Document Detail


Generalized disruption of inherited genomic imprints leads to wide-ranging placental defects and dysregulated fetal growth.
MedLine Citation:
PMID:  23085235     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Monoallelic expression of imprinted genes, including ones solely expressed in the placenta, is essential for normal placental development and fetal growth. To better understand the role of placental imprinting in placental development and fetal growth, we examined conceptuses developing in the absence of maternally derived DNA (cytosine-5-)-methyltransferase 1o (DNMT1o). Absence of DNMT1o results in the partial loss of methylation at imprinted differentially methylated domain (DMD) sequences in the embryo and the placenta. Mid-gestation E9.5 DNMT1o-deficient placentas exhibited structural abnormalities of all tissue layers. At E17.5, all examined placentas had aberrant placental morphology, most notably in the spongiotrophoblast and labyrinth layers. Abnormalities included an expanded volume fraction of spongiotrophoblast tissue with extension of the spongiotrophoblast layer into the labyrinth. Many mutant placentas also demonstrated migration abnormalities of glycogen cells. Additionally, the volume fraction of the labyrinth was reduced, as was the surface area for maternal fetal gas exchange. Despite these placental morphologic abnormalities, approximately one-half of DNMT1o-deficient fetuses survived to late gestation (E17.5). Furthermore, DNMT1o-deficient placentas supported a broad range of fetal growth. The ability of some DNMT1o-deficient and morphologically abnormal placentas to support fetal growth in excess of wild type demonstrates the importance of differential methylation of DMDs and proper imprinting of discrete gene clusters to placental morphogenesis and fetal growth.
Authors:
K P Himes; E Koppes; J Richard Chaillet
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural     Date:  2012-10-17
Journal Detail:
Title:  Developmental biology     Volume:  373     ISSN:  1095-564X     ISO Abbreviation:  Dev. Biol.     Publication Date:  2013 Jan 
Date Detail:
Created Date:  2012-11-27     Completed Date:  2013-01-25     Revised Date:  2014-04-17    
Medline Journal Info:
Nlm Unique ID:  0372762     Medline TA:  Dev Biol     Country:  United States    
Other Details:
Languages:  eng     Pagination:  72-82     Citation Subset:  IM    
Copyright Information:
Copyright © 2012 Elsevier Inc. All rights reserved.
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MeSH Terms
Descriptor/Qualifier:
Animals
DNA (Cytosine-5-)-Methyltransferase / deficiency,  genetics,  metabolism*
DNA Methylation*
DNA Primers / genetics
Female
Genomic Imprinting / physiology*
Histological Techniques
Immunohistochemistry
In Situ Hybridization
Linear Models
Mice
Microarray Analysis
Placenta / embryology*,  metabolism*
Pregnancy
Protein Structure, Tertiary
Statistics, Nonparametric
Grant Support
ID/Acronym/Agency:
K12HD000849/HD/NICHD NIH HHS; R01 HD044133/HD/NICHD NIH HHS; R01 HD044133/HD/NICHD NIH HHS; UL1 TR000005/TR/NCATS NIH HHS
Chemical
Reg. No./Substance:
0/DNA Primers; EC 2.1.1.37/DNA (Cytosine-5-)-Methyltransferase; EC 2.1.1.37/DNA (cytosine-5-)-methyltransferase 1
Comments/Corrections

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