Trophoblastic microRNAs are downregulated in a diabetic pregnancy through an inhibition of Drosha. (15th January 2019)

• Record Type: Journal Article
• Authors: Pendzialek, S. Mareike; Knelangen, Julia M.; Schindler, Maria; Gürke, Jacqueline; Grybel, Katarzyna J.; Gocza, Elen; Fischer, Bernd; Navarrete Santos, Anne
• Is Part Of: Molecular and cellular endocrinology. Volume 480(2019)
• Page Start: 167
• Page End: 179
• Publication Date: 2019-01-15
• Subjects: MicroRNA -- Blastocyst -- Gastrulation -- Diabetes -- Drosha -- Trophoblast; BDNF Brain-derived neurotrophic factor -- C14MC Chromosome 14 microRNA cluster -- C19MC Chromosome 19 microRNA cluster -- CEBPβ CCAAT/Enhancer-binding protein beta -- CREB1 cAMP response element-binding protein -- DGCR8 DiGeorge syndrome critical region 8 -- E2F7 E2F transcription factor 7 -- EB Embryoblast -- ERBB2IP Erbb2 interacting protein -- ESC Embryonic stem cells -- GAPDH Glyceraldehyde 3-phosphate dehydrogenase -- IFNAR1 Interferon alpha and beta receptor 1 -- IGF2 Insulin-like growth factor 2 -- IL1α Interleukin 1 alpha -- IUGR Intrauterine growth restriction -- IVF In vitro fertilisation -- MFE Minimum free energy -- PAPPA Pregnancy-associated plasma protein A -- PLAG1 Pleomorphic adenoma gene 1 -- PTEN Phosphatase and tensin homolog -- p.c. post coitum -- RISC RNA-Induced silencing complex -- SATB1 Special AT-Rich sequence binding protein 1 -- TB Trophoblast -- TGFβ2 Transforming growth factor-beta 2 -- ZEB1 Zinc finger E-box binding homeobox 1; Endocrinology -- Periodicals; Molecular biology -- Periodicals; Cytology -- Periodicals; Endocrinology -- Periodicals; Hormones -- Periodicals; Endocrinologie -- Périodiques; Cytology; Endocrinology; Molecular biology; Periodicals; 573.4
• DOI: 10.1016/j.mce.2018.11.002
• Languages: English
• ISSNs: 0303-7207

Abstract

Abstract: MicroRNAs are promising biological markers for prenatal diagnosis. They regulate placental development and are present in maternal plasma. Maternal metabolic diseases are major risk factors for placental deterioration. We analysed the influence of a maternal insulin-dependent diabetes mellitus on microRNA expression in maternal plasma and in blastocysts employing an in vivo rabbit diabetic pregnancy model and an in vitro embryo culture in hyperglycaemic and hypoinsulinaemic medium. Maternal diabetes led to a marked downregulation of Dicer protein in embryoblast cells and Drosha protein in trophoblast cells. MiR-27b, miR-141 and miR-191 were decreased in trophoblast cells and in maternal plasma of diabetic rabbits. In vitro studies indicate, that maternal hyperglycaemia and hypoinsulinaemia partially contribute to the downregulation of trophoblastic microRNAs. As the altered microRNA expression was detectable in maternal plasma, too, the plasma microRNA signature could serve as an early biological marker for the prediction of trophoblast function during a diabetic pregnancy. Graphical abstract: Highlights: Trophoblastic Drosha and microRNA expression were altered in diabetic blastocysts. Changes in trophoblastic microRNA expression are reflected in maternal plasma. MicroRNAs are present in blastocyst cavity fluid. Insulin and glucose are potent regulators of embryonic microRNA expression.