- Open Access
Higher incidence of sperm granuloma in the epididymis of C57BL/6N mice
Laboratory Animal Research volume 34, pages20–29(2018)
C57BL/6N mice are inbred strains widely used in biomedical research. Hence, a large amount of basic data has been accumulated. However, in the field of histopathology, spontaneous data for relatively younger mice that are used more frequently are not yet abundant, in contrast to data for older mice and their neoplastic lesions. To acquire the essential background data required by various research and toxicological assessments, 120 mice of the C57BL/6N strain (10 and 13 weeks of age) were collected from two institutions (From Korea and Japan) and subjected to histopathological analyses of the major organs (liver, spleen, kidney, thymus, heart, testis, epididymis). The results showed significantly higher incidence of sperm granulomas in the epididymides (10–56%) of these mice, compared with that in other strains or species of lab animals. Upon closer inspection, oligospermia/clear cell hyperplasia, cellular debris, and tubular vacuolation were also observed in the epididymides with sperm granulomas. Moreover, diseased organs were significantly heavier than healthy ones. Immunohistochemical staining showed a significant increase in the chromatic figures of cysteine-dependent aspartate-directed proteases-3 (caspase-3) and cleaved-poly(ADP-ribose) polymerase (c-PARP), and damages to the tubule due to spontaneous apoptosis, which may have led to the sperms leaking out of the tubule, causing the granuloma. To conclude, spontaneous sperm granuloma can occur in 10- and 13-week-old C57BL/6N mice and may thus affect the results of various studies using these mice. Therefore, sperm granuloma in epididymis needs to be carefully considered as an important factor when design the study using C57BL/6N.
Treuting P, Dintzis SM. Comparative Atlas Anatomy and Histology: A Mouse and Human Atlas, Academic Press, Cambridge, 2012; p 5.
Flurkey K, Currer J, Leiter E, Witham B. The Jackson Laboratory Handbook on Genetically Standardized Mice, 6th ed, Maine, The Jackson laboratory, Bar Harbor, 1997; p 138.
Maronpot R, Boorman G, Gaul BW. Pathology of the Mouse Reference and Atlas, Cache River Press, Saint Louis, 1999; pp 1–2.
McInnes EF. Background Lesions in Laboratory Animals A Color Atlas, Sounders Elsevier, Philadelphia, 2012; p 7.
Szymanska H, Lechowska-Piskorowska J, Krysiak E, Strzalkowska A, Unrug-Bielawska K, Grygalewicz B, Skurzak H, Pienkowska-Grela B, Gajewska M. Neoplastic and nonneoplastic lesions in aging mice of unique and common inbred strains contribution to modeling of human neoplastic diseases. Vet Pathol 2014; 51(3): 663–679.
Haines D, Chattopadhyay S, Ward JM. Pathology of aging B6;129 mice. Toxicol Pathol 2001; 29(6): 653–661.
Paranjpe M, Shah S, Denton M, Elbekai RH. Incidence of spontaneous non-neoplastic lesions in transgenic CBYB6F1- Tg(HRAS)2Jic mice. Toxicol Pathol 2013; 41(8): 1137–1145.
Blankenship B, Skaggs H. Findings in historical control harlan RCCHantm: WIST rats from 4-, 13-, 26-week studies. Toxicol Pathol 2013; 41(3): 537–547.
Dixon D, Heider K, Elwell MR. Incidence of nonneoplastic lesions in historical control male and female Fischer-344 rats from 90-day toxicity studies. Toxicol Pathol 1995; 23(3): 338–348.
Lanning L, Creasy D, Chapin R, Mann P, Barlow N, Regan K, Goodman DG. Recommended approaches for the evaluation of testicular and epididymal toxicity. Toxicol Pathol 2002; 30(4): 507–520.
De Grava Kempinas W, Klinefelter GR. Interpreting histopathology in the epididymis. Spermatogenesis 2015; 4(2): e979114.
Haschek W, Rousseaux C, Wallig MA. Haschek and Rousseaux’s Handbook of Toxicologic Pathology, Academic Press, Cambridge, 2013; pp 2557–2558.
Flickinger C, Howard SS. Consequences of Obstruction on the Epididymis. In: The Epididymis: from Molecules to Clinical Practice (Robaire B Hinton B, eds), Kluwer Academic Plenum Publishers, New York, 2002; pp 503–522.
Pritam S, Sahota JAP, Hardisty J, Gopinath C. Toxicologic Pathology: Nonclinical Safety Assessment, Taylor & Francis Group, Abingdon, 2013; p 750.
Wang H, Bloom O, Zhang M, Vishnubhakat J, Ombrellino M, Che J, Frazier A, Yang H, Ivanova S, Borovikova L, Manogue K, Faist E, Abraham E, Andersson J, Andersson U, Molina P, Abumrad N, Sama A, Tracey KJ. HMG-1 as a late mediator of endotoxin lethality in mice. Science 1999; 285(5425): 248–251.
Elmore S. Apoptosis: a review of programmed cell death. Toxicol Pathol 2007; 35(4): 495–516.
Tanida I, Ueno T, Kominami E. LC3 and Autophagy. Methods Mol Biol 2008; 445: 77–88.
Pias E, Ekshyyan O, Rhoads C, Fuseler J, Harrison L, Aw TY. Differential effects of superoxide dismutase isoform expression on hydroperoxide-induced apoptosis in PC-12 cells. J Biol Chem 2003; 278(15): 13294–13301.
Boulares A, Yakovlev A, Ivanova V, Stoica B, Wang G, Iyer S, Smulson M. Role of poly(ADP-ribose) polymerase (PARP) cleavage in apoptosis. Caspase 3-resistant PARP mutant increases rates of apoptosis in transfected cells. J Biol Chem 1999; 274(33): 22932–22940.
Fuchs Y, Steller H. Programmed cell death in animal development and disease. Cell 2011; 147(4): 742–758.
Friedlander RM. Apoptosis and caspases in neurodegenerative diseases. N Engl J Med 2003; 348: 1365–1375.
Thompson CB. Apoptosis in the pathogenesis and treatment of disease. Science 1995; 267(5203): 1456–1462.
Byun H, Song J, Kim Y, Piao L, Won M, Park K, Choi B, Lee H, Hong J, Park J, Seok J, Lee Y, Kang S, Hur GM. Caspase-8 has an essential role in resveratrol-induced apoptosis of rheumatoid fibroblast-like synoviocytes. Rheumatology (Oxford) 2008; 47(3): 301–308.
Dharmapatni A, Smith M, Findlay D, Holding C, Evdokiou A, Ahern MS, Weedon H, Chen P, Screaton G, Xu X, Haynes DR. Elevated expression of caspase-3 inhibitors, survivin and xIAP correlates with low levels of apoptosis in active rheumatoid synovium. Arthritis Res Ther 2009; 11(1): R13.
Lee I, Kim K, Kim S, Baek H, Moon C, Kim S, Yun W, Nam K, Kim H, Kim JC. Apoptotic cell death in rat epididymis following epichlorohydrin treatment. Hum Exp Toxicol 2013; 32(6): 640–646.
Marx J, Brice A, Boston R, Smith AL. Incidence Rates of Spontaneous Disease in Laboratory Mice Used at a Large Biomedical Research Institution. J Am Assoc Lab Anim Sci 2013; 52(6): 782–791.
Fox J, Davisson M, Quimby F, Barthold S, Newcomer Q, Smith AL. Spontaneous Diseases in Commonly used Mouse Strains, the Mouse in Biomedical Research, Academic press, Cambridge, 2012; pp 623–717.
Smith R, Roderick T, Sundberg JP. Microphthalmia and associated abnormalities in inbred black mice. Lab Anim Sci 1994; 44(6): 551–560.
Van Winkle T, Balk MW. Spontaneous corneal opacities in laboratory mice. Lab Anim Sci 1986; 36(3): 248–255.
Li H, Hultcrantz M. Age-related degeneration of the organ of Corti in two genotypes of mice. ORL J Otorhinolaryngol Relat Spec 1994; 56(2): 61–67.
McFadden S, Ding D, Salvi R. Anatomical, metabolic and genetic aspects of age-related hearing loss in mice. Audiology 2001; 40(6): 313–321.
Johnson K, Erway L, Cook S, Willott J, Zheng QY. A major gene affecting age-related hearing loss in C57BL/6J mice. Hear Res 1997; 114(1-2): 83–92.
Johnson K, Zheng QY. Ah12, a second locus affecting age-related hearing loss in mice. Genomics 2002; 80(5): 461–464.
About this article
Cite this article
Park, D., Lee, B., Kim, W. et al. Higher incidence of sperm granuloma in the epididymis of C57BL/6N mice. Lab Anim Res 34, 20–29 (2018) doi:10.5625/lar.2018.34.1.20
- sperm granuloma
- historical background
- spontaneous lesion