The Reproductive Toxicity Valuation of Deoxynivalenol: An Integrated Study from Network Toxicology, Molecular...

Deoxynivalenol (DON), a Fusarium-derived mycotoxin widely found in grain-based feed, has become a major global environmental contaminant. Reproductive toxicity is one of its most important toxic effects, yet systematic investigations covering both male and female reproductive injury remain limited. This study aimed to establish a combined strategy of network toxicology, molecular docking, molecular dynamics simulation, and single-cell RNA sequencing to evaluate the reproductive toxicity of DON. AKT1, EGFR, PIK3CA, PIK3R1, and SRC were identified as key targets involved in DON-induced reproductive injury. For testicular injury, the prolactin, Ras, HIF-1, and AGE-RAGE signaling pathways were closely associated with DON toxicity. For ovarian injury, the PI3K-Akt, HIF-1, prolactin, insulin, and AGE-RAGE signaling pathways were strongly implicated. Molecular docking demonstrated favorable binding affinities between DON and the hub targets, while molecular dynamics simulation further confirmed the stability of the DON-PIK3CA complex. Single-cell RNA sequencing analysis revealed that these five hub genes were highly expressed in both testicular (SRA667709:SRS3065430) and ovarian (SRA638923:SRS2797100) tissues. These findings deepen current understanding of DON-induced reproductive toxicity, provide new insights into the effects of environmental toxins on reproductive health, and offer a theoretical basis for future studies integrating DON exposure with in vivo validation of core targets and signaling pathways.