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Prenatal exposure to paraquat and nanoscaled TiO2 aerosols alters the gene expression of the developing brain
Chemosphere ( IF 8.1 ) Pub Date : 2021-09-16 , DOI: 10.1016/j.chemosphere.2021.132253
Quentin Hamdaoui 1 , Yanis Zekri 2 , Sabine Richard 2 , Denise Aubert 2 , Romain Guyot 2 , Suzy Markossian 2 , Karine Gauthier 2 , François Gaie-Levrel 3 , Anna Bencsik 4 , Frédéric Flamant 2
Affiliation  

Nanopesticides are innovative pesticides involving engineered nanomaterials in their formulation to increase the efficiency of plant protection products, while mitigating their environmental impact. Despite the predicted growth of the nanopesticide use, no data is available on their inhalation toxicity and the potential cocktail effects between their components. In particular, the neurodevelopmental toxicity caused by prenatal exposures might have long lasting consequences. In the present study, we repeatedly exposed gestating mice in a whole-body exposure chamber to three aerosols, involving the paraquat herbicide, nanoscaled titanium dioxide particles (nTiO2), or a mixture of both. Particle number concentrations and total mass concentrations were followed to enable a metrological follow-up of the exposure sessions. Based on the aerosols characteristics, the alveolar deposited dose in mice was then estimated. RNA-seq was used to highlight dysregulations in the striatum of pups in response to the in utero exposure. Modifications in gene expression were identified at post-natal day 14, which might reflect neurodevelopmental alterations in this key brain area. The data suggest an alteration in the mitochondrial function following paraquat exposure, which is reminiscent of the pathological process leading to Parkinson disease. Markers of different cell lineages were dysregulated, showing effects, which were not limited to dopaminergic neurons. Exposure to the nTiO2 aerosol modulated the regulation of cytokines and neurotransmitters pathways, perhaps reflecting a minor neuroinflammation. No synergy was found between paraquat and nTiO2. Instead, the neurodevelopmental effects were surprisingly lower than the one measured for each substance separately.



中文翻译:

产前接触百草枯和纳米二氧化钛气溶胶会改变发育中大脑的基因表达

纳米农药是一种创新农药,其配方中包含工程纳米材料,可提高植物保护产品的效率,同时减轻其对环境的影响。尽管纳米农药的使用预计会增长,但没有关于它们的吸入毒性和其成分之间潜在鸡尾酒效应的数据。特别是,产前暴露引起的神经发育毒性可能会产生长期持久的后果。在本研究中,我们将全身暴露室中的妊娠小鼠反复暴露于三种气溶胶,包括百草枯除草剂、纳米二氧化钛颗粒 (nTiO 2),或两者的混合。跟踪粒子数浓度和总质量浓度,以便对暴露会话进行计量跟踪。根据气溶胶特性,然后估计小鼠的肺泡沉积剂量。RNA-seq 用于突出幼崽纹状体响应子宫内暴露的失调。在出生后第 14 天发现基因表达的改变,这可能反映了这个关键大脑区域的神经发育改变。数据表明,接触百草枯后线粒体功能发生了改变,这让人联想到导致帕金森病的病理过程。不同细胞谱系的标记物失调,显示出不仅限于多巴胺能神经元的影响。接触 nTiO2气雾剂调节细胞因子和神经递质通路的调节,可能反映了轻微的神经炎症。百草枯和 nTiO 2之间没有发现协同作用。相反,神经发育影响出人意料地低于对每种物质分别测量的影响。

更新日期:2021-09-17
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