Damaged male germ cells induce epididymitis in mice
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Updated: Jan 4, 2026
Mouse Models of Epididymitis Induced by Pathogen-Associated Molecular Patterns
Published on: December 12, 2025
Wei-Hua Liu1, Fei Wang1, Xiao-Qin Yu1
1Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences, School of Basic Medicine, Peking Union Medical College, Beijing 100005, China.
Abstract:
Epididymitis can be caused by infectious and noninfectious etiological factors. While microbial infections are responsible for infectious epididymitis, the etiological factors contributing to noninfectious epididymitis remain to be defined. The present study demonstrated that damaged male germ cells (DMGCs) induce epididymitis in mice. Intraperitoneal injection of the alkylating agent busulfan damaged murine male germ cells. Epididymitis was observed in mice 4 weeks after the injection of busulfan and was characterized by massive macrophage infiltration. Epididymitis was coincident with an accumulation of DMGCs in the epididymis. In contrast, busulfan injection into mice lacking male germ cells did not induce epididymitis. DMGCs induced innate immune responses in epididymal epithelial cells (EECs), thereby upregulating the pro-inflammatory cytokines such as tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), and interleukin-1β (IL-1β), as well as the chemokines such as monocyte chemotactic protein-1 (MCP-1), monocyte chemotactic protein-5 (MCP-5), and chemokine ligand-10 (CXCL10). These results suggest that male germ cell damage may induce noninfectious epididymitis through the induction of innate immune responses in EECs. These findings provide novel insights into the mechanisms underlying noninfectious epididymitis, which might aid in the diagnosis and treatment of the disease.
Insights
Damaged male germ cells (DMGCs) trigger noninfectious epididymitis in mice by activating innate immune responses. This discovery offers new pathways for understanding and treating this condition.
Area of Science:
- Reproductive biology
- Immunology
- Urology
Background:
- Epididymitis is caused by infectious and noninfectious factors.
- The causes of noninfectious epididymitis are not fully understood.
- Microbial infections are known causes of infectious epididymitis.
Purpose of the Study:
- To investigate the role of damaged male germ cells (DMGCs) in inducing noninfectious epididymitis.
- To elucidate the underlying mechanisms of DMGC-induced inflammation in the epididymis.
Main Methods:
- Murine male germ cells were damaged using the alkylating agent busulfan via intraperitoneal injection.
- Epididymitis development and characteristics, including immune cell infiltration, were assessed.
- The expression of pro-inflammatory cytokines and chemokines in epididymal epithelial cells (EECs) was analyzed.
Main Results:
- Busulfan-induced DMGCs led to epididymitis in mice, characterized by significant macrophage infiltration.
- Epididymitis onset correlated with the accumulation of DMGCs in the epididymis.
- DMGCs stimulated EECs to upregulate key pro-inflammatory cytokines (TNF-α, IL-6, IL-1β) and chemokines (MCP-1, MCP-5, CXCL10).
- Mice lacking male germ cells did not develop epididymitis after busulfan treatment.
Conclusions:
- Male germ cell damage is a potential etiological factor for noninfectious epididymitis.
- DMGCs induce epididymitis by triggering innate immune responses in epididymal epithelial cells.
- These findings provide new insights into noninfectious epididymitis mechanisms, potentially aiding diagnosis and treatment.
