PMID- 25947892
OWN - NLM
STAT- MEDLINE
DCOM- 20161213
LR  - 20210816
IS  - 1933-7205 (Electronic)
IS  - 1933-7191 (Linking)
VI  - 22
IP  - 12
DP  - 2015 Dec
TI  - GDM Alters Expression of Placental Estrogen Receptor alpha in a Cell Type and 
      Gender-Specific Manner.
PG  - 1488-95
LID - 10.1177/1933719115585147 [doi]
AB  - OBJECTIVE: The nuclear receptor estrogen receptor alpha (ERalpha) is one of the key 
      players in energy balance, insulin resistance, and trophoblast differentiation. 
      We tested the hypothesis that gestational diabetes mellitus (GDM) alters 
      expression of placental ERalpha in a cell type-specific manner and that this 
      regulation may involve epigenetic changes. STUDY DESIGN: Expression of ERalpha was 
      analyzed by immunohistochemistry using the semiquantitative immunoreactive score 
      in 80 placentas (40 GDM/40 controls). Quantitative real-time polymerase chain 
      reaction (PCR) measured ERalpha messenger RNA (mRNA) in decidual tissue. 
      Methylation-specific PCR was performed to analyze 
      cytosine-phosphatidyl-guanine-island methylation of the ERalpha promoter. RESULTS: 
      Expression of ERalpha protein is upregulated (P = .011) in GDM in extravillous 
      trophoblasts but not in syncytiotrophoblast. Gestational diabetes mellitus 
      downregulated ERalpha in decidual vessels only in pregnancies with male but not 
      female fetuses. Furthermore, mRNA of the ERalpha encoding gene estrogen receptor gene 
      1 (ESR1) was increased (+1.77 fold) in GDM decidua when compared to controls (P = 
      .024). In parallel, the promoter of ESR1 was methylated only in decidua of 
      healthy control individuals but not in GDM. CONCLUSION: Gestational diabetes 
      mellitus affects expression of placental ERalpha in a cell type-dependent way, on 
      epigenetic level. These data link GDM with epigenetic deregulations of ERalpha 
      expression and open new insights into the intrauterine programming hypothesis of 
      GDM.
CI  - (c) The Author(s) 2015.
FAU - Knabl, Julia
AU  - Knabl J
AD  - Department of Obstetrics and Gynecology, Ludwig Maximilians Universitat Munchen, 
      Campus Innenstadt, Munich, Germany Klinik Hallerwiese, Department of Obstetrics, 
      Nuremberg, Germany.
FAU - Hiden, Ursula
AU  - Hiden U
AD  - Department of Obstetrics and Gynecology, Ludwig Maximilians Universitat Munchen, 
      Campus Innenstadt, Munich, Germany Department of Obstetrics and Gynecology, 
      Medical University Graz, Graz, Austria.
FAU - Huttenbrenner, Rebecca
AU  - Huttenbrenner R
AD  - Department of Obstetrics and Gynecology, Ludwig Maximilians Universitat Munchen, 
      Campus Innenstadt, Munich, Germany.
FAU - Riedel, Christina
AU  - Riedel C
AD  - Department of Obstetrics and Gynecology, Ludwig Maximilians Universitat Munchen, 
      Campus Innenstadt, Munich, Germany Institut fur Soziale Padiatrie und 
      Jugendmedizin, Ludwig-Maximilians-Universitat Munchen, Munich, Gemany.
FAU - Hutter, Stefan
AU  - Hutter S
AD  - Department of Obstetrics and Gynecology, Ludwig Maximilians Universitat Munchen, 
      Campus Innenstadt, Munich, Germany.
FAU - Kirn, Verena
AU  - Kirn V
AD  - Department of Obstetrics and Gynecology, Ludwig Maximilians Universitat Munchen, 
      Campus Innenstadt, Munich, Germany Department of Obstetrics and Gynecology, 
      University Hospital of Cologne, Cologne, Germany.
FAU - Gunthner-Biller, Margit
AU  - Gunthner-Biller M
AD  - Department of Obstetrics and Gynecology, Ludwig Maximilians Universitat Munchen, 
      Campus Innenstadt, Munich, Germany.
FAU - Desoye, Gernot
AU  - Desoye G
AD  - Department of Obstetrics and Gynecology, Ludwig Maximilians Universitat Munchen, 
      Campus Innenstadt, Munich, Germany Department of Obstetrics and Gynecology, 
      Medical University Graz, Graz, Austria.
FAU - Kainer, Franz
AU  - Kainer F
AD  - Department of Obstetrics and Gynecology, Ludwig Maximilians Universitat Munchen, 
      Campus Innenstadt, Munich, Germany Klinik Hallerwiese, Department of Obstetrics, 
      Nuremberg, Germany.
FAU - Jeschke, Udo
AU  - Jeschke U
AD  - Department of Obstetrics and Gynecology, Ludwig Maximilians Universitat Munchen, 
      Campus Innenstadt, Munich, Germany udo.jeschke@med.uni-muenchen.de.
LA  - eng
PT  - Comparative Study
PT  - Journal Article
DEP - 20150506
PL  - United States
TA  - Reprod Sci
JT  - Reproductive sciences (Thousand Oaks, Calif.)
JID - 101291249
RN  - 0 (ESR1 protein, human)
RN  - 0 (Estrogen Receptor alpha)
RN  - 0 (RNA, Messenger)
SB  - IM
MH  - Adult
MH  - Blood Vessels/metabolism/pathology
MH  - Case-Control Studies
MH  - CpG Islands
MH  - DNA Methylation
MH  - Diabetes, Gestational/genetics/*metabolism/pathology
MH  - Down-Regulation
MH  - Epigenesis, Genetic
MH  - Estrogen Receptor alpha/genetics/*metabolism
MH  - Female
MH  - Fetus/*metabolism
MH  - Gene Expression Regulation, Developmental
MH  - Gestational Age
MH  - Humans
MH  - Immunohistochemistry
MH  - Male
MH  - Placenta/blood supply/*metabolism/pathology
MH  - Pregnancy
MH  - Promoter Regions, Genetic
MH  - RNA, Messenger/genetics/metabolism
MH  - Real-Time Polymerase Chain Reaction
MH  - Reverse Transcriptase Polymerase Chain Reaction
MH  - Sex Determination Processes
MH  - Sex Factors
MH  - Trophoblasts/metabolism/pathology
OTO - NOTNLM
OT  - estrogen
OT  - gestational diabetes
OT  - methylation
OT  - nuclear receptor
OT  - trophoblast
EDAT- 2015/05/08 06:00
MHDA- 2016/12/15 06:00
CRDT- 2015/05/08 06:00
PHST- 2015/05/08 06:00 [entrez]
PHST- 2015/05/08 06:00 [pubmed]
PHST- 2016/12/15 06:00 [medline]
AID - 1933719115585147 [pii]
AID - 10.1177/1933719115585147 [doi]
PST - ppublish
SO  - Reprod Sci. 2015 Dec;22(12):1488-95. doi: 10.1177/1933719115585147. Epub 2015 May 
      6.