ReviewPrenatal environmental exposures, epigenetics, and disease
Introduction
Following a brief summary of the role of epigenetics in early development and disease, this review focuses on the evidence that the prenatal/fetal period is highly susceptible to epigenomic dysregulation with implications for health, both lifelong and transgenerationally. We then offer examples of developmental exposure to various environmental pollutants shown to induce epigenetic changes and neurodevelopmental deficits and diseases. Interactions between toxic and environmental exposures and genetic, nutritional and social factors that can exacerbate effects are then described. Finally, two case studies are provided to illustrate the strengths and limitations of available epigenetic data and the potential of using epigenetic markers to forge causal links between toxic environmental exposures and neurodevelopmental outcomes. In this section, we summarize evidence that epigenetic alterations in endocrine and immune pathways are directly involved in the adverse neurodevelopmental effects associated with in utero exposure to the two classic endocrine disruptors, polycyclic aromatic hydrocarbons (PAHs) and bisphenol A (BPA).
Section snippets
The role of epigenetics in early development and disease: the prenatal/fetal window of susceptibility
Epigenetics is the study of heritable changes in gene expression or phenotype occurring without changes in DNA sequence [1]. For general reviews, see [2], [3], [4]. The genetic information in DNA has been likened to the notes of an orchestral score and epigenetics to the conductor who interprets the score and controls the dynamics of the symphonic performance [5]. While new epigenetic mechanisms are being uncovered, the best characterized are DNA methylation, changes in histone proteins around
Prenatal exposure to environmental pollutants, related health effects, and epigenetic dysregulation
As reviewed by Baccarelli and Bollati [57], studies in adults have demonstrated epigenetic changes related to environmental exposure to metals, air pollution, benzene and persistent organic pollutants. For example, in a study of adult coke oven workers and controls, global and IL-6 hypermethylation and p53 hypomethylation were associated with PAH exposure [58]. In workers exposed to the leukemogen, benzene, epigenomic data showed effects of benzene on DNA methylation of a number of specific
Case studies: a proposed epigenetic mechanism for the neurodevelopmental effects of in utero exposure to PAHs and BPA
The prior section has reviewed the evidence that diverse prenatal environmental exposures increase risk of various diseases in the offspring and in some cases their grandchildren, that they also alter the epigenome, and that epigenetic dysregulation may mediate their adverse health effects. In contrast, in the following section we present two case studies in which we propose that epigenetic alterations in endocrine and immune pathways are directly involved in the neurodevelopmental effects
Transgenerational effects of prenatal exposures
As we have seen, the role of prenatally acquired somatic epigenetic alterations in disease has been quite widely studied, mostly in experimental models. Less well characterized are epigenetic events that are inherited through the germline from parent to child and transmitted to subsequent generations [181].
There is growing evidence that environmental variations experienced by both fathers and mothers may lead to phenotypic variation in the development and behavior of offspring resulting from
Emerging evidence that nutritional, genetic and psychosocial factors may influence DNA methylation by environmental toxicants
Experimental animal studies have shown that the epigenetic reprogramming by behavioral factors is reversible by nutritional factors. For example, Weaver and colleagues showed that the programming of the GR exon 1 promoter associated with low grooming maternal care, as well as the resulting stress response and behavioral phenotypes, were reversible by administration of a methyl donor precursor or a histone deacetylase (HDAC) inhibitor [189]. Other investigators have shown that the effects of
Implications for prevention of childhood, adult and multigenerational disease: conclusions
Most of the research to date has focused on the critical role of epigenetics in mediating the effects of social experience and nutrition [197], [198]. However, there is also compelling human and experimental evidence that prenatal environmental exposures to endocrine disruptors and other environmental xenobiotics, acting alone or in combination with genetic, nutritional, or psychosocial factors, adversely affect human development and health in childhood and possibly over the lifecourse, and
Conflict of interest statement
The authors have no conflicts of interest.
Acknowledgments
The Center's research is supported by NIEHS, US EPA, and several private foundations and donors including 5PO1ES009600 NIEHS; RD834509 EPA; and 1 P50 ES015905 NIEHS.
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