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Updated: Aug 18, 2026
Mouse Models of Epididymitis Induced by Pathogen-Associated Molecular Patterns
Published on: December 12, 2025
Epididymal sperm granuloma induced by chronic administration of 2-methylimidazole in B6C3F1 mice
Yoshiro Tani1, Paul M Foster, Robert C Sills
1Laboratory of Experimental Pathology, National Institute of Environmental Sciences, NIH, Research Triangle Park, NC 27709, USA.
Abstract:
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.
Insights
Two-year exposure to 2-methylimidazole (2-MI) in male mice caused dose-related epididymal sperm granulomas (SGs) and testicular germinal epithelial atrophy (GEA). These findings highlight potential reproductive toxicity risks associated with 2-MI exposure.
Area of Science:
- Toxicology
- Reproductive Toxicology
- Histopathology
Background:
- 2-methylimidazole (2-MI) is a chemical used in various industrial applications.
- Previous studies indicated potential health effects of 2-MI, necessitating further investigation into its toxicological profile.
Purpose of the Study:
- To characterize the induction and histopathological features of 2-MI-induced sperm granulomas (SGs) in male B6C3F1 mice.
- To evaluate the relationship between 2-MI exposure, SG formation, and testicular germinal epithelial atrophy (GEA).
Main Methods:
- Male B6C3F1 mice were administered diets containing 0, 625, 1250, or 2500 ppm 2-MI for 105 weeks.
- Histopathological examination of testes and epididymides was performed to assess lesion incidence and severity.
- Dose-response relationships were analyzed for SG and GEA development.
Main Results:
- A dose-related increase in the incidence of epididymal SGs was observed in mice exposed to 2-MI.
- Histologically, SGs were characterized by ruptured epididymal ducts and interstitial macrophage aggregations, primarily in the proximal caput epididymis.
- Incidences of testicular germinal epithelial atrophy (GEA) increased with 2-MI dose, and all mice with SGs also exhibited GEA, often more severe.
Conclusions:
- Chronic 2-MI exposure in male B6C3F1 mice can induce epididymal SGs.
- 2-MI-induced SGs are associated with testicular GEA, suggesting a potential pathway for reproductive toxicity.
- The findings underscore the importance of evaluating the reproductive health effects of 2-MI in toxicological assessments.
