Glyphosate-based herbicide exposure in rats: Protective effect of coenzyme Q10 on testicular toxicity

Roundup, the most widely used glyphosate-based herbicide (GBH), contains glyphosate (GLY) as its main active ingredient and was used in this study to model GBH-induced reproductive toxicity. This study aimed to investigate the protective role of Coenzyme Q10 (CoQ10) against GLY-related testicular and sperm damage, focusing on oxidative stress, inflammation, and apoptosis pathways. Forty-two adult male ICR mice were divided into five groups: control (no treatment), sham, CoQ10 (200 mg/kg-BW/day), GLY (Roundup-500 mg/kg-BW/day), and GLY+CoQ10 (Roundup-500 mg/kg-BW/day + CoQ10-200 mg/kg-BW/day). All treatments were administered orally for 35 days. Histopathological, immunohistochemical (Ki-67, Nrf2), biochemical (MDA, GSH, TAS, TOS, OSI), hormonal (testosterone, LH), and molecular (Western blot: Nrf2, Keap1, HO-1, TLR4, NF-κB, Bax, Bcl-2) analyses were conducted. Conventional and functional sperm parameters were also assessed. GLY reduced testicular weight and disrupted histoarchitecture, which was ameliorated by CoQ10. GLY increased oxidative stress markers (↑MDA, TOS, OSI; ↓GSH, TAS), while CoQ10 significantly restored redox balance. GLY suppressed the Nrf2/Keap1/HO-1 antioxidant pathway; CoQ10 reactivated it. TLR4/NF-κB inflammatory signaling was upregulated by GLY and downregulated by CoQ10. GLY induced apoptosis (↑Bax, ↓Bcl-2), which was reversed by CoQ10. Sperm motility, viability, and membrane integrity declined with GLY but improved with CoQ10. Hormonal analysis showed reduced testosterone and elevated LH in the GLY group; CoQ10 normalized testosterone and partially corrected LH levels. In conclusion, CoQ10 mitigated GLY-induced testicular toxicity by modulating oxidative stress, inflammation, and apoptosis, highlighting its therapeutic potential for male reproductive protection.