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Background  In non-obstructive azoospermia, histological patterns of Sertoli cell-only Syndrome (SCO) and hypospermatogenesis (H) are commonly found. In these pathologies, Leydig cell hyperplasia (LCH) is detected in some patients. Since TGF-β1 is involved in cellular proliferation/development, the aim of this work was to analyze the expression of TGF-β1, its receptors TGFBRII, TGFBRI (ALK-1 and ALK-5), and the co-receptor endoglin in human biopsies from patients with idiopathic infertility.    Methods  Specific immunostaining of TGF-β1, its receptors TGFBRII, TGFBRI (ALK-1 and ALK-5), co-receptor endoglin and Smads proteins, were carried out in testicular biopsies from normal and infertile men with SCO or H. Gene expression of TGF-β1 system were made in biopsies from infertile patients with semi-quantitative and quantitative PCR.    Results  Immunohistochemical studies revealed that TGF-β1 and its specific receptors are present in Leydig cells in biopsies from normal tissue or patients with SCO or H with or without LCH. Smad proteins, which are involved in TGF-β1 signaling, are also detected in both their phosphorylated (activated) and dephosphorylated form in all samples  TGF-β1, ALK-1  and  endoglin  gene expression are stronger in human biopsies with LCH than in those with SCO or H. Neither  TGFBRII  nor  ALK-5  gene expression showed significant differences between pathologies. A significant correlation between  ALK-1  and  endoglin  expression was observed.    Conclusions  In conclusion, the high levels of mRNA and protein expression of the TGF-β1 system in patients with LCH, particularly  ALK1  and its correlation with  endoglin , suggest that these proteins acting in concert might be, at least in part, committed actors in the Leydig cell hyperplasia.

Expression of the TGF-beta1 system in human testicular pathologies