环境剂量磷酸三(1,3-二氯异丙基)酯多代暴露对斑马鱼子代仔鱼的神经发育毒性
Neurodevelopmental Toxicity of Zebrafish Offspring after Multigenerational Exposure to Tris (1,3-dichloro-2-propyl) phosphate at Environmental Concentrations
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摘要: 为探究环境剂量磷酸三(1,3-二氯异丙基)酯(TDCIPP)多代暴露对生物体的影响，选取斑马鱼为模型，研究了斑马鱼暴露于0、3、30和300 ng L−1 TDCIPP至3代后，对每一代子代5 dpf仔鱼神经发育的毒性效应。研究结果表明，F0代暴露于300 ng L−1 TDCIPP 120 d后所产F1代仔鱼的孵化率显著性下降，存活率显著性降低；但对F2代和F3代仔鱼的这些终点指标均无显著性影响。运动行为结果表明，F0代暴露于3和300 ng L−1 TDCIPP 120 d会导致F1代仔鱼在光暗周期刺激下的游泳速度受到抑制，并伴随着神经元发育基因(ngn1)以及轴突生长标志基因(α1-tubulin、netrin1b和zn5)的显著性上调，相关性分析表明，游泳速度的抑制与ngn1、α1-tubulin和zn5这3个基因的表达显著相关。但对F2代仔鱼，仅300 ng L−1 TDCIPP导致其游泳速度在黑暗刺激下显著性下降，且导致神经发育和再生相关基因(elavl3、gap43、gfap和shha)表达量显著性下降，但游泳速度的下降与基因表达无显著相关性。继续暴露至F3代仔鱼时，TDCIPP暴露对运动行为不再有显著影响。研究表明，环境剂量TDCIPP多代暴露对子代仔鱼具有神经发育毒性，表现为运动行为受损和神经发育相关基因表达量的改变，但毒性效应随着暴露代数的增加而减弱。
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关键词:
- 磷酸三(1,3-二氯异丙基)酯 /
- 斑马鱼 /
- 神经发育毒性 /
- 多代暴露 /
- 环境剂量
Abstract: In order to investigate the multigenerational exposure effects of TDCIPP at environmental concentrations, we selected zebrafish (Danio rerio) as a model and studied the developmental neurotoxicity on 5 dpf zebrafish larvae of each generation after exposure to 0, 3, 30 and 300 ng L−1 TDCIPP for three consecutive generations. Our results showed that hatching rates and survival rates were significantly affected in the 5 dpf larvae of F1 generation, but were unaffected in 5 dpf larvae of neither F2 nor F3 generation. Behavioral measurements showed that exposure to 3 or 300 ng L−1 TDCIPP significantly decreased the swimming behavior response of the 5 dpf larvae of F1 generation to both light and dark stimulation. TDCIPP exposure significantly increased expression of the neural marker gene ngn1 and axon-related genes (α1-tubulin, netrin1b and zn5) in F1 larvae. In addition, correlation analysis showed that the inhibition of swimming speed was significantly correlated with the expression of genes, i.e., ngn1, α1-tubulin and zn5, which suggested that the disturbance on nerve development might lead to the abnormal behaviors in F1 larvae. For F2 larvae, only 300 ng L−1 TDCIPP caused a significant decrease in swimming speed under dark stimulation, and resulted in a significant decrease in the expression of genes related to nerve development and regeneration (elavl3, gap43, gfap, and shha). However, there was no significant correlation between the inhibition of behaviors and the altered expressions of genes in F2 larvae. For F3 larvae, TDCIPP exposure no longer had a significant effect on motor behavior. Taken together, our results showed that the multigenerational exposure to TDCIPP at environmental concentrations had neurodevelopmental toxicity to the offspring larvae, which exhibited changes in motor behavior and/or expressions of neurodevelopment-related genes, but the toxic effects decreased with the increase of number of generations being exposed. -
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