Prenatal Bisphenol A Exposure is Linked to Epigenetic Changes in Glutamate Receptor Subunit Gene Grin2b in Female Rats and Humans

Abstract

Bisphenol A (BPA) exposure has been linked to neurodevelopmental disorders and to effects on epigenetic regulation, such as DNA methylation, at genes involved in brain function. High doses of BPA have been shown to change expression and regulation of one such gene, Grin2b, in mice. Yet, if such changes occur at relevant doses in animals and humans has not been addressed. We investigated if low-dose developmental BPA exposure affects DNA methylation and expression of Grin2b in brains of adult rats. Furthermore, we assessed associations between prenatal BPA exposure and Grin2b methylation in 7-year old children. We found that Grin2b mRNA expression was increased and DNA methylation decreased in female, but not in male rats. In humans, prenatal BPA exposure was associated with increased methylation levels in girls. Additionally, low APGAR scores, a predictor for increased risk for neurodevelopmental diseases, were associated with higher Grin2b methylation levels in girls. Thus, we could link developmental BPA exposure and low APGAR scores to changes in the epigenetic regulation of Grin2b, a gene important for neuronal function, in a sexual dimorphic fashion. Discrepancies in exact locations and directions of the DNA methylation change might reflect differences between species, analysed tissues, exposure level and/or timing.

Contributors

Joëlle Rüegg:

ORCID: http://orcid.org/0000-0002-6580-9201

[e-mail]

Journal

Journal ID (nlm-ta): Sci Rep

Journal ID (iso-abbrev): Sci Rep

Title: Scientific Reports

Publisher: Nature Publishing Group UK (London )

ISSN (Electronic): 2045-2322

Publication date (Electronic): 27 July 2018

Publication date PMC-release: 27 July 2018

Publication date Collection: 2018

Volume: 8

Affiliations

[1 ]Swetox, Karolinska Institutet, Unit of Toxicology Sciences, Forskargatan 20, 151 36 Södertälje, Sweden

[2 ]Karolinska Institutet, Department of Clinical Neuroscience, Centre for Molecular Medicine (CMM), 171 64 Solna, Sweden

[3 ]Karlstad University, Department of Health Sciences, 651 88 Karlstad, Sweden

[4 ]Uppsala University, Department of Medical Sciences, Occupational and Environmental Medicine, 751 85 Uppsala, Sweden

[5 ]ISNI 0000 0001 0930 2361, GRID grid.4514.4, Lund University, Division of Occupational and Environmental Medicine, , Lund University, ; 221 85 Lund, Sweden

[6 ]ISNI 0000 0001 0670 2351, GRID grid.59734.3c, Icahn School of Medicine at Mount Sinai, ; New York, NY USA

Article

Publisher ID: 29732

DOI: 10.1038/s41598-018-29732-9

PMC ID: 6063959

PubMed ID: 30054528

Copyright statement: © The Author(s) 2018

License:

Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.

Funding

Funded by: FundRef https://doi.org/10.13039/501100001862, Svenska Forskningsrådet Formas (Swedish Research Council Formas);

Award ID: 216-2013-1966

Award ID: 216-2012-475

Award ID: 216-2013-1966

Award ID: 216-2013-1966

Award Recipient : Ali Alavian-Ghavanini Ping-I Lin Sabina Risén Rimfors Mandy Tang

Funded by: FundRef https://doi.org/10.13039/501100007601, EC | Horizon 2020 (European Union Framework Programme for Research and Innovation);

Award ID: 634880

Award ID: 634880

Award Recipient : Ping-I Lin Carl-Gustaf Bornehag

Categories

Subject: Article

Custom metadata

issue-copyright-statement © The Author(s) 2018