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.

Abstract

SCOPE:

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.

METHODS AND RESULTS:

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 S-adenosylmethionine:S-adenosylhomocysteine ratios were reduced in FD. In liver, spleen, and placenta, the lowest levels of apolipoprotein AI (ApoAI) were observed in Mthfr(+/-) mice fed FD. Increased interferon-gamma (IFN-γ) was observed in spleen and placentae due to FD or Mthfr genotype. Plasma homocysteine correlated negatively with liver and spleen ApoAI, and positively with IFN-γ.

CONCLUSION:

Low dietary folate or Mthfr 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.

• Authors: Leonie G Mikael, Jill Pancer, Xinyin Jiang, Qing Wu, Marie Caudill, Rima Rozen
• Journal: Molecular nutrition & food research (Mol Nutr Food Res) Vol. 57 Issue 4 Pg. 661-70 (Apr 2013) ISSN: 1613-4133 [Electronic] Germany
• PMID: 23112124 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: © 2012 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Chemical References

• Apolipoprotein A-I
• Homocysteine
• Betaine
• S-Adenosylmethionine
• Interferon-gamma
• Folic Acid
• S-Adenosylhomocysteine
• Methylenetetrahydrofolate Reductase (NADPH2)
• Choline

Topics

• Animals
• Apolipoprotein A-I (metabolism)
• Betaine (analysis, metabolism)
• Choline (analysis, metabolism)
• Diet
• Female
• Folic Acid (administration & dosage)
• Folic Acid Deficiency (complications, pathology)
• Homocysteine (blood)
• Homocystinuria (complications, pathology)
• Interferon-gamma (metabolism)
• Liver (metabolism, pathology)
• Male
• Methylation
• Methylenetetrahydrofolate Reductase (NADPH2) (deficiency, genetics, metabolism)
• Mice
• Mice, Inbred BALB C
• Mice, Transgenic
• Muscle Spasticity (complications, pathology)
• Placenta (metabolism, pathology)
• Pregnancy
• Pregnancy Complications (genetics, metabolism)
• Psychotic Disorders (complications, pathology)
• S-Adenosylhomocysteine (analysis, metabolism)
• S-Adenosylmethionine (analysis, metabolism)
• Spleen (metabolism, pathology)