Abstract
The epigenome of an individual can be altered by endogenous hormones, environment, age, diet, and exposure to endocrine disrupting chemicals (EDCs), and the effects of these modifications can be seen across generations. Epigenetic modifications to the genome can alter the phenotype of the individual without altering the DNA sequence itself. Epigenetic modifications include DNA methylation, histone modification, and aberrant microRNA (miRNA) expression; they begin during germ cell development and embryogenesis and continue until death. Hormone modulation occurs during the ageing process due to epigenetic modifications. Maternal overnutrition or undernutrition can affect the epigenome of the fetus, and the effects can be seen throughout life. Furthermore, maternal care during the childhood of the offspring can lead to different phenotypes seen in adulthood. Diseases controlled by the endocrine system, such as obesity and diabetes, as well as infertility in females can be associated with epigenetic changes. Not only can these phenotypes be seen in F1, but also some chemical effects can be passed through the germline and have effects transgenerationally, and the phenotypes are seen in F3. The following literature review expands upon these topics and discusses the state of the science related to epigenetic effects of age, diet, and EDCs on the endocrine system.
Highlights
Epigenetic reprogramming occurs during germ cell development and embryogenesis, and epigenetic modifications influence the expression of genes, creating phenotypic expression, without changing the genetic sequence [1]
Heijmans et al [53] studied whether periconceptional exposure to famine during the early stages of development is associated with differences in Insulin-like growth factor 2 (IGF2) differentially methylated regions (DMR) in adults
Endocrine Disrupting Compounds (EDCs) can act on sex-steroid hormone receptors, so during critical developmental periods if the fetus is exposed to EDCs, remethylation could occur within the germ cells, and these effects can be observed in subsequent generations [64]
Summary
Epigenetic reprogramming occurs during germ cell development and embryogenesis, and epigenetic modifications influence the expression of genes, creating phenotypic expression, without changing the genetic sequence [1]. There are three known epigenetic mechanisms of endocrine disruption: DNA methylation, histone modification, and aberrant miRNA expression. Increasing CORT in the CeA induced H3K9 deacetylation and inhibited histone deacetylases in the CeA and reduced anxiety-like behavior [21] Ovarian functions such as folliculogenesis, oocyte maturation, ovulation, and luteal function are controlled by microRNA (miRNA) signalling [12]. Maternal behavior produces stable alterations in DNA methylation and chromatin structure which affects the gene expression in offspring [29]. Differences in the genomic distribution of 5-methylcytosine DNA and histone acetylation play a role in gene expression in monozygous twins [32]. Environmental factors that affect expression of various genes include exposure to TCDD, maternal behavior to the offspring, stress during childhood, and placental exposure to metals and metalloids. Expression of growth imprinting genes H19 and Igf, GR, NR3C1, and 11β-HSD2
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