Type 1 Diabetes Mellitus and the First Trimester Placenta: Hyperglycemia-Induced Effects on Trophoblast Proliferation,Cell Cycle Regulators,and Invasion |
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Authors: | Alejandro Majali-Martinez Ursula Weiss-Fuchs Heidi Miedl Desiree Forstner Julia Bandres-Meriz Denise Hoch Josip Djelmis Marina Ivanisevic Ursula Hiden Martin Gauster Gernot Desoye |
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Affiliation: | 1.Department of Obstetrics and Gynecology, Medical University of Graz, 8036 Graz, Austria; (A.M.-M.); (U.W.-F.); (H.M.); (J.B.-M.); (D.H.); (U.H.);2.Division of Cell Biology, Histology and Embryology, Gottfried Schatz Research Centre for Cell Signaling, Metabolism and Ageing, Medical University of Graz, 8010 Graz, Austria; (D.F.); (M.G.);3.Department of Obstetrics and Gynecology, University Hospital Centre Zagreb, 10000 Zagreb, Croatia; (J.D.); (M.I.) |
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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. |
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Keywords: | diabetes glucose human trophoblasts early pregnancy |
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