Sex- and Diet-Specific Changes of Imprinted Gene Expression and DNA Methylation in Mouse Placenta under a High-Fat Diet
Open accessAbstract
BACKGROUND: Changes in imprinted gene dosage in the placenta may compromise the prenatal control of nutritional resources. Indeed monoallelic behaviour and sensitivity to changes in regional epigenetic state render imprinted genes both vulnerable and adaptable. METHODS AND FINDINGS: We investigated whether a high-fat diet (HFD) during pregnancy modified the expression of imprinted genes and local and global DNA methylation patterns in the placenta. Pregnant mice were fed a HFD or a control diet (CD) during the first 15 days of gestation. We compared gene expression patterns in total placenta homogenates, for male and female offspring, by the RT-qPCR analysis of 20 imprinted genes. Sexual dimorphism and sensitivity to diet were observed for nine genes from four clusters on chromosomes 6, 7, 12 and 17. As assessed by in situ hybridization, these changes were not due to variation in the proportions of the placental layers. Bisulphite-sequencing analysis of 30 CpGs within the differentially methylated region (DMR) of the chromosome 17 cluster revealed sex- and diet-specific differential methylation of individual CpGs in two conspicuous subregions. Bioinformatic analysis suggested that these differentially methylated CpGs might lie within recognition elements or binding sites for transcription factors or factors involved in chromatin remodelling. Placental global DNA methylation, as assessed by the LUMA technique, was also sexually dimorphic on the CD, with lower methylation levels in male than in female placentae. The HFD led to global DNA hypomethylation only in female placenta. Bisulphite pyrosequencing showed that neither B1 nor LINE repetitive elements could account for these differences in DNA methylation. CONCLUSIONS: A HFD during gestation triggers sex-specific epigenetic alterations within CpG and throughout the genome, together with the deregulation of clusters of imprinted genes important in the control of many cellular, metabolic and physiological functions potentially involved in adaptation and/or evolution. These findings highlight the importance of studying both sexes in epidemiological protocols and dietary interventions.
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The global methylation pattern of the placenta is different between males and females, even when exposed to the same in utero environment.
“Of note, Gallou-Kabani et al. showed that the global methylation pattern of the placenta was different between male and females, even though they were exposed to the same in utero environment [148].”
From Developmental programming of offspring adipose tissue biology and obesity risk (2021) · cites this paper as [148]
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Self-citation
- Authors
- Gallou-Kabani, C., Gabory, A., Tost, J., Karimi, M., Mayeur, S., Lesage, J., Boudadi, E., Gross, M.-S., Taurelle, J., Vigé, A., Breton, C., Reusens, B., Remacle, C., Vieau, D., Ekström, T. J., Jais, J.-P., & Junien, C.
- Affiliations
- Hôpital Necker-Enfants Malades (FR)
- Commissariat à l'Énergie Atomique et aux Énergies Alternatives (FR)
- Karolinska Institutet (SE)
- Université de Lille (FR)
- UCLouvain (BE)
- Corresponding author
- Junien, Claudine
- ORCID
- Venue
- PLoS ONE
- Publisher
- Public Library of Science (PLoS)
- Published
- 2010-12-21
- Volume
- 5
- Issue
- 12
- Pages
- e14398
- ISSN
- 1932-6203 (ISSN-L)
- PMC
- PMC3006175
- OpenAlex
- W2157038986
- Cited by
- 229
- References
- 124
- Citations by year
- 2026: 1 · 2025: 9 · 2024: 5 · 2023: 5 · 2022: 10 · 2021: 11 · 2020: 16 · 2019: 13 · 2018: 27 · 2017: 22 · 2016: 14 · 2015: 24 · 2014: 12 · 2013: 31 · 2012: 23
- FWCI
- 10.80
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Locations
- PLoS ONE (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- HAL (submittedVersion, other-oa)
- Digital Access to Libraries (submittedVersion, other-oa)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Funders
- Agence Nationale de la Recherche (ANR-06-PNRA-0022)
- Institut National de la Santé et de la Recherche Médicale
- Cancerfonden
- Institut National de la Recherche Agronomique
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetic Syndromes and Imprinting
- Health Sciences › Medicine › Pediatrics, Perinatology and Child Health › Birth, Development, and Health
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Epigenetics and DNA Methylation
- Keywords
- genomic imprinting, imprinted gene expression, placenta, high-fat diet, maternal diet, sex differences, DNA methylation, differentially methylated regions, global DNA hypomethylation, monoallelic expression, epigenetic inheritance
- MeSH terms
- Alleles, Animals, Animal Feed, Dietary Fats, Female, Gene Expression Regulation, Male, Placenta, Pregnancy, Pregnancy, Animal, Sex Factors, Genomic Imprinting, Gene Dosage, DNA Methylation, Epigenesis, Genetic, Mice
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