Abstract
The epigenetic effects on DNA methylation, histone modification, and expression of non-coding RNAs (including microRNAs) of environmental chemicals such as bisphenol A (BPA) and phthalates have expanded our understanding of the etiology of human complex diseases such as cancers and diabetes. Multiple lines of evidence from in vitro and in vivo models have established that epigenetic modifications caused by in utero exposure to environmental toxicants can induce alterations in gene expression that may persist throughout life. Epigenetics is an important mechanism in the ability of environmental chemicals to influence health and disease, and BPA and phthalates are epigenetically toxic. The epigenetic effect of BPA was clearly demonstrated in viable yellow mice by decreasing CpG methylation upstream of the Agouti gene, and the hypomethylating effect of BPA was prevented by maternal dietary supplementation with a methyl donor like folic acid or the phytoestrogen genistein. Histone H3 was found to be trimethylated at lysine 27 by BPA effect on EZH2 in a human breast cancer cell line and mice. BPA exposure of human placental cell lines has been shown to alter microRNA expression levels, and specifically, miR-146a was strongly induced by BPA treatment. In human breast cancer MCF7 cells, treatment with the phthalate BBP led to demethylation of estrogen receptor (ESR1) promoter-associated CpG islands, indicating that altered ESR1 mRNA expression by BBP is due to aberrant DNA methylation. Maternal exposure to phthalate DEHP was also shown to increase DNA methylation and expression levels of DNA methyltransferases in mouse testis. Further, some epigenetic effects of BPA and phthalates in female rats were found to be transgenerational. Finally, the available new technologies for global analysis of epigenetic alterations will provide insight into the extent and patterns of alterations between human normal and diseased tissues. In vitro models such as human embryonic stem cells may be extremely useful in bettering the understanding of epigenetic effects on human development, health and disease, because the formation of embryoid bodies in vitro is very similar to the early stage of embryogenesis.
Highlights
Plastics are widely used in modern life, and their unbound chemicals bisphenol A (BPA) and phthalates can leach out into the surrounding environment
It remains to be investigated if any bioaccumulation of epigenetic impacts can be reversed/eliminated after exposure to BPA and phthalates is discontinued
The differential DNA methylation was reported to be transgenerational after exposure of gestating female rats to mixture of BPA and phthalate, but the synergistic impact of both BPA and phthalate remain to be determined
Summary
Plastics are widely used in modern life, and their unbound chemicals bisphenol A (BPA) and phthalates can leach out into the surrounding environment. Multiple lines of evidences from in vitro and in vivo models have established that epigenetic modifications caused by in utero exposure to environmental toxicants can induce alterations in gene expression that may persist throughout life. In the last few years, many investigations have examined the relationships between exposure to environmental chemicals and epigenetic effects, and identified several toxicants that modify epigenetic marks Most of these studies conducted so far have focused on DNA methylation, whereas only a few recent investigations have studied the effects of environmental chemicals on histone modifications and expression of microRNAs [12]. We review the epigenetic effects, as well as toxicogenomics, toxicities and health effects, of environmental toxicants BPA and phthalates derived from in vitro models, animal and human studies
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