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Microarray analysis reveals higher gestational folic Acid alters expression of genes in the cerebellum of mice offspring-a pilot study.

Barua S, Kuizon S, Chadman KK, Brown WT, Junaid MA - Brain Sci (2015)

Bottom Line: Microarray analysis was used to investigate the genome wide gene expression profile in the cerebellum from day old pups.Several transcription factors, imprinted genes, neuro-developmental genes and genes associated with autism spectrum disorder exhibited altered expression levels.These findings suggest that higher gestational FA potentially dysregulates gene expression in the offspring brain and such changes may adversely alter fetal programming and overall brain development.

View Article: PubMed Central - PubMed

Affiliation: Developmental Biochemistry, New York State Institute for Basic Research in Developmental Disabilities, 1050 Forest Hill Road, Staten Island, NY 10314, USA. subitbarua@gmail.com.

ABSTRACT
Folate is a water-soluble vitamin that is critical for nucleotide synthesis and can modulate methylation of DNA by altering one-carbon metabolism. Previous studies have shown that folate status during pregnancy is associated with various congenital defects including the risk of aberrant neural tube closure. Maternal exposure to a methyl supplemented diet also can alter DNA methylation and gene expression, which may influence the phenotype of offspring. We investigated if higher gestational folic acid (FA) in the diet dysregulates the expression of genes in the cerebellum of offspring in C57BL/6 J mice. One week before gestation and throughout the pregnancy, groups of dams were supplemented with FA either at 2 mg/kg or 20 mg/kg of diet. Microarray analysis was used to investigate the genome wide gene expression profile in the cerebellum from day old pups. Our results revealed that exposure to the higher dose FA diet during gestation dysregulated expression of several genes in the cerebellum of both male and female pups. Several transcription factors, imprinted genes, neuro-developmental genes and genes associated with autism spectrum disorder exhibited altered expression levels. These findings suggest that higher gestational FA potentially dysregulates gene expression in the offspring brain and such changes may adversely alter fetal programming and overall brain development.

No MeSH data available.


Related in: MedlinePlus

Overview of differential gene expression in the cerebellum of P1 pups. The distribution of (a) down-regulated genes, as well as (b) up-regulated genes, between male (MCB) and female (FCB) pups from higher gestational FA.
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brainsci-05-00014-f001: Overview of differential gene expression in the cerebellum of P1 pups. The distribution of (a) down-regulated genes, as well as (b) up-regulated genes, between male (MCB) and female (FCB) pups from higher gestational FA.

Mentions: In the microarray analysis of transcripts from 2 mg FA group vs. 20 mg FA group of postnatal day one (P1) pups, the expression pattern of a significant number of genes were found to be altered by ≥2.5 fold at a significance of p > 0.05. Overall, in male pups the expression patterns of 1076 transcripts were down-regulated (Supplementary Table S1) and 499 transcripts were up-regulated (Supplementary Table S2) in the cerebellum from the 20 mg maternal FA group. In female pups, the expressions of 4764 transcripts (Supplementary Table S3) were down-regulated and 1511 transcripts (Supplementary Table S4) were up-regulated. The expression of 339 transcripts that were down-regulated and 152 transcripts that were up-regulated by ≥2.5 fold in pups’ cerebellum were common for both the genders in the 20 mg maternal FA group (Figure 1). These results of microarray data illustrate that higher maternal FA during gestation can induce significant alterations in the expression of transcripts in offspring brain cerebellum. The data further suggests that in addition to the FA dose, there is an interaction between maternal FA dose and its role in modulating the gene expression levels depending on the sex of the offspring.


Microarray analysis reveals higher gestational folic Acid alters expression of genes in the cerebellum of mice offspring-a pilot study.

Barua S, Kuizon S, Chadman KK, Brown WT, Junaid MA - Brain Sci (2015)

Overview of differential gene expression in the cerebellum of P1 pups. The distribution of (a) down-regulated genes, as well as (b) up-regulated genes, between male (MCB) and female (FCB) pups from higher gestational FA.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4390789&req=5

brainsci-05-00014-f001: Overview of differential gene expression in the cerebellum of P1 pups. The distribution of (a) down-regulated genes, as well as (b) up-regulated genes, between male (MCB) and female (FCB) pups from higher gestational FA.
Mentions: In the microarray analysis of transcripts from 2 mg FA group vs. 20 mg FA group of postnatal day one (P1) pups, the expression pattern of a significant number of genes were found to be altered by ≥2.5 fold at a significance of p > 0.05. Overall, in male pups the expression patterns of 1076 transcripts were down-regulated (Supplementary Table S1) and 499 transcripts were up-regulated (Supplementary Table S2) in the cerebellum from the 20 mg maternal FA group. In female pups, the expressions of 4764 transcripts (Supplementary Table S3) were down-regulated and 1511 transcripts (Supplementary Table S4) were up-regulated. The expression of 339 transcripts that were down-regulated and 152 transcripts that were up-regulated by ≥2.5 fold in pups’ cerebellum were common for both the genders in the 20 mg maternal FA group (Figure 1). These results of microarray data illustrate that higher maternal FA during gestation can induce significant alterations in the expression of transcripts in offspring brain cerebellum. The data further suggests that in addition to the FA dose, there is an interaction between maternal FA dose and its role in modulating the gene expression levels depending on the sex of the offspring.

Bottom Line: Microarray analysis was used to investigate the genome wide gene expression profile in the cerebellum from day old pups.Several transcription factors, imprinted genes, neuro-developmental genes and genes associated with autism spectrum disorder exhibited altered expression levels.These findings suggest that higher gestational FA potentially dysregulates gene expression in the offspring brain and such changes may adversely alter fetal programming and overall brain development.

View Article: PubMed Central - PubMed

Affiliation: Developmental Biochemistry, New York State Institute for Basic Research in Developmental Disabilities, 1050 Forest Hill Road, Staten Island, NY 10314, USA. subitbarua@gmail.com.

ABSTRACT
Folate is a water-soluble vitamin that is critical for nucleotide synthesis and can modulate methylation of DNA by altering one-carbon metabolism. Previous studies have shown that folate status during pregnancy is associated with various congenital defects including the risk of aberrant neural tube closure. Maternal exposure to a methyl supplemented diet also can alter DNA methylation and gene expression, which may influence the phenotype of offspring. We investigated if higher gestational folic acid (FA) in the diet dysregulates the expression of genes in the cerebellum of offspring in C57BL/6 J mice. One week before gestation and throughout the pregnancy, groups of dams were supplemented with FA either at 2 mg/kg or 20 mg/kg of diet. Microarray analysis was used to investigate the genome wide gene expression profile in the cerebellum from day old pups. Our results revealed that exposure to the higher dose FA diet during gestation dysregulated expression of several genes in the cerebellum of both male and female pups. Several transcription factors, imprinted genes, neuro-developmental genes and genes associated with autism spectrum disorder exhibited altered expression levels. These findings suggest that higher gestational FA potentially dysregulates gene expression in the offspring brain and such changes may adversely alter fetal programming and overall brain development.

No MeSH data available.


Related in: MedlinePlus