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High (5X) 5-methyltetrahydrofolate (MTHF) vs folic acid (FA) pregnancy diets on hypothalamic gene expression of Wistar rat dams upon birth.

ABSTRACT: 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.

ORGANISM(S): Rattus norvegicus

PROVIDER: GSE161954 | GEO | 2020/11/23

REPOSITORIES: GEO

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High (5X) 5-methyltetrahydrofolate (MTHF) vs folic acid (FA) pregnancy diets on hypothalamic gene expression of Wistar rat dams upon birth.

Project description:High (5X) 5-methyltetrahydrofolate (MTHF) vs folic acid (FA) pregnancy diets on hypothalamic gene expression of Wistar rat dams upon birth.

| PRJNA680036 | ENA

Organ-specific gene expression changes in the fetal liver and placenta in response to maternal folate depletion

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

Maternal folic acid overconsumption in mice leads to sex-specific transcriptional alterations in cerebral cortex in offspring

Project description:Recent concerns have been raised regarding high folate intake during pregnancy and lactation, particularly following food fortiﬁcation and increased vitamin supplement use. Epidemiologic studies have shown that high folic acid (FA) intake can negatively impact motor and neurocognitive development in offspring. We used microarray to investigate the mechanisms by which a supplemented diet containing 5-fold higher FA than recommended (FASD) affects brain function in both male and female offspring.

2024-03-03 | GSE134588 | GEO

Maternal folic acid over consumption in mice leads to sex-specific transcriptional alterations in cerebral cortex in offspring

Project description:Recent concerns have been raised regarding high folate intake during pregnancy and lactation, particularly following food fortiﬁcation and increased vitamin supplement use. Epidemiologic studies have shown that high folic acid (FA) intake can negatively impact motor and neurocognitive development in offspring. We used microarray to investigate the impact of a supplemented diet containing 5-fold higher FA than recommended (5xFASD) on cerebral transcription profile in both male and female postnatal day (P) 30 pups. We also studied gene expression changes due to sex.

2022-03-15 | GSE193355 | GEO

Expression and Metabolic Profiles in a Panel of Five Neural Tube Defect Mouse Models

Project description:Neural tube defects (NTDs) are serious birth defects with an estimated worldwide incidence of 1 per 1,000 live births. The multifactorial nature of NTDs in humans has made it difficult to elucidate pathogenesis mechanisms. However, a strong relationship has been established between folate-homocysteine metabolism and NTD risk. Prevention of a substantial proportion of fetal NTDs can be achieved through maternal folic acid (FA) supplementation. However the mechanism by which FA exerts its beneficial effect remains unclear. METHODS: To improve our understanding of the underlying mechanisms of NTD pathogenesis and the ways in which folate exerts its beneficial effect, we analyzed mRNA profiles as well as folate and vitamin B12 levels in five NTD mouse mutants whose response to dietary FA was previously established. RESULTS: Differentially expressed genes representing the effect of each NTD-causing mutation were identified and associated with biologic pathways. Interestingly, the panel of NTD mutants collectively revealed pathways related to two nuclear receptors, retinoid X receptor (RXR) and pregnane X receptor (PXR), suggesting that these pathways may be related to a shared mechanism of NTD development. Moreover, the NTD-causing mutations that were associated with FA responsiveness had expression profiles that were related to folate-homocysteine metabolic pathways. These pathways were not strongly associated with mutants that do not respond to FA supplementation, implying that FA may be beneficial when the NTD mutation affects pathways related to folate-homocysteine metabolism. 5 groups of NTD mutants were studied. From each mutant group Heterozygous (test) and wild-type (control) female pups were used for this study at 6-8 weeks of age. 4 biological replicates were used for each of the test and control groups of each mutant. All mice used for the experiments were fasted 4-5 hours before dissection. A total of 36 samples were analyzed.

2013-09-30 | E-GEOD-51285 | biostudies-arrayexpress

Maternal folic acid mild over consumption in mice leads to sex-specific transcriptional alterations in E17.5 embryonic cerebrum

Project description:Food fortification of folic acid (FA) and increased use of vitamin supplements have raised concerns over high folate intake periconceptionally. We reported that diet containing 5-fold higher FA than recommended for mice (5xFASD) during pregnancy, resulted in neurobehavioral abnormalities (hyperactivity and short-term memory impairment) in newborns. Our goal was to determine the origins of these changes and the underlying mechanisms by examing potential transcription changes in E17.5 embryonic cerebrum. We used microarrays to compare the E17.5 cerebral gene expression changes by 5xFASD and indentified different transcription profiles due to diet or sex.

2022-03-15 | GSE193352 | GEO

Expression and Metabolic Profiles in a Panel of Five Neural Tube Defect Mouse Models

2013-09-30 | GSE51285 | GEO

Gene promoter DNA methylation patterns have limited role in orchestrating transcriptional changes in the fetal liver in response to maternal folate depletion during pregnancy.

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

FolR1 gene ablation-induced changes in gene expression in mouse conotrucus tissue and developing heart

Project description:Defective function of FolR1 in mice results in inadequate transport, accumulation, or metabolism of folate during cardiovascular morphogenesis. We have observed cardiovascular abnormalities including outflow track defects and aortic arch artery defects in these genetically compromised mice. In order to investigate the mechanisms underlying the failure to complete cardiac development in the transgenic mouse model, we studied gene expression difference between FolR1 knockout embryos and normal embryos during outflow track septation (GD11:12, GSM78976 ... GSM78987), and studied gene expression difference between FolR1 knockout embryos and normal embryos during embryonic heart development(GD9:00 and GD10:00, GSM79024 ... GSM79035). Keywords: gene ablation response Pregnant FolR1 heterozygotic dams were supplemented with s-folinic acid 6.25mg/kg/day p.o. At GD11:12, 3 control embryos and 3 null embryos were harvested from 6 different dams. From these embryos, the conotruncus tissue of developing heart was dissected and RNA extracted. These RNA samples were used for hybridization on commercially available CodeLink UniSet 10K Bioarray. Pregnant FolR1 heterozygotic dams were supplemented with s-folinic acid 6.25mg/kg/day p.o. At GD9:00 and GD10:00, 3 control embryos and 3 null embryos were harvested from 6 different dams for each timepoint. From these embryos, the heart tissue of developing heart was dissected and RNA extracted. These RNA samples were used for hybridization on commercially available CodeLink UniSet 20K Bioarray.

2006-02-20 | E-GEOD-3487 | biostudies-arrayexpress

Maternal folic acid mild over consumption in mice leads to sex-specific transcriptional alterations in embryonic placenta

Project description:Food fortification and increased use of multivitamins have led to concerns over high folate intake periconceptionally. We reported that diets containing 5-fold higher FA than recommended for mice (5xFASD) during pregnancy, resulted in deficiency of methylenetetrahydrofolate reductase (MTHFR) and altered choline/methyl metabolism, with neurobehavioral abnormalities in newborns. Our goal was to determine whether these changes had their origins in the placenta during embryonic development. We used microarrays to compare the placental gene expression changes by 5xFASD and indentified different gene expression profiles due to diet or sex.

2021-06-11 | GSE164408 | GEO

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