Background: 6PPD-Quinone, a tire rubber-derived environmental contaminant, has recently been linked to reproductive toxicity. Resveratrol is a natural polyphenol with antioxidant and anti-apoptotic properties that may protect against toxicant-induced testicular injury.
Objective: This study investigated the protective effect of resveratrol against 6PPD-quinone -induced male reproductive toxicity in rats.
Methods: Forty adult male rats were randomly divided into four groups: control, 6PPD-quinone, resveratrol, and 6PPD-Q + RES. After 60 days of treatment, epididymal sperm parameters, including motility, viability, morphology, concentration, and acrosomal integrity, were evaluated. Sperm DNA fragmentation, chromatin maturity, and nuclear chromatin condensation were assessed using cytochemical staining methods additionally to testicular expression of Tjp1, SYCP3, and Dnah1 was measured by RT-qPCR.
Results: 6PPD-quinone significantly reduced sperm motility, viability, normal morphology, concentration, and acrosomal integrity compared with the control group. It also increased sperm DNA fragmentation, abnormal chromatin maturity, and defective nuclear chromatin condensation. At the molecular level, 6PPD-Q downregulated testicular genes related to barrier integrity, meiosis, and sperm flagellar function. Resveratrol co-treatment significantly improved sperm quality parameters, reduced DNA and chromatin abnormalities, and increased Tjp1, SYCP3, and Dnah1 expression compared with 6PPD-Q treatment alone.
Conclusion: 6PPD-Q induces male reproductive toxicity in rats through impairment of sperm function, sperm nuclear integrity, chromatin status, and testicular gene expression. Resveratrol attenuates these alterations, supporting its potential protective role against emerging tire rubber-derived reproductive toxicants.