Hepatic transcriptome and DNA methylation patterns following perinatal and chronic BPS exposure in male mice
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RESEARCH ARTICLE
Open Access
Hepatic transcriptome and DNA methylation patterns following perinatal and chronic BPS exposure in male mice Axelle Brulport1,2,3, Daniel Vaiman4,5,6, Elias Bou-Maroun7, Marie-Christine Chagnon1,2,3 and Ludovic Le Corre1,2,3*
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. Keywords: Bisphenol S, Perinatal and chronic exposure, Liver, DNA methylation, Transcriptome
Background Since the ban of Bisphenol A (BPA) in the baby bottles (Europe Union: regulation 321/2011, North America since 2009–2010, China since 2011) and the other use restrictions of this substance in relation to these reprotoxic and endocrine disruptor properties, manufacturers may use Bisphenol S (BPS), a structural analogue with similar endocrine disrupting and technological properties [1–3]. BPA and BPS are chemicals used as monomers in the manufacture of plastics and resins. Nearly sixty * Correspondence: [email protected] 1 Université de Bourgogne Franche-Comté, LNC UMR1231, F-21000 Dijon, France 2 AgroSup, LNC UMR1231, 1 Esplanade Erasme, 21000 Dijon, France Full list of author information is available at the end of the article
industrial sectors are potential users of these substances leading to daily human exposure. For example, they are present in polycarbonate (BPA) and polyether sulfone (BPS) plastics, paints, varnishes, thermal papers and paperboards, inks, glues, electronic and electrical components, cosmetics, medical, surgical and dental equipment, kitchen utensils and packaging in contact with food products [4]. Currently, BPS is approved for food contact materials with one restriction (EU 10/2011): a specific mig
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