Knabl Julia, Hiden Ursula, Hüttenbrenner Rebecca, Riedel Christina, Hutter Stefan, Kirn Verena, Günthner-Biller Margit, Desoye Gernot, Kainer Franz, Jeschke Udo
Department of Obstetrics and Gynecology, Ludwig Maximilians Universität München, Campus Innenstadt, Munich, Germany Klinik Hallerwiese, Department of Obstetrics, Nuremberg, Germany.
Department of Obstetrics and Gynecology, Ludwig Maximilians Universität München, Campus Innenstadt, Munich, Germany Department of Obstetrics and Gynecology, Medical University Graz, Graz, Austria.
Reprod Sci. 2015 Dec;22(12):1488-95. doi: 10.1177/1933719115585147. Epub 2015 May 6.
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.
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.
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.
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.
核受体雌激素受体α（ERα）是能量平衡、胰岛素抵抗和滋养层细胞分化的关键参与者之一。我们检验了以下假设：妊娠期糖尿病（GDM）以细胞类型特异性方式改变胎盘ERα的表达，且这种调节可能涉及表观遗传变化。
采用半定量免疫反应评分法，通过免疫组织化学分析80例胎盘（40例GDM/40例对照）中ERα的表达。采用定量实时聚合酶链反应（PCR）检测蜕膜组织中ERα信使核糖核酸（mRNA）。进行甲基化特异性PCR分析ERα启动子的胞嘧啶-磷酸-鸟嘌呤岛甲基化。
GDM时，绒毛外滋养层细胞中ERα蛋白表达上调（P = 0.011），而合体滋养层细胞中未上调。妊娠期糖尿病仅在男性胎儿而非女性胎儿的妊娠中使蜕膜血管中的ERα下调。此外，与对照组相比，GDM蜕膜中ERα编码基因雌激素受体基因1（ESR1）的mRNA增加（+1.77倍）（P = 0.024）。同时，ESR1启动子仅在健康对照个体的蜕膜中甲基化，而在GDM中未甲基化。
妊娠期糖尿病在表观遗传水平上以细胞类型依赖的方式影响胎盘ERα的表达。这些数据将GDM与ERα表达的表观遗传失调联系起来，并为GDM的宫内编程假说提供了新的见解。
