<p>Background: Azoospermia, the complete absence of sperm in the ejaculate, is a major cause of male infertility. Sertoli cells are essential for spermatogenesis, and disruptions in innate immune immune pathways, particularly Toll-like receptors (TLRs), may impair their function. This study investigated the expression of TLR1&ndash;10 and downstream signaling molecules (MYD88, NFKB, TRIF, IRF3, and TRAM) in Sertoli cells of azoospermic patients.<br /> Methods: Testicular tissue were collected from 20 azoospermic men undergoing testicular sperm extraction (TESE). Patients were categorized into two TESE positive (sperm present, n=10) and TESE negative (sperm absent, n=10). Sertoli cells were isolated using enzyme digestion and purified via fluorescence-activated cell sorting (FACS). Gene expression of TLR1&ndash;10 and signaling molecules was quantified by RT-PCR. Data were analyzed using independent-samples T-test, with significance set at p&lt;0.05.&nbsp;<br /> Results: Significant downregulation was detected in TLR10 (20.6-fold, p&lt;0.0001), TLR9 (4.6-fold, p&lt;0.05), TLR7 (4.8-fold, p&lt;0.01), TLR6 (12.4-fold, p&lt;0.05), TLR5 (13.5-fold, p&lt;0.001), TLR4 (3.2-fold, p&lt;0.05), and TLR3 (3.1-fold, p&lt;0.01). Among signaling molecules, MYD88 (4.1-fold, p&lt;0.01) and IRF3 (4.2-fold, p&lt;0.05) showed significant reductions, indicating impaired immune signaling in Sertoli cells of TESE-negative men.<br /> Conclusion: Altered expression of TLRs and associated signaling molecules in Sertoli cells of azoospermic men suggests innate immune dysregulation as a potential mecha-nism underlying defective spermatogenesis. These findings highlight immune privilege-associated pathways as possible targets for developing diagnostic biomarkers and novel therapeutic approaches for male infertility.</p>