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High Gestational Folic Acid Supplementation Alters Expression of Imprinted and Candidate Autism Susceptibility Genes in a sex-Specific Manner in Mouse Offspring

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Abstract

Maternal nutrients play critical roles in modulating epigenetic events and exert long-term influences on the progeny’s health. Folic acid (FA) supplementation during pregnancy has decreased the incidence of neural tube defects in newborns, but the influence of high doses of maternal FA supplementation on infants’ brain development is unclear. The present study was aimed at investigating the effects of a high dose of gestational FA on the expression of genes in the cerebral hemispheres (CHs) of 1-day-old pups. One week prior to mating and throughout the entire period of gestation, female C57BL/6J mice were fed a diet, containing FA at either 2 mg/kg (control diet (CD)) or 20 mg/kg (high maternal folic acid (HMFA)). At postnatal day 1, pups from different dams were sacrificed and CH tissues were collected. Quantitative RT-PCR and Western blot analysis confirmed sex-specific alterations in the expression of several genes that modulate various cellular functions (P < 0.05) in pups from the HMFA group. Genomic DNA methylation analysis showed no difference in the level of overall methylation in pups from the HMFA group. These findings demonstrate that HMFA supplementation alters offsprings’ CH gene expression in a sex-specific manner. These changes may influence infants’ brain development.

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Abbreviations

FA:

Folic acid

NTDs:

Neural tube defects

CD:

Control dose

HMFA:

High maternal folic acid

5-mC:

5-Methylcytosine

CH:

Cerebral hemisphere

SEM:

Standard error of the mean

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Acknowledgments

Financial support from the March of Dimes Foundation (12-FY12-170) and the New York State Office for People with Developmental Disabilities is gratefully acknowledged. We acknowledge Ms. Maureen Marlow for help with editorial corrections with the manuscript.

Authors' Contributions

WTB and MAJ conceived the experiments; SB, WTB, and MAJ designed the experiments; SB, SK, and MAJ performed the experiments; SB, SK, and MAJ analyzed the data; SB, SK, WTB, and MAJ contributed reagents/materials/analysis tools; SB wrote the paper; and WTB and MAJ critically revised the manuscript.

Financial Support

Financial support from the March of Dimes Foundation (12-FY12-170) and the New York State Office for People with Developmental Disabilities is gratefully acknowledged.

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Authors and Affiliations

  1. Structural Neurobiology Laboratory, Department of Developmental Biochemistry, New York State Institute for Basic Research in Developmental Disabilities, 1050 Forest Hill Road, Staten Island, NY, 10314, USA

    Subit Barua, Salomon Kuizon & Mohammed A. Junaid

  2. Department of Pathology and Cell Biology, College of Physicians and Surgeons, Columbia University, 630 West 168th Street, New York, NY, 10032, USA

    Subit Barua

  3. Department of Human Genetics, New York State Institute for Basic Research in Developmental Disabilities, 1050 Forest Hill Road, Staten Island, NY, 10314, USA

    W. Ted Brown

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  1. Subit Barua
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  4. Mohammed A. Junaid
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Correspondence to Mohammed A. Junaid.

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Electronic Supplementary Material

Figure S1

The schematic diagram of the experimental design for this study (GIF 670 kb)

High Resolution Image (TIFF 277 kb)

Table S1

List of primers used in this study (DOCX 12 kb)

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Barua, S., Kuizon, S., Ted Brown, W. et al. High Gestational Folic Acid Supplementation Alters Expression of Imprinted and Candidate Autism Susceptibility Genes in a sex-Specific Manner in Mouse Offspring. J Mol Neurosci 58, 277–286 (2016). https://doi.org/10.1007/s12031-015-0673-8

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