Di-(2-ethylhexyl) phthalate (DEHP), a ubiquitous environmental pollutant, significantly impairs the male reproductive function. Astaxanthin (ASX), a natural carotenoid with potent antioxidant properties, has demonstrated protective effects on reproductive health. This study aimed to investigate the protective effects of ASX and its underlying mechanisms against DEHP-induced testicular injury. Results demonstrated that ASX supplementation significantly attenuated DEHP-induced testicular injury. Bioinformatics analysis suggested that the molecular mechanisms of ASX may involve cell cycle regulation and apoptosis with Cdk2 as a potential target. In vivo and in vitro experiments confirmed that ASX alleviates DEHP-induced cell cycle arrest and apoptosis by up-regulating Cdk2 expression. This study demonstrates that ASX alleviates DEHP-induced testicular dysfunction via the Cdk2-mediated inhibition of cell cycle arrest and apoptosis. Dietary supplementation with ASX may represent an effective intervention strategy to prevent the adverse effects of DEHP on testes.
Keywords: apoptosis; astaxanthin; cell cycle; di-(2-ethylhexyl) phthalate; network pharmacology; testicular injury.