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Epididymal Sperm Granuloma Induced by Chronic Administration of 2-Methylimidazole in B6C3F₁ Mice

¹ Laboratory of Experimental Pathology
² Laboratory of Molecular Toxicology
³ Toxicology Operations Branch
⁴ Biostatistics Branch, National Institute of Environmental Health Sciences, National Institutes of Health, Research Triangle Park, North Carolina 27709, USA

Correspondence: Address correspondence to: Abraham Nyska, Laboratory of Experimental Pathology, National Institute of Environmental Health Sciences, P. O. Box 12233, Mail Drop B3-06, Research Triangle Park, North Carolina 27709, USA; e-mail:nyska{at}niehs.nih.gov

Two-year mouse and rat bioassay studies of 2-methylimidazole (2-MI) conducted by the National Toxicology Program revealed that epididymal sperm granuloma(SG)s occurred only in male B6C3F₁ mice in a dose-related manner. The present study characterized 2-MI-induced SGs in these epididymides. Groups of 50 male B6C3F₁ mice were fed diets containing 0, 625, 1250, or 2500 ppm 2-MI for 105 weeks; the doses were equivalent to average daily doses of approximately 13, 40, or 130 mg/kg. Testes and epididymides were histopathologically reexamined. 2-Methylimidazole increased the incidence of epididymal SGs (0%, 0%, 6%, 12%, respectively). Histologically, most of the SGs exhibited rupture of epididymal ducts with focal aggregations of macrophages in interstitia. Lesions occurred in the proximal caput of the epididymis and/or efferent ducts, not in the corpus and cauda. In the testis, incidences of germinal epithelial atrophy (GEA) increased dose-relatedly (2%, 8%, 16%, 28%, respectively). All mice with epididymal SG developed testicular GEA. The grading scores of testicular GEA tended to be more severe in mice with SGs than those without. No epididymal SG or testicular GEA was observed in 6-month-interim-sacrificed mice. The results imply that 2-year treatment of B6C3F₁ mice with 2-MI can induce epididymal SGs, primarily followed by more severe testicular GEA. The potential mechanism of SG induction by 2-MI is discussed.

Key Words: 2-Methylimidazole • epididymis • sperm granuloma • testis • germinal epithelium • mice

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