Epigenetic Transgenerational Inheritance of the Effects of Obesogen Exposure

Frontiers in Endocrinology

Toshi Shioda¹  Bruce Blumberg²  Erika M. Joloya³  Jeongbin Seo³  Nicole Mohajer⁴ 

[1] Center for Cancer Research, Massachusetts General Hospital, Charlestown, MA, United States;Department of Biomedical Engineering, University of California, Irvine, CA, United States;Department of Developmental and Cell Biology, University of California, Irvine, CA, United States;Department of Pharmaceutical Sciences, University of California, Irvine, CA, United States;

关键词: epigenetics;    transgenerational;    obesogen;    endocrine disrupting chemicals;    transgenerational inheritance;    obesity;   

DOI  :  10.3389/fendo.2021.787580

来源: DOAJ

【 摘 要 】

Obesity and metabolic disorders have become a worldwide pandemic affecting millions of people. Although obesity is a multifaceted disease, there is growing evidence supporting the obesogen hypothesis, which proposes that exposure to a subset of endocrine disrupting chemicals (EDCs), known as obesogens, promotes obesity. While these effects can be observed in vitro using cell models, in vivo and human epidemiological studies have strengthened this hypothesis. Evidence from animal models showed that the effects of obesogen exposure can be inherited transgenerationally through at least the F4 generation. Transgenerational effects of EDC exposure predispose future generations to undesirable phenotypic traits and diseases, including obesity and related metabolic disorders. The exact mechanisms through which phenotypic traits are passed from an exposed organism to their offspring, without altering the primary DNA sequence, remain largely unknown. Recent research has provided strong evidence suggesting that a variety of epigenetic mechanisms may underlie transgenerational inheritance. These include differential DNA methylation, histone methylation, histone retention, the expression and/or deposition of non-coding RNAs and large-scale alterations in chromatin structure and organization. This review highlights the most recent advances in the field of epigenetics with respect to the transgenerational effects of environmental obesogens. We highlight throughout the paper the strengths and weaknesses of the evidence for proposed mechanisms underlying transgenerational inheritance and why none of these is sufficient to fully explain the phenomenon. We propose that changes in higher order chromatin organization and structure may be a plausible explanation for how some disease predispositions are heritable through multiple generations, including those that were not exposed. A solid understanding of these possible mechanisms is essential to fully understanding how environmental exposures can lead to inherited susceptibility to diseases such as obesity.

【 授权许可】

Unknown