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

Alavian-Ghavanini, Ali ; Lin, Ping I. ; Lind, P. Monica ; Risén Rimfors, Sabina ; Halin Lejonklou, Margareta ; Dunder, Linda ; Tang, Mandy ; Lindh, Christian LU orcid ; Bornehag, Carl Gustaf LU and Rüegg, Joëlle (2018) In Scientific Reports 8(1).
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,... (More)

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.

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organization
publishing date
type
Contribution to journal
publication status
published
subject
in
Scientific Reports
volume
8
issue
1
article number
11315
publisher
Nature Publishing Group
external identifiers
  • scopus:85050804534
  • pmid:30054528
ISSN
2045-2322
DOI
10.1038/s41598-018-29732-9
language
English
LU publication?
yes
id
599ddc23-8e31-4f16-a7a1-0828fd897b25
date added to LUP
2018-08-15 15:19:54
date last changed
2024-06-11 18:46:14
@article{599ddc23-8e31-4f16-a7a1-0828fd897b25,
  abstract     = {{<p>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.</p>}},
  author       = {{Alavian-Ghavanini, Ali and Lin, Ping I. and Lind, P. Monica and Risén Rimfors, Sabina and Halin Lejonklou, Margareta and Dunder, Linda and Tang, Mandy and Lindh, Christian and Bornehag, Carl Gustaf and Rüegg, Joëlle}},
  issn         = {{2045-2322}},
  language     = {{eng}},
  month        = {{07}},
  number       = {{1}},
  publisher    = {{Nature Publishing Group}},
  series       = {{Scientific Reports}},
  title        = {{Prenatal Bisphenol A Exposure is Linked to Epigenetic Changes in Glutamate Receptor Subunit Gene Grin2b in Female Rats and Humans}},
  url          = {{http://dx.doi.org/10.1038/s41598-018-29732-9}},
  doi          = {{10.1038/s41598-018-29732-9}},
  volume       = {{8}},
  year         = {{2018}},
}