Long-chain chlorinated paraffins (LCCPs) exposure induces testicular aging damage by triggering mitochondrial...

Area of Science:

• Environmental Toxicology
• Reproductive Biology
• Cellular Biology

Background:

• Long-chain chlorinated paraffins (LCCPs) are prevalent environmental pollutants.
• Limited understanding exists regarding LCCPs' toxic effects on the male reproductive system.

Purpose of the Study:

• To investigate the impact of LCCPs on testicular cell senescence.
• To elucidate the underlying regulatory mechanisms of LCCPs-induced testicular toxicity.

Main Methods:

• Utilized GC-1 and TM4 testicular cell models.
• Employed Western blot, flow cytometry, immunofluorescence, and confocal microscopy.
• Assessed senescence markers (SA-β-Gal, p16, p21), oxidative stress, and mitochondrial function.

Main Results:

• LCCPs significantly induced testicular cell senescence, increased ROS, and elevated inflammatory cytokines.
• LCCPs impaired TFEB nuclear translocation, leading to lysosomal dysfunction and reduced mitophagy.
• Mitochondrial dysfunction and dsDNA release activated pyroptosis; in vivo studies confirmed inflammation and reduced collagen in mouse testes.

Conclusions:

• LCCPs exposure induces testicular cell senescence and pyroptosis via lysosomal and mitochondrial dysfunction.
• This study provides critical insights into the toxicological mechanisms of LCCPs on male reproductive health.