The Role of Interleukin-17 in male fertility disorders
Final Report Abstract
The aim of the funded project was the investigation of chronic inflammatory processes in the ejaculate of subfertile men. The focus was on interleukin (IL)-17-associated immune reactions, which play a central role in both chronic inflammation and autoimmune reactions. It could demonstrated that IL-17A, IL-17E, IL-17F, IL-21, IL-23 and CCL20 were detectable in the seminal plasma of subfertile men and there was a significant correlation between these IL-17-associated cytokines. In particular, IL-17A and CCL20 could be regularly detected in significant concentrations. A correlation of IL-17A to other pro-inflammatory cytokines, such as IL-6, IL-8 and TNF-alpha could be demonstrated. In addition, there was an inverse correlation of IL-17A, IL-6 and TNF-alpha to sperm motility. A correlation of IL-17A to other standard sperm analysis parameters, such as sperm count, concentration, morphology and vitality could not be shown. The concentration of IL-17A was independent of other inflammatory parameters, such as leukocytes or reactive oxidative stress (ROS). Only a significant connection of IL-6 to ROS could be detected. The expression of receptors of IL-17A, CCL20, TNF-alpha, TNF-alpha and IL-8 on sperm were also studied. In this regard, an expression of IL-17 receptors (R) and IL-6R on the middle piece and flagellum of the sperms was shown, while CCR-6 was mainly detectable on the flagellum of the sperms and TNF-alphaRI/II was expressed in the post-acrosomal segment of the sperms. In contrast, IL-8R showed only a weak expression on sperms. A association of the expression of cytokine receptors on sperm and standard spermogram parameters was not detected. In functional experiments, it could be shown that CCL20, which was detectable in the perifollicular fluid of ovaries, is involved in the chemotaxis of sperm via CCR6 on the flagellum. Sperms of men with high IL-17 and CCL20 concentrations showed a significantly lower chemotaxis compared to CCL20. Stimulation of sperms with IL17A and IL-6 led to a significant reduction in motility, while stimulation with TNF-alpha led to an increase of sperm apoptosis. In summary, in subfertile men an association of IL-17 to other pro-inflammatory cytokines in the ejaculate could be shown, the expression and localization of cytokine receptors on sperms was demonstrated and the negative impact of pro-inflammatory cytokines IL-17A/CCL20, IL-6 and TNF-alpha on sperm function could be shown. Based on the data collected in this project, a specific anti-inflammatory therapy of subfertile men appears appropriate and clinical studies should analyze this hypothesis in the future.
Publications
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CCL20-CCR6 axis directs sperm–oocyte interaction and its dysregulation correlates/associates with male infertility‡. Biology of Reproduction, 103(3), 630-642.
Duan, Yong-Gang; Wehry, U. P.; Buhren, B. A.; Schrumpf, H.; Oláh, P.; Bünemann, E.; Yu, C.-F.; Chen, S.-J.; Müller, A.; Hirchenhain, J.; Lierop, A.; Novak, N.; Cai, Zhi-Ming; Krüssel, J. S.; Schuppe, H.-C.; Haidl, G.; Gerber, P. A.; Allam, J.-P. & Homey, B.
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Human spermatozoa of male patients with subfertility express the interleukin‐6 receptor. Andrologia, 52(4).
Djourabchi, Borojerdi Amir Shervin; Welchowski, Thomas; Peng, Wenming; Buchen, Alexa; Novak, Natalija; Haidl, Gerhard; Duan, Yong‐Gang & Allam, Jean‐Pierre
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Natural killer and NKT cells in the male reproductive tract. Journal of Reproductive Immunology, 142, 103178.
Duan, Yong-Gang; Gong, Jialei; Yeung, William S.B.; Haidl, Gerhard & Allam, Jean-Pierre
