{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,10]],"date-time":"2026-07-10T15:44:19Z","timestamp":1783698259151,"version":"3.55.0"},"reference-count":38,"publisher":"MDPI AG","issue":"12","license":[{"start":{"date-parts":[[2023,6,12]],"date-time":"2023-06-12T00:00:00Z","timestamp":1686528000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Diagnostics"],"abstract":"<jats:p>Gestational diabetes mellitus (GDM) is a metabolic disease that can affect placental villous maturation and villous vascularity. The main effects of GDM on placental growth are a delay of villous maturation (DVM) and decreased formation of vasculo-syncytial membranes (VSM). Human equilibrative nucleoside transporter-1 (hENT1) is an adenosine transporter expressed in the human umbilical vein endothelial cells (HUVEC) and human placental microvascular endothelium cells (hPMEC). Its role is crucial in maintaining physiological fetal adenosine levels during pregnancy, and its reduction has been described in GDM. Twenty-four placentas from pregnancies with a confirmed diagnosis of GDMd and twenty-four matched non-GDM placentas (controls) were retrospectively analyzed to investigate the immunohistochemical expression of hENT1 in HUVEC and hPMEC. The study included the quantitative evaluation of VSM\/mm2 in placental tissue and the immunohistochemical quantitative evaluation of Ki-67, PHH3, and p57 in villous trophoblast. hENT1 expression was higher in all the vascular districts of the control cases compared to the GDMd placentas (p &lt; 0.0001). The VSM\/mm2 were lower in the GDMd cases, while the Ki-67, PHH3, and p57 were higher when compared to the control cases. To our knowledge, this is the first report of hENT1 expression in the human placentas of GDM patients. The absence\/low expression of hENT1 in all the GDMd patients may indicate a potential role in microvascular adaptative mechanisms. The trophoblasts\u2019 proliferative\/antiapoptotic pattern (high Ki-67, high PHH3, and high p57 count) may explain the statistically significant lower number of VSM\/mm2 found in the GDMd cases.<\/jats:p>","DOI":"10.3390\/diagnostics13122034","type":"journal-article","created":{"date-parts":[[2023,6,13]],"date-time":"2023-06-13T01:35:30Z","timestamp":1686620130000},"page":"2034","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":7,"title":["Gestational Diabetes\u2014Placental Expression of Human Equilibrative Nucleoside Transporter 1 (hENT1): Is Delayed Villous Maturation an Adaptive Pattern?"],"prefix":"10.3390","volume":"13","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-5313-0971","authenticated-orcid":false,"given":"Cinzia","family":"Giacometti","sequence":"first","affiliation":[{"name":"Pathology Unit, Department of Diagnostic Services, ULSS 6 \u201cEuganea\u201d, 35131 Padova, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4619-4827","authenticated-orcid":false,"given":"Kathrin","family":"Ludwig","sequence":"additional","affiliation":[{"name":"Pathology Unit, Department of Medicine, University of Padova, 35128 Padova, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Monica","family":"Guidi","sequence":"additional","affiliation":[{"name":"Gynecology & Obstretics Unit, Department of Women\u2019s Health, Cittadella Hospital, ULSS 6 \u201cEuganea\u201d, 35013 Padova, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elvira","family":"Colantuono","sequence":"additional","affiliation":[{"name":"Gynecology & Obstretics Unit, Department of Women\u2019s Health, Camposampiero Hospital, ULSS 6 \u201cEuganea\u201d, 35012 Padova, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anna","family":"Coracina","sequence":"additional","affiliation":[{"name":"Diabetology Unit, Department of Medicine, Camposampiero Hospital, ULSS 6 \u201cEuganea\u201d, 35012 Padova, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marcello","family":"Rigano","sequence":"additional","affiliation":[{"name":"Gynecology & Obstretics Unit, Department of Women\u2019s Health, Camposampiero Hospital, ULSS 6 \u201cEuganea\u201d, 35012 Padova, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mauro","family":"Cassaro","sequence":"additional","affiliation":[{"name":"Pathology Unit, Department of Diagnostic Services, ULSS 6 \u201cEuganea\u201d, 35131 Padova, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1976-5663","authenticated-orcid":false,"given":"Alessandro","family":"Ambrosi","sequence":"additional","affiliation":[{"name":"School of Medicine, Vita-Salute San Raffaele University, 20132 Milano, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2023,6,12]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"American Diabetes Association (2013). 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