TY - JOUR
T1 - Transgenerational neuroendocrine disruption of reproduction
AU - Walker, Deena M.
AU - Gore, Andrea C.
N1 - Funding Information:
We are grateful to David Crews for helpful discussions and comments on this manuscript. Belinda Lehmkuhle provided expert assistance with the figures. Work described in this article was supported by NIH 1RC1 ES018139.
PY - 2011/4
Y1 - 2011/4
N2 - Exposure to endocrine disrupting chemicals (EDCs) is associated with dysfunctions of metabolism, energy balance, thyroid function and reproduction, and an increased risk of endocrine cancers. These multifactorial disorders can be 'programmed' through molecular epigenetic changes induced by exposure to EDCs early in life, the expression of which may not manifest until adulthood. In some cases, EDCs have detrimental effects on subsequent generations, which indicates that traits for disease predisposition may be passed to future generations by nongenomic inheritance. This Review discusses current understanding of the epigenetic mechanisms that underlie sexual differentiation of reproductive neuroendocrine systems in mammals and summarizes the literature on transgenerational epigenetic effects of representative EDCs: vinclozolin, diethylstilbesterol, bisphenol A and polychlorinated biphenyls. The article differentiates between context-dependent epigenetic transgenerational changes-namely, those that require environmental exposure, either via the EDC itself or through behavioral or physiological differences in parents-and germline-dependent epigenetic mechanisms. These processes, albeit discrete, are not mutually exclusive and can involve similar molecular mechanisms including DNA methylation and histone modifications and may predispose exposed individuals to transgenerational disruption of reproductive processes. New insights stress the crucial need to develop a clear understanding of how EDCs may program the epigenome of exposed individuals and their descendants.
AB - Exposure to endocrine disrupting chemicals (EDCs) is associated with dysfunctions of metabolism, energy balance, thyroid function and reproduction, and an increased risk of endocrine cancers. These multifactorial disorders can be 'programmed' through molecular epigenetic changes induced by exposure to EDCs early in life, the expression of which may not manifest until adulthood. In some cases, EDCs have detrimental effects on subsequent generations, which indicates that traits for disease predisposition may be passed to future generations by nongenomic inheritance. This Review discusses current understanding of the epigenetic mechanisms that underlie sexual differentiation of reproductive neuroendocrine systems in mammals and summarizes the literature on transgenerational epigenetic effects of representative EDCs: vinclozolin, diethylstilbesterol, bisphenol A and polychlorinated biphenyls. The article differentiates between context-dependent epigenetic transgenerational changes-namely, those that require environmental exposure, either via the EDC itself or through behavioral or physiological differences in parents-and germline-dependent epigenetic mechanisms. These processes, albeit discrete, are not mutually exclusive and can involve similar molecular mechanisms including DNA methylation and histone modifications and may predispose exposed individuals to transgenerational disruption of reproductive processes. New insights stress the crucial need to develop a clear understanding of how EDCs may program the epigenome of exposed individuals and their descendants.
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U2 - 10.1038/nrendo.2010.215
DO - 10.1038/nrendo.2010.215
M3 - Review article
C2 - 21263448
AN - SCOPUS:79953075510
SN - 1759-5029
VL - 7
SP - 197
EP - 207
JO - Nature Reviews Endocrinology
JF - Nature Reviews Endocrinology
IS - 4
ER -