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

被引:89
作者
Nguyen, Tara [1 ]
Li, Gerard E. [1 ]
Chen, Hui [1 ]
Cranfield, Charles G. [1 ]
McGrath, Kristine C. [1 ]
Gorrie, Catherine A. [1 ]
机构
[1] Univ Technol Sydney, Fac Sci, Sch Life Sci, Sydney, NSW, Australia
关键词
ELEVATED PLUS-MAZE; DNA METHYLTRANSFERASES DNMT3A; ANXIETY-RELATED BEHAVIOR; INFANT-DEATH-SYNDROME; LOW-BIRTH-WEIGHT; SMOKE EXPOSURE; AURORA-A; FLAVORING CHEMICALS; ANTISOCIAL-BEHAVIOR; MITOTIC DELAY;
D O I
10.1021/acs.chemrestox.8b00084
中图分类号
R914 [药物化学];
学科分类号
100701 ;
摘要
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.
引用
收藏
页码:601 / 611
页数:11
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