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围产期暴露于双酚A的成年雌性C57BL/6JxFVB小鼠的肝脏DNA甲基化分析

Liver DNA methylation analysis in adult female C57BL/6JxFVB mice following perinatal exposure to bisphenol A.

作者信息

van Esterik J C J, Vitins A P, Hodemaekers H M, Kamstra J H, Legler J, Pennings J L A, Steegenga W T, Lute C, Jelinek J, Issa J P J, Dollé M E T, van der Ven L T M

机构信息

Center for Health Protection, National Institute for Public Health and the Environment (RIVM), PO Box 1, 3720 BA Bilthoven, The Netherlands; Department of Chemistry and Biology, Institute for Environmental Studies (IVM), VU University, De Boelelaan 1085, 1081 HV Amsterdam, The Netherlands.

Center for Health Protection, National Institute for Public Health and the Environment (RIVM), PO Box 1, 3720 BA Bilthoven, The Netherlands.

出版信息

Toxicol Lett. 2015 Jan 5;232(1):293-300. doi: 10.1016/j.toxlet.2014.10.021. Epub 2014 Oct 17.

Abstract

Bisphenol A (BPA) is a compound released from plastics and other consumer products used in everyday life. BPA exposure early in fetal development is proposed to contribute to programming of chronic diseases like obesity and diabetes, by affecting DNA methylation levels. Previously, we showed that in utero and lactational exposure of C57BL/6JxFVB hybrid mice via maternal feed using a dose range of 0-3000μg/kg body weight/day resulted in a sex-dependent altered metabolic phenotype in offspring at 23 weeks of age. The most univocal effects were observed in females, with reduced body weights and related metabolic effects associated with perinatal BPA exposure. To identify whether the effects of BPA in females are associated with changes in DNA methylation, this was analyzed in liver, which is important in energy homeostasis. Measurement of global DNA methylation did not show any changes. Genome-wide DNA methylation analysis at specific CpG sites in control and 3000μg/kg body weight/day females with the digital restriction enzyme analysis of methylation (DREAM) assay revealed potential differences, that could, however, not be confirmed by bisulfite pyrosequencing. Overall, we demonstrated that the observed altered metabolic phenotype in female offspring after maternal exposure to BPA was not detectably associated with liver DNA methylation changes. Still, other tissues may be more informative.

摘要

双酚A(BPA)是一种从日常生活中使用的塑料和其他消费品中释放出来的化合物。胎儿发育早期接触BPA被认为会通过影响DNA甲基化水平,导致肥胖和糖尿病等慢性疾病的编程。此前,我们发现,通过母体饲料对C57BL/6JxFVB杂交小鼠进行子宫内和哺乳期暴露,剂量范围为0 - 3000μg/kg体重/天,会导致23周龄后代出现性别依赖性的代谢表型改变。在雌性小鼠中观察到的最明确的影响是,围产期暴露于BPA会导致体重减轻以及相关的代谢影响。为了确定BPA对雌性小鼠的影响是否与DNA甲基化变化有关,我们对肝脏进行了分析,因为肝脏在能量稳态中起着重要作用。整体DNA甲基化测量未显示任何变化。使用甲基化数字限制酶分析(DREAM)检测法对对照组和3000μg/kg体重/天的雌性小鼠特定CpG位点进行全基因组DNA甲基化分析,发现了潜在差异,然而,亚硫酸氢盐焦磷酸测序无法证实这些差异。总体而言,我们证明,母体暴露于BPA后,在雌性后代中观察到的代谢表型改变与肝脏DNA甲基化变化没有明显关联。不过,其他组织可能更具参考价值。

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