Trihexyl phosphate exposure disrupts mitophagy and activates mtDNA-cGAS-STING signaling to drive pyroptosis and steroidogenic impairment in Leydig cells - PubMed
5 hours ago
- #Mitochondrial dysfunction
- #Pyroptosis
- #Steroidogenesis
- Trihexyl phosphate (THP) exposure reduces serum testosterone in male mice without altering LH/FSH levels.
- THP disrupts PINK1/Parkin-mediated mitophagy, leading to mitochondrial dysfunction and mtDNA leakage.
- The leaked mtDNA activates the cGAS-STING-TBK1-IRF3 pathway, triggering NLRP3 inflammasome signaling and pyroptosis.
- Steroidogenic genes/proteins (NR5A1, SCARB1, STAR) are downregulated, and CYP11A1 + Leydig cell populations diminish.
- Interventions like urolithin A and STING knockdown mitigate THP-induced testosterone suppression.
- The study suggests mitophagy enhancement and cGAS-STING inhibition as potential therapeutic strategies.