Developmental effects and lipid disturbances of zebrafish embryos exposed to three newly recognized bisphenol A analogues

Bisphenol G (BPG), bisphenol M (BPM) and bisphenol TMC (BPTMC), are newly recognized analogues of bisphenol A (BPA), which have been detected in multiple environmental media. However, the understanding of their negative impacts on environmental health is limited. In this study, zebrafish embryos were exposed to BPA and the three analogues (0.1, 10, and 1000 μg/L) to identify their developmental toxic effects. According to our results, all of the three analogues induced significant developmental disorders on zebrafish embryos including inhibited yolk sac absorption, altered heart rate, and teratogenic effects. Oil Red O staining indicated lipid accumulation in the yolk sac region of zebrafish after bisphenol analogues exposure, which was consistent with the delayed yolk uptake. Untargeted lipidomic analysis indicated the abundance of triacylglycerol, ceramide and fatty acids was significantly altered by the three analogues. The combined analysis of lipidomics and transcriptomics results indicated BPG and BPM affected lipid metabolism by disrupting peroxisome proliferator-activated receptor pathway and interfering with lipid homeostasis and transport. This partly explained the morphological changes of embryos after bisphenol exposure. In conclusion, our study reveals that BPG, BPM and BPTMC possess acute and developmental toxicity toward zebrafish, and the developmental abnormalities are associated with the disturbances in lipid metabolism.