Tris(4-chlorophenyl)methane and tris(4-chlorophenyl)methanol disrupt pancreatic organogenesis and gene expression in zebrafish embryos

三(4-氯苯基)甲烷和三(4-氯苯基)甲醇破坏斑马鱼胚胎的胰腺器官发生和基因表达

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作者:Peyton W Wilson, Christine Cho, Nicholas Allsing, Saleha Khanum, Pria Bose, Ava Grubschmidt, Karilyn E Sant

Conclusion

Overall, our data suggest that TCPM and TCPMOH may be hazardous to embryonic growth and development.

Methods

Zebrafish embryos were exposed to 50 nM TCPM or TCPMOH beginning at 24 hr postfertilization (hpf) and exposures were refreshed daily. At 96 hpf, pancreatic growth and islet area were directly visualized in Tg(ptf1a::GFP) and Tg(insulin::GFP) embryos, respectively, using microscopy. Gene expression was assessed at 100 hpf with RNA sequencing.

Results

Islet and total pancreas area were reduced by 20.8% and 13% in embryos exposed to 50 nM TCPMOH compared to controls. TCPM did not induce significant morphological changes to the developing pancreas, indicating TCPMOH, but not TCPM, impairs pancreatic development despite similarity in molecular responses. Transcriptomic responses to TCPM and TCPMOH were correlated (R2 = .903), and pathway analysis found downregulation of processes including retinol metabolism, circadian rhythm, and steroid biosynthesis.

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