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The fetal programming effect of prenatal smoking on Igf1r and Igf1 methylation is organ- and sex-specific
The impact of prenatal smoke exposure (PSE) on DNA methylation has been demonstrated in blood samples from children of smoking mothers, but evidence for sex-dependent smoke-induced effects is limited. As the identified differentially methylated genes can be associated with developmental processes, a...
Autores principales: | , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Taylor & Francis
2018
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5810788/ https://www.ncbi.nlm.nih.gov/pubmed/29160127 http://dx.doi.org/10.1080/15592294.2017.1403691 |
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author | Meyer, Karolin F. Verkaik-Schakel, Rikst Nynke Timens, Wim Kobzik, Lester Plösch, Torsten Hylkema, Machteld N. |
author_facet | Meyer, Karolin F. Verkaik-Schakel, Rikst Nynke Timens, Wim Kobzik, Lester Plösch, Torsten Hylkema, Machteld N. |
author_sort | Meyer, Karolin F. |
collection | PubMed |
description | The impact of prenatal smoke exposure (PSE) on DNA methylation has been demonstrated in blood samples from children of smoking mothers, but evidence for sex-dependent smoke-induced effects is limited. As the identified differentially methylated genes can be associated with developmental processes, and insulin-like growth factors (IGFs) play a critical role in prenatal tissue growth, we hypothesized that PSE induces fetal programming of Igf1r and Igf1. Using a mouse model of smoking during pregnancy, we show that PSE alters promoter methylation of Igf1r and Igf1 and deregulates their gene expression in lung and liver of fetal (E17.5) and neonatal (D3) mouse offspring. By further comparing female versus male, lung versus liver, or fetal versus neonatal time point, our results demonstrate that CpG site-specific aberrant methylation patterns sex-dependently vary per organ and time point. Moreover, PSE reduces gene expression of Igf1r and Igf1, dependent on organ, sex, and offspring's age. Our results indicate that PSE may be a source of organ-specific rather than general systemic fetal programming. This is exemplified here by gene promoter methylation and mRNA levels of Igf1r and Igf1, together with a sex- and organ-specific naturally established correlation of both parameters that is affected by prenatal smoke exposure. Moreover, the comparison of fetuses with neonates suggests a CpG site-dependent reversibility/persistence of PSE-induced differential methylation patterns. |
format | Online Article Text |
id | pubmed-5810788 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2018 |
publisher | Taylor & Francis |
record_format | MEDLINE/PubMed |
spelling | pubmed-58107882018-02-15 The fetal programming effect of prenatal smoking on Igf1r and Igf1 methylation is organ- and sex-specific Meyer, Karolin F. Verkaik-Schakel, Rikst Nynke Timens, Wim Kobzik, Lester Plösch, Torsten Hylkema, Machteld N. Epigenetics Research Papers The impact of prenatal smoke exposure (PSE) on DNA methylation has been demonstrated in blood samples from children of smoking mothers, but evidence for sex-dependent smoke-induced effects is limited. As the identified differentially methylated genes can be associated with developmental processes, and insulin-like growth factors (IGFs) play a critical role in prenatal tissue growth, we hypothesized that PSE induces fetal programming of Igf1r and Igf1. Using a mouse model of smoking during pregnancy, we show that PSE alters promoter methylation of Igf1r and Igf1 and deregulates their gene expression in lung and liver of fetal (E17.5) and neonatal (D3) mouse offspring. By further comparing female versus male, lung versus liver, or fetal versus neonatal time point, our results demonstrate that CpG site-specific aberrant methylation patterns sex-dependently vary per organ and time point. Moreover, PSE reduces gene expression of Igf1r and Igf1, dependent on organ, sex, and offspring's age. Our results indicate that PSE may be a source of organ-specific rather than general systemic fetal programming. This is exemplified here by gene promoter methylation and mRNA levels of Igf1r and Igf1, together with a sex- and organ-specific naturally established correlation of both parameters that is affected by prenatal smoke exposure. Moreover, the comparison of fetuses with neonates suggests a CpG site-dependent reversibility/persistence of PSE-induced differential methylation patterns. Taylor & Francis 2018-02-07 /pmc/articles/PMC5810788/ /pubmed/29160127 http://dx.doi.org/10.1080/15592294.2017.1403691 Text en © 2018 Karolin F. Meyer, Rikst Nynke Verkaik-Schakel, Wim Timens, Lester Kobzik, Torsten Plösch and Machteld N. Hylkema. Published with license by Taylor & Francis http://creativecommons.org/licenses/by-nc-nd/4.0/ This is an Open Access article distributed under the terms of the Creative Commons Attribution-NonCommercial-NoDerivatives License (http://creativecommons.org/licenses/by-nc-nd/4.0/), which permits non-commercial re-use, distribution, and reproduction in any medium, provided the original work is properly cited, and is not altered, transformed, or built upon in any way. |
spellingShingle | Research Papers Meyer, Karolin F. Verkaik-Schakel, Rikst Nynke Timens, Wim Kobzik, Lester Plösch, Torsten Hylkema, Machteld N. The fetal programming effect of prenatal smoking on Igf1r and Igf1 methylation is organ- and sex-specific |
title | The fetal programming effect of prenatal smoking on Igf1r and Igf1 methylation is organ- and sex-specific |
title_full | The fetal programming effect of prenatal smoking on Igf1r and Igf1 methylation is organ- and sex-specific |
title_fullStr | The fetal programming effect of prenatal smoking on Igf1r and Igf1 methylation is organ- and sex-specific |
title_full_unstemmed | The fetal programming effect of prenatal smoking on Igf1r and Igf1 methylation is organ- and sex-specific |
title_short | The fetal programming effect of prenatal smoking on Igf1r and Igf1 methylation is organ- and sex-specific |
title_sort | fetal programming effect of prenatal smoking on igf1r and igf1 methylation is organ- and sex-specific |
topic | Research Papers |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5810788/ https://www.ncbi.nlm.nih.gov/pubmed/29160127 http://dx.doi.org/10.1080/15592294.2017.1403691 |
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