Interferon γ, IL-17, and IL-1β impair sperm motility and viability and induce sperm apoptosis

Urogenital inflammation is a known cause of male infertility. Increased levels of inflammatory cytokines, leukocyte counts and oxidative stress are highly detrimental for sperm quality thus compromising male fertility. Although cytokines affect sperm by recruiting and activating leukocytes consequently inducing tissue inflam-mation and oxidative stress, scarce to absent data have been reported about the putative direct effects of in-flammatory cytokines on spermatozoa. Herein, we analyzed whether IFN gamma, IL-17A, IL-1 beta, and IL-8 can alter human sperm motility and viability per se. Fractions of viable and motile spermatozoa from normospermic healthy donors were in vitro incubated with recombinant human IFN gamma, IL-17A, IL-1 beta or IL-8 and sperm ROS production, motility, viability and apoptosis were analyzed. Sperm exposed to different concentrations of IFN gamma, IL-17A and IL-1 beta, or a combination of them, for either 1 or 3 h showed significantly increased levels of mito-chondrial ROS production and reduced motility and viability with respect to sperm incubated with vehicle. Moreover, the exposure to IFN gamma, IL-17A and IL-1 beta resulted in significantly higher levels of early and/or late apoptotic and/or necrotic spermatozoa. Interestingly, no significant differences in sperm motility, viability and apoptosis were observed in sperm incubated with the concentrations of IL-8 analyzed, for either 1 or 3 h, with respect to sperm incubated with vehicle. In conclusion, our results indicate that IFN gamma, IL-17A and IL-1 beta per se impair sperm motility and decreases viability by triggering increased mitochondrial ROS production and inducing sperm apoptosis. Our results suggest that screening inflammatory cytokines in semen would be an additional helpful tool for the diagnostic workup of male infertility.