Epigenetics, Evolution, Endocrine Disruption, Health, and Disease (original) (raw)
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Epigenetic Transgenerational Actions of Endocrine Disruptors
Endocrinology, 2006
Environmental factors have a significant impact on biology. Therefore, environmental toxicants through similar mechanisms can modulate biological systems to influence physiology and promote disease states. The majority of environmental toxicants do not have the capacity to modulate DNA sequence, but can alter the epigenome. In the event an environmental toxicant such as an endocrine disruptor modifies the epigenome of a somatic cell, this may promote disease in the individual exposed, but not be transmitted to the next generation. In the event a toxicant modifies the epigenome of the germ line permanently, then the disease promoted can become transgenerationaly transmitted to subsequent progeny. The current review focuses on the ability of environmental factors such as endocrine disruptors to promote transgenerational phenotypes.
Transgenerational epigenetic actions of environmental compounds
Endocrine disrupting chemicals are known for their capacity to alter development and reproduction in mammals. One of the periods most sensitive to endocrine disruptor exposure is embryonic gonadal sex determination, when the germ line is undergoing epigenetic programming and DNA re-methylation. Epigenetic changes derived from exposure to endocrine disruptors have been described in several tissues and organisms. Endocrine disruptor induced epigenetic changes may have a wide range of phenotypic consequences, leading to disease conditions such as cancers, reproductive defects and obesity. Interestingly, the incidence of some diseases resulting from exposure to endocrine disruptors can be transgenerationally transmitted. In particular, exposure to the endocrine disruptor vinclozolin during early development is capable of inducing adult onset disease states that can be perpetuated across multiple generations. Environmental compounds such as endocrine disruptors can produce changes in the genome without altering DNA sequence. These changes are epigenetic in basis and can produce phenotypes that perpetuate transgenerationally. The suggestion that environmental factors can reprogram early development to induce epigenetic transgenerational phenotypes is a new paradigm in biology that will open new avenues for studies in disease etiology, reproduction and evolutionary biology.
Environmental Toxicology and Pharmacology, 2017
Environmental Epigenomics is a developing field to study the epigenetic effect on human health from exposure to environmental factors. Endocrine disrupting chemicals have been detected primarily in pharmaceutical drugs, personal care products, food additives, and food containers. Exposure to endocrine-disrupting chemicals (EDCs) has been associated with a high incidence and prevalence of many endocrine-related disorders in humans. Nevertheless, further evidence is needed to establish a correlation between exposure to EDC and human disorders. Conventional detection of EDCs is based on chemical structure and concentration sample analysis. However, substantial evidence has emerged, suggesting that cell exposure to EDCs leads to epigenetic changes, independently of its chemical structure with nonmonotonic low-dose responses. Consequently, a paradigm shift in toxicology assessment of EDCs is proposed based on a comprehensive review of analytical techniques used to evaluate the epigenetic effects. Fundamental insights reported elsewhere are compared in order to establish DNA methylation analysis as a viable method for assessing endocrine disruptors beyond the conventional study approach of chemical structure and concentration analysis.
Endocrine disrupters: the new players able to affect the epigenome
Frontiers in Cell and Developmental Biology, 2015
Epigenetics represents the way by which the environment is able to program the genome; there are three main levels of epigenetic control on genome: DNA methylation, post-translational histone modification and microRNA expression. The term Epigenetics has been widened by NIH to include "both heritable changes in gene activity and expression but also stable, long-term alterations in the transcriptional potential of a cell that are not necessarily heritable." These changes might be produced mostly by the early life environment and might affect health influencing the susceptibility to develop diseases, from cancer to mental disorder, during the entire life span. The most studied environmental influences acting on epigenome are diet, infections, wasting, child care, smoking and environmental pollutants, in particular endocrine disrupters (EDs). These are environmental xenobiotics able to interfere with the normal development of the male and female reproductive systems of wildlife, of experimental animals and possibly of humans, disrupting the normal reproductive functions. Data from literature indicate that EDs can act at different levels of epigenetic control, in some cases transgenerationally, in particular when the exposure to these compounds occurs during the prenatal and earliest period of life. Some of the best characterized EDs will be considered in this review. Among the EDs, vinclozolin (VZ), and methoxychlor (MXC) promote epigenetic transgenerational effects. Polychlorinated biphenils (PCBs), the most widespread environmental EDs, affect histone post-translational modifications in a dimorphic way, possibly as the result of an alteration of gene expression of the enzymes involved in histone modification, as the demethylase Jarid1b, an enzyme also involved in regulating the interaction of androgens with their receptor.
PLoS ONE, 2012
Environmental factors during fetal development can induce a permanent epigenetic change in the germ line (sperm) that then transmits epigenetic transgenerational inheritance of adult-onset disease in the absence of any subsequent exposure. The epigenetic transgenerational actions of various environmental compounds and relevant mixtures were investigated with the use of a pesticide mixture (permethrin and insect repellant DEET), a plastic mixture (bisphenol A and phthalates), dioxin (TCDD) and a hydrocarbon mixture (jet fuel, JP8). After transient exposure of F0 gestating female rats during the period of embryonic gonadal sex determination, the subsequent F1-F3 generations were obtained in the absence of any environmental exposure. The effects on the F1, F2 and F3 generations pubertal onset and gonadal function were assessed. The plastics, dioxin and jet fuel were found to promote early-onset female puberty transgenerationally (F3 generation). Spermatogenic cell apoptosis was affected transgenerationally. Ovarian primordial follicle pool size was significantly decreased with all treatments transgenerationally. Differential DNA methylation of the F3 generation sperm promoter epigenome was examined. Differential DNA methylation regions (DMR) were identified in the sperm of all exposure lineage males and found to be consistent within a specific exposure lineage, but different between the exposures. Several genomic features of the DMR, such as low density CpG content, were identified. Exposure-specific epigenetic biomarkers were identified that may allow for the assessment of ancestral environmental exposures associated with adult onset disease.
Impact of Endocrine Disruptors upon Non-Genetic Inheritance
International Journal of Molecular Sciences, 2022
Similar to environmental factors, EDCs (endocrine-disrupting chemicals) can influence gene expression without modifying the DNA sequence. It is commonly accepted that the transgenerational inheritance of parentally acquired traits is conveyed by epigenetic alterations also known as “epimutations”. DNA methylation, acetylation, histone modification, RNA-mediated effects and extracellular vesicle effects are the mechanisms that have been described so far to be responsible for these epimutations. They may lead to the transgenerational inheritance of diverse phenotypes in the progeny when they occur in the germ cells of an affected individual. While EDC-induced health effects have dramatically increased over the past decade, limited effects on sperm epigenetics have been described. However, there has been a gain of interest in this issue in recent years. The gametes (sperm and oocyte) represent targets for EDCs and thus a route for environmentally induced changes over several generation...
Journal of Neuroendocrinology, 2014
Oestrogens play an important role in development and function of the brain and reproductive tract. Accordingly, it is considered that developmental exposure to environmental oestrogens can disrupt neural and reproductive tract development, potentially resulting in long‐term alterations in neurobehaviour and reproductive function. Many chemicals have been shown to have oestrogenic activity, whereas others affect oestrogen production and turnover, resulting in the disruption of oestrogen signalling pathways. However, these mechanisms and the concentrations required to induce these effects cannot account for the myriad adverse effects of environmental toxicants on oestrogen‐sensitive target tissues. Hence, alternative mechanisms are assumed to underlie the adverse effects documented in experimental animal models and thus could be important to human health. In this review, the epigenetic regulation of gene expression is explored as a potential target of environmental toxicants including...
The Role of Environmental Exposures and the Epigenome in Health and Disease
Environmental and Molecular Mutagenesis
The genetic material of every organism exists within the context of regulatory networks that govern gene expression, collectively called the epigenome. Epigenetics has taken center stage in the study of diseases such as cancer and diabetes, but its integration into the field of environmental health is still emerging. As the Environmental Mutagenesis and Genomics Society (EMGS) celebrates its 50th Anniversary this year, we have come together to review and summarize the seminal advances in the field of environmental epigenomics. Specifically, we focus on the role epigenetics may play in multigenerational and transgenerational transmission of environmentally induced health effects. We also summarize state of the art techniques for evaluating the epigenome, environmental epigenetic analysis, and the emerging field of epigenome editing. Finally, we evaluate transposon epigenetics as they relate to environmental exposures and explore the role of noncoding RNA as biomarkers of environmental exposures. Although the field has advanced over the past several decades, including being recognized by EMGS with its own Special Interest Group, recently renamed Epigenomics, we are excited about the opportunities for environmental epigenetic science in the next 50 years.
Epigenetic transgenerational actions of environmental factors in disease etiology
Trends in Endocrinology & Metabolism, 2010
The ability of environmental factors to promote a phenotype or disease state not only in the individual exposed but also in subsequent progeny for multiple generations is termed transgenerational inheritance. The majority of environmental factors such as nutrition or toxicants such as endocrine disruptors do not promote genetic mutations or alterations in DNA sequence. In contrast, these factors have the capacity to alter the epigenome. Epimutations in the germ line that become permanently programmed can allow transmission of epigenetic transgenerational phenotypes. This review provides an overview of the epigenetics and biology of how environmental factors can promote transgenerational phenotypes and disease.