Role Of Tumor Necrosis Factor Alpha In Lipopolysaccharide-induced Testicular Dysfunction And Epididymitis In Mice

Background and objectives:The systemic inflammation may impair male fertility,underlying mechanisms remain poorly understood.The present study investigates the effect of lipopolysaccharide(LPS)-induced systemic inflammation on the testis and epididymis in mice.Materials and methods:Mouse models were used in the present study,and LPS injection mimic bacterial infection.After intraperitoneal injection of LPS,at a dose of 3 mg/kg body weight,we examined the impairments of testis and epididymis.Spermatogenesis was analyzed by(Periodic Acid Schiff)PAS staining;apoptosis of germ cells were determined by TUNEL;biotin tracing method was used to evaluate the permeability of testicular blood-testis barrier(BTB).Histopathology of epididymis were examined by HE staining;fibrosis of epididymis were stained using Masson;infiltration of leukocytes were identified by immunochemistry.Expression of proinflammatory cytokines were analyzed by real time qRT-PCR and ELISA.Results:Intraperitoneal injection of LPS significantly decreased testosterone production and induced cytokines production in short time,including tumor necrosis factor alpha(TNF-a),interleukin 6(IL-6),monocyte chemotactic protein 1(MCP-1)and C-X-C motif chemokine ligand 10(CXCL10).LPS significantly impaired blood-testis barrier permeability and spermatogenesis.Moreover,an epididymitis characterized by leukocyte infiltrations and fibrosis was observed in the cauda epididymis post LPS injection.Apoptotic germ cells were significantly increased post LPS injection.LPS-induced impairments of the testis and epididymis were abolished in TNF-?-/-mice.Moreover,pomalidomide,a TNF-? inhibitor,blocked LPS-induced testicular damages and epididymitis.Conclusions:LPS-induced TNF-? production plays a critical role in impairing testicular functions and resulting in epididymal inflammation.The intervention on TNF-? production would be a feasible approach for the prevention and treatment of inflammatory impairment on male fertility due to bacterial infection.