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邻苯二甲酸二丁酯破坏胚胎斑马鱼的肌肉、运动和感觉神经元发育。

Di-butyl phthalate disrupts muscle, motor and sensory neuron development in embryonic zebrafish.

机构信息

Department of Biology, Sacred Heart University, Fairfield, CT, United States of America.

Department of Biology, Sacred Heart University, Fairfield, CT, United States of America.

出版信息

Neurotoxicol Teratol. 2023 May-Jun;97:107179. doi: 10.1016/j.ntt.2023.107179. Epub 2023 May 5.

Abstract

Phthalates are added to plastics to enhance its flexibility, durability and transparency. Phthalates are not covalently bound to plastics and leach into the environment. Phthalates are now pervasive and ubiquitously present in the atmosphere, soil and sediment, surface and wastewater. Phthalates are known endocrine disruptors and their effects on male and female reproduction are well noted. However, studies on the developmental effects of di-butyl phthalate (DBP) are limited. Here we investigated the developmental toxicity of DBP on motor and sensory neuron populations and the muscle structures motor neurons innervate using the zebrafish vertebrate model system. We investigated these effects during the time window of development spanning the period where embryonic patterning determines adult structures. We found that treatment with 2.5 μM DBP from 6 h post-fertilization (hpf) until 72hpf induces loss and disorganization of primary motor neuron innervation of the somatic tissue with concomitant disruptions to muscle fiber organization. Furthermore, we found disruptions to sensory motor neuron development including defects in dorsal root ganglion and their peripherally extending axons. Rohon-Beard sensory neurons were also disrupted showing loss of the bilateral soma positioning along the length of the spinal cord and their afferent axonal projections to the epithelium. Thus, we concluded that DBP is toxic to developing motor and sensory neurons during embryonic development.

摘要

邻苯二甲酸酯被添加到塑料中以增强其柔韧性、耐久性和透明度。邻苯二甲酸酯与塑料没有共价结合,而是会浸出到环境中。邻苯二甲酸酯现在无处不在,普遍存在于大气、土壤和沉积物、地表水和废水中。邻苯二甲酸酯是已知的内分泌干扰物,其对男性和女性生殖的影响已得到充分证实。然而,关于邻苯二甲酸二丁酯(DBP)的发育毒性研究有限。在这里,我们使用斑马鱼脊椎动物模型系统研究了 DBP 对运动和感觉神经元群体以及运动神经元支配的肌肉结构的发育毒性。我们在胚胎形态发生决定成年结构的发育窗口期研究了这些影响。我们发现,从受精后 6 小时(hpf)到 72 小时(hpf),用 2.5μM DBP 处理会导致躯体组织中的初级运动神经元支配丧失和紊乱,同时肌肉纤维组织也受到破坏。此外,我们发现感觉运动神经元的发育受到干扰,包括背根神经节及其外周延伸轴突的缺陷。Rohon-Beard 感觉神经元也受到干扰,表现为双侧体沿脊髓长度定位丧失,以及它们向上皮的传入轴突投射。因此,我们得出结论,DBP 在胚胎发育过程中对发育中的运动和感觉神经元具有毒性。

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