{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,28]],"date-time":"2026-10-28T21:54:43Z","timestamp":1793224483286,"version":"4.5.0"},"reference-count":52,"publisher":"MDPI AG","issue":"4","license":[{"start":{"date-parts":[[2024,2,6]],"date-time":"2024-02-06T00:00:00Z","timestamp":1707177600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Throughout pregnancy, some degree of insulin resistance is necessary to divert glucose towards the developing foetus. In gestational diabetes mellitus (GDM), insulin resistance is exacerbated in combination with insulin deficiency, causing new-onset maternal hyperglycaemia. The rapid reversal of insulin resistance following delivery strongly implicates the placenta in GDM pathogenesis. In this case\u2013control study, we investigated the proteomic cargo of human syncytiotrophoblast-derived extracellular vesicles (STBEVs), which facilitate maternal\u2013fetal signalling during pregnancy, in a UK-based cohort comprising patients with a gestational age of 38\u201340 weeks. Medium\/large (m\/l) and small (s) STBEVs were isolated from GDM (n = 4) and normal (n = 5) placentae using ex vivo dual-lobe perfusion and subjected to mass spectrometry. Bioinformatics were used to identify differentially carried proteins and mechanistic pathways. In m\/lSTBEVs, 56 proteins were differently expressed while in sSTBEVs, no proteins reached statistical difference. Differences were also observed in the proteomic cargo between m\/lSTBEVs and sSTBEVs, indicating that the two subtypes of STBEVs may have divergent modes of action and downstream effects. In silico functional enrichment analysis of differentially expressed proteins in m\/lSTBEVs from GDM and normal pregnancy found positive regulation of cytoskeleton organisation as the most significantly enriched biological process. This work presents the first comparison of two populations of STBEVs\u2019 protein cargos (m\/l and sSTBEVs) from GDM and normal pregnancy isolated using placenta perfusion. Further investigation of differentially expressed proteins may contribute to an understanding of GDM pathogenesis and the development of novel diagnostic and therapeutic tools.<\/jats:p>","DOI":"10.3390\/ijms25041947","type":"journal-article","created":{"date-parts":[[2024,2,6]],"date-time":"2024-02-06T03:22:31Z","timestamp":1707189751000},"page":"1947","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":9,"title":["Protein Profiling of Placental Extracellular Vesicles in Gestational Diabetes Mellitus"],"prefix":"10.3390","volume":"25","author":[{"given":"Neva","family":"Kandzija","sequence":"first","affiliation":[{"name":"Nuffield Department of Women\u2019s and Reproductive Health, University of Oxford, Oxford OX3 9DU, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sophie","family":"Payne","sequence":"additional","affiliation":[{"name":"Nuffield Department of Women\u2019s and Reproductive Health, University of Oxford, Oxford OX3 9DU, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"William R.","family":"Cooke","sequence":"additional","affiliation":[{"name":"Nuffield Department of Women\u2019s and Reproductive Health, University of Oxford, Oxford OX3 9DU, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Faheem","family":"Seedat","sequence":"additional","affiliation":[{"name":"Nuffield Department of Women\u2019s and Reproductive Health, University of Oxford, Oxford OX3 9DU, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9715-5951","authenticated-orcid":false,"given":"Roman","family":"Fischer","sequence":"additional","affiliation":[{"name":"Nuffield Department of Medicine, University of Oxford, OX3 7BN Oxford, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6012-2574","authenticated-orcid":false,"given":"Manu","family":"Vatish","sequence":"additional","affiliation":[{"name":"Nuffield Department of Women\u2019s and Reproductive Health, University of Oxford, Oxford OX3 9DU, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2024,2,6]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1367","DOI":"10.1172\/JCI115724","article-title":"Facilitative glucose transporters: Regulatory mechanisms and dysregulation in diabetes","volume":"89","author":"Kahn","year":"1992","journal-title":"J. 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