High (5X) 5-methyltetrahydrofolate (MTHF) vs folic acid (FA) pregnancy diets on hypothalamic gene expression of Wistar rat dams upon birth.
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PROVIDER: PRJNA680036 | ENA |
REPOSITORIES: ENA
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Project description:This study compared the effects of 5X requirements of FA (10mg/kg) vs equimolar 5-methyletetrahydrofolate (MTHF, 10.4mg/kg) provided during pregnancy on hypothalamic (arcuate nucleus of the hypothalamus) gene expression profiles of Wistar rat dams upon birth. Methods: Whole-transcriptome analysis by RNA-sequencing was performed with Illumina HiSeq 2500 instrument (paired-end 2x125 bp sequencing at a depth of ≈20 million paired reads per sample). Sequence reads that passed quality filters were aligned to the rat genome using STAR aligner and differential gene expression was analyzed by DESeq2 using a padj <0.05. SYBR Green assay was used to validate candidate genes via qRT–PCR. Results: A total of 279 genes were identified to be differentially expressed genes in the hypothalamus of dams at birth fed high (5X) MTHF compared to 5X-FA diets during pregnancy, with 170 up-regulated and 109 down-regulated genes. Using goseq for pathway enrichment analysis, we identified several enriched pathways that associated with the long-term phenotype of the dam including the KEGG neuroactive-ligand receptor interaction pathway. Conclusion: This study provides novel insight towards the differential effects of folate form during pregnancy on regulating dynamic changes in gene expression of the maternal brain upon birth. The results of our study may led to hypothesis testing to identify novel candidate genes and pathways targeted by folate during pregnancy that have a role in disease on-set and/or prevention.
2020-11-23 | GSE161954 | GEO
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:Treatments for kidney fibrosis represent an urgent yet unmet clinical need. Effective therapies are limited due to not well understood molecular pathogenesis. We aimed at generating a comprehensive and integrated multi-omics data set (RNA/ microRNA transcriptomics and proteomics) of fibrotic kidneys which will be searchable through a user-friendly web application. Therefore, two commonly used mouse models were utilized: a reversible chemical-induced injury model (folic acid (FA) induced nephropathy) and an irreversible surgical-induced fibrosis model (unilateral ureteral obstruction (UUO)). RNA and small RNA sequencing as well as MS/MS with 10-plex tandem mass tags proteomics were performed with kidney samples from different time points over the course of fibrosis development. In summary, we present temporal and integrated multi-omics data from fibrotic mouse kidneys which are accessible through an interrogation tool to provide a searchable transcriptome and proteome for kidney fibrosis researcher.
2019-05-09 | PXD011453 | Pride
Project description:Folic acid is involved in DNA methylation, thereby it can potentially induce gene silencing. We used microarrays to detect the transcripts that are showing different expressions after short-term folic acid (FA) treatment.
2022-04-20 | GSE186084 | GEO
Project description:The effect of folic acid (FA) on breast cancer (BC) risk is uncertain. We hypothesised that this uncertainty may be due, in part, to differential effects of FA between BC cells with different phenotype. To test this we investigated the effect of treatment with FA concentrations within the range of unmetabolised FA reported in humans on the expression of the transcriptomes of non-transformed (MCF10a) and cancerous (MCF7 and Hs578T) BC cells. Total RNA obtained from three breast cancer cell lines (MCF10a, MCF7, Hs578T) treated with 100nmoles/l folic acid untreated control cells. Six replicates per treatment group.
2015-05-08 | E-GEOD-68651 | biostudies-arrayexpress
Project description:Folic acid is present in pre-natal vitamins, fortified cereal grains and multi-vitamin supplements. High intake of folic acid through these sources has resulted in populations with increased levels of serum folate and unmetabolized folic acid. Although the benefits of folic acid in the prevention of neural tube defects are undeniable, the impact of long-term consumption of folic acid on the prostate is not fully understood. In this study, we used a rodent model to test whether dietary folic acid (FA) supplementation changes prostate homeostasis and response to androgen deprivation. Although intact prostate weights do not differ between diet groups, we made the surprising observation that dietary folic acid supplementation confers partial resistance to castration-mediated prostate involution. More specifically, male mice that were fed a folic acid supplemented diet and then castrated had greater prostate wet weights, greater prostatic luminal epithelial cell heights, and more abundant RNAs encoding prostate secretory proteins compared to mice that were fed a control diet and castrated. We used RNA-seq to identify signaling pathways enriched in the castrated prostates from folic acid supplemented diet fed mice compared to control mice. We observed differential expression of genes involved in several metabolic pathways in the FA supplemented mice. Together, our results show that dietary FA supplementation can impact metabolism in the prostate and attenuate the prostate’s response to androgen deprivation. This has important implications for androgen deprivation therapies used in the treatment of prostate disease, as consumption of high levels of folic acid could reduce the efficacy of these treatments.
2018-08-22 | GSE116299 | GEO
Project description:The effect of folic acid (FA) on breast cancer (BC) risk is uncertain. We hypothesised that this uncertainty may be due, in part, to differential effects of FA between BC cells with different phenotype. To test this we investigated the effect of treatment with FA concentrations within the range of unmetabolised FA reported in humans on the expression of the transcriptomes of non-transformed (MCF10a) and cancerous (MCF7 and Hs578T) BC cells.
2015-05-08 | GSE68651 | GEO
Project description:Maternal vitamins and micronutrients during gestational periods have profound impact on the developmemt of newborns as well as influence susceptibility to chronic conditions. Folic acid is indicated to women during pregnancies to prevent occurrence of neural tube defects in infants. Recently, evidence is emerging of the epigenetic effects of folic acid. Since epigenetic changes are crucial in developing fetus, we investigated the effect of maternal higher folic acid supplementation on the gene expression in offspring brains to identify if brain development may be affected. Our results revealed that maternal exposure of higher dose FA diet during gestation dysregulates expression of several genes in the cerebellum of both male and female pups. Dysregulated genes included several transcriptional factors, imprinted genes, neurodevelopmental genes and genes associated with autism spectrum disorder. Adult, 8- to 10-week-old C57BL/6J mice were used in all the experiments and handled according to the protocol reviewed and approved by the Institute for Basic Research Institutional Animal Care and Use Committee. One week prior to mating and throughout the pregnancy two groups of female mice were fed with custom AIN-93G amino acidM-bM-^@M-^Sbased diet (Research Diet, Inc. New-Brunswick, NJ), which contained folic acid (FA) at 2mg/kg and 20 mg/kg diet. At postnatal day one (P1), from FA at 2 mg/kg group: male pupsM-bM-^@M-^Y n=3 and female pupsM-bM-^@M-^Y n=3 were sacrificed by cervical dislocation and cerebellum tissues were collected. From FA at 20 mg/kg group: male pupsM-bM-^@M-^Y n=6 and female pups n=6 were similarly processed. All tissues were snapped frozen and stored at -80M-BM-0C until downstream analysis was performed.
2015-01-26 | E-GEOD-60531 | biostudies-arrayexpress
Project description:Kidney fibrosis represents an urgent unmet clinical need due to the lack of effective therapies and inadequate understanding of the molecular pathogenesis. We have generated a comprehensive and integrated multi-omics data set (proteomics, mRNA and small RNA transcriptomics) of fibrotic kidneys that is searchable through a user-friendly web application. Two commonly used mouse models were utilized: a reversible chemical-induced injury model (folic acid (FA) induced nephropathy) and an irreversible surgically-induced fibrosis model (unilateral ureteral obstruction (UUO)). mRNA and small RNA sequencing as well as 10-plex tandem mass tag (TMT) proteomics were performed with kidney samples from different time points over the course of fibrosis development. The bioinformatics workflow used to process, technically validate, and integrate the single data sets will be described. In summary, we present temporal and integrated multi-omics data from fibrotic mouse kidneys that are accessible through an interrogation tool to provide a searchable transcriptome and proteome for kidney fibrosis researchers.
2019-05-07 | GSE126181 | GEO
Project description:[6S]-5-methyltetrahydrofolic acid (MTHF) is a proposed replacement for folic acid (FA) in diets and prenatal supplements. This study compared the effects of these two forms on maternal metabolism and hypothalamic gene expression. Pregnant Wistar rats received an AIN-93G diet with recommended FA (1X, 2 mg/kg, control), 5X-FA or equimolar levels of MTHF. During lactation they received the control diet and then a high fat diet for 19-weeks post-weaning. Body weight, adiposity, food intake, energy expenditure, plasma hormones, folate, and 1-carbon metabolites were measured. RNA-sequencing of the hypothalamus was conducted at parturition. Weight-loss from weaning to 1-week post-weaning was less in dams fed either form of the 5X vs. 1X folate diets, but final weight-gain was higher in 5X-MTHF vs. 5X-FA dams. Both doses of the MTHF diets led to 8% higher food intake and associated with lower plasma leptin at parturition, but higher leptin at 19-weeks and insulin resistance at 1-week post-weaning. RNA-sequencing revealed 279 differentially expressed genes in the hypothalamus in 5X-MTHF vs. 5X-FA dams. These findings indicate that MTHF and FA differ in their programing effects on maternal phenotype, and a potential adverse role of either form when given at the higher doses.
| S-EPMC7823556 | biostudies-literature