Coenzyme Q10 protects against glyphosate-based herbicide-induced testicular and sperm toxicity by modulating Nrf2/Keap1/HO-1 and TLR4/NF-κB pathways.

Roundup, the most widely used glyphosate-based herbicide (GBH), contains glyphosate (GLY) as its main active ingredient and was used to model GBH-induced reproductive toxicity in this study. We aimed to investigate the protective effect of coenzyme Q10 (CoQ10) against GLY-induced testicular and sperm damage, focusing on oxidative stress, inflammation, and apoptosis. Unlike previous studies, this work provides the first integrated evidence combining histopathological, biochemical, hormonal, and molecular assessments with functional sperm analyses, and uniquely demonstrates how CoQ10 modulates both antioxidant (Nrf2/Keap1/HO-1) and inflammatory (TLR4/NF-κB) pathways in GBH-induced testicular injury. Forty-two adult male ICR mice were assigned to five groups: control, sham, CoQ10 (200 mg/kg/day), GLY (500 mg/kg/day), and GLY + CoQ10 (500 + 200 mg/kg/day). The treatments were administered orally for 35 days, corresponding to one spermatogenesis cycle. GLY reduced testicular weight, disrupted histoarchitecture, increased oxidative stress (↑MDA, TOS, OSI; ↓GSH, TAS), suppressed Nrf2/Keap1/HO-1 signaling, upregulated TLR4/NF-κB, and triggered apoptosis (↑Bax, ↓Bcl-2). It also impaired sperm parameters (concentration, motility, morphology, viability, membrane integrity) and increased mitochondrial ROS, while reducing testosterone and elevating LH. CoQ10 co-treatment alleviated these alterations by restoring redox balance, normalizing signaling pathways, improving sperm quality, and correcting hormonal changes. In conclusion, CoQ10 mitigates GLY-induced testicular toxicity by modulating oxidative stress, inflammation, and apoptosis, highlighting its novel therapeutic potential for protecting male fertility against GBH exposure.