Advanced

Selective Survival of Embryos Can Explain DNA Methylation Signatures of Adverse Prenatal Environments

Tobi, Elmar W.; van den Heuvel, Joost; Zwaan, Bas J.; Lumey, L. H.; Heijmans, Bastiaan T. and Uller, Tobias LU (2018) In Cell Reports 25(10). p.4-2667
Abstract

An adverse intrauterine environment is associated with long-term physiological changes in offspring. These are believed to be mediated by epigenomic marks, including DNA methylation (DNAm). Changes in DNAm are often interpreted as damage or plastic responses of the embryo. Here, we propose that stochastic DNAm variation, generated during remodeling of the epigenome after fertilization, contributes to DNAm signatures of prenatal adversity through differential survival of embryos. Using a mathematical model of re-methylation in the early embryo, we demonstrate that selection, but not plasticity, will generate a characteristic reduction in DNAm variance at loci that contribute to survival. Such a reduction in DNAm variance was apparent in... (More)

An adverse intrauterine environment is associated with long-term physiological changes in offspring. These are believed to be mediated by epigenomic marks, including DNA methylation (DNAm). Changes in DNAm are often interpreted as damage or plastic responses of the embryo. Here, we propose that stochastic DNAm variation, generated during remodeling of the epigenome after fertilization, contributes to DNAm signatures of prenatal adversity through differential survival of embryos. Using a mathematical model of re-methylation in the early embryo, we demonstrate that selection, but not plasticity, will generate a characteristic reduction in DNAm variance at loci that contribute to survival. Such a reduction in DNAm variance was apparent in a human cohort prenatally exposed to the Dutch famine, illustrating that it is possible to detect a signature of selection on epigenomic variation. Selection should be considered as a possible mechanism linking prenatal adversity to subsequent health and may have implications when evaluating interventions. Tobi et al. hypothesize that prenatal adversity can cause selection on epigenomic profiles in utero. Their model predicts that such selection reduces the variance in DNA methylation at genomic regions that contribute to survival, which is testable and detectable in empirical data from the Dutch famine.

(Less)
Please use this url to cite or link to this publication:
author
organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
developmental origins, DNA methylation, plasticity, selection
in
Cell Reports
volume
25
issue
10
pages
4 - 2667
publisher
Cell Press
external identifiers
  • scopus:85057837601
ISSN
2211-1247
DOI
10.1016/j.celrep.2018.11.023
language
English
LU publication?
yes
id
652fcdb3-bf6f-45c3-83ef-44489c37c376
date added to LUP
2018-12-18 14:44:37
date last changed
2019-10-15 06:52:46
@article{652fcdb3-bf6f-45c3-83ef-44489c37c376,
  abstract     = {<p>An adverse intrauterine environment is associated with long-term physiological changes in offspring. These are believed to be mediated by epigenomic marks, including DNA methylation (DNAm). Changes in DNAm are often interpreted as damage or plastic responses of the embryo. Here, we propose that stochastic DNAm variation, generated during remodeling of the epigenome after fertilization, contributes to DNAm signatures of prenatal adversity through differential survival of embryos. Using a mathematical model of re-methylation in the early embryo, we demonstrate that selection, but not plasticity, will generate a characteristic reduction in DNAm variance at loci that contribute to survival. Such a reduction in DNAm variance was apparent in a human cohort prenatally exposed to the Dutch famine, illustrating that it is possible to detect a signature of selection on epigenomic variation. Selection should be considered as a possible mechanism linking prenatal adversity to subsequent health and may have implications when evaluating interventions. Tobi et al. hypothesize that prenatal adversity can cause selection on epigenomic profiles in utero. Their model predicts that such selection reduces the variance in DNA methylation at genomic regions that contribute to survival, which is testable and detectable in empirical data from the Dutch famine.</p>},
  author       = {Tobi, Elmar W. and van den Heuvel, Joost and Zwaan, Bas J. and Lumey, L. H. and Heijmans, Bastiaan T. and Uller, Tobias},
  issn         = {2211-1247},
  keyword      = {developmental origins,DNA methylation,plasticity,selection},
  language     = {eng},
  number       = {10},
  pages        = {4--2667},
  publisher    = {Cell Press},
  series       = {Cell Reports},
  title        = {Selective Survival of Embryos Can Explain DNA Methylation Signatures of Adverse Prenatal Environments},
  url          = {http://dx.doi.org/10.1016/j.celrep.2018.11.023},
  volume       = {25},
  year         = {2018},
}