Reduced syncytin-1 expression levels in placental syndromes correlates with epigenetic hypermethylation of the ERVW-1 promoter region

Autor: Pamela L. Strissel, Florian Faschingbauer, Arif B. Ekici, Elisabeth Stiegler, Ulf Dammer, Fabian B. Fahlbusch, Tamme W. Goecke, Matthias W. Beckmann, Matthias Ruebner, Reiner Strick
Jazyk: angličtina
Rok vydání: 2013
Předmět:
Methyltransferase
Placenta
lcsh:Medicine
Pregnancy Proteins
DNA Methyltransferase 3A
Epigenesis
Genetic
Labor and Delivery
Pregnancy
Gene expression
DNA (Cytosine-5-)-Methyltransferases
Promoter Regions
Genetic
lcsh:Science
reproductive and urinary physiology
Multidisciplinary
Obstetrics and Gynecology
Cell Differentiation
Methylation
Chromatin
Up-Regulation
medicine.anatomical_structure
DNA methylation
embryonic structures
Medicine
Epigenetics
Female
DNA modification
Research Article
Medizinische Fakultät -ohne weitere Spezifikation
DNA transcription
Down-Regulation
Biology
Cell Line
Syncytiotrophoblast
Hypertensive Disorders in Pregnancy
Genetics
medicine
Humans
ddc:610
lcsh:R
DNA Helicases
Gene Products
env
Promoter
DNA
DNA Methylation
Molecular biology
Pregnancy Complications
lcsh:Q
Developmental Biology
Zdroj: PLoS ONE, Vol 8, Iss 2, p e56145 (2013)
PLoS ONE
ISSN: 1932-6203
Popis: Terminal differentiation of villous cytotrophoblasts (CT) ends in formation of the multinucleated syncytiotrophoblast representing the fetal-maternal interface. Aberrations during this cell-fusion process are associated with Intrauterine Growth Restriction (IUGR), Preeclampsia (PE) and High Elevated Liver and Low Platelets (HELLP) Syndrome. Syncytin-1, the envelope gene of the human Endogenous Retrovirus ERVW-1, is one of the most important genes involved in cell-fusion and showed decreased gene expression during these pathological pregnancies. The aim of this study was to determine the methylation pattern of the entire promoter of ERVW-1 and to correlate these findings with the expression profile of Syncytin-1 in the placental syndromes. 14 isolated villous cytotrophoblasts from control (n = 3), IUGR (n = 3), PE (n = 3), PE/IUGR (n = 3) and HELLP/IUGR (n = 2) placentae were used to determine the mean methylation level (ML) for the ERVW-1 promoter region. ML rose significantly from 29% in control CTs to 49% in IUGR, 53% in PE, 47% in PE/IUGR and 64% in HELLP/IUGR indicating an epigenetic down-regulation of Syncytin-1 by promoter hypermethylation. DNA demethylation of the trophoblast like cell lines BeWo, JEG-3 and JAR with 5-AZA-2'desoxycytidine (AZA) showed an increased Syncytin-1 expression and fusion ability in all cell lines. Promoter activity of the 5'LTR could be inhibited by hypermethylation 42-fold using a luciferase based reporter-gene assay. Finally overexpression of the methyltransferases DNMT3a and LSH could be responsible for a decreased Syncytin-1 expression by promoter hypermethylation of ERVW-1. Our study linked decreased Syncytin-1 expression to an epigenetic hypermethylation of the entire promoter of ERVW-1. Based on our findings we are predicting a broad aberrant epigenetic DNA-methylation pattern in pathological placentae affecting placentogenesis, but also the development of the fetus and the mother during pregnancy.
Databáze: OpenAIRE
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