MON-147 - Somatic Cell Dysfunction and Intratesticular Hormonal Imbalance in Idiopathic Sertoli Cell-Only Syndrome

Background: Sertoli Cell-Only Syndrome (SCOS) is the most frequent histopathological phenotype in men with non-obstructive azoospermia, yet its molecular basis remains unknown in a substantial proportion of idiopathic cases. Disruption of Sertoli and Leydig cell function, potentially related to impaired differentiation or dedifferentiation processes, may represent a key mechanism underlying this condition.

Objective: To evaluate Sertoli and Leydig cell functional status in idiopathic SCOS by integrating gonadotropin, testosterone, estradiol, and key glycoprotein markers of Sertoli cell function in serum and testicular tissue with histopathological features of testicular biopsies.

Methods: A cross-sectional case–control study was conducted including 32 men with idiopathic SCOS and 24 controls with obstructive azoospermia and normal spermatogenesis. Gonadotropins, testosterone, estradiol, anti-Müllerian hormone (AMH), and inhibin B (InhB) were measured (immunoassays) in serum (S-) and testicular tissue homogenates (TT-). Hormonal parameters were compared using the Mann–Whitney U or χ2 tests and correlated with semi-quantitative histopathological features using Spearman’s analysis.

Results: SCOS patients exhibited reduced levels of S-InhB (IQR: 10–33 vs. 161–298 pg/mL), S-AMH (IQR: 3–9 vs. 7–13 ng/mL), and TT-InhB (IQR: 28-244 vs. 373-2051 pg/mg) (all p < 0.01), whereas TT-AMH levels were similar to controls. Serum and testicular levels were significantly correlated for both AMH (r = 0.403, p = 0.003) and InhB (r = 0.516, p < 0.001). S-FSH and S-LH levels were inversely correlated with S-InhB and TT-InhB concentrations (p < 0.001), and S-AMH levels were negatively associated with TT-testosterone concentrations (r = −0.51, p < 0.01). SCOS cases displayed increased numbers of Sertoli cells per tubule (IQR: 8–33 vs. 9–18) and Leydig cells per cluster (IQR: 3–23 vs. 2–11), as well as a higher proportion of subjects with basement membrane fibrosis, tubular atrophy, and reduced tubular diameter (p < 0.05). Lower S-AMH and S-InhB levels were consistently associated with adverse histological features and reduced testosterone-to-LH ratios (p < 0.01). Involutive morphological changes in Sertoli cells were inversely associated with TT-InhB concentrations (r = −0.38, p = 0.04), but not with AMH levels.

Conclusions: Idiopathic SCOS is characterized by profound somatic cell dysfunction, integrating impaired Sertoli cell endocrine activity, altered gonadotropin feedback, and morpho-functional abnormalities of Leydig cells. The broader range of associations observed for testicular inhibin B compared with AMH suggests that inhibin B may represent a more sensitive marker of Sertoli cell status in the setting of severe spermatogenic failure, highlighting testicular hormonal imbalance as a potential translational indicator of microenvironment disruption.

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