Inflammatory mediators exert toxic effects of oxidative stress on human spermatozoa Running title: Male genital tract inflammation and oxidative stress

Epidemiological studies regarding male infertility have revealed that more and more infertile men suffer from acute or chronic inflammations of the genitourinary tract which often occur without any symptoms. The inflammatory reactions within the male genital tract are inevitably connected with oxidative stress. Growing evidence indicates that imbalance between pro-and antioxidative 5 substances in semen leads to metabolic and functional disorders of male germ cells and possibly may be a primary cause of some types of infertility. The infectious factor and local tissue damage can lead to the infiltration of leukocytes to the inflammatory site. This is in an obvious way connected with the production and release of great amounts of reactive oxygen species triggering the immune response directed against the infectious agent, and at the same time secreting 10 numerous biological substances, escalating the inflammation. Some of them appear to be proteases and proinflammatory cytokines. Extended exposure of spermatozoa to the reactive oxygen species can be a reason for sperm membrane lipids peroxidation. Many premises point to the co-activity of inflammatory mediators in exerting toxic effects on spermatozoa. Local influence of biologically active substances released by activated leukocytes in the course of the 15 inflammatory response and the mutual interactions of variety of factors at the site (bacteria, leukocytes, proinflammatory cytokines) seem to present a puzzle which has been frequently taken up.