PMID- 22186035
OWN - NLM
STAT- MEDLINE
DCOM- 20120423
LR  - 20211203
IS  - 1349-3329 (Electronic)
IS  - 0040-8727 (Linking)
VI  - 226
IP  - 1
DP  - 2012 Jan
TI  - Maternal undernutrition induces the expression of hypoxia-related genes in the 
      fetal brain.
PG  - 37-44
AB  - Maternal undernutrition during pregnancy is a risk factor for cerebrovascular and 
      cardiovascular diseases in adulthood. Hypoxia-inducible factor 1 alpha (HIF1alpha) 
      plays an essential role in cellular hypoxic responses, and its increased 
      expression is associated with cerebrovascular and cardiovascular diseases. 
      However, it is not known whether maternal undernutrition influences HIF1alpha 
      expression in the fetal brain. We therefore analyzed the expression levels of 
      HIF1alpha and its downstream genes in the fetal brain (day 17.5 of gestation, 1-2 
      days before birth). Maternal undernutrition did not noticeably affect the fetal 
      body and brain weights. Both HIF1alpha mRNA and protein levels were increased in the 
      brain under maternal undernutrition, despite the absence of hypoxia, as judged by 
      the staining profile with hypoxyprobe-1 that identifies hypoxic cells. 
      Importantly, maternal undernutrition caused the accumulation of HIF1alpha protein in 
      oligodendrocyte precursor cells at the subventricular zone, a site of 
      neurogenesis in the fetal brain. Maternal undernutrition also increased the mRNA 
      level of mammalian target of rapamycin (mTOR), which could increase the level of 
      HIF1alpha protein under normoxia. Furthermore, microarray analysis revealed that 
      expression levels of mRNAs for 10 HIF1alpha downstream targets, including enolase 1 
      and hexokinase 1, were increased in the fetal brain under maternal 
      undernutrition. Thus, the biochemical consequence of maternal undernutrition is 
      similar to that of mild hypoxia. In conclusion, maternal undernutrition induces 
      the expression of HIF1alpha in oligodendrocyte precursor cells at the subventricular 
      zone, and it also induces the expression of hypoxia-related genes in the fetal 
      brain probably via activation of the mTOR pathway.
FAU - Ito, Takuya
AU  - Ito T
AD  - Innovation of New Biomedical Engineering Center, Tohoku University, Aoba-ku, 
      Sendai, Japan. i-takuya@med.tohoku.ac.jp
FAU - Funamoto, Kiyoe
AU  - Funamoto K
FAU - Sato, Naoaki
AU  - Sato N
FAU - Nakamura, Ai
AU  - Nakamura A
FAU - Tanabe, Kaori
AU  - Tanabe K
FAU - Hoshiai, Tetsuro
AU  - Hoshiai T
FAU - Suenaga, Kaori
AU  - Suenaga K
FAU - Sugawara, Junichi
AU  - Sugawara J
FAU - Nagase, Satoru
AU  - Nagase S
FAU - Okamura, Kunihiro
AU  - Okamura K
FAU - Yaegashi, Nobuo
AU  - Yaegashi N
FAU - Kimura, Yoshitaka
AU  - Kimura Y
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - Japan
TA  - Tohoku J Exp Med
JT  - The Tohoku journal of experimental medicine
JID - 0417355
RN  - 0 (DNA Primers)
RN  - 0 (Hif1a protein, mouse)
RN  - 0 (Hypoxia-Inducible Factor 1, alpha Subunit)
RN  - EC 2.7.1.1 (HK1 protein, mouse)
RN  - EC 2.7.1.1 (Hexokinase)
RN  - EC 2.7.1.1 (mTOR protein, mouse)
RN  - EC 2.7.11.1 (TOR Serine-Threonine Kinases)
RN  - EC 4.2.1.11 (Eno1 protein, mouse)
RN  - EC 4.2.1.11 (Phosphopyruvate Hydratase)
SB  - IM
MH  - Animals
MH  - DNA Primers/genetics
MH  - Female
MH  - Fetus/*metabolism
MH  - Gene Expression Regulation, Developmental/*physiology
MH  - Hexokinase/metabolism
MH  - Hypoxia/genetics/*metabolism
MH  - Hypoxia-Inducible Factor 1, alpha Subunit/*metabolism
MH  - Immunohistochemistry
MH  - Malnutrition/*physiopathology
MH  - Maternal Nutritional Physiological Phenomena/genetics/*physiology
MH  - Mice
MH  - Mice, Inbred C57BL
MH  - Microarray Analysis
MH  - Phosphopyruvate Hydratase/metabolism
MH  - Pregnancy
MH  - Real-Time Polymerase Chain Reaction
MH  - Statistics, Nonparametric
MH  - TOR Serine-Threonine Kinases/metabolism
EDAT- 2011/12/22 06:00
MHDA- 2012/04/24 06:00
CRDT- 2011/12/22 06:00
PHST- 2011/12/22 06:00 [entrez]
PHST- 2011/12/22 06:00 [pubmed]
PHST- 2012/04/24 06:00 [medline]
AID - JST.JSTAGE/tjem/226.37 [pii]
AID - 10.1620/tjem.226.37 [doi]
PST - ppublish
SO  - Tohoku J Exp Med. 2012 Jan;226(1):37-44. doi: 10.1620/tjem.226.37.