Macrophages in testes of infertile men: regulation by melatonin

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

Buenos Aires

Congreso; Latin American Symposium of Reproductive Immunology; 2011

American Society for Reproductive Immunology

Introduction: We have previously described that the number of testicular macrophages (MAC) is increased in biopsies from infertile men compared with that found in normal testes (Frungieri et al, Fertil Steril 78:298,2002). We have also demonstrated a direct effect of melatonin (Mel) on androgen production in hamster testes (Frungieri et al, Endocrinology 146:1541,2005). The goal of this study was to investigate the presence of Mel in testicular biopsies from patients with hypospermatogenesis (H) and Sertoli cell only syndrome (SCO), and its influence on testicular MAC. Materials, Methods and Results: Mel concentration in human testes was determined by ELISA (pg/g tissue: 19.317+2.008, n=7), and showed negative correlation coefficient (r) values with the overall testicular CD68-immunoreactive MAC number (r =0.877, P<0.05), as well as with the number of MAC located in the interstitium, tubular wall and tubular lumen (r =0.838, 0.797 and 0.860, respectively, P<0.05). Testicular Mel levels also showed a negative correlation with the expression of the proliferating cell nuclear antigen (PCNA) determined by immunoblotting (r =0.847, P<0.05). Using laser microdissection and RT-PCR, we found expression of TNFa and its receptor TNF-R1 in testes oh infertile patients. Moreover, we reported a negative correlation between testicular Mel concentration and TNFa (r =0.810, P<0.05). By immunoblotting and qPCR, we have seen the inhibition of PCNA and TNFa expression by Mel in a human MAC cell line (THP-1). Conclusion: Our study suggests that Mel exerts an antiproliferative effect on testicular MAC and thus, participates in the modulation of inflammatory status in infertile men.