Is Environmental Epigenetics Relevant to Endocrine Disease?
Endocrine disrupting chemicals that are structurally similar to steroid or amine hormones have the potential to mimic endocrine endpoints at the receptor level. Endocrine disrupting chemicals may dysregulate hormone-mediated gene expression through changes in signal transduction and through epigenetic changes. However, epigenetic-induced alteration in gene expression may occur outside of receptor-mediated effects and has emerged as an alternative way in which environmental compounds may exert endocrine effects. We discuss general implications of DNA methylation, histone modification, micro RNAs, and other more recently recognized epigenetic modifications for endocrinology, and we discuss potential for transgenerational inheritance of epigenetic marks. We also review concepts related to environmental epigenetics and relevance for endocrinology through three broad examples, (1) effect of prenatal and early-life under- and overnutrition on future metabolic disease, (2) effect of lifetime environmental exposures such as ionizing radiation on endocrine cancer risk, and (3) potential for compounds previously classified as endocrine disrupting to additionally or alternatively exert effects through epigenetic mechanisms. The field of environmental epigenetics is still nascent, and additional studies are needed to confirm and reinforce data derived from animal models and preliminary human studies. Current evidence suggests that environmental exposures may significantly impact expression of endocrine-related genes and thereby affect clinical endocrine outcomes.
KeywordsDiethylstilbestrol (DES) Toxic Substances Control Act (TSCA) DNA methyltransferase (DNMT) Methyl binding proteins (MBPs) Cytosine-phosphate-guanine (CpG) Histone deacetylases (HDACs) High fat diet (HFD) Bisphenol A (BPA)
Declaration of Interest
The authors declare that there is no conflict of interest that could be perceived as prejudicing the impartiality of the research reported.
The authors have received support from the following grants from the US National Institutes of Health: P30ES000002, R21ES019773, R21ES020010, R01ES020268, R01ES013744, R01ES014930, R01ES021357, P42ES016454, and K12 DK094721-02; from the Agency of Healthcare Research and Quality: T32 HS00063; and from Harvard School of Public Health.
- Bennett KL, Lee W, Lamarre E, Zhang X, Seth R, Scharpf J et al (2010) HPV status-independent association of alcohol and tobacco exposure or prior radiation therapy with promoter methylation of FUSSEL18, EBF3, IRX1, and SEPT9, but not SLC5A8, in head and neck squamous cell carcinomas. Genes Chromosomes Cancer 49:319–326PubMedGoogle Scholar
- Boeke CE, Baccarelli A, Kleinman KP, Burris HH, Litonjua AA, Rifas-Shiman SL et al (2012) Gestational intake of methyl donors and global LINE-1 DNA methylation in maternal and cord blood: prospective results from a folate-replete population. Epigenetics 7:253–260CrossRefPubMedCentralPubMedGoogle Scholar
- Burdge GC, Slater-Jefferies J, Torrens C, Phillips ES, Hanson MA, Lillycrop KA (2007) Dietary protein restriction of pregnant rats in the F0 generation induces altered methylation of hepatic gene promoters in the adult male offspring in the F1 and F2 generations. Br J Nutr 97:435–439CrossRefPubMedCentralPubMedGoogle Scholar
- Caudill CM, Zhu Z, Ciampi R, Stringer JR, Nikiforov YE (2005) Dose-dependent generation of RET/PTC in human thyroid cells after in vitro exposure to gamma-radiation: a model of carcinogenic chromosomal rearrangement induced by ionizing radiation. J Clin Endocrinol Metab 90:2364–2369CrossRefPubMedGoogle Scholar
- Inawaka K, Kawabe M, Takahashi S, Doi Y, Tomigahara Y, Tarui H et al (2009) Maternal exposure to anti-androgenic compounds, vinclozolin, flutamide and procymidone, has no effects on spermatogenesis and DNA methylation in male rats of subsequent generations. Toxicol Appl Pharmacol 237:178–187CrossRefPubMedGoogle Scholar
- Sinclair KD, Allegrucci C, Singh R, Gardner DS, Sebastian S, Bispham J et al (2007) DNA methylation, insulin resistance, and blood pressure in offspring determined by maternal periconceptional B vitamin and methionine status. Proc Natl Acad Sci U S A 104:19351–19356CrossRefPubMedCentralPubMedGoogle Scholar
- Waddington C (1942) The epigenome. Endeavour 1:18–20Google Scholar