Endocrine disrupters: the new players able to affect the epigenome

Abstract

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.

Passing experiences on to future generations: endocrine disruptors and transgenerational inheritance of epimutations in brain and sperm

“…The mechanism by which EDCs interact with and alter the epigenome is not currently known, although there is ample evidence to show epigenetic alterations in F1 individuals or in cell lines exposed to phthalates [48], parabens [49], diethylstilbestrol [50,51], and PCBs [52]. A particularly compelling theory [53] is that nuclear steroid hormone receptors, with which many EDCs interact either directly or indirectly, may be the point of convergence between EDCs and the epigenome. Interestingly, Casati et al, (2015) provided evidence that PCBs initiate downstream transcription of androgen sensitive genes via a histone demethylase, Jarid1b, that interacts with the androgen receptor [54].…”

Embryonic atrazine exposure alters zebrafish and human miRNAs associated with angiogenesis, cancer, and neurodevelopment

“…Investigating the effects of EDCs on epigenetics and in particular, miRNAs, is beginning to come into view in order to define mechanisms of toxic action (Casati et al, 2015; Hsu et al, 2009; Tilghman et al, 2012). To date, no studies have been completed examining the effects of atrazine on miRNA expression.…”

Interaction between prenatal pesticide exposure and a common polymorphism in the PON1 gene on DNA methylation in genes associated with cardio-metabolic disease risk—an exploratory study

“…Furthermore, during fetal development extensive de- and re-methylation events are taking place making this period highly vulnerable for epigenetic changes caused by environmental conditions [25]. Indeed, emerging evidence in experimental animals and in humans associate altered DNA methylation patterns with a variety of prenatal exposures including dietary factors, parental care, infections, smoking, and environmental pollutants [26–31]. In experimental animals, early life changes in DNA methylation have been associated with diet-induced obesity and insulin resistance [32].…”