Julia Knabl1, Ursula Hiden2, Rebecca Hüttenbrenner3, Christina Riedel4, Stefan Hutter3, Verena Kirn5, Margit Günthner-Biller3, Gernot Desoye2, Franz Kainer1, Udo Jeschke6. 1. Department of Obstetrics and Gynecology, Ludwig Maximilians Universität München, Campus Innenstadt, Munich, Germany Klinik Hallerwiese, Department of Obstetrics, Nuremberg, Germany. 2. Department of Obstetrics and Gynecology, Ludwig Maximilians Universität München, Campus Innenstadt, Munich, Germany Department of Obstetrics and Gynecology, Medical University Graz, Graz, Austria. 3. Department of Obstetrics and Gynecology, Ludwig Maximilians Universität München, Campus Innenstadt, Munich, Germany. 4. Department of Obstetrics and Gynecology, Ludwig Maximilians Universität München, Campus Innenstadt, Munich, Germany Institut für Soziale Pädiatrie und Jugendmedizin, Ludwig-Maximilians-Universität München, Munich, Gemany. 5. Department of Obstetrics and Gynecology, Ludwig Maximilians Universität München, Campus Innenstadt, Munich, Germany Department of Obstetrics and Gynecology, University Hospital of Cologne, Cologne, Germany. 6. Department of Obstetrics and Gynecology, Ludwig Maximilians Universität München, Campus Innenstadt, Munich, Germany udo.jeschke@med.uni-muenchen.de.
Abstract
OBJECTIVE: The nuclear receptor estrogen receptor α (ERα) 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 ERα in a cell type-specific manner and that this regulation may involve epigenetic changes. STUDY DESIGN: Expression of ERα was analyzed by immunohistochemistry using the semiquantitative immunoreactive score in 80 placentas (40 GDM/40 controls). Quantitative real-time polymerase chain reaction (PCR) measured ERα messenger RNA (mRNA) in decidual tissue. Methylation-specific PCR was performed to analyze cytosine-phosphatidyl-guanine-island methylation of the ERα promoter. RESULTS: Expression of ERα protein is upregulated (P = .011) in GDM in extravillous trophoblasts but not in syncytiotrophoblast. Gestational diabetes mellitus downregulated ERα in decidual vessels only in pregnancies with male but not female fetuses. Furthermore, mRNA of the ERα 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 ERα in a cell type-dependent way, on epigenetic level. These data link GDM with epigenetic deregulations of ERα expression and open new insights into the intrauterine programming hypothesis of GDM.
OBJECTIVE: The nuclear receptor estrogen receptor α (ERα) 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 ERα in a cell type-specific manner and that this regulation may involve epigenetic changes. STUDY DESIGN: Expression of ERα was analyzed by immunohistochemistry using the semiquantitative immunoreactive score in 80 placentas (40 GDM/40 controls). Quantitative real-time polymerase chain reaction (PCR) measured ERα messenger RNA (mRNA) in decidual tissue. Methylation-specific PCR was performed to analyze cytosine-phosphatidyl-guanine-island methylation of the ERα promoter. RESULTS: Expression of ERα protein is upregulated (P = .011) in GDM in extravillous trophoblasts but not in syncytiotrophoblast. Gestational diabetes mellitus downregulated ERα in decidual vessels only in pregnancies with male but not female fetuses. Furthermore, mRNA of the ERα 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 ERα in a cell type-dependent way, on epigenetic level. These data link GDM with epigenetic deregulations of ERα expression and open new insights into the intrauterine programming hypothesis of GDM.
Authors: Laura Hahn; Sarah Meister; Mareike Mannewitz; Susanne Beyer; Stefanie Corradini; Uwe Hasbargen; Sven Mahner; Udo Jeschke; Thomas Kolben; Alexander Burges Journal: Biomolecules Date: 2022-05-15
Authors: Stefan Hutter; Julia Knabl; Ulrich Andergassen; Simone Hofmann; Christina Kuhn; Sven Mahner; Petra Arck; Udo Jeschke Journal: Int J Mol Sci Date: 2016-04-07 Impact factor: 5.923
Authors: Julia Knabl; Lena de Maiziere; Rebecca Hüttenbrenner; Stefan Hutter; Julia Jückstock; Sven Mahner; Franz Kainer; Gernot Desoye; Udo Jeschke Journal: Int J Mol Sci Date: 2020-06-05 Impact factor: 5.923