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

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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.

Detaljer

Författare
  • Ali Alavian-Ghavanini
  • Ping I. Lin
  • P. Monica Lind
  • Sabina Risén Rimfors
  • Margareta Halin Lejonklou
  • Linda Dunder
  • Mandy Tang
  • Christian Lindh
  • Carl Gustaf Bornehag
  • Joëlle Rüegg
Enheter & grupper
Externa organisationer
  • Karolinska Institute
  • Karlstad University
  • Uppsala universitet, Historiska institutionen
  • Icahn School of Medicine at Mount Sinai
Forskningsområden

Ämnesklassifikation (UKÄ) – OBLIGATORISK

  • Farmakologi och toxikologi
Originalspråkengelska
Artikelnummer11315
TidskriftScientific Reports
Volym8
Utgåva nummer1
StatusPublished - 2018 jul 27
PublikationskategoriForskning
Peer review utfördJa