Maternal Diets Trigger Sex-Specific Divergent Trajectories of Gene Expression and Epigenetic Systems in Mouse Placenta
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Males and females responses to gestational overnutrition set the stage for subsequent sex-specific differences in adult onset non communicable diseases. Placenta, as a widely recognized programming agent, contibutes to the underlying processes. According to our previous findings, a high-fat diet during gestation triggers sex-specific epigenetic alterations within CpG and throughout the genome, together with the deregulation of clusters of imprinted genes. We further investigated the impact of diet and sex on placental histology, transcriptomic and epigenetic signatures in mice. Both basal gene expression and response to maternal high-fat diet were sexually dimorphic in whole placentas. Numerous genes showed sexually dimorphic expression, but only 11 genes regardless of the diet. In line with the key role of genes belonging to the sex chromosomes, 3 of these genes were Y-specific and 3 were X-specific. Amongst all the genes that were differentially expressed under a high-fat diet, only 16 genes were consistently affected in both males and females. The differences were not only quantitative but remarkably qualitative. The biological functions and networks of genes dysregulated differed markedly between the sexes. Seven genes of the epigenetic machinery were dysregulated, due to effects of diet, sex or both, including the Y- and X-linked histone demethylase paralogues Kdm5c and Kdm5d, which could mark differently male and female epigenomes. The DNA methyltransferase cofactor Dnmt3l gene expression was affected, reminiscent of our previous observation of changes in global DNA methylation. Overall, this striking sexual dimorphism of programming trajectories impose a considerable revision of the current dietary interventions protocols.
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Sex-dependent differences in gene expression are likely to underlie the contrasting placental responses observed following exposure to high-fat/low-fat diets, glucocorticoids, or hypoxia in mice.
“Nonetheless, sex-dependent differences in gene expression are likely to underlie the contrasting placental responses observed following exposure to high-fat/low-fat diets (202, 356), glucocorticoids (132), or hypoxia (133, 363) in mice.”
From Placental Origins of Chronic Disease (2016) · cites this paper as [202]
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- Authors
- Gabory, A., Ferry, L., Fajardy, I., Jouneau, L., Gothié, J.-D., Vigé, A., Fleur, C., Mayeur, S., Gallou-Kabani, C., Gross, M.-S., Attig, L., Vambergue, A., Lesage, J., Reusens, B., Vieau, D., Remacle, C., Jais, J.-P., & Junien, C.
- Affiliations
- Hôpital Necker-Enfants Malades (FR)
- École Nationale Vétérinaire d'Alfort (FR)
- Centre Hospitalier Universitaire de Lille (FR)
- Université de Lille (FR)
- UCLouvain (BE)
- Corresponding author
- Junien, Claudine
- Venue
- PLoS ONE
- Publisher
- Public Library of Science (PLoS)
- Published
- 2012-11-05
- Volume
- 7
- Issue
- 11
- Pages
- e47986
- ISSN
- 1932-6203 (ISSN-L)
- PMC
- PMC3489896
- OpenAlex
- W2160171719
- Cited by
- 204
- References
- 73
- Citations by year
- 2026: 8 · 2025: 5 · 2024: 6 · 2023: 7 · 2022: 12 · 2021: 13 · 2020: 16 · 2019: 18 · 2018: 21 · 2017: 19 · 2016: 19 · 2015: 21 · 2014: 13 · 2013: 26
- FWCI
- 16.82
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Locations
- PLoS ONE (publishedVersion, cc-by)
- Europe PMC (PubMed Central) (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- HAL (submittedVersion, other-oa)
- Figshare (submittedVersion, cc-by)
- 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 Recherche Agronomique
- Topics
- Health Sciences › Medicine › Pediatrics, Perinatology and Child Health › Birth, Development, and Health
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetic Syndromes and Imprinting
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Epigenetics and DNA Methylation
- Keywords
- placenta, maternal high-fat diet, sex differences, epigenetics, DNA methylation, imprinted genes, placental transcriptome, KDM5C, KDM5D, DNMT3L, sex chromosomes, developmental programming, non-communicable diseases, mouse model
- MeSH terms
- Animals, DNA (Cytosine-5-)-Methyltransferases, Female, Male, Oxidoreductases, N-Demethylating, Placenta, Pregnancy, Prenatal Exposure Delayed Effects, Sex Characteristics, Gene Expression, Gene Expression Regulation, Enzymologic, Oligonucleotide Array Sequence Analysis, Prenatal Nutritional Physiological Phenomena, Epigenesis, Genetic, Mice, Histone Demethylases, Diet, High-Fat, Transcriptome
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