Curcumin Protects Mouse Spermatogonia from Triptolide-Induced Injury Through Modulation of Ferroptosis-Related...

Area of Science:

• Reproductive Toxicology
• Cell Biology
• Biochemistry

Background:

• Triptolide (TP) is a potent anti-inflammatory and immunosuppressive drug.
• TP's clinical use is limited by male reproductive toxicity, specifically damage to spermatogonia.
• Curcumin, a natural antioxidant, may offer protection, but its mechanisms against TP-induced damage are unclear.

Purpose of the Study:

• To investigate the protective effects of curcumin against Triptolide-induced damage in mouse spermatogonia.
• To elucidate the underlying molecular mechanisms, focusing on ferroptosis-related pathways.

Main Methods:

• Proteomic analysis of mouse GC-1 cells to identify curcumin's protective mechanisms.
• Validation using CCK-8 assays, apoptosis detection, and measurements of reactive oxygen species (ROS), glutathione (GSH), malondialdehyde (MDA), and Fe²⁺.
• Gene and protein expression analysis via qPCR and Western blotting, alongside histological examination (HE staining, immunofluorescence).

Main Results:

• Proteomic analysis indicated curcumin ameliorates TP-induced damage by modulating ferroptosis pathways.
• Curcumin increased GSH levels and decreased MDA, ROS, and Fe²⁺, reducing lipid peroxidation in cells and testicular tissue.
• Upregulation of Nrf2, Gclc, and Map1lc3a, and downregulation of Tfrc and Dmt1 were observed, confirming curcumin's protective role.

Conclusions:

• Curcumin effectively protects mouse spermatogonia against Triptolide-induced damage.
• Protection is achieved by regulating ferroptosis-related pathways through modulation of Nrf2, Gclc, Map1lc3a, Tfrc, and Dmt1 expression.
• Curcumin represents a potential therapeutic agent to mitigate TP's male reproductive toxicity.