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Type 1 Diabetes Mellitus and the First Trimester Placenta: Hyperglycemia-Induced Effects on Trophoblast Proliferation, Cell Cycle Regulators, and Invasion

Type 1 diabetes mellitus (T1DM) is associated with reduced fetal growth in early pregnancy, but a contributing role of the placenta has remained elusive. Thus, we investigated whether T1DM alters placental development in the first trimester. Using a protein array, the level of 60 cell-cycle-related...

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Autores principales: Majali-Martinez, Alejandro, Weiss-Fuchs, Ursula, Miedl, Heidi, Forstner, Desiree, Bandres-Meriz, Julia, Hoch, Denise, Djelmis, Josip, Ivanisevic, Marina, Hiden, Ursula, Gauster, Martin, Desoye, Gernot
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8539403/
https://www.ncbi.nlm.nih.gov/pubmed/34681648
http://dx.doi.org/10.3390/ijms222010989
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author Majali-Martinez, Alejandro
Weiss-Fuchs, Ursula
Miedl, Heidi
Forstner, Desiree
Bandres-Meriz, Julia
Hoch, Denise
Djelmis, Josip
Ivanisevic, Marina
Hiden, Ursula
Gauster, Martin
Desoye, Gernot
author_facet Majali-Martinez, Alejandro
Weiss-Fuchs, Ursula
Miedl, Heidi
Forstner, Desiree
Bandres-Meriz, Julia
Hoch, Denise
Djelmis, Josip
Ivanisevic, Marina
Hiden, Ursula
Gauster, Martin
Desoye, Gernot
author_sort Majali-Martinez, Alejandro
collection PubMed
description Type 1 diabetes mellitus (T1DM) is associated with reduced fetal growth in early pregnancy, but a contributing role of the placenta has remained elusive. Thus, we investigated whether T1DM alters placental development in the first trimester. Using a protein array, the level of 60 cell-cycle-related proteins was determined in human first trimester placental tissue (gestational week 5–11) from control (n = 11) and T1DM pregnancies (n = 12). Primary trophoblasts (gestational week 7–12, n = 32) were incubated in the absence (control) or presence of hyperglycemia (25 mM D-glucose) and hyperosmolarity (5.5 mM D-glucose + 19.5 mM D-mannitol). We quantified the number of viable and dead trophoblasts (CASY Counter) and assessed cell cycle distribution (FACS) and trophoblast invasion using a transwell assay. T1DM was associated with a significant (p < 0.05) downregulation of Ki67 (−26%), chk1 (−25%), and p73 (−26%). The number of viable trophoblasts was reduced under hyperglycemia (−23%) and hyperosmolarity (−18%), whereas trophoblast invasion was increased only under hyperglycemia (+6%). Trophoblast cell death and cell cycle distribution remained unaffected. Collectively, our data demonstrate that hyperglycemia decreases trophoblast proliferation as a potential contributing factor to the reduced placental growth in T1DM in vivo.
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spelling pubmed-85394032021-10-24 Type 1 Diabetes Mellitus and the First Trimester Placenta: Hyperglycemia-Induced Effects on Trophoblast Proliferation, Cell Cycle Regulators, and Invasion Majali-Martinez, Alejandro Weiss-Fuchs, Ursula Miedl, Heidi Forstner, Desiree Bandres-Meriz, Julia Hoch, Denise Djelmis, Josip Ivanisevic, Marina Hiden, Ursula Gauster, Martin Desoye, Gernot Int J Mol Sci Communication Type 1 diabetes mellitus (T1DM) is associated with reduced fetal growth in early pregnancy, but a contributing role of the placenta has remained elusive. Thus, we investigated whether T1DM alters placental development in the first trimester. Using a protein array, the level of 60 cell-cycle-related proteins was determined in human first trimester placental tissue (gestational week 5–11) from control (n = 11) and T1DM pregnancies (n = 12). Primary trophoblasts (gestational week 7–12, n = 32) were incubated in the absence (control) or presence of hyperglycemia (25 mM D-glucose) and hyperosmolarity (5.5 mM D-glucose + 19.5 mM D-mannitol). We quantified the number of viable and dead trophoblasts (CASY Counter) and assessed cell cycle distribution (FACS) and trophoblast invasion using a transwell assay. T1DM was associated with a significant (p < 0.05) downregulation of Ki67 (−26%), chk1 (−25%), and p73 (−26%). The number of viable trophoblasts was reduced under hyperglycemia (−23%) and hyperosmolarity (−18%), whereas trophoblast invasion was increased only under hyperglycemia (+6%). Trophoblast cell death and cell cycle distribution remained unaffected. Collectively, our data demonstrate that hyperglycemia decreases trophoblast proliferation as a potential contributing factor to the reduced placental growth in T1DM in vivo. MDPI 2021-10-12 /pmc/articles/PMC8539403/ /pubmed/34681648 http://dx.doi.org/10.3390/ijms222010989 Text en © 2021 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Communication
Majali-Martinez, Alejandro
Weiss-Fuchs, Ursula
Miedl, Heidi
Forstner, Desiree
Bandres-Meriz, Julia
Hoch, Denise
Djelmis, Josip
Ivanisevic, Marina
Hiden, Ursula
Gauster, Martin
Desoye, Gernot
Type 1 Diabetes Mellitus and the First Trimester Placenta: Hyperglycemia-Induced Effects on Trophoblast Proliferation, Cell Cycle Regulators, and Invasion
title Type 1 Diabetes Mellitus and the First Trimester Placenta: Hyperglycemia-Induced Effects on Trophoblast Proliferation, Cell Cycle Regulators, and Invasion
title_full Type 1 Diabetes Mellitus and the First Trimester Placenta: Hyperglycemia-Induced Effects on Trophoblast Proliferation, Cell Cycle Regulators, and Invasion
title_fullStr Type 1 Diabetes Mellitus and the First Trimester Placenta: Hyperglycemia-Induced Effects on Trophoblast Proliferation, Cell Cycle Regulators, and Invasion
title_full_unstemmed Type 1 Diabetes Mellitus and the First Trimester Placenta: Hyperglycemia-Induced Effects on Trophoblast Proliferation, Cell Cycle Regulators, and Invasion
title_short Type 1 Diabetes Mellitus and the First Trimester Placenta: Hyperglycemia-Induced Effects on Trophoblast Proliferation, Cell Cycle Regulators, and Invasion
title_sort type 1 diabetes mellitus and the first trimester placenta: hyperglycemia-induced effects on trophoblast proliferation, cell cycle regulators, and invasion
topic Communication
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8539403/
https://www.ncbi.nlm.nih.gov/pubmed/34681648
http://dx.doi.org/10.3390/ijms222010989
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