Environmentally relevant exposure to tetrabromobisphenol A induces reproductive toxicity via regulating glucose-6-phosphate 1-dehydrogenase and sperm activation in Caenorhabditis elegans

Tetrabromobisphenol A (TBBPA), a ubiquitous brominated flame-retardant environmental pollutant, has been reported to cause reproductive toxicity by chronic exposure. However, the acute reproductive risk and mechanisms of TBBPA toxicity to individuals, especially at environmentally relevant levels, remains a topic of debate. In this study, Caenorhabditis elegans was used to investigate the reproductive toxicity of acute exposure to TBBPA at environmentally relevant doses. The reproductive end points (embryonic lethality ratio and brood size), oxidative stress, sperm activation, and molecular docking were evaluated. Results showed that, after 24 h of TBBPA treatment, even at the lowest concentration (1 μg/L), the embryonic lethality ratio of C. elegans increased significantly, from 1.63 % to 3.03 %. Furthermore, TBBPA induced oxidative stress with significantly increased expression of sod-3 in C. elegans, which further raised the level of reproductive toxicity through inhibiting the activation of sperm in nematodes. In addition, molecular docking suggested TBBPA might compete for the glucose-6-phosphate-binding site of glucose-6-phosphate 1-dehydrogenase, resulting in oxidative stress generation. Accordingly, our findings indicate that even acute exposure to environmental concentrations of TBBPA may induce reproductive toxicity through reducing sperm activation in nematodes.