{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,21]],"date-time":"2026-08-21T04:58:22Z","timestamp":1787288302606,"version":"build-2736575974"},"reference-count":42,"publisher":"MDPI AG","issue":"20","license":[{"start":{"date-parts":[[2021,10,12]],"date-time":"2021-10-12T00:00:00Z","timestamp":1633996800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100004061","name":"Oesterreichische Nationalbank","doi-asserted-by":"publisher","award":["17950"],"award-info":[{"award-number":["17950"]}],"id":[{"id":"10.13039\/501100004061","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>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\u201311) from control (n = 11) and T1DM pregnancies (n = 12). Primary trophoblasts (gestational week 7\u201312, 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 &lt; 0.05) downregulation of Ki67 (\u221226%), chk1 (\u221225%), and p73 (\u221226%). The number of viable trophoblasts was reduced under hyperglycemia (\u221223%) and hyperosmolarity (\u221218%), 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.<\/jats:p>","DOI":"10.3390\/ijms222010989","type":"journal-article","created":{"date-parts":[[2021,10,12]],"date-time":"2021-10-12T17:29:18Z","timestamp":1634059758000},"page":"10989","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":21,"title":["Type 1 Diabetes Mellitus and the First Trimester Placenta: Hyperglycemia-Induced Effects on Trophoblast Proliferation, Cell Cycle Regulators, and Invasion"],"prefix":"10.3390","volume":"22","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-9009-5810","authenticated-orcid":false,"given":"Alejandro","family":"Majali-Martinez","sequence":"first","affiliation":[{"name":"Department of Obstetrics and Gynecology, Medical University of Graz, 8036 Graz, Austria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ursula","family":"Weiss-Fuchs","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynecology, Medical University of Graz, 8036 Graz, Austria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4575-639X","authenticated-orcid":false,"given":"Heidi","family":"Miedl","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynecology, Medical University of Graz, 8036 Graz, Austria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5451-7580","authenticated-orcid":false,"given":"Desiree","family":"Forstner","sequence":"additional","affiliation":[{"name":"Division of Cell Biology, Histology and Embryology, Gottfried Schatz Research Centre for Cell Signaling, Metabolism and Ageing, Medical University of Graz, 8010 Graz, Austria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9672-5844","authenticated-orcid":false,"given":"Julia","family":"Bandres-Meriz","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynecology, Medical University of Graz, 8036 Graz, Austria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7169-7007","authenticated-orcid":false,"given":"Denise","family":"Hoch","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynecology, Medical University of Graz, 8036 Graz, Austria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Josip","family":"Djelmis","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynecology, University Hospital Centre Zagreb, 10000 Zagreb, Croatia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marina","family":"Ivanisevic","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynecology, University Hospital Centre Zagreb, 10000 Zagreb, Croatia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ursula","family":"Hiden","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynecology, Medical University of Graz, 8036 Graz, Austria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0386-6857","authenticated-orcid":false,"given":"Martin","family":"Gauster","sequence":"additional","affiliation":[{"name":"Division of Cell Biology, Histology and Embryology, Gottfried Schatz Research Centre for Cell Signaling, Metabolism and Ageing, Medical University of Graz, 8010 Graz, Austria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5715-3230","authenticated-orcid":false,"given":"Gernot","family":"Desoye","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynecology, Medical University of Graz, 8036 Graz, Austria"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2021,10,12]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"20140066","DOI":"10.1098\/rstb.2014.0066","article-title":"The placenta: A multifaceted, transient organ","volume":"370","author":"Burton","year":"2015","journal-title":"Philos. 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