Inflammatory networks in the control of spermatogenesis : chronic inflammation in an immunologically privileged...

Spermatogenesis is a complex, organized process involving intimate interactions between the developing germ cells and supporting Sertoli cells. The process is also highly regulated. Studies suggest that regulation in the seminiferous epithelium involves molecules normally associated with either immune or inflammatory processes; in particular, interleukin 1a (IL1a), IL6, tumor necrosis factor (TNFa), activin A and nitric oxide (NO). While there is considerable evidence that these inflammatory mediators have effects on spermatogonial and spermatocyte development as well as critical supportive functions of the Sertoli cells, which are undoubtedly of considerable importance during testicular inflammation, there remains some skepticism regarding the significance of these molecules with respect to normal testicular function. Nonetheless, it is evident that expression of these regulators varies across the cycle of the seminiferous epithelium in a consistent manner, with major changes in production coinciding with key events within the cycle. This review summarizes the evidence supporting the hypothesis that inflammatory cytokines play a role in normal testicular spermatogenesis, as well as in the etiology of inflammation induced sub-fertility. The balance of data leads to the striking conclusion that the cycle of the seminiferous epithelium resembles a chronic inflammatory event. This appears to be a somewhat paradoxical assertion, since the testis is an immunologically privileged tissue based on its well-established ability to support grafts with minimal rejection responses. However, it may be argued that local immunoregulatory mechanisms, which confer protection from immunity on both transplanted tissues and the developing spermatogenic cells, are equally necessary to prevent local inflammation responses associated with the spermatogenic process from activating the adaptive immune response.