Document Detail

Unbalanced placental expression of imprinted genes in human intrauterine growth restriction.
MedLine Citation:
PMID:  16125225     Owner:  NLM     Status:  MEDLINE    
Imprinted genes control fetal and placental growth in mice and in rare human syndromes, but the role of these genes in sporadic intrauterine growth restriction (IUGR) is less well-studied. We measured the ratio of mRNA from a maternally expressed imprinted gene, PHLDA2, to that from a paternally expressed imprinted gene, MEST, by Northern blotting in 38 IUGR-associated placentae and 75 non-IUGR placentae and found an increase in the PHLDA2/MEST mRNA ratio in IUGR (p=0.0001). Altered expression of PHLDA2 and MEST was not accompanied by changes in DNA methylation within their imprinting centers, and immunohistochemistry showed PHLDA2 protein appropriately restricted to villous and intermediate cytotrophoblast in the IUGR placentae. We next did a genome-wide survey of mRNA expression in 14 IUGR placentae with maternal vascular under-perfusion compared to 15 non-IUGR placentae using Affymetrix U133A microarrays. In this series six imprinted genes were differentially expressed by ANOVA with a Benjamini-Hochberg false discovery rate of 0.05, with increased expression of PHLDA2 and decreased expression of MEST, MEG3, GATM, GNAS and PLAGL1 in IUGR placentae. At lower significance, we found IGF2 mRNA decreased and CDKN1C mRNA increased in the IUGR cases. We confirmed the significant reduction in MEG3 non-translated RNA in IUGR placentae by Northern blotting. In addition to imprinted genes, the microarray data highlighted non-imprinted genes acting in endocrine signaling (LEP, CRH, HPGD, INHBA), tissue growth (IGF1), immune modulation (INDO, PSG-family genes), oxidative metabolism (GLRX), vascular function (AGTR1, DSCR1) and metabolite transport (SLC-family solute carriers) as differentially expressed in IUGR vs. non-IUGR placentae.
J McMinn; M Wei; N Schupf; J Cusmai; E B Johnson; A C Smith; R Weksberg; H M Thaker; B Tycko
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2005-08-24
Journal Detail:
Title:  Placenta     Volume:  27     ISSN:  0143-4004     ISO Abbreviation:  Placenta     Publication Date:    2006 Jun-Jul
Date Detail:
Created Date:  2006-05-01     Completed Date:  2006-06-22     Revised Date:  2006-11-15    
Medline Journal Info:
Nlm Unique ID:  8006349     Medline TA:  Placenta     Country:  England    
Other Details:
Languages:  eng     Pagination:  540-9     Citation Subset:  IM    
Institute for Cancer Genetics, Columbia University Medical Center, New York, NY 10032, USA.
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MeSH Terms
Blotting, Northern
Blotting, Southern
Fetal Growth Retardation / genetics*,  metabolism
Gene Expression Profiling
Gene Expression Regulation, Developmental*
Genomic Imprinting*
Nuclear Proteins / genetics*,  metabolism
Oligonucleotide Array Sequence Analysis
Placenta / metabolism*
Proteins / genetics*,  metabolism
RNA, Messenger / metabolism
Reg. No./Substance:
0/Nuclear Proteins; 0/Proteins; 0/RNA, Messenger; 0/TSSC3 protein; 0/mesoderm specific transcript protein

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