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Expression of epigenetic machinery genes is sensitive to maternal obesity and weight loss in relation to fetal growth in mice
BACKGROUND: Maternal obesity impacts fetal growth and pregnancy outcomes. To counteract the deleterious effects of obesity on fertility and pregnancy issue, preconceptional weight loss is recommended to obese women. Whether this weight loss is beneficial/detrimental for offspring remains poorly expl...
Autores principales: | , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
BioMed Central
2016
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4769534/ https://www.ncbi.nlm.nih.gov/pubmed/26925174 http://dx.doi.org/10.1186/s13148-016-0188-3 |
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author | Panchenko, Polina E. Voisin, Sarah Jouin, Mélanie Jouneau, Luc Prézelin, Audrey Lecoutre, Simon Breton, Christophe Jammes, Hélène Junien, Claudine Gabory, Anne |
author_facet | Panchenko, Polina E. Voisin, Sarah Jouin, Mélanie Jouneau, Luc Prézelin, Audrey Lecoutre, Simon Breton, Christophe Jammes, Hélène Junien, Claudine Gabory, Anne |
author_sort | Panchenko, Polina E. |
collection | PubMed |
description | BACKGROUND: Maternal obesity impacts fetal growth and pregnancy outcomes. To counteract the deleterious effects of obesity on fertility and pregnancy issue, preconceptional weight loss is recommended to obese women. Whether this weight loss is beneficial/detrimental for offspring remains poorly explored. Epigenetic mechanisms could be affected by maternal weight changes, perturbing expression of key developmental genes in the placenta or fetus. Our aim was to investigate the effects of chronic maternal obesity on feto-placental growth along with the underlying epigenetic mechanisms. We also tested whether preconceptional weight loss could alleviate these effects. RESULTS: Female mice were fed either a control diet (CTRL group), a high-fat diet (obese (OB) group), or a high-fat diet switched to a control diet 2 months before conception (weight loss (WL) group). At mating, OB females presented an obese phenotype while WL females normalized metabolic parameters. At embryonic day 18.5 (E18.5), fetuses from OB females presented fetal growth restriction (FGR; −13 %) and 28 % of the fetuses were small for gestational age (SGA). Fetuses from WL females normalized this phenotype. The expression of 60 epigenetic machinery genes and 32 metabolic genes was measured in the fetal liver, placental labyrinth, and junctional zone. We revealed 23 genes altered by maternal weight trajectories in at least one of three tissues. The fetal liver and placental labyrinth were more responsive to maternal obesity than junctional zone. One third (18/60) of the epigenetic machinery genes were differentially expressed between at least two maternal groups. Interestingly, genes involved in the histone acetylation pathway were particularly altered (13/18). In OB group, lysine acetyltransferases and Bromodomain-containing protein 2 were upregulated, while most histone deacetylases were downregulated. In WL group, the expression of only a subset of these genes was normalized. CONCLUSIONS: This study highlights the high sensitivity of the epigenetic machinery gene expression, and particularly the histone acetylation pathway, to maternal obesity. These obesity-induced transcriptional changes could alter the placental and the hepatic epigenome, leading to FGR. Preconceptional weight loss appears beneficial to fetal growth, but some effects of previous obesity were retained in offspring phenotype. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s13148-016-0188-3) contains supplementary material, which is available to authorized users. |
format | Online Article Text |
id | pubmed-4769534 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2016 |
publisher | BioMed Central |
record_format | MEDLINE/PubMed |
spelling | pubmed-47695342016-02-28 Expression of epigenetic machinery genes is sensitive to maternal obesity and weight loss in relation to fetal growth in mice Panchenko, Polina E. Voisin, Sarah Jouin, Mélanie Jouneau, Luc Prézelin, Audrey Lecoutre, Simon Breton, Christophe Jammes, Hélène Junien, Claudine Gabory, Anne Clin Epigenetics Research BACKGROUND: Maternal obesity impacts fetal growth and pregnancy outcomes. To counteract the deleterious effects of obesity on fertility and pregnancy issue, preconceptional weight loss is recommended to obese women. Whether this weight loss is beneficial/detrimental for offspring remains poorly explored. Epigenetic mechanisms could be affected by maternal weight changes, perturbing expression of key developmental genes in the placenta or fetus. Our aim was to investigate the effects of chronic maternal obesity on feto-placental growth along with the underlying epigenetic mechanisms. We also tested whether preconceptional weight loss could alleviate these effects. RESULTS: Female mice were fed either a control diet (CTRL group), a high-fat diet (obese (OB) group), or a high-fat diet switched to a control diet 2 months before conception (weight loss (WL) group). At mating, OB females presented an obese phenotype while WL females normalized metabolic parameters. At embryonic day 18.5 (E18.5), fetuses from OB females presented fetal growth restriction (FGR; −13 %) and 28 % of the fetuses were small for gestational age (SGA). Fetuses from WL females normalized this phenotype. The expression of 60 epigenetic machinery genes and 32 metabolic genes was measured in the fetal liver, placental labyrinth, and junctional zone. We revealed 23 genes altered by maternal weight trajectories in at least one of three tissues. The fetal liver and placental labyrinth were more responsive to maternal obesity than junctional zone. One third (18/60) of the epigenetic machinery genes were differentially expressed between at least two maternal groups. Interestingly, genes involved in the histone acetylation pathway were particularly altered (13/18). In OB group, lysine acetyltransferases and Bromodomain-containing protein 2 were upregulated, while most histone deacetylases were downregulated. In WL group, the expression of only a subset of these genes was normalized. CONCLUSIONS: This study highlights the high sensitivity of the epigenetic machinery gene expression, and particularly the histone acetylation pathway, to maternal obesity. These obesity-induced transcriptional changes could alter the placental and the hepatic epigenome, leading to FGR. Preconceptional weight loss appears beneficial to fetal growth, but some effects of previous obesity were retained in offspring phenotype. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s13148-016-0188-3) contains supplementary material, which is available to authorized users. BioMed Central 2016-02-27 /pmc/articles/PMC4769534/ /pubmed/26925174 http://dx.doi.org/10.1186/s13148-016-0188-3 Text en © Panchenko et al. 2016 Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated. |
spellingShingle | Research Panchenko, Polina E. Voisin, Sarah Jouin, Mélanie Jouneau, Luc Prézelin, Audrey Lecoutre, Simon Breton, Christophe Jammes, Hélène Junien, Claudine Gabory, Anne Expression of epigenetic machinery genes is sensitive to maternal obesity and weight loss in relation to fetal growth in mice |
title | Expression of epigenetic machinery genes is sensitive to maternal obesity and weight loss in relation to fetal growth in mice |
title_full | Expression of epigenetic machinery genes is sensitive to maternal obesity and weight loss in relation to fetal growth in mice |
title_fullStr | Expression of epigenetic machinery genes is sensitive to maternal obesity and weight loss in relation to fetal growth in mice |
title_full_unstemmed | Expression of epigenetic machinery genes is sensitive to maternal obesity and weight loss in relation to fetal growth in mice |
title_short | Expression of epigenetic machinery genes is sensitive to maternal obesity and weight loss in relation to fetal growth in mice |
title_sort | expression of epigenetic machinery genes is sensitive to maternal obesity and weight loss in relation to fetal growth in mice |
topic | Research |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4769534/ https://www.ncbi.nlm.nih.gov/pubmed/26925174 http://dx.doi.org/10.1186/s13148-016-0188-3 |
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