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围产期和慢性 BPS 暴露后雄性小鼠的肝转录组和 DNA 甲基化模式。

Hepatic transcriptome and DNA methylation patterns following perinatal and chronic BPS exposure in male mice.

机构信息

Université de Bourgogne Franche-Comté, LNC UMR1231, F-21000, Dijon, France.

AgroSup, LNC UMR1231, 1 Esplanade Erasme, 21000, Dijon, France.

出版信息

BMC Genomics. 2020 Dec 9;21(1):881. doi: 10.1186/s12864-020-07294-3.

Abstract

BACKGROUND

Bisphenol S (BPS) is a common bisphenol A (BPA) substitute, since BPA is virtually banned worldwide. However, BPS and BPA have both endocrine disrupting properties. Their effects appear mostly in adulthood following perinatal exposures. The objective of the present study was to investigate the impact of perinatal and chronic exposure to BPS at the low dose of 1.5 μg/kg body weight/day on the transcriptome and methylome of the liver in 23 weeks-old C57BL6/J male mice.

RESULTS

This multi-omic study highlights a major impact of BPS on gene expression (374 significant deregulated genes) and Gene Set Enrichment Analysis show an enrichment focused on several biological pathways related to metabolic liver regulation. BPS exposure also induces a hypomethylation in 58.5% of the differentially methylated regions (DMR). Systematic connections were not found between gene expression and methylation profile excepted for 18 genes, including 4 genes involved in lipid metabolism pathways (Fasn, Hmgcr, Elovl6, Lpin1), which were downregulated and featured differentially methylated CpGs in their exons or introns.

CONCLUSIONS

This descriptive study shows an impact of BPS on biological pathways mainly related to an integrative disruption of metabolism (energy metabolism, detoxification, protein and steroid metabolism) and, like most high-throughput studies, contributes to the identification of potential exposure biomarkers.

摘要

背景

双酚 S(BPS)是一种常见的双酚 A(BPA)替代品,因为 BPA 几乎在全球范围内被禁用。然而,BPS 和 BPA 都具有内分泌干扰特性。它们的影响主要出现在成年期,继而过早接触。本研究的目的是调查围产期和慢性接触低剂量 1.5μg/kg 体重/天的 BPS 对 23 周龄 C57BL6/J 雄性小鼠肝脏转录组和甲基组的影响。

结果

这项多组学研究突出了 BPS 对基因表达(374 个显著失调基因)的重大影响,基因集富集分析显示,与代谢性肝脏调节相关的几个生物学途径富集。BPS 暴露还导致 58.5%的差异甲基化区域(DMR)发生低甲基化。除了 18 个基因外,未发现基因表达和甲基化谱之间存在系统联系,这 18 个基因包括 4 个参与脂质代谢途径的基因(Fasn、Hmgcr、Elovl6、Lpin1),这些基因下调,并在其外显子或内含子中表现出差异甲基化 CpG。

结论

这项描述性研究表明,BPS 对生物途径有影响,主要与代谢(能量代谢、解毒、蛋白质和类固醇代谢)的综合失调有关,并且与大多数高通量研究一样,有助于识别潜在的暴露生物标志物。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/afc9/7727143/9229549fcc8f/12864_2020_7294_Fig1_HTML.jpg

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