  PubMed  Google Scholar 

  • Wekerle H, Begemann M. In vitro induction of experimental autoimmune: characterization of a primary T lymphocyte response against self antigens. Eur J Immunol. 1978;8:294–302.

    Article  CAS  PubMed  Google Scholar 

  • Wekerle H. Immunological T cell memory in the in vitro-induced experimental autoimmune orchitis. Specificity of the reaction and tissue distribution of the autoantigens. J Exp Med. 1978;147:233–50.

    Google Scholar 

  • Wheeler K, Tardif S, Rival C, Luu B, Bui E, del-Rio R, Teuscher C, Sparwasser T, Hardy D, Tung KSK. Regulatory T cells control tolerogenic versus autoimmune response to sperm in vasectomy. Proc Natl Acad Sci U S A. 2011;108:7511–6.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Yamanouchi-Ueno A, Nakatyama Y, Doi K. Characteristics of testicular lesions in mice infected with a low dose of encephalomyocarditis (EMC) virus. Exp Mol Pathol. 2004;77:72–9.

    Article  CAS  PubMed  Google Scholar 

  • Yantorno C, Debanne MT, Vottero-Cima E. Autoimmune orchitis induced by autoimmunization with seminal plasma in the rabbit. J Reprod Fertil. 1971;27:311–20.

    Article  CAS  PubMed  Google Scholar 

  • Yokochi T, Ikeda H, Inoue Y, Kimura Y, Ito H, Fujii Y, Kato N. Characterization of autoantigens relevant to experimental autoimmune orchitis (EAO) in mice immunized with a mixture of syngeneic testis homogenate and Klebsiella O3 Lipopolysaccharide. Am J Reprod Immunol. 1990;22:42–8.

    Article  CAS  PubMed  Google Scholar 

  • Yoshida S, Nomoto K, Himeno K, Takeya K. Immune response to syngeneic or autologous testicular cells in mice. I. Augmented delayed footpad reaction in cyclophosphamide-treated mice. Clin Exp Immunol. 1979;38:211–7.

    Google Scholar 

  • Yule TD, Montoya GD, Russell LD, Williams TM, Tung KSK. Autoimmunogenic germ cells exist outside the blood testis barrier. J Immunol. 1988;141:1161–7.

    CAS  PubMed  Google Scholar 

  • Yule TD, Mahi-Brown CA, Tung KS. Role of testicular autoantigens and influence of lymphokines in testicular autoimmune disease. J Reprod Immunol. 1990;18:89–103.

    Article  CAS  PubMed  Google Scholar 

  • Yule TD, Tung KSK. Experimental autoimmune orchitis induced by testis and sperm antigen-specific T cell clones: an important pathogenic cytokines is tumor necrosis factor. Endocrinology. 1993;133:1098–107.

    Article  CAS  PubMed  Google Scholar 

  • Zhou ZZ, Zeng Y, Steenstra R, Hickey WF, Teuscher C. Actively-induced experimental allergic orchitis (EAO) in Lewis/NCR rats: sequential histo-and immunopathologic analysis. Autoimmunity. 1989;3:125–34.

    Article  CAS  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Anatomy, Tokyo Medical University, Shinjyuku-ku, Tokyo, Japan

    Masahiro Itoh

Authors
  1. Masahiro Itoh
    View author publications

    You can also search for this author in PubMed Google Scholar

Rights and permissions

Reprints and permissions

Copyright information

© 2017 Springer Japan

About this chapter

Cite this chapter

Itoh, M. (2017). Testicular Autoimmunity by the Systemic Treatment with Immuno-Potentiating Agents in Experimental Animals. In: Testicular Autoimmunity. Springer, Tokyo. https://doi.org/10.1007/978-4-431-54460-9_5

Download citation

  • DOI: https://doi.org/10.1007/978-4-431-54460-9_5

  • Published:

  • Publisher Name: Springer, Tokyo

  • Print ISBN: 978-4-431-54459-3

  • Online ISBN: 978-4-431-54460-9

  • eBook Packages: MedicineMedicine (R0)

Publish with us

Policies and ethics

Search

Navigation