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Pregnancy exposure to carbon black nanoparticles induced neurobehavioral deficits that are associated with altered m6A modification in offspring.
NeuroToxicology ( IF 3.4 ) Pub Date : 2020-08-09 , DOI: 10.1016/j.neuro.2020.07.004
Shanshan Zhang 1 , Pan Meng 2 , Shuqun Cheng 1 , Xuejun Jiang 3 , Jun Zhang 4 , Xia Qin 5 , Qianghu Tang 1 , Lulu Bai 1 , Zhen Zou 6 , Chengzhi Chen 7
Affiliation  

Increasing occupational and accidental exposure to carbon black nanoparticles (CBNPs) raise concerns over their possible effects on the nervous system. However, the influences of CBNPs on the neurodevelopment remain unclear. Thus, in this study, pregnant mice were exposed to different doses of CBNPs by intranasal instillation on gestation days 9–18. Our results demonstrated that maternal exposure to CBNPs caused significant changes on maternal behaviors. Pregnancy exposure to CBNPs also delayed the onset of incisor eruption, testes descent and vaginal opening in offspring, and caused the reduced body weight until adulthood. In the neurobehavioral tests, CBNPs-exposed offspring exhibited the elevated latency of negative geotaxis and surface right reflex, reduced grasping time and increased cliff avoidance. Histopathological changes were present in F1 generation but not in F2 generation. Intriguingly, our data revealed that the levels of total m6A modification were significantly decreased by CBNPs. Similar trends were observed on the mRNA expressions of m6A methyltransferases and demethylases. In summary, these findings provide the novel evidence that pregnancy exposure to CBNPs affects the maternal behaviors and partially induces the neurobehavioral, muscular and histopathological changes in offspring. Of note, these adverse effects may be associated with reduced levels of total m6A modification in brain.



中文翻译:

妊娠期暴露于炭黑纳米颗粒会导致神经行为缺陷,这与子代 m6A 修饰的改变有关。

越来越多的职业和意外接触炭黑纳米粒子 (CBNP) 引发了人们对其可能对神经系统产生影响的担忧。然而,CBNPs对神经发育的影响仍不清楚。因此,在本研究中,怀孕小鼠在妊娠第 9-18 天通过鼻内滴注暴露于不同剂量的 CBNP。我们的研究结果表明,母亲接触 CBNP 会导致母亲行为发生显着变化。妊娠期暴露于 CBNPs 还延迟了后代门牙萌出、睾丸下降和阴道开口的发生,并导致体重下降,直至成年。在神经行为测试中,暴露于 CBNPs 的后代表现出负趋向性和表面右反射的潜伏期升高,抓握时间减少,悬崖回避增加。F1代存在组织病理学改变,F2代不存在。有趣的是,我们的数据显示,总 m 的水平6 CBNP 显着降低了 A 修饰。在 m 6 A 甲基转移酶和去甲基酶的 mRNA 表达上观察到类似的趋势。总之,这些发现提供了新的证据,证明妊娠期暴露于 CBNPs 会影响母体行为,并部分诱导后代的神经行为、肌肉和组织病理学变化。值得注意的是,这些不利影响可能与大脑中总 m 6 A 修饰水平降低有关。

更新日期:2020-09-10
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