Low dietary folate and methylenetetrahydrofolate reductase deficiency may lead to pregnancy complications through modulation of ApoAI and IFN‐γ in spleen and placenta, and through reduction of methylation potential. Issue 4 (30th October 2012)

• Record Type: Journal Article
• Authors: Mikael, Leonie G.; Pancer, Jill; Jiang, Xinyin; Wu, Qing; Caudill, Marie; Rozen, Rima; Ulrich, Cornelia M.; Miller, Joshua W.
• Is Part Of: Molecular nutrition & food research. Volume 57:Issue 4(2013:Apr.)
• Page Start: 661
• Page End: 670
• Publication Date: 2012-10-30
• Subjects: Food -- Biotechnology -- Periodicals; Food -- Microbiology -- Periodicals; Nutrition -- Periodicals; Food -- Toxicology -- Periodicals; Nutrition -- Periodicals; Food Microbiology -- Periodicals; Food Technology -- Periodicals; Molecular Biology -- Periodicals; 664.0705
• DOI: 10.1002/mnfr.201200152
• Languages: English
• ISSNs: 1613-4125

Abstract

<abstract abstract-type="main"> <title> <x xml:space="preserve">Abstract</x> </title> <sec id="mnfr1848-sec-0010" sec-type="section"> <title>Scope</title> <p>Genetic or nutritional disturbances in folate metabolism lead to hyperhomocysteinemia and adverse reproductive outcomes. Folate‐dependent homocysteine remethylation is required for methylation reactions and may influence choline/betaine metabolism. Hyperhomocysteinemia has been suggested to play a role in inflammation. The goal of this study was to determine whether folate‐related pregnancy complications could be due to altered expression of some inflammatory mediators or due to disturbances in methylation intermediates.</p> </sec> <sec id="mnfr1848-sec-0020" sec-type="section"> <title>Methods and results</title> <p>Pregnant mice with or without a deficiency of methylenetetrahydrofolate reductase (MTHFR) were fed control diets or folate‐deficient (FD) diets; tissues were collected at embryonic day 14.5. FD decreased plasma phosphocholine and increased plasma glycerophosphocholine and lysophosphatidylcholine. Liver betaine, phosphocholine, and <italic>S</italic>‐adenosylmethionine:<italic>S</italic>‐adenosylhomocysteine ratios were reduced in FD. In liver, spleen, and placenta, the lowest levels of apolipoprotein AI (ApoAI) were observed in <italic>Mthfr</italic><sup>+/–</sup> mice fed FD. Increased interferon‐gamma (IFN‐γ) was observed in spleen and placentae due to FD or <italic>Mthfr</italic> genotype. Plasma homocysteine correlated negatively with liver and spleen ApoAI, and positively with IFN‐γ.</p> </sec> <sec id="mnfr1848-sec-0030" sec-type="section"> <title>Conclusion</title> <p>Low dietary folate or <italic>Mthfr</italic> deficiency during pregnancy may result in adverse pregnancy outcomes by altering expression of the inflammatory mediators ApoAI and IFN‐γ in spleen and placenta. Disturbances in choline metabolism or methylation reactions may also play a role.</p> </sec> </abstract>