Comparative pharyngeal cartilage developmental toxicity of bisphenol A, bisphenol S and bisphenol AF to zebrafish (Danio rerio) larvae: A combination of morphometry and global transcriptome analyses.

Exposure to BPA is recently shown to affect cartilage development in teleost fishes; whether BPS and BPAF, its two most frequently used phenolic analogues have similar effect, however, remains unclear. Here, we utilize zebrafish (Danio rerio) as an in-vivo larval model for systematic comparison of the pharyngeal arch-derived cartilage developmental toxicity of BPA, BPS and BPAF. Zebrafish are continuously exposed to three bisphenol analogues (3-BPs) at a range of concentrations since the embryonic stage (0.5 hpf), and identified cartilage malformations of the mandibular and hyoid pharyngeal arches at larval stage (120 hpf). BPA and BPAF prolong length and broaden cartilage angles; however, BPS shortens length and narrows the angles of skull cartilages. The results of the comparative transcriptome show that FoxO and MAPK signaling pathways are closely associated with the toxicity of BPA and BPAF, while BPS exposure affects energy metabolism-related pathways. Moreover, exposure to 3-BPs have an impact on the oxidative stress status. Our data collectively indicate that BPS and BPAF may not be safer than BPA regarding the impact on pharyngeal cartilage development in fish model, the mechanisms still need explorations, and that these two analogues should be applied with caution.