Generation of Reactive Oxygen Species by Leukocytes and Sperm Following Exposure to Urogenital Tract Infection

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Abstract
The association between male urogenital tract infection (UTI) and infertility is still controversial. Oxidative stress caused by reactive oxygen species (ROS) in semen has been suggested to be an important factor in the etiology of poor sperm function through peroxidative damage to the cell membrane. This study explored the potential association between the ROS generation and UTIs by examining ROS production by sperm and seminal leukocytes in response to various infectious and cytokine stimulating factors. Semen and blood samples were obtained from 17 normal donors. Highly motile pure sperm, poorly motile sperm, and polymorphonuclear leukocytes (PMN) were isolated and exposed to various infectious and stimulating factors, including lipopolysaccharide (LPS), gamma interferon (γ-IFN), tumor necrosis factor-alpha (TNF-α), granulocyte, macrophage-colony stimulating factor (GM-CSF), and phorbol myristate acetate (PMA). ROS generation was determined by measuring luminescence in a luminometer. In this study, purified PMNs produced high levels of ROS, and this production was markedly enhanced in the presence of cytokines, LPS, as well as PMA. Pure motile sperm produced low levels of ROS, and ROS production was not enhanced by addition of bacterial products or cytokines. In conclusion, PMNs in semen are the major source of ROS, and ROS production by these cells is enhanced by bacterial products and cytokines. Detection of activation markers and/or soluble factors produced by activated leukocytes in the urogenital tract or semen could enhance the diagnosis and lead to improved therapy of male infertility due to subclinical genital tract infections.

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