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

ABSTRACT: 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.

ORGANISM(S): Mus musculus

PROVIDER: GSE134588 | GEO | 2024/03/03

REPOSITORIES: GEO

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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

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

A folic acid-enriched diet attenuates prostate involution in response to androgen deprivation

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

Maternal folic acid supplementation alters gene expression in the offspring brain

2013-09-09 | GSE45607 | GEO

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 supplementation alters gene expression in the offspring brain

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

Nanopore sequencing reveals the roles of spermatozoal DNA N6-Methyladenine modification in mediating transgenerational lipid metabolism disorder induced by folic acid excessive consumption in chicken [RNA-seq]

Project description:Increased consumption of folic acid is prevalent due to its beneficial effects to help protecting from genome damage. Growing evidence is emphasizing the side effects pointing to excessive dietary intake. Effects of paternal folic acid excessive consumption on the offspring and its transgenerational inheritance mechanism remain elusive. We hypothesize that the folic acid excessive consumption will alter sperm DNA N6-methyladenine (6mA) and 5-methylcytosine (5mC) methylation, and heritably influence offspring metabolic homeostasis. This is the results of mRNA sequencing part

2020-12-16 | GSE163238 | GEO

Higher maternal folic acid during gestation dysregulates expression of several genes in mice offspring cerebellum

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

Folic acid treatment of colorectal cancer cell lines

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

Study of Folic Acid, Calcium and Vitamin D in Preventing Colorectal Polyps and Colorectal Cancer

Project description:Folic acid (FA) and its derivatives (folate) which play a role in nucleotide synthesis and methylation reactions as well as calcium and vitamin D are assumed to be effective in the prevention of colorectal polyps and Colorectal cancer (CRC). The aim of this study is to investigate the roles of FA as well as calcium and vitamin D in the prevention of CRC.

| 2161109 | ecrin-mdr-crc

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