Maternal folic acid overconsumption in mice leads to sex-specific transcriptional alterations in cerebral cortex in offspring
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PROVIDER: PRJNA555715 | ENA |
REPOSITORIES: ENA
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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
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
Project description:Maternal folic acid over consumption in mice leads to sex-specific transcriptional alterations in cerebral cortex in offspring
| PRJNA795956 | ENA
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: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: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.
2015-01-26 | GSE60531 | GEO
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.
2013-09-09 | GSE45607 | 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: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: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