PMID- 22259189
OWN - NLM
STAT- MEDLINE
DCOM- 20120418
LR  - 20230216
IS  - 1541-6100 (Electronic)
IS  - 0022-3166 (Linking)
VI  - 142
IP  - 3
DP  - 2012 Mar
TI  - Disturbed one-carbon metabolism causing adverse reproductive outcomes in mice is 
      associated with altered expression of apolipoprotein AI and inflammatory 
      mediators PPARalpha, interferon-gamma, and interleukin-10.
PG  - 411-8
LID - 10.3945/jn.111.151753 [doi]
AB  - Low dietary choline or deficiency of methylenetetrahydrofolate reductase (Mthfr) 
      leads to hyperhomocysteinemia (Hhcy) and adverse reproductive outcomes. 
      Homocysteine reduces synthesis of ApoAI, the major lipoprotein in 
      HDL-cholesterol; ApoAI is regulated by PPARalpha and has antiinflammatory properties. 
      Our aim was to determine whether pregnancy complications due to genetic or 
      nutritional deficiencies in 1-carbon metabolism could relate to dysregulation of 
      ApoAI and inflammatory mediators. We fed pregnant mice, with or without a 
      deficiency of Mthfr, control or choline-deficient (ChDD) diets for 10-12 wk and 
      examined levels of ApoAI, PPARalpha, IFNgamma, and IL-10. ApoAI mRNA was reduced in 
      livers of Mthfr(+/-) mice and ApoAI protein was reduced due to Mthfr deficiency 
      or choline deficiency in liver and plasma. Placental ApoAI protein was also 
      reduced due to Mthfr genotype or choline-deficient diet and in developmentally 
      delayed embryos. Reduced liver PPARalpha expression (mRNA and protein) was observed 
      in ChDD-fed mice and was associated with increased methylation of a CpG 
      dinucleotide in its promoter. Hepatic IFNgamma increased due to genotype, and 
      placental IFNgamma was higher in Mthfr(+/-) ChDD-fed dams compared to Mthfr(+/+) mice 
      fed ChDD or Mthfr(+/-) mice fed CD. IL-10 was reduced in livers of ChDD-fed mice. 
      We propose that a deficiency of dietary choline or Mthfr leads to Hhcy and 
      reduced expression of maternal ApoAI, with reduced ApoAI transfer to embryo. 
      Disturbances in 1-carbon metabolism also reduce maternal PPARalpha expression, 
      possibly through promoter hypermethylation, and increase IFNgamma and decrease IL-10 
      levels. This disturbance of the T helper (Th1) (IFNgamma):Th2 (IL-10) ratio and the 
      increase in inflammatory mediators may contribute to pregnancy complications.
FAU - Mikael, Leonie G
AU  - Mikael LG
AD  - Department of Human Genetics, McGill University, Montreal Children's Hospital 
      Research Institute, Montreal, QC, Canada.
FAU - Pancer, Jill
AU  - Pancer J
FAU - Wu, Qing
AU  - Wu Q
FAU - Rozen, Rima
AU  - Rozen R
LA  - eng
GR  - Canadian Institutes of Health Research/Canada
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20120118
PL  - United States
TA  - J Nutr
JT  - The Journal of nutrition
JID - 0404243
RN  - 0 (Apolipoprotein A-I)
RN  - 0 (IL10 protein, mouse)
RN  - 0 (Inflammation Mediators)
RN  - 0 (PPAR alpha)
RN  - 0 (RNA, Messenger)
RN  - 0LVT1QZ0BA (Homocysteine)
RN  - 130068-27-8 (Interleukin-10)
RN  - 82115-62-6 (Interferon-gamma)
RN  - EC 1.5.1.20 (Methylenetetrahydrofolate Reductase (NADPH2))
RN  - Methylenetetrahydrofolate reductase deficiency
SB  - IM
MH  - Animals
MH  - Apolipoprotein A-I/blood/genetics/*metabolism
MH  - Choline Deficiency/complications/metabolism
MH  - DNA Methylation
MH  - Female
MH  - Gene Expression
MH  - Homocysteine/blood/metabolism
MH  - Homocystinuria/complications/genetics/metabolism
MH  - Hyperhomocysteinemia/complications/metabolism
MH  - Inflammation Mediators/blood/metabolism
MH  - Interferon-gamma/*metabolism
MH  - Interleukin-10/*metabolism
MH  - Liver/metabolism
MH  - Male
MH  - Methylenetetrahydrofolate Reductase (NADPH2)/deficiency/genetics/metabolism
MH  - Mice
MH  - Mice, Inbred BALB C
MH  - Mice, Knockout
MH  - Muscle Spasticity/complications/genetics/metabolism
MH  - PPAR alpha/genetics/*metabolism
MH  - Placenta/metabolism
MH  - Pregnancy
MH  - Pregnancy Complications/*etiology/genetics/metabolism
MH  - Promoter Regions, Genetic
MH  - Psychotic Disorders/complications/genetics/metabolism
MH  - RNA, Messenger/genetics/metabolism
EDAT- 2012/01/20 06:00
MHDA- 2012/04/19 06:00
CRDT- 2012/01/20 06:00
PHST- 2012/01/20 06:00 [entrez]
PHST- 2012/01/20 06:00 [pubmed]
PHST- 2012/04/19 06:00 [medline]
AID - S0022-3166(22)02870-X [pii]
AID - 10.3945/jn.111.151753 [doi]
PST - ppublish
SO  - J Nutr. 2012 Mar;142(3):411-8. doi: 10.3945/jn.111.151753. Epub 2012 Jan 18.