Oxidative stress, spermatozoa and leukocytic infiltration: relationships forged by the opposing forces of microbial invasion and the search for perfection

This review addresses the complex relationships that exist between spermatozoa and the immune system and highlights the role of oxidative stress in regulating the direction and functional relevance of these interactions. Spermatozoa are potentially antigenic; however, in the testes and epididymis these cells are sequestered behind physical barriers and benefit from a tolerogenic state generated through the mediation of indoleamine dioxygenase. In the female there are no such barriers; however, inseminated spermatozoa are protected by the concomitant presence of seminal plasma. The latter possesses immunosuppressive properties, a powerful array of antioxidants and cytokines that modulate the immunological response to semen deposition. Subsequent to insemination, leukocytic infiltration of the female tract occurs to facilitate the removal of millions of residual moribund and senescent spermatozoa, while allowing the most competent cells to ascend to the site of fertilization. The post-insemination phagocytosis of non-viable spermatozoa is 'silent' in the sense that no reactive oxygen species (ROS) or pro-inflammatory cytokines are generated. The silent phagocytosis of senescent spermatozoa is a response to markers, such as phosphatidylserine, which are expressed on the surface of spermatozoa as they engage in the intrinsic apoptotic cascade. By contrast, infection can bring fully activated leukocytes into the male reproductive tract that are actively generating ROS and releasing pro-inflammatory cytokines. Such free-radical-generating leukocytes have the potential to seriously damage the functionality of spermatozoa as well as the integrity of their DNA, particularly in vitro, when these cells are devoid of the antioxidant protection afforded by seminal plasma.