Aging, Environment, & DiseaseDNA Methylation and HydroxymethylationHistone Modifications

Put down that water bottle! BPA Exposure Alters Epigenetic Profile in Neurons

shutterstock_97971080Bisphenol A (BPA) is an industrial chemical that is present in many consumer products, including plastic bottles and other food and beverage containers.  Although BPA has been used routinely since the 1960s, exposure to BPA has recently gained a lot of attention due to its proposed effect on brain development. Previous studies have reported that environmental exposure to BPA likely has a significant impact on childhood behavior and learning development.  Additionally, BPA is known to epigenetically affect the developing nervous system; however, the molecular mechanisms are not well understood. Liedtke’s group from Duke University recently reported that BPA exposure can delay the perinatal chloride shift in cortical neurons, which is a critical step in neuron development, through epigenetic regulation of potassium chloride cotransporter 2 (Kcc2) gene expression – providing a molecular link between BPA and neurological disorders.

KCC2 plays a critical role during brain development by maintaining low intracellular chloride levels through chloride extrusion from mature neurons. The authors showed that BPA exposure down-regulated Kcc2 expression in both human and rat cortical neurons. This effect was sexually dimorphic because BPA-mediated decrease of Kcc2 expression was greater in female neurons than in male neurons.  Additionally, BPA exposure also increased chloride concentration within neurons, which delayed the perinatal chloride shift, and thus delayed neuron maturation.  Increased migration of interneurons was also visualized in BPA-exposed cells. Using chromatin immunoprecipitation (ChIP) assays, the authors discovered that BPA exposure led to increased binding of the repressor protein MECP2 at the Kcc2 promoter.  They also observed decreased binding of a euchromatin marker, histone H3 acetylated on lysine 9, to the Kcc2 promoter following BPA exposure.  Treatment with the HDAC inhibitor Trichostatin A and siRNA-mediated silencing of HDACs both partially rescued the repressive effects of BPA on Kcc2 expression, suggesting a role for histone modifications in regulating Kcc2 expression.

To better understand the effects of in utero BPA exposure on brain development, the authors analyzed the Kcc2 promoter activity in BPA-fed mice. Kcc2 promoter activity in pups decreased after in utero BPA exposure and treatment with the DNA methyltransferase inhibitor decitabine partially rescued the BPA effect, further suggesting that epigenetic profiles are altered following BPA exposure.

Taken together, these findings strongly suggest that alterations in epigenetic mechanisms, such as histone modifications and DNA methylation, play significant roles in the BPA-induced effects on brain development. What are your thoughts? Do you try to minimize BPA exposure? Do you believe in and trust current BPA-free products on the market?

 

Yeo M, Berglund K, Hanna M, Guo JU, Kittur J, Torres MD, Abramowitz J, Busciglio J, Gao Y, Birnbaumer L, & Liedtke WB (2013). Bisphenol A delays the perinatal chloride shift in cortical neurons by epigenetic effects on the Kcc2 promoter. Proceedings of the National Academy of Sciences of the United States of America, 110 (11), 4315-20 PMID: 23440186

http://www.ncbi.nlm.nih.gov/pubmed/23440186

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Yap C.C., Ph.D

Yap C.C., Ph.D

Yap gained her degrees in Midwest, found her first job in East Coast and finally settled down in West Coast. Yap enjoys travel and her next travel destination is Europe.

  • Christine

    Interesting article! Did the authors comment on how long the observed BPA-induced epigenetic changes were maintained following removal of BPA exposure? If these are long-term changes, it seems like avoiding BPA products now is almost futile considering that most of us probably had a lot of exposure prior to the correlation between BPA and adverse effects (that said, I’d still avoid it if possible!). Also, is it known whether any of these changes are heritable?

    • Hi Christine! Thanks for your questions and comments. The authors did not investigate how stable the BPA-induced epigenetic changes were. Epigenetic changes that we acquire during our lives can potentially be passed on to future generations, but it is not yet known whether the changes seen following BPA exposure are inherited. The epigenetic changes seen in the pups were the result of BPA treatment in utero, suggesting that avoiding BPA while pregnant could be important for proper brain development.