Tris(2,3-dibromopropyl) Isocyanurate Modulates Oxidative Stress and Autophagy-Related Pathways in Mouse GC-1...

Area of Science:

• Reproductive Toxicology
• Cellular Stress Response
• Autophagy Research

Background:

• Tris-2,3-dibromopropyl isocyanurate (TBC) is a brominated flame retardant with suspected reproductive toxicity.
• The impact of TBC on autophagy in reproductive cells is not well understood.
• Apoptosis is implicated in TBC cytotoxicity, but autophagy's role requires further investigation.

Purpose of the Study:

• To investigate the effects of TBC on autophagy-related processes in GC-1 (spg) spermatogenic cells.
• To elucidate the molecular mechanisms underlying TBC-induced reproductive cell damage.
• To assess TBC's impact on cellular homeostasis, including ER stress, oxidative stress, and cell cycle.

Main Methods:

• Utilized GC-1 (spg) cell line as an in vitro model for testis-derived cells.
• Assessed cellular metabolic activity, gene expression (PPARγ), protein phosphorylation (mTOR, IRE1), autophagy markers, cell cycle progression, and reactive oxygen species (ROS) production.
• Employed time-dependent treatment with TBC.

Main Results:

• TBC significantly reduced cellular metabolic activity in a time-dependent manner.
• Observed increased PPARγ gene expression, decreased p-mTOR, and increased p-IRE1, indicating ER stress activation.
• Detected modulation of autophagy markers, G0/G1 cell cycle arrest, and elevated ROS production.

Conclusions:

• TBC disrupts cell homeostasis in spermatogenic cells via ER stress, oxidative stress, and cell cycle dysregulation.
• Autophagy pathways may be modulated as a cellular response to TBC-induced stress.
• These findings suggest TBC poses a risk for reproductive toxicity through multiple cellular disruption mechanisms.