Toxic effects of exogenous retinoic acid on the neurodevelopment of zebrafish (Danio rerio) embryos

IF 2.6 3区医学 Q3 NEUROSCIENCES

Neurotoxicology and teratology Pub Date : 2023-09-07 DOI:10.1016/j.ntt.2023.107291

Xiaoxuan Wang , Ting Ma , Cizhao Wei , Juan Liu , Ting Yu , Yu Zou , Song Liu , Zheqiong Yang , Jinlei Xi

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引用次数: 0

Abstract

Endogenous retinoic acid (RA) is essential for embryonic development and maintaining adult physiological processes. Human-caused RA residues in the environment threaten the survival of organisms in the environment. We employed zebrafish as a model to explore the developmental impacts of excess RA. We used exogenous RA to raise the amount of RA signal in the embryos and looked at the effects of excess RA on embryonic morphological development. Upregulation of the RA signal significantly reduced embryo hatching and increased embryo malformation. To further understand the neurotoxic impact of RA signaling on early neurodevelopment, we measured the expression of neurodevelopmental marker genes and cell death and proliferation markers in zebrafish embryos. Exogenous RA disrupted stem cell (SC) and neuron marker gene expression and exacerbated apoptosis in the embryos. Furthermore, we looked into the links between the transcriptional coactivator RBM14 and RA signaling to better understand the mechanism of RA neurotoxicity. There was a negative interaction between RA signaling and the transcription coactivator RBM14, and the morpholino-induced RBM14 down-regulation can partially block the effects of RAR antagonist BMS493-induced RA signaling inhibition on embryonic malformation and cell apoptosis. In conclusion, exogenous RA causes neurodevelopmental toxicity, and RBM14 may be involved in this neurotoxic process.

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外源性维甲酸对斑马鱼胚胎神经发育的毒性作用。

内源性视黄酸（RA）对胚胎发育和维持成人生理过程至关重要。人类在环境中造成的RA残留物威胁着环境中生物体的生存。我们采用斑马鱼作为模型来探索过度RA对发育的影响。我们使用外源性RA来提高胚胎中RA信号的量，并观察过量RA对胚胎形态发育的影响。RA信号的上调显著降低了胚胎孵化率，增加了胚胎畸形。为了进一步了解RA信号对早期神经发育的神经毒性影响，我们测量了斑马鱼胚胎中神经发育标记基因以及细胞死亡和增殖标记的表达。外源性RA破坏了胚胎中干细胞（SC）和神经元标志物基因的表达，并加剧了细胞凋亡。此外，我们研究了转录共激活因子RBM14和RA信号传导之间的联系，以更好地了解RA神经毒性的机制。RA信号传导与转录共激活因子RBM14之间存在负相互作用，吗啉诱导的RBM14下调可以部分阻断RAR拮抗剂BMS493诱导的RA信号传导抑制对胚胎畸形和细胞凋亡的影响。总之，外源性RA会引起神经发育毒性，RBM14可能参与了这一神经毒性过程。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Neurotoxicology and teratology 医学-毒理学

CiteScore

5.60

自引率

10.30%

发文量

审稿时长

58 days

期刊介绍： Neurotoxicology and Teratology provides a forum for publishing new information regarding the effects of chemical and physical agents on the developing, adult or aging nervous system. In this context, the fields of neurotoxicology and teratology include studies of agent-induced alterations of nervous system function, with a focus on behavioral outcomes and their underlying physiological and neurochemical mechanisms. The Journal publishes original, peer-reviewed Research Reports of experimental, clinical, and epidemiological studies that address the neurotoxicity and/or functional teratology of pesticides, solvents, heavy metals, nanomaterials, organometals, industrial compounds, mixtures, drugs of abuse, pharmaceuticals, animal and plant toxins, atmospheric reaction products, and physical agents such as radiation and noise. These reports include traditional mammalian neurotoxicology experiments, human studies, studies using non-mammalian animal models, and mechanistic studies in vivo or in vitro. Special Issues, Reviews, Commentaries, Meeting Reports, and Symposium Papers provide timely updates on areas that have reached a critical point of synthesis, on aspects of a scientific field undergoing rapid change, or on areas that present special methodological or interpretive problems. Theoretical Articles address concepts and potential mechanisms underlying actions of agents of interest in the nervous system. The Journal also publishes Brief Communications that concisely describe a new method, technique, apparatus, or experimental result.