Abstract
BackgroundIn 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.MethodsSpecific 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.ResultsImmunohistochemical 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.ConclusionsIn 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.
Highlights
In non-obstructive azoospermia, histological patterns of Sertoli cell-only Syndrome (SCO) and hypospermatogenesis (H) are commonly found
The most common histological patterns found in testicular biopsies of azoospermic men are either Sertoli cell-only Syndrome (SCO) or hypospermatogenesis (H) [1]
The diagnosis of azoospermia was based on the analysis of at least two semen samples collected at different times and two replicates of each sample were centrifuged at 3000 × g for 15 min
Summary
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. The most common histological patterns found in testicular biopsies of azoospermic men (non-obstructive azoospermia) are either Sertoli cell-only Syndrome (SCO) or hypospermatogenesis (H) [1]. LCH may be induced by a number of hormones, enzymes and chemicals [3] In this context, some reports have indicated that LH, androgens and/or even estrogens might stimulate the division of Leydig cells [4,5]. A number of intratesticular factors are known to influence Leydig cell steroidogenic function [6] Among these factors, TGF-b1 modulates Leydig cell steroidogenesis [7] and proliferation [8,9]. Sanderson et al [10] have demonstrated that, in transgenic mice overexpressing TGF-b1, Leydig cells are prominent
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