Mus musculus strain:C57BL/6J
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA239632 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR3280386_1.fastq.gz | Fastqsanger.gz | |||
| SRR3280386_2.fastq.gz | Fastqsanger.gz | |||
| SRR3280387_1.fastq.gz | Fastqsanger.gz | |||
| SRR3280387_2.fastq.gz | Fastqsanger.gz | |||
| SRR3280388_1.fastq.gz | Fastqsanger.gz |
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Similar Datasets
Project description:Maternal dietary folic acid induced DNA methylation changes at single base resolution in C57BL/6J mice offspring brain cerebellum
| PRJNA313960 | ENA
Project description:Defects in homocysteine and folate metabolism are associated with increased risks for neural tube and congenital heart defects, cardiovascular disease and stroke, cancers, and neurodegeneration. In many but not all cases, dietary supplementation with folate significantly reduces the severity and incidence of these conditions. Common polymorphisms modulate these metabolic pathways and disease risks, but do not fully account for the particular birth defects and adult diseases that occur in at-risk individuals. To test whether other pathways contribute to disease pathogenesis, we analyzed global and pathway-specific changes in gene expression and levels of selected metabolites after depletion and repletion of dietary folate in two genetically distinct inbred strains of mice. Compared to the C57BL/6J strain, A/J showed greater homeostatic response to folate perturbation by retaining a higher serum folate level and minimizing global gene expression changes. Remarkably, folate perturbation led to systematic strain-specific differences only in the expression profile of the cholesterol biosynthesis pathway and translated to changes in levels of serum and liver total cholesterol. By genetically increasing serum and liver total cholesterol levels in APOE deficient mice, we modestly but significantly improved folate retention during folate depletion, suggesting an interplay between homocysteine and folate metabolism and cholesterol metabolism. Absence of measurable changes in global methylation patterns or amelioration of effects with supplementation with an alternative methyl donor suggest that dietary folate perturbations do not act through large-scale or general changes in methylation. These results suggest that homeostatic responses in cholesterol metabolism contribute to the beneficial effects of dietary folate supplementation. Keywords: time course, stress response, diet, genetic, homeostasis Six-week old female C57BL/6J and B6.129P2-Apoetm1Unc/J (Piedrahita et al. 1992) mice were purchased from the Jackson Laboratory. All mice were raised on a control diet containing four ppm folic acid (Basal Diet 5755, TestDiet) for one week before the start of studies. Mice were then placed on folic acid deficient diet (58C3, TestDiet) containing 1% succinylsulfathiazole, a non-absorbable antibiotic commonly used to suppress folate production by bacteria in the intestine, for 14 days. A subset of these mice were placed back on control diet for 7 days after 14 day depletion. There were three groups of mice that underwent folic acid depletion and repletion. ApoE knockout mice on C57BL/6J background, C57BL/6J mice supplemented with 25mM choline and 50mM saccharine in drinking water, and C57BL/6J mice supplemented with 50mM saccharine. Saccharine was used to reduce the bitter taste of choline in the drinking water. We also had C57BL/6J mice on the control diet for 14 days and 21 days. These mice served as controls for treated mice from each time point during hybridization. The folate level in the control diet for this study was significantly lower than the previous study (GSE9242) due to greater loss of folic acid by irradiation of the diet. There were eight replicate mice per treatment group per folic acid perturbation protocol. An equal amount (by weight) of liver tissue from eight replicate mice was separated into two pools of four replicate tissues each. Pooled RNA from treated mice and pooled RNA from control mice for each time point were aminoallyl labeled with Cy3 and Cy5 in duplicate with reversing of dyes.
2008-08-27 | E-GEOD-9243 | biostudies-arrayexpress
Project description:We determined the effects of excess folic acid supplementation (5x recommendation) on maternal and fetal offspring metabolic health. Using a mouse (female C57BL/6J) model of gestational dibetes (GDM; 45% kcal fat diet) and control mice (10% kcal diet) we show that folic acid supplementation increased weight gain and fat mass in both GDM and control mice but improved insulin sensitivity in GDM mice and worsened insulin sensitivity in control mice. We found no unmetabolized folic acid in liver from supplemented mice suggesting the metabolic effects of folic acid supplementation may not be due to unmetabolized folic acid. Male fetal (gestational day 18.5) offspring from folic acid supplemented dams (GDM and control) had greater beta cell mass and density than those from unsupplemented dams; this was not observed in female offspring. Differential sex-specific hepatic gene expression profiles were observed in the offspring from supplemented dams but this differed between GDM and controls. Our findings suggest that folic acid supplementation affects insulin sensitivity in female mice, but is dependent on their metabolic phenotype, and has sex-specific effects on offspring pancreas and liver.
2023-09-29 | GSE237149 | GEO
Project description:Folic acid supplements prior to and during gestation are recommended and necessary to prevent neural tube defects in developing embryos. But there are also studies suggesting possible adverse effects of high-dose folic acid supplementation. Here, we address whether maternal dietary folic acid supplementation at 40 mg/kg chow (FD), restricted to a period prior to conception, affects gene expression in the offspring generation.
2017-06-08 | GSE80587 | GEO
Project description:Growing evidence supports the hypothesis that the in utero environment can have profound implications for fetal development and for offspring health in later life. Current theory suggests that conditions experienced in utero prepare, or ‘programme’, the fetus for its anticipated post-natal environment. The mechanisms responsible for these programming events are poorly understood but are likely to involve gene expression changes. Folate is essential for normal fetal development and inadequate maternal folate supply during pregnancy has long term adverse effects on the offspring. We tested the hypothesis that inadequate folate supply during pregnancy alters offspring programming through altered gene expression. Female C57BL/6J mice were fed diets containing 2 mg folic acid/kg or 0.4 mg folic acid/kg for 4 weeks before mating and throughout pregnancy. At 17.5 day gestation, genome-wide gene expression in fetal liver and placenta of male offspring was measured by microarray analysis. In the fetal liver, 989 genes (555 up-regulated, 434 down-regulated) were expressed differentially in response to maternal folate depletion, with 460 genes expressed differentially (250 up-regulated, 255 down-regulated) in the placenta. Only 25 differentially expressed genes were common between organs, revealing that maternal folate intake during pregnancy influences fetal gene expression in a highly organ specific manner which, we propose, reflects prioritised protection of essential organ-specific functions.
2016-06-14 | E-MTAB-3940 | biostudies-arrayexpress
Project description:Defects in homocysteine and folate metabolism are associated with increased risks for neural tube and congenital heart defects, cardiovascular disease and stroke, cancers, and neurodegeneration. In many but not all cases, dietary supplementation with folate significantly reduces the severity and incidence of these conditions. Common polymorphisms modulate these metabolic pathways and disease risks, but do not fully account for the particular birth defects and adult diseases that occur in at-risk individuals. To test whether other pathways contribute to disease pathogenesis, we analyzed global and pathway-specific changes in gene expression and levels of selected metabolites after depletion and repletion of dietary folate in two genetically distinct inbred strains of mice. Compared to the C57BL/6J strain, A/J showed greater homeostatic response to folate perturbation by retaining a higher serum folate level and minimizing global gene expression changes. Remarkably, folate perturbation led to systematic strain-specific differences only in the expression profile of the cholesterol biosynthesis pathway and translated to changes in levels of serum and liver total cholesterol. By genetically increasing serum and liver total cholesterol levels in APOE deficient mice, we modestly but significantly improved folate retention during folate depletion, suggesting an interplay between homocysteine and folate metabolism and cholesterol metabolism. Absence of measurable changes in global methylation patterns or amelioration of effects with supplementation with an alternative methyl donor suggest that dietary folate perturbations do not act through large-scale or general changes in methylation. These results suggest that homeostatic responses in cholesterol metabolism contribute to the beneficial effects of dietary folate supplementation. Keywords: time course, stress response, diet, genetic, homeostasis Six-week old female A/J and C57BL/6J mice were purchased from the Jackson Laboratory. All mice were raised on a control diet containing four ppm folic acid (Basal Diet 5755, TestDiet) for one week before the start of studies. Selected mice were then placed on folic acid deficient diet (58C3, TestDiet) containing 1% succinylsulfathiazole, a non-absorbable antibiotic commonly used to suppress folate production by bacteria in the intestine. We had nine different treatment plans per strain with eight replicate mice per treatment. There were four folic acid depletion treatment in which mice were placed on folic acid deficient diet for 1, 2, 7, or 14 days. There were two folic acid repletion treatment in which mice were placed on folic acid deficient diet for 14 days followed by 1 day on control diet and another set of mice on 14 days of folic acid deficient diet followed by 7 days of control diet. There were three control time points in which mice were placed on the control diet for 0, 9, or 22 days. Eight biological replicate liver tissue from each treatment was pooled and total RNA from each pool and total RNA from Universal Mouse Reference RNA (Stratagene) were aminoallyl labeled with Cy3 and Cy5 in duplicate, with reversing of dyes.
2008-08-27 | E-GEOD-9242 | biostudies-arrayexpress
Project description:The reprogramming of parental methylomes is essential for embryonic development. In mammals, paternal 5-methylcytosines (5mCs) have been proposed to be actively converted to oxidized bases. These paternal oxidized bases and maternal 5mCs are believed to be passively diluted by cell divisions. By generating single-base resolution, allele-specific DNA methylomes from mouse gametes, early embryos, and primordial germ cell (PGC), as well as single-base-resolution maps of oxidized cytosine bases for early embryos, we report the existence of 5hmC and 5fC in both maternal and paternal genomes and find that 5mC or its oxidized derivatives, at the majority of demethylated CpGs, are converted to unmodified cytosines independent of passive dilution from gametes to four-cell embryos. Therefore, we conclude that paternal methylome and at least a significant proportion of maternal methylome go through active demethylation during embryonic development. Additionally, all the known imprinting control regions (ICRs) were classified into germ-line or somatic ICRs. The cross of two mouse strains was performed using DBA/2J as the paternal strain and C57BL/6J as the maternal strain. The hybrid embryos were collected at 2-cell, 4-cell, ICM, E6.5, E7.5 stages. Female and male E13.5 PGC samples (B6; 129S4-Pou5f1tm2Jae/J) were collected from timed mating of C57BL/6J female mice. MethylC-Seq: oocytes (C57BL/6J), sperm (DBA/2J), 2-cell embryos, 4-cell embryos, ICM, E6.5 embryos, E7.5 embryos, E13.5 female PGCs and E13.5 male PGCs. TAB-Seq: 2-cell embryos. fCAB-Seq: 2-cell embryos. RNA-Seq: oocytes (C57BL/6J).
2014-05-12 | E-GEOD-56697 | biostudies-arrayexpress
Project description:Studies have indicated that altered maternal micronutrients and vitamins influence the development and susceptibility of newborns to chronic diseases. Among these, folic acid (FA) plays a key role in the synthesis and repair of DNA, along with maintenance of epigenetic DNA methylation. Deficiency of FA has been associated with the pathogenesis of neural tube defects. Since FA can modulate DNA methylation and affect gene expression, we investigated the effect of gestational FA supplementation on the expression of genes in the offspring brain. Our results suggest that a maternal ten-fold increase in FA supplementation alters the expression and dysregulates a number of genes in the offspring brain, including many involved in development. While a number of genes that were dysregulated were common to both male and female pups, there were sex differences in gene expression changes. C57BL/6J female mice were separated into two groups of ten mice and supplemented with a custom diet. One week prior to mating the low-dose group of female mice were fed a custom AIN-93G amino acidM-bM-^@M-^Sbased diet (Research Diet, Inc. New-Brunswick, NJ), with FA at 0.4 mg/kg, while the high-dose group received FA at 4 mg/kg diet. Tissues from the cerebral hemisphere of three independent pups of same gender were pooled together. A total of three microarray gene expression studies have been performed (0.4mg/kg or 4mg/kg both male and female) and the mean was used for comparison.
2013-09-09 | E-GEOD-45607 | biostudies-arrayexpress
Project description:Early life exposures are critical in fetal programming and may influence function and health in later life. Adequate maternal folate consumption during pregnancy is essential for healthy fetal development and long-term offspring health. The mechanisms underlying fetal programming are poorly understood, but are likely to involve gene regulation. Epigenetic marks, including DNA methylation, regulate gene expression and are modifiable by folate supply. We observed before transcriptional changes in fetal liver in response to maternal folate depletion and hypothesised that these changes are due to altered gene promoter methylation. Female C57BL/6J mice were fed diets containing 2âmg or 0.4âmg folic acid/kg for 4âweeks before mating and throughout pregnancy. At 17.5 day gestation, genome-wide gene expression and promoter methylation were measured by microarray analysis in male fetal livers.
2016-06-14 | E-MTAB-4013 | biostudies-arrayexpress
Project description:Evaluation of transgenerational influence of paternal dietary methyl substrates on offspring and grand-offspring brain and behavior Dietary intake of methyl donors, such as folic acid and methionine, shows considerable intra-individual variation in human populations. While it is recognized that maternal departures from the optimum of dietary methyl donor intake can increase the risk for mental health issues and neurological disorders in offspring, it has not been explored whether paternal dietary methyl donor intake influences behavioral and cognitive functions in the next generation. Here, we report that elevated paternal dietary methyl donor intake in a mouse model, transiently applied prior to mating, resulted in offspring animals (MD F1 mice) with deficits in hippocampus-dependent learning and memory, impaired hippocampal synaptic plasticity and reduced hippocampal theta oscillations. Gene expression analyses revealed altered expression of the methionine adenosyltransferase Mat2a and BK channel subunit Kcnmb2, which was associated with changes in Kcnmb2 promoter methylation in MD F1 mice. These phenomena did not extend into the F2 offspring generation. Together, our data indicate that paternal dietary factors influence cognitive and neural functions in the offspring generation.
2017-04-20 | GSE90158 | GEO