Protein Profiling of Placental Extracellular Vesicles in Gestational Diabetes Mellitus
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 ins...
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MDPI AG
2024-02-01
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| Series: | International Journal of Molecular Sciences |
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| Online Access: | https://www.mdpi.com/1422-0067/25/4/1947 |
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| author | Neva Kandzija Sophie Payne William R. Cooke Faheem Seedat Roman Fischer Manu Vatish |
| author_facet | Neva Kandzija Sophie Payne William R. Cooke Faheem Seedat Roman Fischer Manu Vatish |
| author_sort | Neva Kandzija |
| collection | DOAJ |
| description | 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–control study, we investigated the proteomic cargo of human syncytiotrophoblast-derived extracellular vesicles (STBEVs), which facilitate maternal–fetal signalling during pregnancy, in a UK-based cohort comprising patients with a gestational age of 38–40 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’ 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. |
| first_indexed | 2024-03-07T22:29:31Z |
| format | Article |
| id | doaj.art-3e57ef911d8e4db48821ca970b971d4c |
| institution | Directory Open Access Journal |
| issn | 1661-6596 1422-0067 |
| language | English |
| last_indexed | 2024-03-07T22:29:31Z |
| publishDate | 2024-02-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | International Journal of Molecular Sciences |
| spelling | doaj.art-3e57ef911d8e4db48821ca970b971d4c2024-02-23T15:19:10ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672024-02-01254194710.3390/ijms25041947Protein Profiling of Placental Extracellular Vesicles in Gestational Diabetes MellitusNeva Kandzija0Sophie Payne1William R. Cooke2Faheem Seedat3Roman Fischer4Manu Vatish5Nuffield Department of Women’s and Reproductive Health, University of Oxford, Oxford OX3 9DU, UKNuffield Department of Women’s and Reproductive Health, University of Oxford, Oxford OX3 9DU, UKNuffield Department of Women’s and Reproductive Health, University of Oxford, Oxford OX3 9DU, UKNuffield Department of Women’s and Reproductive Health, University of Oxford, Oxford OX3 9DU, UKNuffield Department of Medicine, University of Oxford, OX3 7BN Oxford, UKNuffield Department of Women’s and Reproductive Health, University of Oxford, Oxford OX3 9DU, UKThroughout 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–control study, we investigated the proteomic cargo of human syncytiotrophoblast-derived extracellular vesicles (STBEVs), which facilitate maternal–fetal signalling during pregnancy, in a UK-based cohort comprising patients with a gestational age of 38–40 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’ 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.https://www.mdpi.com/1422-0067/25/4/1947syncitiotrophoblast extracellular vesicleproteomicsgestational diabetes mellitusplacentapregnancy |
| spellingShingle | Neva Kandzija Sophie Payne William R. Cooke Faheem Seedat Roman Fischer Manu Vatish Protein Profiling of Placental Extracellular Vesicles in Gestational Diabetes Mellitus International Journal of Molecular Sciences syncitiotrophoblast extracellular vesicle proteomics gestational diabetes mellitus placenta pregnancy |
| title | Protein Profiling of Placental Extracellular Vesicles in Gestational Diabetes Mellitus |
| title_full | Protein Profiling of Placental Extracellular Vesicles in Gestational Diabetes Mellitus |
| title_fullStr | Protein Profiling of Placental Extracellular Vesicles in Gestational Diabetes Mellitus |
| title_full_unstemmed | Protein Profiling of Placental Extracellular Vesicles in Gestational Diabetes Mellitus |
| title_short | Protein Profiling of Placental Extracellular Vesicles in Gestational Diabetes Mellitus |
| title_sort | protein profiling of placental extracellular vesicles in gestational diabetes mellitus |
| topic | syncitiotrophoblast extracellular vesicle proteomics gestational diabetes mellitus placenta pregnancy |
| url | https://www.mdpi.com/1422-0067/25/4/1947 |
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