Chronic Arsenic Exposure Induced Reproductive Toxicity by Promoting Ferroptosis and the Protective Effects of Xylo-Oligosaccharides.

Arsenic, a toxic metalloid widespread in groundwater, induces multi-organ damage upon chronic exposure. The male reproductive system, which is crucial for species propagation, requires a stable testicular microenvironment to function properly. Although the reproductive system is recognized as one of the most sensitive targets of arsenic toxicity, the underlying molecular mechanisms and effective intervention strategies remain incompletely understood. In this study, we systematically evaluated the impact of chronic arsenic exposure on testicular function in male C57BL/6J mice administered sodium arsenite (NaAsO₂) in their drinking water for six months. Our results found that chronic arsenic exposure decreased sperm quality, induced testicular oxidative stress and inflammation, and caused the blood-testicular barrier(BTB) injury in mice. Meanwhile, chronic arsenic exposure increased the Fe²⁺ content and the levels of ferroptosis-related mRNA/protein, and decreased the mRNA/protein levels of Nrf2/GPX4 signaling pathway in the testis. Notably, supplementation with Xylo-oligosaccharides (XOS) derived from Miscanthus lutarioriparius effectively alleviated the arsenic-induced decline in sperm quality, testicular damage, oxidative stress and inflammation. Further mechanistic investigation revealed that XOS exerts its protective effects by activating the Nrf2/GPX4 signaling pathway in the testes, thereby inhibiting the ferroptosis process. Overall, our findings provide a potential preventive strategy against arsenic-induced male reproductive injury.