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Abstract

Volume 22, Issue 5 (September 2020) 22, 472–480; 10.4103/aja.aja_116_19

Damaged male germ cells induce epididymitis in mice

Wei-Hua Liu, Fei Wang, Xiao-Qin Yu, Han Wu, Mao-Lei Gong, Ran Chen, Wen-Jing Zhang, Rui-Qin Han, Ai-Jie Liu, Yong-Mei Chen, Dai-Shu Han

Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences, School of Basic Medicine, Peking Union Medical College, Beijing 100005, China

Correspondence: Dr. DS Han (dshan@ibms.pumc.edu.cn)

Date of Submission 25-Mar-2019 Date of Acceptance 19-Aug-2019 Date of Web Publication 01-Nov-2019

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.

Keywords: busulfan; epididymitis; innate immune response; male germ cell; male infertility

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