Melatonin concentration in testes of infertile men: its inverse correlation with the number of testicular immune cells (macrophages and mast cells).

ROSSI SP; MATZKIN ME; TERRADAS C; PONZIO R; PUIGDOMENECH E; LEVALLE O; CALANDRA RS; FRUNGIERI MB

Hamburgo

Congreso; Joint International Congress of the American Society for Reproductive Immunology (ASRI) and the European Society for Reproductive Immunology (ESRI); 2012

American Society for Reproductive Immunology (ASRI) and the European Society for Reproductive Immunology (ESRI)

We have previously described that the number of testicular macrophages (MAC) and mast cells (MC) is increased in biopsies from infertile men compared with that found in normal testes (Meineke et al, Fertil Steril 74:239, 2000; Frungieri et al, Fertil Steril 78:298,2002). We have also demonstrated a direct effect of melatonin on androgen production in Syrian hamster testes (Frungieri et al, Endocrinology 146:1541, 2005). Problem: The goal of this study was to investigate the presence of melatonin in testicular biopsies from patients with hypospermatogenesis (H) and Sertoli cell only Syndrome (SCO), and its influence on testicular MAC and MC. Methods: i) The number of testicular MAC and MC was evaluated in human testicular biopsies by immunohistochemical assays; ii) Using the laser capture microdissection (LCM) technique, CD68-immunoreactive MAC and tryptase-immunoreactive MC were isolated from testes of infertile patients. Subsequently, the material was subjected to RT-PCR analysis; iii) Melatonin concentration in human testes was determined by ELISA; iv) TNFa expression in human testicular biopsies was determined by immunoblotting. Results: By LCM and RT-PCR we found the expression of the melatonin receptor subtype mel1a, in testicular MAC and MC. Melatonin concentration in human testes [fmol/g tissue (media±SEM), H: 39.551±6.290, n=9; SCO: 39.104±3.164, n=5] showed negative correlation coefficient (r) values with the overall testicular CD68-immunoreactive MAC number (r =0.693, P<0.05), as well as with the number of MAC located in the interstitium, tubular wall and tubular lumen (r =0.712, 0.661 and 0.634, respectively, P<0.05). Testicular melatonin levels also showed an inverse correlation with the expression of TNFa (r =0.661, P<0.05). Using LCM and RT-PCR, we found expression of TNFa and its receptor TNF-R1 in testicular CD68-immunoreactive MAC of infertile patients. Furthermore, melatonin concentration in human testes exhibited a negative correlation with the overall testicular tryptase-immunoreactive MC, the number of MC located in the interstitial compartment, and the number of MC detected in the tubular wall (r =0.684, 0.715 and 0.673, respectively, P<0.05). Conclusion: Our study suggests that melatonin could exert an antiproliferative effect on testicular MAC and MC and thus, participates in the modulation of inflammatory status in infertile men.