Rodent Model of Experimental Autoimmune-Orchitis: History
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Subjects: Endocrinology & Metabolism
Contributor:
Fabian Hemm

The rodent model of experimental autoimmune-orchitis (EAO) was established to analyze the underlying mechanisms of male infertility and causes of reduced testosterone concentration.

  • experimental autoimmune-orchitis
  • osteoporosis
  • mouse model
  • biomechanical properties
  • rodent model
  • Complete Freund’s Adjuvant
  • Bordetella pertussis toxin
Testicular inflammation is mainly caused by bacterial infections, either sexually transmitted or from the urinary tract, and often develops a chronic asymptomatic disease progression [1][2][3][4]. Therefore, orchitis can persist over prolonged periods until adequate therapy is started and may result in irreversible long-term damage regarding the reproductive system [2][3]. In this regard, inflammatory infiltrates in the testicular interstitium, damaged seminiferous tubules and disorder of spermatogenesis have been illustrated [2]. In most cases inflammation affects epididymides as well, and leads to a combined epididymo-orchitis [1][2]. Consequently, orchitis, or rather epididymo-orchitis, represents a frequent cause of fertility disorders in young men [3][5]. However, the majority of fertility disorders are diagnosed a long time after the initial inflammatory process. Thus, in vitro and in vivo models are crucial to investigate the underlying processes of epididymo-orchitis and its complications. In this context the rodent model of experimental autoimmune-orchitis (EAO) represents a well-established animal model to evaluate the processes of testicular inflammation, consequences regarding the reproductive functionality and possible therapy options [6][7][8][9]. Furthermore, EAO was found to significantly reduce the testosterone concentration in rats in a similar way to human orchitis [6]. Androgens are known to represent a major impact factor regarding bone metabolism in men [10][11][12]. Accordingly, a study focused on the bone status in a mouse model of EAO illustrated significant alterations regarding bone metabolism, bone mass, bone microarchitecture and bone mineralization resulting in decreased biomechanical stability [13]. But, due to significant alterations following immunization with complete Freund’s adjuvant (CFA) alone, the mouse model of EAO currently appears to be inappropriate to examine the effects of orchitis regarding bone metabolism [13].
EAO is typically induced by active immunization with testicular homogenate in CFA [14]. The testicular homogenate is prepared from decapsulated testes collected from adult syngeneic mice and homogenized in sterile 0.9% NaCl at a ratio of 1:1. For immunization, testicular homogenate is mixed with CFA at a ratio of 1:1. In mice, four subcutaneous injections with a total volume of 200 μL (50 μL per injection site) per immunization are conducted dorsally under anaesthesia. Simultaneously, intraperitoneal injection of 100 ng Bordetella pertussis toxin in 100 μL Munõz Buffer (25 mM Tris, 0.5 M NaCl, 0.017% Triton X-100, pH 7.6) [15] is carried out in order to boost the immune reaction. In total, animals are immunized three times every 14 days. As an adjuvant control group, age-matched mice receive CFA mixed with 0.9% NaCl instead of testicular homogenate combined with Bordetella pertussis toxin following the same procedure. An additional control group of age-matched mice remains completely untreated. Depending on the purpose of the current study, euthanasia is conducted after individual time periods between 30 and 80 days after the first immunization [14].

This entry is adapted from the peer-reviewed paper 10.3390/ijms22157858

References

  1. G. Haidl; J. P. Allam; H.-C. Schuppe; Chronic epididymitis: impact on semen parameters and therapeutic options. Andrologia 2008, 40, 92-96, 10.1111/j.1439-0272.2007.00819.x.
  2. H.-C. Schuppe; A. Meinhardt; J. P. Allam; M. Bergmann; W. Weidner; G. Haidl; Chronic orchitis: a neglected cause of male infertility?. Andrologia 2008, 40, 84-91, 10.1111/j.1439-0272.2008.00837.x.
  3. Hans-Christian Schuppe; Adrian Pilatz; Hamid Hossain; Thorsten Diemer; Florian Wagenlehner; Wolfgang Weidner; Urogenital Infection as a Risk Factor for Male Infertility. Deutsches Aerzteblatt Online 2017, 114, 339-346, 10.3238/ARZTEBL.2017.0339.
  4. W. Weidner; A. Pilatz; Th. Diemer; H. C. Schuppe; A. Rusz; F. Wagenlehner; Male urogenital infections: impact of infection and inflammation on ejaculate parameters. World Journal of Urology 2013, 31, 717-723, 10.1007/s00345-013-1082-7.
  5. G R Dohle; Giovanni M. Colpi; T B Hargreave; G K Papp; A Jungwirth; W Weidner; EAU Guidelines on Male Infertility. European Urology 2005, 48, 703-711, 10.1016/j.eururo.2005.06.002.
  6. Monika Fijak; Eva Schneider; Jörg Klug; Sudhanshu Bhushan; Holger Hackstein; Gerhard Schuler; Malgorzata Wygrecka; Jörg Gromoll; Andreas Meinhardt; Testosterone Replacement Effectively Inhibits the Development of Experimental Autoimmune Orchitis in Rats: Evidence for a Direct Role of Testosterone on Regulatory T Cell Expansion. The Journal of Immunology 2011, 186, 5162-5172, 10.4049/jimmunol.1001958.
  7. Nour Nicolas; Julie A Muir; Susan Hayward; Justin L Chen; Peter Stanton; Paul Gregorevic; David M De Kretser; Kate Loveland; Sudhanshu Bhushan; Andreas Meinhardt; et al. Induction of experimental autoimmune orchitis in mice: responses to elevated circulating levels of the activin-binding protein, follistatin. Reproduction 2017, 154, 293-305, 10.1530/rep-17-0010.
  8. Kenneth S.K. Tung; Mechanisms of autoimmune disease in the testis and ovary. Human Reproduction Update 1995, 1, 35-50, 10.1093/humupd/1.1.35.
  9. Monika Fijak; Adrian Pilatz; Mark P Hedger; Nour Nicolas; Sudhanshu Bhushan; Vera Michel; Kenneth S K Tung; Hans-Christian Schuppe; Andreas Meinhardt; Infectious, inflammatory and ‘autoimmune’ male factor infertility: how do rodent models inform clinical practice?. Human Reproduction Update 2018, 24, 416-441, 10.1093/humupd/dmy009.
  10. Diana Rucker; Shereen Ezzat; Anastasia Diamandi; Javad Khosravi; David A. Hanley; IGF-I and testosterone levels as predictors of bone mineral density in healthy, community-dwelling men. Clinical Endocrinology 2004, 60, 491-499, 10.1111/j.1365-2265.2004.02006.x.
  11. A. D. Mooradian; J. E. Morley; S. G. Korenman; Biological Actions of Androgens. Endocrine Reviews 1987, 8, 1-28, 10.1210/edrv-8-1-1.
  12. Bart L. Clarke; Sundeep Khosla; Androgens and bone. Steroids 2009, 74, 296-305, 10.1016/j.steroids.2008.10.003.
  13. Fabian Hemm; Monika Fijak; Jan Belikan; Marian Kampschulte; Thaqif El Khassawna; Adrian Pilatz; Christian Heiss; Katrin Lips; Bone Status in a Mouse Model of Experimental Autoimmune-Orchitis. International Journal of Molecular Sciences 2021, 22, 7858, 10.3390/ijms22157858.
  14. Nour Nicolas; Vera Michel; Sudhanshu Bhushan; Eva Wahle; Susan Hayward; Helen Ludlow; David M. De Kretser; Kate Loveland; Hans-Christian Schuppe; Andreas Meinhardt; et al. Testicular activin and follistatin levels are elevated during the course of experimental autoimmune epididymo–orchitis in mice. Scientific Reports 2017, 7, srep42391, 10.1038/srep42391.
  15. S Kohno; J A Munoz; T M Williams; C Teuscher; C C Bernard; K S Tung; Immunopathology of murine experimental allergic orchitis.. The Journal of Immunology 1983, 130, 2675-82, .
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