Maternal high-fat diet alters Tet-mediated epigenetic regulation during heart development [RNA-Seq]
Ontology highlight
ABSTRACT:
ORGANISM(S): Mus musculus
PROVIDER: GSE271882 | GEO | 2025/08/01
REPOSITORIES: GEO
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Project description:Our study suggested a direct link between maternal high-fat diet exposure and TET-mediated epigenetic regulation during heart development. Furthermore, we also uncovered beneficial effects of maternal vitamin C intake to protect heart development under maternal obesity conditions
2025-08-01 | GSE271883 | GEO
Project description:Maternal exposure to balanced nutrition is critical for supporting embryonic development. Exposure to imbalanced nutrition during pregnancy, such as a high-fat diet (HFD), has been reported to negatively impact offspring, leading to conditions such as congenital heart disease. One possible mechanism is that metabolic stress from imbalanced food intake alters the function of epigenetic regulators, leading to abnormal transcriptional output in embryos. In this study, we observed that maternal exposure to a high-fat diet led to noncompaction cardiomyopathy (NCC) in embryos at E15.5. At the molecular level, maternal HFD exposure resulted in significantly reduced 5hmC production and chromatin remodeling in embryonic heart tissue collected from E15.5 embryos. Interestingly, maternal vitamin C treatment countered the negative impact of HFD exposure and restored the metabolic changes observed in pregnant mice, as well as the NCC phenotype observed in E15.5 embryos. This restoration is possibly due to the replenishment of iron, a co-factor of the Tet enzyme, in its reduced form. We further used a cardiac-specific Tet-triple knockout mouse model to confirm that the cardioprotective outcomes of maternal vitamin C treatment in HFD conditions are attributable to the enhanced activity of TET enzymes. Collectively, our results suggest a crosstalk between maternal nutrition exposure, such as HFD or vitamin C, and epigenetic rewriting during embryonic heart development。
2024-09-18 | GSE252640 | GEO
Project description:Maternal high-fat diet alters Tet-mediated epigenetic regulation during heart development
| PRJNA1061550 | ENA
Project description:Maternal high-fat diet alters Tet-mediated epigenetic regulation during heart development [ATAC-Seq]
| PRJNA1133796 | ENA
Project description:Maternal high-fat diet alters Tet-mediated epigenetic regulation during heart development [RNA-Seq]
| PRJNA1133797 | ENA
Project description:Imbalanced dietary intake, such as a high-fat diet (HFD) during pregnancy, has been associated with adverse offspring outcomes. Metabolic stress from imbalanced food intake alters the function of epigenetic regulators, resulting in abnormal transcriptional outputs in embryos to cause congenital disorders. We report herein that maternal HFD exposure causes metabolic changes in pregnant mice and non-compaction cardiomyopathy (NCC) in E15.5 embryos, accompanied by decreased 5-hydroxymethylcytosine (5hmC) levels and altered chromatin accessibility in embryonic heart tissues. Remarkably, maternal vitamin C supplementation mitigates these detrimental effects, likely by restoring iron, a cofactor for Tet enzymes, in a reduced state. Using a genetic approach, we further demonstrated that the cardioprotective benefits of vitamin C under HFD conditions are attributable to enhanced Tet activity. Our results highlight an interaction between maternal diet, specifically HFD or vitamin C, and epigenetic modifications during early heart development, emphasizing the importance of balanced maternal nutrition for healthy embryonic development.
| S-EPMC11388159 | biostudies-literature
Project description:We performed RNA-seq analysis for evaluating the effect of maternal high-fructose intake on fetal brown fat development. We find that maternal high-fructose intake induces myogenic signature in fetal brown fat, indicating impairment of brown fat development by maternal high-fructose intake.
2022-01-15 | GSE193031 | GEO
Project description:The origins of congenital heart diseases, the most common congenital diseases are still largely unknown. Environmental factors are now emerging as major causes of these diseases. Vitamin D deficiency has become a public health burden, notably for childbearing age, pregnant and breastfeeding women. Since maternal 25-hydroxyvitamin D (25(OH)D) determined fetal and neonatal 25(OH)D status, foetuses exposed to insufficient levels of vitamin D, may feature developmental defects.Herein, we investigated the effects of maternal vitamin D deficiency on cardiovascular defects in early and later life of offsprings as well as the molecular mechanisms underlying vitamin D effect.Eight weeks before and during pregnancy, C57BL/6JRj female mice received a sufficient or vitamin D deficient diet ((1.0 IU/g in control vs 0.0 IU/g in Vitamin D Deficient (VDD) group). E16.5 Embryos of maternal VDD diet featured hypertrophic heart revealed by a thicker left ventricular (LV) wall and septum. RNAseq analysis of LV revealed 1555 transcripts differentially expressed in the VDD group and among them cardiac transcription factors and constitutive cardiac genes (tbx5, gata4, myl2). Anti-Vitamin D receptor (VDR) Chip-seq from chromatin of E16.5 LV uncovered different targeting of tbx5 and tbx3 loci by VDR in the VDD vs control embryos. Anti-CTCF ChIP-loop experiments focusing on the Tbx3 and Tbx5 loci uncovered a change in the Topology Associated Domains associated with these loci. Herein, we investigated the effects of maternal vitamin D deficiency on cardiovascular defects in early and later life of offsprings as well as the molecular mechanisms underlying vitamin D effect.Eight weeks before and during pregnancy, C57BL/6JRj female mice received a sufficient or vitamin D deficient diet ((1.0 IU/g in control vs 0.0 IU/g in Vitamin D Deficient (VDD) group). E16.5 Embryos of maternal VDD diet featured hypertrophic heart revealed by a thicker left ventricular (LV) wall and septum. RNAseq analysis of LV revealed 1555 transcripts differentially expressed in the VDD group and among them cardiac transcription factors and constitutive cardiac genes (tbx5, gata4, myl2). Anti-Vitamin D receptor (VDR) Chip-seq from chromatin of E16.5 LV uncovered different targeting of tbx5 and tbx3 loci by VDR in the VDD vs control embryos. Anti-CTCF ChIP-loop experiments focusing on the Tbx3 and Tbx5 loci uncovered a change in the Topology Associated Domains associated with these loci.
2023-12-31 | GSE162895 | GEO
Project description:DNA methylation is a heritable epigenetic modification involved in gene silencing, imprinting, and the suppression of retrotransposons. Global DNA demethylation occurs in the early embryo and the germline and may be mediated by Tet (ten-eleven-translocation) enzymes, which convert 5-methylcytosine (mC) to 5-hydroxymethylcytosine (hmC). Tet enzymes have been extensively studied in mouse embryonic stem (ES) cells, which are generally cultured in the absence of Vitamin C, a potential co-factor for Fe(II) 2-oxoglutarate dioxygenase enzymes like Tets. Here we report that addition of Vitamin C to ES cells promotes Tet activity leading to a rapid and global increase in hmC. This is followed by DNA demethylation of numerous gene promoters and up-regulation of demethylated germline genes. Tet1 binding is enriched near the transcription start site (TSS) of genes affected by Vitamin C treatment. Importantly, Vitamin C, but not other antioxidants, enhances the activity of recombinant human Tet1 in a biochemical assay and the Vitamin C-induced changes in hmC and mC are entirely suppressed in Tet1/2 double knockout (Tet DKO) ES cells. Vitamin C has the strongest effects on regions that gain methylation in cultured ES cells compared to blastocysts and in vivo are methylated only after implantation. In contrast, imprinted regions and intracisternal A-particle (IAP) elements, which are resistant to demethylation in the early embryo, are resistant to Vitamin C-induced DNA demethylation. Collectively, this study establishes that Vitamin C is a direct regulator of Tet activity and DNA methylation fidelity in ES cells. Oct4-GiP mouse embryonic stem (ES) cells were cultured in the presence or absence of Vitamin C (L-ascorbic acid 2-phosphate, 200 M-NM-<g/ml) for 72 hours. RNA was harvested from biological triplicates for each condition and hybridized to Affymetrix microarrays. Cells were maintained in N2B27 medium supplemented with LIF (1000 U/ml), MEK inhibitor PD0325901 (1 M-NM-<M), and GSK3M-NM-2 inhibitor CHIR99021 (3 M-NM-<M).
2013-06-30 | E-GEOD-46319 | biostudies-arrayexpress
Project description:DNA methylation is a heritable epigenetic modification involved in gene silencing, imprinting, and the suppression of retrotransposons. Global DNA demethylation occurs in the early embryo and the germline and may be mediated by Tet (ten-eleven-translocation) enzymes, which convert 5-methylcytosine (mC) to 5-hydroxymethylcytosine (hmC). Tet enzymes have been extensively studied in mouse embryonic stem (ES) cells, which are generally cultured in the absence of Vitamin C, a potential co-factor for Fe(II) 2-oxoglutarate dioxygenase enzymes like Tets. Here we report that addition of Vitamin C to ES cells promotes Tet activity leading to a rapid and global increase in hmC. This is followed by DNA demethylation of numerous gene promoters and up-regulation of demethylated germline genes. Tet1 binding is enriched near the transcription start site (TSS) of genes affected by Vitamin C treatment. Importantly, Vitamin C, but not other antioxidants, enhances the activity of recombinant human Tet1 in a biochemical assay and the Vitamin C-induced changes in hmC and mC are entirely suppressed in Tet1/2 double knockout (Tet DKO) ES cells. Vitamin C has the strongest effects on regions that gain methylation in cultured ES cells compared to blastocysts and in vivo are methylated only after implantation. In contrast, imprinted regions and intracisternal A-particle (IAP) elements, which are resistant to demethylation in the early embryo, are resistant to Vitamin C-induced DNA demethylation. Collectively, this study establishes that Vitamin C is a direct regulator of Tet activity and DNA methylation fidelity in ES cells.
2013-06-30 | GSE46319 | GEO