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Prenatal Bisphenol A Exposure is Linked to Epigenetic Changes in Glutamate Receptor Subunit Gene Grin2b in Female Rats and Humans
Karolinska Inst, Unit Toxicol Sci, Swetox, Forskargatan 20, S-15136 Sodertalje, Sweden;Karolinska Inst, Dept Clin Neurosci, CMM, S-17164 Solna, Sweden.
Karlstad Univ, Dept Hlth Sci, S-65188 Karlstad, Sweden.
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Occupational and Environmental Medicine.ORCID iD: 0000-0002-8949-3555
Karolinska Inst, Unit Toxicol Sci, Swetox, Forskargatan 20, S-15136 Sodertalje, Sweden.
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2018 (English)In: Scientific Reports, ISSN 2045-2322, E-ISSN 2045-2322, Vol. 8, article id 11315Article in journal (Refereed) Published
Abstract [en]

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, Iow 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 Iow 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.

Place, publisher, year, edition, pages
2018. Vol. 8, article id 11315
National Category
Pharmacology and Toxicology
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URN: urn:nbn:se:uu:diva-361996DOI: 10.1038/s41598-018-29732-9ISI: 000439965200008PubMedID: 30054528OAI: oai:DiVA.org:uu-361996DiVA, id: diva2:1253949
Funder
EU, Horizon 2020, 634880Swedish Research Council, 216-2012-475Swedish Research Council, 210-2012-1502Swedish Research Council, 216-2013-1966Available from: 2018-10-08 Created: 2018-10-08 Last updated: 2018-10-08Bibliographically approved

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Lind, P. MonicaLejonklou, Margareta HalinDunder, Linda

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