Features of gonadal dysgenesis and Leydig cell impairment in testes with Sertoli cell-only syndrome

Abstract

Introduction: There is evidence that disturbed spermatogenesis is associated with impaired Leydig cell function and that it may be the result of testicular dysgenesis during fetal/infant development. Sertoli cell-only syndrome (SCOS) is defined by complete lack of germ cells in the seminiferous epithelium. The pathogenesis of SCOS is still not well understood. The aim of the study is to evaluate testes with SCOS focusing on morphometric signs of testicular dysgenesis and markers of Leydig cell (LC) function in relation to hormonal status of studied infertile men.

Materials and methods: Forty-nine testicular biopsies of patients with SCOS and 15 controls with normal spermatogenesis (NOR) were studied. In each biopsy the seminiferous tubule diameter (STD), thickness of tubular membrane (TM), area fraction of intertubular space (AFIS) were measured and semi-quantitative assessment of the LC number was performed (LC-score). The results of histological examination were correlated with serum levels of FSH, LH, testosterone (T) and T/LH ratio.

Results: In SCOS group testicular volume (median [M]: 16.0 vs. 29.5; p < 0.001) and STD (M: 141.7 vs. 190.2; p < 0.001) were lower, while TM (M: 9.8 vs. 6.4; p < 0.001) and AFIS (M: 47.6 vs. 27.6; p < 0.001) were significantly higher in comparison to NOR group. LC-score was higher in SCOS than in NOR group (M: 2.2 vs. 1.1; p < 0.001). Abnormal AFIS and STD were present in 43% of SCOS biopsies and among them in 81% the increased LC-score was found. In SCOS group, the subjects had significantly higher levels of both gonadotropins (FSH, M: 19.9 vs. 3.4; p < 0.001; LH, M: 7.1 vs. 4.2; p < 0.001). Total serum testosterone level did not differ between studied groups; however, T/LH ratio was significantly lower in SCOS group (M: 2.3 vs. 3.8; p < 0.001). Negative correlation between LC-score and STD was observed in SCOS group (r = -0.48; p < 0.001). AFIS correlated positively with serum FSH level in NOR (r = 0.53; p < 0.05) and SCOS (r = 0.41; p < 0.05) group, while with LH, and negatively with T/LH ratio, only in SCOS (LH, r = 0.37; p < 0.05; T/LH, r = -0.36; p < 0.05) group.

Conclusions: We have shown that substantial number of testes from subjects with SCOS presented abnormal morphometric features, which are recognized as the signs of testicular dysgenesis. Additionally, an increased number of Leydig cells simultaneously with abnormal T/LH ratio were found, which suggests an impaired function of these cells. Increased serum levels of LH and also FSH, may reflect dysfunction of Leydig cells. It seems that reproductive hormones levels reflect also the condition of testicular structure, and that FSH may be related to the changes in intertubular space area independently of impaired Leydig cell function.

Keywords: FSH; LH; Leydig cells; Sertoli cell-only syndrome; histology; morphometric assessment; testicular biopsy; testicular dysgenesis syndrome; testosterone.