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miR-29b 触发滴滴涕暴露后斑马鱼心脏毒性的表观遗传调控。

miR-29b-triggered epigenetic regulation of cardiotoxicity following exposure to deltamethrin in zebrafish.

机构信息

Institute of Pesticide and Environmental Toxicology, College of Agriculture and Biotechnology, Zhejiang University, Hangzhou 310058, PR China.

Institute of Pesticide and Environmental Toxicology, College of Agriculture and Biotechnology, Zhejiang University, Hangzhou 310058, PR China; Research Centre for the Oceans and Human Health, City University of Hong Kong Shenzhen Research Institute, Shenzhen 518057, PR China; Department Evolutionary Ecology and Environmental Toxicology, Faculty Biological Sciences, Goethe University 10 Frankfurt, Frankfurt am Main 60438, Germany.

出版信息

J Hazard Mater. 2024 Sep 5;476:135213. doi: 10.1016/j.jhazmat.2024.135213. Epub 2024 Jul 15.

Abstract

Deltamethrin is a classical pyrethroid insecticide that is frequently detected in aquatic environments and organisms. Furthermore, deltamethrin has been detected in samples related to human health and is a potential risk to public health. This study aimed to investigate the mechanism of cardiotoxicity induced by deltamethrin. Zebrafish were exposed to 0.005, 0.05, or 0.5 μg/L deltamethrin for 28 days. The results showed a significant reduction in male reproduction compared to female reproduction. Additionally, the heart rate decreased by 15.75 % in F1 after parental exposure to 0.5 μg/L deltamethrin. To evaluate cardiotoxicity, deltamethrin was administered to the zebrafish embryos. By using miRNA-Seq and bioinformatics analysis, it was discovered that miR-29b functions as a toxic regulator by targeting dnmts. The overexpression of miR-29b and inhibition of dnmts resulted in cardiac abnormalities, such as pericardial edema, bradycardia, and abnormal expression of genes related to the heart. Similar changes in the levels of miR-29b and dnmts were also detected in the gonads of F0 males and F1 embryos, confirming their effects. Overall, the results suggest that deltamethrin may have adverse effects on heart development in early-stage zebrafish and on reproduction in adult zebrafish. Furthermore, epigenetic modifications may threaten the cardiac function of offspring.

摘要

溴氰菊酯是一种常用于检测水生环境和生物体的经典拟除虫菊酯杀虫剂。此外,溴氰菊酯已在与人类健康相关的样本中被检测到,对公众健康构成潜在风险。本研究旨在探讨溴氰菊酯引起心脏毒性的机制。将斑马鱼暴露于 0.005、0.05 或 0.5μg/L 的溴氰菊酯中 28 天。结果显示,与雌性生殖相比,雄性生殖显著减少。此外,在母体暴露于 0.5μg/L 的溴氰菊酯后,F1 的心率下降了 15.75%。为了评估心脏毒性,将溴氰菊酯施用于斑马鱼胚胎。通过使用 miRNA-Seq 和生物信息学分析,发现 miR-29b 通过靶向 dnmts 作为一种毒性调节剂发挥作用。miR-29b 的过表达和 dnmts 的抑制导致心脏异常,如心包水肿、心动过缓和与心脏相关的基因表达异常。在 F0 雄性和 F1 胚胎的性腺中也检测到 miR-29b 和 dnmts 水平的类似变化,证实了它们的作用。总的来说,这些结果表明溴氰菊酯可能对早期斑马鱼心脏发育和成年斑马鱼生殖产生不良影响。此外,表观遗传修饰可能威胁后代的心脏功能。

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