Epigenetics as a mechanism linking developmental exposures to long-term toxicity

被引：134

作者：

Barouki, R. ^{[1
,2
]}

Melen, E. ^{[3
,4
,5
]}

Herceg, Z. ^{[6
]}

Beckers, J. ^{[7
,8
,9
]}

Chen, J. ^{[10
]}

Karagas, M. ^{[11
]}

Puga, A. ^{[12
]}

Xia, Y. ^{[12
]}

Chadwick, L. ^{[13
]}

Yan, W. ^{[14
,15
]}

Audouze, K. ^{[16
]}

Slama, R. ^{[17
]}

Heindel, J. ^{[18
]}

Grandjean, P. ^{[19
,20
]}

Kawamoto, T. ^{[21
]}

Nohara, K. ^{[22
]}

机构：

[1] Univ Paris 05, INSERM UMR S 1124, Paris, France

[2] Hop Necker Enfants Malad, AP HP, Serv Biochim Metabol & Prote, Paris, France

[3] Karolinska Inst, Inst Environm Med, Stockholm, Sweden

[4] Stockholm Cty Council, Sachs Children & Youth Hosp, Stockholm, Sweden

[5] Stockholm Cty Council, Ctr Occupat & Environm Med, Stockholm, Sweden

[6] Int Agcy Res Canc, Epigenet Grp, 150 Cours Albert Thomas, F-69008 Lyon, France

[7] Helmholtz Zentrum Munchen GmbH, Inst Expt Genet, D-85764 Neuherberg, Germany

[8] Tech Univ Munich, Expt Genet, D-85354 Freising Weihenstephan, Germany

[9] German Ctr Diabet Res DZD, D-85764 Neuherberg, Germany

[10] Icahn Sch Med Mt Sinai, Dept Environm Med & Publ Hlth, New York, NY 10029 USA

[11] Childrens Environm Hlth & Dis Prevent Res Ctr Dar, Dept Epidemiol, Hanover, NH USA

[12] Univ Cincinnati, Coll Med, Dept Environm Hlth, Cincinnati, OH 45267 USA

[13] NIEHS, POB 12233, Res Triangle Pk, NC 27709 USA

[14] Univ Nevada, Dept Physiol & Cell Biol, Reno Sch Med, 1664 North Virginia St,MS575, Reno, NV 89557 USA

[15] Univ Nevada, Dept Biol, 1664 North Virginia St, Reno, NV 89557 USA

[16] Univ Paris Diderot, INSERM UMR S973, Mol Therapeut Sil, Paris, France

[17] Univ Grenoble Alpes, CNRS UMR 5309, Inst Adv Biosci, INSERM U1209, Grenoble, France

[18] Commonweal, Program Endocrine Disrupt Strategies, Bolinas, CA USA

[19] Harvard TH Chan Sch Publ Hlth, Dept Environm Hlth, Boston, MA USA

[20] Univ Southern Denmark, Dept Environm Med, Odense, Denmark

[21] Univ Occupat & Environm Hlth, Dept Environm Hlth, Kitakyushu, Fukuoka 8078555, Japan

[22] Natl Inst Environm Studies, Ctr Hlth & Environm Risk Res, Tsukuba, Ibaraki 3058506, Japan

来源：

ENVIRONMENT INTERNATIONAL | 2018年 / 114卷

基金：

瑞典研究理事会;

关键词：

Endocrine disrupting compounds; Tobacco smoking; Particulate matter; Developmental vulnerability; Mechanistic toxicology; DNA METHYLATION CHANGES; AMBIENT AIR-POLLUTION; DIET-INDUCED OBESITY; BODY-MASS INDEX; ENDOCRINE DISRUPTORS; PRENATAL EXPOSURE; TRANSGENERATIONAL INHERITANCE; MATERNAL OBESITY; ENVIRONMENTAL STRESSORS; PHTHALATE EXPOSURE;

D O I：

10.1016/j.envint.2018.02.014

中图分类号：

X [环境科学、安全科学];

学科分类号：

08 ; 0830 ;

摘要：

A variety of experimental and epidemiological studies lend support to the Developmental Origin of Health and Disease (DOHaD) concept. Yet, the actual mechanisms accounting for mid- and long-term effects of early-life exposures remain unclear. Epigenetic alterations such as changes in DNA methylation, histone modifications and the expression of certain RNAs have been suggested as possible mediators of long-term health effects of environmental stressors. This report captures discussions and conclusions debated during the last Prenatal Programming and Toxicity meeting held in Japan. Its first aim is to propose a number of criteria that are critical to support the primary contribution of epigenetics in DOHaD and intergenerational transmission of environmental stressors effects. The main criteria are the full characterization of the stressors, the actual window of exposure, the target tissue and function, the specificity of the epigenetic changes and the biological plausibility of the linkage between those changes and health outcomes. The second aim is to discuss long-term effects of a number of stressors such as smoking, air pollution and endocrine disruptors in order to identify the arguments supporting the involvement of an epigenetic mechanism. Based on the developed criteria, missing evidence and suggestions for future research will be identified. The third aim is to critically analyze the evidence supporting the involvement of epigenetic mechanisms in intergenerational and transgenerational effects of environmental exposure and to particularly discuss the role of placenta and sperm. While the article is not a systematic review and is not meant to be exhaustive, it critically assesses the contribution of epigenetics in the long-term effects of environmental exposures as well as provides insight for future research.

引用

页码：77 / 86

页数：10

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