Limits...
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

Schematic diagram of the study design illustrating main experimental approach.
© Copyright Policy
Related In: Results  -  Collection

License
getmorefigures.php?uid=PMC4390789&req=5

brainsci-05-00014-f002: Schematic diagram of the study design illustrating main experimental approach.

Mentions: While analysis of the microarray data revealed that the expression of a number of genes exhibited the same direction of change in both male and female pups from the higher gestational FA group (Figure 2), the expressions of several other genes were sex biased. Indeed, we found that the expression of genes in the cerebellum of female pups were more vulnerable to the changes induced by higher gestational FA. It shows that the in utero exposure of gestational FA may have a different impact depending upon the gender of the progeny, and it may have distinct mechanisms of alterations and consequences. Though the precise mechanism of such changes cannot be established from the present study, it confirms our previous data showing that the gestational FA induces differential alterations in methylation and gene expression in the brain of offspring depending upon gender of the progeny [10]. Of note, several previous studies have shown strong evidence that the susceptibility to neuropsychiatric and neurodegenerative diseases varies between men and women [45,46,47]; and maternal diet can significantly influence fetal outcomes including biasing offspring sex ratio [48]. Moreover, a recent study has shown widespread differences in the splicing and expression of genes in human brain between male and female [49]. Another study has shown that the maturation of GABAA signaling follows sex-specific patterns, which correlate with brain developmental expression profiles [50]. The switch from GABA being excitatory to inhibitory occurs earlier in females than in males.


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)

Schematic diagram of the study design illustrating main experimental approach.
© Copyright Policy
Related In: Results  -  Collection

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

brainsci-05-00014-f002: Schematic diagram of the study design illustrating main experimental approach.
Mentions: While analysis of the microarray data revealed that the expression of a number of genes exhibited the same direction of change in both male and female pups from the higher gestational FA group (Figure 2), the expressions of several other genes were sex biased. Indeed, we found that the expression of genes in the cerebellum of female pups were more vulnerable to the changes induced by higher gestational FA. It shows that the in utero exposure of gestational FA may have a different impact depending upon the gender of the progeny, and it may have distinct mechanisms of alterations and consequences. Though the precise mechanism of such changes cannot be established from the present study, it confirms our previous data showing that the gestational FA induces differential alterations in methylation and gene expression in the brain of offspring depending upon gender of the progeny [10]. Of note, several previous studies have shown strong evidence that the susceptibility to neuropsychiatric and neurodegenerative diseases varies between men and women [45,46,47]; and maternal diet can significantly influence fetal outcomes including biasing offspring sex ratio [48]. Moreover, a recent study has shown widespread differences in the splicing and expression of genes in human brain between male and female [49]. Another study has shown that the maturation of GABAA signaling follows sex-specific patterns, which correlate with brain developmental expression profiles [50]. The switch from GABA being excitatory to inhibitory occurs earlier in females than in males.

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