The impact of triadimenol on male fertility: An in vitro study and molecular docking examination

Abstract

Triadimenol, a triazole fungicide, induces various adverse effects including neurotoxicity, hepatotoxicity, and developmental/reproductive toxicity in non-target organisms. Occupational exposure generally occurs in male agricultural workers. Investigating the effects of triadimenol on three different testicular cell lines would be valuable in elucidating the mechanisms underlying male reproductive issues or infertility. This preliminary study examines the potential toxic effects of triadimenol exposure in Leydig (TM3), Sertoli (TM4), and mouse-derived Spermatogonia (GC-1) cell lines, which are representative of the male reproductive system in vitro. The median inhibitory concentration (IC₅₀) values of triadimenol were found to be 121.35 μM, 332.1 μM, and 349.49 μM in TM3, TM4, and GC-1 cells, respectively. The exposure doses were determined to range from 0 to 100 µM in TM3 cell line and 0–300 µM in TM4 and GC-1 cell lines. Reactive oxygen species (ROS) production, reduced glutathione (GSH) content, malondialdehyde (MDA) and protein carbonyl levels, and genotoxicity were examined. TM3 cell line was more resistant to oxidative damage than the other cell lines, while TM4 cell line was found to be more sensitive in terms of protein carbonyl formation. Triadimenol damaged DNA in TM3 cell line (≥16.93), TM4 cell line (≥9.18), and GC-1 cell line (≥3.28). Additionally, the docking score of triadimenol on the active site of steroid 5-α-reductase 2 (5αR2), which converts testosterone to 5α-dihydrotestosterone, was not close. The results emphasised that the toxicity of triadimenol was cell-specific. Overall, triadimenol disrupted male fertility by affecting spermatogenesis, testosterone production, germ cell support, and sperm quality.