Multi-generation reproductive toxicity of RDX and the involved signal pathways in Caenorhabditis elegans

As one of the most frequently used explosives, hexahydro-1,3,5-trinitro-1,3,5-triazine (RDX) can cause persistent pollution in the environment, leading to the potential ecological threat crossing the generations. In this study, we employed Caenorhabditis elegans to explore the toxic effects of RDX on the parental and offspring worms and the involved signaling pathways. Exposure up to 1000 ng/mL of RDX produced a significant increase in reactive oxygen species (ROS) production, germ cell apoptosis, and decrease in eggs laid. Various mutants were used to demonstrate the RDX-induced apoptosis signaling pathway, and the metabolism of RDX in the nematodes was found related to cytochrome P450 and GST through RNA sequencing. Exposure of parental worms to RDX produced significant reproductive toxicity in F1 and F2, but was recovered in F3 and F4. The transgenerational effects were associated with the decreased expression of met-2, spr-5, and set-2. Our findings revealed the signaling pathways related to the reproductive toxicity caused by RDX in C. elegans and their future generations, which provided the basis for further exploration of the ecological risks of energetic compounds in the environment.