Document Detail


Mid-gestational gene expression profile in placenta and link to pregnancy complications.
MedLine Citation:
PMID:  23145134     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Despite the importance of placenta in mediating rapid physiological changes in pregnancy, data on temporal dynamics of placental gene expression are limited. We completed the first transcriptome profiling of human placental gene expression dynamics (GeneChips, Affymetrix®; ~47,000 transcripts) from early to mid-gestation (n = 10; gestational weeks 5-18) and report 154 genes with significant transcriptional changes (ANOVA, FDR P<0.1). TaqMan RT-qPCR analysis (n = 43; gestational weeks 5-41) confirmed a significant (ANOVA and t-test, FDR P<0.05) mid-gestational peak of placental gene expression for BMP5, CCNG2, CDH11, FST, GATM, GPR183, ITGBL1, PLAGL1, SLC16A10 and STC1, followed by sharp decrease in mRNA levels at term (t-test, FDR P<0.05). We hypothesized that normal course of late pregnancy may be affected when genes characteristic to mid-gestation placenta remain highly expressed until term, and analyzed their expression in term placentas from normal and complicated pregnancies [preeclampsia (PE), n = 12; gestational diabetes mellitus (GDM), n = 12; small- and large-for-gestational-age newborns (SGA, LGA), n = 12+12]. STC1 (stanniocalcin 1) exhibited increased mRNA levels in all studied complications, with the most significant effect in PE- and SGA-groups (t-test, FDR P<0.05). In post-partum maternal plasma, the highest STC1 hormone levels (ELISA, n = 129) were found in women who had developed PE and delivered a SGA newborn (median 731 vs 418 pg/ml in controls; ANCOVA, P = 0.00048). Significantly higher expression (t-test, FDR P<0.05) of CCNG2 and LYPD6 accompanied with enhanced immunostaining of the protein was detected in placental sections of PE and GDM cases (n = 15). Our study demonstrates the importance of temporal dynamics of placental transcriptional regulation across three trimesters of gestation. Interestingly, many genes with high expression in mid-gestation placenta have also been implicated in adult complex disease, promoting the discussion on the role of placenta in developmental programming. The discovery of elevated maternal plasma STC1 in pregnancy complications warrants further investigations of its potential as a biomarker.
Authors:
Liis Uusküla; Jaana Männik; Kristiina Rull; Ave Minajeva; Sulev Kõks; Pille Vaas; Pille Teesalu; Jüri Reimand; Maris Laan
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2012-11-07
Journal Detail:
Title:  PloS one     Volume:  7     ISSN:  1932-6203     ISO Abbreviation:  PLoS ONE     Publication Date:  2012  
Date Detail:
Created Date:  2012-11-12     Completed Date:  2013-06-25     Revised Date:  2013-07-11    
Medline Journal Info:
Nlm Unique ID:  101285081     Medline TA:  PLoS One     Country:  United States    
Other Details:
Languages:  eng     Pagination:  e49248     Citation Subset:  IM    
Affiliation:
Human Molecular Genetics Group, Institute of Molecular and Cell Biology, University of Tartu, Tartu, Estonia.
Data Bank Information
Bank Name/Acc. No.:
GEO/GSE22490;  GSE37901
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MeSH Terms
Descriptor/Qualifier:
Adolescent
Adult
Antigens, Ly / analysis,  genetics,  metabolism
Cyclin G2 / analysis,  genetics,  metabolism
Diabetes, Gestational / genetics
Female
Fetal Development / genetics
Fetal Growth Retardation / genetics
Gene Expression Profiling
Genetic Markers
Glycoproteins / blood*
Humans
Placenta / metabolism*
Pre-Eclampsia / genetics
Pregnancy
Pregnancy Complications / genetics*
Pregnancy Trimester, First
Pregnancy Trimester, Second
Transcriptome*
Grant Support
ID/Acronym/Agency:
55005617//Howard Hughes Medical Institute; //Wellcome Trust
Chemical
Reg. No./Substance:
0/Antigens, Ly; 0/CCNG2 protein, human; 0/Cyclin G2; 0/Genetic Markers; 0/Glycoproteins; 0/LYPD6 protein, human; 76687-96-2/teleocalcin
Comments/Corrections

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