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母鼠电子烟暴露可导致子代认知和表观遗传改变:一项基于小鼠模型的研究。

Maternal E-Cigarette Exposure Results in Cognitive and Epigenetic Alterations in Offspring in a Mouse Model.

机构信息

School of Life Sciences, Faculty of Science , University of Technology Sydney , Sydney , New South Wales , Australia.

出版信息

Chem Res Toxicol. 2018 Jul 16;31(7):601-611. doi: 10.1021/acs.chemrestox.8b00084. Epub 2018 Jun 15.

Abstract

Electronic cigarette (e-cigarette) use is on the rise worldwide and is particularly attractive to young people and as a smoking substitute by pregnant woman. There is a perception in pregnant women and women of child-bearing age that the use of e-cigarettes (vaping) is safer than smoking tobacco cigarettes during pregnancy. However, there is little evidence to support this perception. Here, we examined the offspring from mouse dams that had been exposed during and after pregnancy to ambient air (sham) ( n = 8), e-cigarette aerosols with nicotine ( n = 8), or e-cigarette aerosols without nicotine ( n = 8). Offspring underwent cognitive testing at 12 weeks of age and epigenetic testing of brain tissues at 1 day, 20 days, and 13 weeks after birth. The findings showed deficits in short-term memory, reduced anxiety, and hyperactivity in offspring following maternal e-cigarette exposure using the novel object recognition and elevated plus maze tests. In addition, global DNA methylation was increased in the brains of offspring soon after birth. Using a quantitative-PCR array specific to chromatin modification enzymes on genomic DNA and histones,13 key genes were identified to be significantly altered in the offspring brains from the e-cigarette groups compared to the nonexposed groups. The changes to genes Aurka, Aurkb, Aurkc, Kdm5c, Kdm6b, Dnmt3a, Dnmt3b, and Atf2, all associated with modulating neurological activity, were validated using RT-qPCR. In conclusion, in a mouse model, maternal exposure to e-cigarette aerosols resulted in both cognitive and epigenetic changes in offspring. This suggests that the use of e-cigarettes during pregnancy may have hitherto undetected neurological consequences on newborns.

摘要

电子烟(电子香烟)的使用在全球范围内呈上升趋势,尤其对年轻人和孕妇来说,电子烟是香烟的替代品。孕妇和育龄妇女普遍认为,怀孕期间使用电子烟(蒸气)比吸香烟更安全。然而,几乎没有证据支持这种看法。在这里,我们检查了在怀孕期间和怀孕后暴露于环境空气中(假)(n = 8)、含尼古丁的电子烟气溶胶(n = 8)或不含尼古丁的电子烟气溶胶(n = 8)的鼠母体的后代。后代在 12 周龄时进行认知测试,并在出生后 1 天、20 天和 13 周时进行脑组织的表观遗传测试。研究结果表明,在通过新物体识别和高架十字迷宫测试对后代进行测试后,其短期记忆出现缺陷,焦虑减少,并且母亲使用电子烟暴露后其后代出现多动。此外,后代出生后不久大脑中的全基因组甲基化增加。使用针对基因组 DNA 和组蛋白上染色质修饰酶的定量 PCR 阵列,在电子烟组与未暴露组的后代大脑中发现 13 个关键基因发生了显著改变。 Aurka、 Aurkb、 Aurkc、 Kdm5c、 Kdm6b、 Dnmt3a、 Dnmt3b 和 Atf2 等与调节神经活动相关的基因的改变使用 RT-qPCR 进行了验证。总之,在小鼠模型中,母体暴露于电子烟气溶胶会导致后代出现认知和表观遗传变化。这表明怀孕期间使用电子烟可能对新生儿产生迄今为止尚未被发现的神经后果。

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