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Long-term Behavioral and Reproductive Consequences of Embryonic Exposure to Low-dose Toxicants
Published on: March 6, 2018
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Epigenetics as a mechanism linking developmental exposures to long-term toxicity
R Barouki1, E Melén2, Z Herceg3
1INSERM UMR-S 1124, Université Paris Descartes, Paris, France; Service de Biochimie Métabolomique et Protéomique, Hôpital Necker Enfants Malades, AP-HP, Paris, France.
Environment International
|March 3, 2018
Summary
Epigenetic alterations may mediate long-term health effects from early-life exposures, supporting the Developmental Origin of Health and Disease (DOHaD) concept. This review proposes criteria to assess epigenetics
Area of Science:
- Environmental Epigenetics
- Developmental Toxicology
- Reproductive Health
Background:
- The Developmental Origin of Health and Disease (DOHaD) concept links early-life exposures to later health outcomes.
- Mechanisms underlying long-term effects of early-life exposures, including environmental stressors, are not fully understood.
- Epigenetic modifications (DNA methylation, histone modifications, RNA expression) are proposed mediators.
Purpose of the Study:
- To propose criteria for evaluating epigenetics' role in DOHaD and intergenerational effects of environmental stressors.
- To discuss evidence for epigenetic involvement in long-term effects of specific stressors (smoking, air pollution, endocrine disruptors).
- To critically analyze epigenetic mechanisms in intergenerational/transgenerational environmental exposure effects, focusing on placenta and sperm.
Main Methods:
- Discussion and consensus building from the Prenatal Programming and Toxicity meeting.
- Development of criteria for assessing epigenetic contributions to DOHaD.
- Critical analysis of existing literature on environmental stressors and epigenetic modifications.
Main Results:
- Key criteria proposed include: full characterization of stressors, exposure window, target tissue/function, epigenetic specificity, and biological plausibility.
- Analysis identified areas with missing evidence and suggested future research directions for specific stressors.
- Evidence for epigenetic involvement in intergenerational/transgenerational effects was critically assessed, highlighting the roles of placenta and sperm.
Conclusions:
- Epigenetics is a plausible mechanism mediating long-term health effects of early-life environmental exposures.
- Established criteria are crucial for robustly demonstrating epigenetic contributions to DOHaD and intergenerational effects.
- Further research is needed to elucidate specific epigenetic pathways and their role across generations.
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