Study on the Toxicity and Mechanism of Tritiated Water on the Cardiac Development of Zebrafish

• 1、School of Radiation Medicine and Protection, Medical College of Soochow University

Abstract：Objective: To investigate the cardiovascular toxicity of tritiated water to zebrafish and its mechanism. Methods: 2~3 hpf zebrafish embryos were exposed to 3.7*10^4 Bq/ml tritiated water to observe the changes of heart rate of zebrafish RT-PCR was used to detect the expression levels of tnnc1a, tpm4a, tpm4b related genes after exposure to tritium water; CRISPR/Cas9 technology was used to establish tnnc1a, tpm4a gene knockout zebrafish model, and to observe the cardiac development after exposure to tritium water. Results: the heart rate of zebrafish increased significantly at 36 hpf and 60 hpf, and the gene expression levels of tnnc1a, tpm4a and tpm4b decreased significantly at 36 hpf, 48 hpf and 60 hpf, and increased significantly at 120 hpf. After tnnc1a or tpm4a gene knockout, the heart rate decreased significantly after tritium exposure at 36 hpf, 60 hpf and 120 hpf; the malformation rate of zebrafish embryos increased after tnnc1a gene knockout, but the morphology of zebrafish embryos did not change significantly after tpm4a gene knockout. Conclusion: exposure to tritiated water can induce the increase of heart rate in zebrafish embryos/juveniles through TnC/TPM4 pathway. The regulation of tnnc1a and tpm4a on heart rate is mainly in the late embryonic development (120 hpf), and tnnc1a plays an important role in the growth and development of heart and whole body.

Keywords： Tritium water zebrafish heart rate tnnc1a tpm4a