The Role of Interleukin-17 in male fertility disorders

• Applicant: Professor Dr. Jean-Pierre Allam
• Subject Area: Reproductive Medicine, Urology
• Term: from 2018 to 2021
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 407670728

Chronic inflammation of the male genital tract is considered as one of the major causes for male sub- and infertility. However, to date neither consensus based nor validated therapeutic options exist. Within chronic inflammation pro-inflammatory cytokines of the interleukin (IL)-17 family mainly produced by Th17 cells play a central role. The cytokine family comprises IL-17A to IL-17F sharing homologies but also function of which latter might differ among the several cytokines. Especially IL-17A is well known to be not only involved in chronic inflammation but also autoimmunity. In this regard recent published data could demonstrate the presence of IL-17A in chronic epidydimitis as well as in chronic orchitis with azoospermia suggesting an autoimmunological background in orchitis with destruction of spermatozoa (SPZ) at least in part. So, we postulate that chronic male urogenital tract inflammation is associated with a Th17 immune response leading to subfertility and in a later time point to infertility. To data little is know about how IL-17 might impact on SPZ. Thus the aim of this project is to investigate (i) which members of the IL-17 cytokine family are present in the ejaculate of subfertile men with chronic inflammation compared to normal control, (ii) whether a correlation of IL-17 cytokines to alterations of standard spermiogram parameters can be demonstrated, (iiI) which cell types within the ejaculate represent the major source for IL-17, (iv) which structures of SPZ express the receptor for IL-17 (IL-17R), (v) the effect of IL-17R activation on SPZ in respect to SPZ function and (iv) the effect of simultaneous co-stimulation with other cytokines known for having a synergistic or antagonistic interaction with IL-17.The short-term aim of this project is to identify immunological mechanisms involved in male sub- and infertility. The WHO estimates an increase of 2 million infertile couples in which the male partner contributes in 50% of cases. The long-term aim of this project is to develop a rational basis for future therapeutic approaches in the treatment of male sub- and infertility disorders associated with IL-17 immune responses such as blocking of IL-17. Therefore this project opens new therapeutic perspectives in the field of reproductive medicine in which to date recent developments focus more on the female side.

• DFG Programme: Research Grants
• Co-Investigator: Professorin Dr. Natalija Novak