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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...
Autores principales: | , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
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MDPI
2021
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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. |
format | Online Article Text |
id | pubmed-8539403 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
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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