Tris(2,3‐dibromopropyl) Isocyanurate Modulates Oxidative Stress and Autophagy‐Related Pathways in Mouse GC‐1 Spermatogenic Cells In Vitro

Tris-2,3-dibromopropyl isocyanurate (TBC), a brominated flame retardant widely used in industrial applications, raises increasing concerns due to its potential reproductive toxicity. While the role of apoptosis in TBC-induced cytotoxicity is partially understood, its effects on autophagy in reproductive cells remain underexplored. Therefore, the present study aimed to determine the impact of TBC on autophagy-related processes in GC-1 (spg) spermatogenic cell line as an in vitro model of testis-derived cells. Our findings demonstrate that TBC significantly reduces cellular metabolic activity in a time-dependent manner. Molecular analysis revealed an upregulation of PPARγ gene expression, accompanied by a decrease in phosphorylated mTOR (p-mTOR) levels and a concurrent increase in phosphorylated IRE1 (p-IRE1), indicating activation of endoplasmic reticulum (ER) stress pathways. Furthermore, TBC exposure was associated with modulation of autophagy-related markers, suggesting a potential adaptive or compensatory cellular response to stress conditions. Cell cycle analysis showed arrest in the G0/G1 phase, while ROS quantification indicated elevated reactive oxygen species production upon treatment. Collectively, our data suggest that TBC disrupts cell homeostasis through ER stress-associated signaling, oxidative stress, and cell cycle regulation, which may contribute to its potential reproductive toxicity.