title: 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: METHODS
  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.
  
  
  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.
  
  
  CONCLUSIONS
  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.affiliation: Department of Human Genetics, McGill University, Montreal Children's Hospital Research Institute, Montreal, QC, Canada.
authors.forename: Leonie G
authors.initials: LG
authors.lastname: Mikael
authors.forename: Jill
authors.initials: J
authors.lastname: Pancer
authors.forename: Xinyin
authors.initials: X
authors.lastname: Jiang
authors.forename: Qing
authors.initials: Q
authors.lastname: Wu
authors.forename: Marie
authors.initials: M
authors.lastname: Caudill
authors.forename: Rima
authors.initials: R
authors.lastname: Rozen
mesh_terms: D000818:Animals; D016632:Apolipoprotein A-I / Q000378:metabolism*; D001622:Betaine / Q000032:analysis / Q000378:metabolism; D002794:Choline / Q000032:analysis / Q000378:metabolism; D004032:Diet; D005260:Female; D005492:Folic Acid / Q000008:administration & dosage*; D005494:Folic Acid Deficiency / Q000150:complications / Q000473:pathology; D006710:Homocysteine / Q000097:blood; D006712:Homocystinuria / Q000150:complications / Q000473:pathology; D007371:Interferon-gamma / Q000378:metabolism*; D008099:Liver / Q000378:metabolism / Q000473:pathology; D008297:Male; D008745:Methylation; D042965:Methylenetetrahydrofolate Reductase (NADPH2) / Q000172:deficiency / Q000235:genetics* / Q000378:metabolism; D051379:Mice; D008807:Mice, Inbred BALB C; D008822:Mice, Transgenic; D009128:Muscle Spasticity / Q000150:complications / Q000473:pathology; D010920:Placenta / Q000378:metabolism / Q000473:pathology; D011247:Pregnancy; D011248:Pregnancy Complications / Q000235:genetics* / Q000378:metabolism; D011618:Psychotic Disorders / Q000150:complications / Q000473:pathology; D012435:S-Adenosylhomocysteine / Q000032:analysis / Q000378:metabolism; D012436:S-Adenosylmethionine / Q000032:analysis / Q000378:metabolism; D013154:Spleen / Q000378:metabolism / Q000473:pathology
chemical_list: D016632:Apolipoprotein A-I; D006710:Homocysteine; D001622:Betaine; D012436:S-Adenosylmethionine; D007371:Interferon-gamma; D005492:Folic Acid; D012435:S-Adenosylhomocysteine; D042965:Methylenetetrahydrofolate Reductase (NADPH2); D002794:Choline