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Majali-Martinez, A; Weiss-Fuchs, U; Miedl, H; Forstner, D; Bandres-Meriz, J; Hoch, D; Djelmis, J; Ivanisevic, M; Hiden, U; Gauster, M; Desoye, G.
Type 1 Diabetes Mellitus and the First Trimester Placenta: Hyperglycemia-Induced Effects on Trophoblast Proliferation, Cell Cycle Regulators, and Invasion.
Int J Mol Sci. 2021; 22(20):
Doi: 10.3390/ijms222010989
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PubMed
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- Leading authors Med Uni Graz
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Desoye Gernot
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Majali Martinez Alejandro
- Co-authors Med Uni Graz
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Bandrés Mériz Julia
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Forstner Desiree
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Gauster Martin
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Hiden Ursula
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Hoch Denise
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Miedl Heidi
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- Abstract:
- 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.
- Find related publications in this database (Keywords)
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diabetes
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glucose
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human trophoblasts
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early pregnancy