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产前双酚A暴露会改变小鼠海马体中的DNA甲基化水平吗?:一项使用高灵敏度甲基化组技术的分析。

Does the prenatal bisphenol A exposure alter DNA methylation levels in the mouse hippocampus?: An analysis using a high-sensitivity methylome technique.

作者信息

Aiba Toshiki, Saito Toshiyuki, Hayashi Akiko, Sato Shinji, Yunokawa Harunobu, Maruyama Toru, Fujibuchi Wataru, Ohsako Seiichiroh

机构信息

1Laboratory of Environmental Health Science, Center for Disease Biology and Integrative Medicine, Graduate School of Medicine, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo, 113-8654 Japan.

2Department of Radiation Effects Research, National Institutes for Quantum and Radiological Science and Technology, 4-9-1 Anagawa, Inage-ku, Chiba, 263-8555 Japan.

出版信息

Genes Environ. 2018 Jun 4;40:12. doi: 10.1186/s41021-018-0099-y. eCollection 2018.

Abstract

BACKGROUND

There is still considerable debate about the effects of exposure to bisphenol A (BPA) an endocrine disrupter at low doses. Recently, many studies using animal models have shown that prenatal BPA exposure induces behavioral and neuronal disorders due to epigenetic changes in the brain. However, striking evidence of epigenomic changes has to be shown.

METHODS

To investigate whether low-dose BPA exposure in the fetal stage can alter CpG methylation levels in the central nervous system, the hippocampus of the inbred C57BL/6 J mouse as the target tissue was collected to detect alterations in CpG methylation levels using a highly sensitive method of genome-wide DNA methylation analysis, methylated site display-amplified fragment length polymorphism (MSD-AFLP).

RESULTS

BPA showed the sex-hormone like effects on male reproductive organs. Although we examined the methylation levels of 43,840 CpG sites in the control and BPA (200 μg/kg/day)-treated group (6 mice per group), we found no statistically significant changes in methylation levels in any CpG sites.

CONCLUSIONS

At least under the experimental condition in this study, it is considered that the effect of low-dose BPA exposure during the fetal stage on hippocampal DNA methylation levels is extremely small.

摘要

背景

关于低剂量接触双酚A(BPA,一种内分泌干扰物)的影响仍存在相当大的争议。最近,许多使用动物模型的研究表明,产前接触双酚A会因大脑中的表观遗传变化而导致行为和神经紊乱。然而,必须展示表观基因组变化的显著证据。

方法

为了研究胎儿期低剂量接触双酚A是否会改变中枢神经系统中的CpG甲基化水平,收集近交系C57BL/6 J小鼠的海马作为靶组织,使用一种高灵敏度的全基因组DNA甲基化分析方法——甲基化位点展示-扩增片段长度多态性(MSD-AFLP)来检测CpG甲基化水平的变化。

结果

双酚A对雄性生殖器官表现出类似性激素的作用。尽管我们检测了对照组和双酚A(200μg/kg/天)处理组(每组6只小鼠)中43,840个CpG位点的甲基化水平,但我们发现任何CpG位点的甲基化水平均无统计学上的显著变化。

结论

至少在本研究的实验条件下,认为胎儿期低剂量接触双酚A对海马DNA甲基化水平的影响极小。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/baa8/5985587/faf6141cd419/41021_2018_99_Fig1_HTML.jpg

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