High intake of folic acid disrupts embryonic development in mice

Authors

  • Laura Pickell,

    1. Department of Human Genetics, McGill University and Montreal Children's Hospital Research Institute, Montreal, Quebec, Canada
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  • Katharine Brown,

    1. Department of Biology, McGill University and Montreal Children's Hospital Research Institute, Montreal, Quebec, Canada
    Current affiliation:
    1. Department of Nutritional Sciences and Toxicology, University of California, Berkeley, CA 94720
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  • Deqiang Li,

    1. Department of Human Genetics, McGill University and Montreal Children's Hospital Research Institute, Montreal, Quebec, Canada
    2. Department of Pediatrics, McGill University and Montreal Children's Hospital Research Institute, Montreal, Quebec, Canada
    Current affiliation:
    1. Department of Medical and Molecular Genetics, Indiana University School of Medicine, Indianapolis, IN 46202
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  • Xiao-Ling Wang,

    1. Department of Human Genetics, McGill University and Montreal Children's Hospital Research Institute, Montreal, Quebec, Canada
    2. Department of Pediatrics, McGill University and Montreal Children's Hospital Research Institute, Montreal, Quebec, Canada
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  • Liyuan Deng,

    1. Department of Human Genetics, McGill University and Montreal Children's Hospital Research Institute, Montreal, Quebec, Canada
    2. Department of Pediatrics, McGill University and Montreal Children's Hospital Research Institute, Montreal, Quebec, Canada
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  • Qing Wu,

    1. Department of Human Genetics, McGill University and Montreal Children's Hospital Research Institute, Montreal, Quebec, Canada
    2. Department of Pediatrics, McGill University and Montreal Children's Hospital Research Institute, Montreal, Quebec, Canada
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  • Jacob Selhub,

    1. Jean Mayer United States Department of Agriculture Human Nutrition Research Center on Aging, Tufts University, Boston, Massachusetts
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  • Li Luo,

    1. Department of Human Genetics, McGill University and Montreal Children's Hospital Research Institute, Montreal, Quebec, Canada
    2. Department of Pediatrics, McGill University and Montreal Children's Hospital Research Institute, Montreal, Quebec, Canada
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  • Loydie Jerome-Majewska,

    1. Department of Human Genetics, McGill University and Montreal Children's Hospital Research Institute, Montreal, Quebec, Canada
    2. Department of Pediatrics, McGill University and Montreal Children's Hospital Research Institute, Montreal, Quebec, Canada
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  • Rima Rozen

    Corresponding author
    1. Department of Human Genetics, McGill University and Montreal Children's Hospital Research Institute, Montreal, Quebec, Canada
    2. Department of Biology, McGill University and Montreal Children's Hospital Research Institute, Montreal, Quebec, Canada
    3. Department of Pediatrics, McGill University and Montreal Children's Hospital Research Institute, Montreal, Quebec, Canada
    • McGill-Montreal Children's Hospital Research Institute, 4060 St. Catherine's Street West, Room 242, Montreal, QC, Canada H3Z 2Z3
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Abstract

BACKGROUND

Folic acid fortification and supplementation has increased folate intake and blood folate concentrations and successfully reduced the incidence of neural tube defects. However, the developmental consequences of high folate intake are unknown. This study investigated the impact of high folate intake, alone or with methylenetetrahydrofolate reductase (MTHFR) deficiency, on embryonic and placental development in mice.

METHODS

Mthfr +/+ or +/− pregnant mice on a control diet (CD; recommended intake of folic acid for rodents) or folic acid-supplemented diet (FASD; 20-fold higher than the recommended intake) were examined for embryonic loss, delay, and defects at 10.5 and 14.5 days post coitum (dpc); 10.5-dpc placenta, and 14.5-dpc embryo hearts were studied histologically.

RESULTS

Total plasma folate was 10-fold higher in FASD compared to CD mice; plasma homocysteine levels were not affected by diet. At 10.5 dpc, the FASD was associated with embryonic delay and growth retardation, and may confer susceptibility to embryonic defects. The FASD did not adversely affect 10.5-dpc placental development. At 14.5 dpc, embryos from the FASD Mthfr +/+ group were delayed and the FASD was associated with thinner ventricular walls in embryonic hearts. There was a significant interaction between maternal MTHFR deficiency and a high folate diet for several developmental outcomes.

CONCLUSIONS

Our study suggests that high folate intake may have adverse effects on fetal mouse development and that maternal MTHFR deficiency may improve or rescue some of the adverse outcomes. These findings underscore the need for additional studies on the potential negative impact of high folate intake during pregnancy. Birth Defects Research (Part A), 2011. © 2010 Wiley-Liss, Inc.

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