The effect and mechanisms of nano cerium dioxide (Nano-CeO2) on cardiovascular development in zebrafish (Danio rerio)

The widespread application of nano-cerium dioxide (Nano-CeO 2 ) in agriculture, industry, and other fields has led to an increasing amount of it being released into the environment and becoming a pollutant with potential biological hazards. However, studies on the effects of ceria on cardiovascular development were limited. This study aims to detect the cardiovascular toxicity of Nano-CeO 2 , focusing on its impact on zebrafish hematopoietic function and cardiac development, and to explore its potential molecular mechanisms. We found that exposing zebrafish embryos to different concentrations of Nano-CeO 2 after 6 hpf of fertilization does not hinder the growth and development of zebrafish embryos during their early life stages. However, RNA-Seq analysis indicates that the hematopoietic system of zebrafish is suppressed, the ECM-receptor interaction pathway is disrupted, and the expression of related genes is significantly downregulated. The results of o-dianisidine staining, neutral red staining, and Sudan black staining showed that the hemoglobin, macrophages, and neutrophils of zebrafish were reduced, and the vascular dysplasia of zebrafish was observed. Meanwhile, Reactive oxygen species (ROS) accumulated in the heart of zebrafish larvae treated with Nano-CeO 2 , and heart development-related genes ( nppa , hand2 , nppb , nkx2.5 , and myh7 ) were significantly down-regulated, while gata4 was up-regulated. The addition of the integrin agonist manganese ions restored the expression of genes related to ECM-receptor interaction pathways, alleviating cardiovascular abnormalities caused by Nano-CeO 2 . Besides, significant changes in cardiac histopathology were observed with long-term exposure (120 d post-fertilization), indicating that Nano-CeO 2 exposure affected the development of the cardiovascular system in zebrafish. In summary, acute and chronic exposure to Nano-CeO 2 exhibits cardiovascular toxicity in zebrafish, affecting hematopoietic function and cardiac development, and the mechanism may be related to the ECM-receptor interaction pathway. This study provides useful information for a comprehensive understanding of the toxicity mechanisms and environmental risks of Nano-CeO 2 .