A cross-sectional analysis of syncytiotrophoblast membrane extracellular vesicles–derived transcriptomic biomarkers in early-onset preeclampsia

BackgroundPreeclampsia (PE) is a pregnancy-specific hypertensive disorder affecting 2%–8% of pregnancies worldwide. Biomarker(s) for the disorder exists, but while these have excellent negative predictive value, their positive predictive value is poor. Extracellular vesicles released by the placenta...

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Main Authors: Toluwalase Awoyemi, Wei Zhang, Maryam Rahbar, Adam Cribbs, Prasanna Logenthiran, Shuhan Jiang, Gavin Collett, Ana Sofia Cerdeira, Manu Vatish
Format: Article
Language:English
Published: Frontiers Media S.A. 2023-11-01
Series:Frontiers in Cardiovascular Medicine
Subjects:
Online Access:https://www.frontiersin.org/articles/10.3389/fcvm.2023.1291642/full
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author Toluwalase Awoyemi
Wei Zhang
Maryam Rahbar
Adam Cribbs
Prasanna Logenthiran
Shuhan Jiang
Gavin Collett
Ana Sofia Cerdeira
Manu Vatish
author_facet Toluwalase Awoyemi
Wei Zhang
Maryam Rahbar
Adam Cribbs
Prasanna Logenthiran
Shuhan Jiang
Gavin Collett
Ana Sofia Cerdeira
Manu Vatish
author_sort Toluwalase Awoyemi
collection DOAJ
description BackgroundPreeclampsia (PE) is a pregnancy-specific hypertensive disorder affecting 2%–8% of pregnancies worldwide. Biomarker(s) for the disorder exists, but while these have excellent negative predictive value, their positive predictive value is poor. Extracellular vesicles released by the placenta into the maternal circulation, syncytiotrophoblast membrane extracellular vesicles (STB-EVs), have been identified as being involved in PE with the potential to act as liquid biopsies.ObjectiveThe objective of this study was to identify the difference in the transcriptome of placenta and STB-EVs between preeclampsia and normal pregnancy (NP) and mechanistic pathways.Methods/study designWe performed RNA-sequencing on placental tissue, medium/large and small STB-EVs from PE (n = 6) and NP (n = 6), followed by bioinformatic analysis to identify targets that could be used in the future for EV-based diagnostic tests for preeclampsia. Some of the identified biomarkers were validated with real-time polymerase chain reactions.ResultsOur analysis identified a difference in the transcriptomic STB-EV cargo between PE and NP. We then identified and verified the differential expression of FLNB, COL17A1, SLC45A4, LEP, HTRA4, PAPP-A2, EBI3, HSD17B1, FSTL3, INHBA, SIGLEC6, and CGB3. Our analysis also identified interesting mechanistic processes via an in silico prediction of STB-EV-based mechanistic pathways.ConclusionsIn this study, using comprehensive profiling of differentially expressed/carried genes of three linked sample subtypes in PE, we identified potential biomarkers and mechanistic gene pathways that may be important in the pathophysiology of PE and could be further explored in future studies.
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spelling doaj.art-53352e9765b5447aabed917fbd41864d2023-11-30T08:16:18ZengFrontiers Media S.A.Frontiers in Cardiovascular Medicine2297-055X2023-11-011010.3389/fcvm.2023.12916421291642A cross-sectional analysis of syncytiotrophoblast membrane extracellular vesicles–derived transcriptomic biomarkers in early-onset preeclampsiaToluwalase Awoyemi0Wei Zhang1Maryam Rahbar2Adam Cribbs3Prasanna Logenthiran4Shuhan Jiang5Gavin Collett6Ana Sofia Cerdeira7Manu Vatish8Nuffield Department of Women’s & Reproductive Health, University of Oxford, Oxford, United KingdomNuffield Department of Women’s & Reproductive Health, University of Oxford, Oxford, United KingdomNuffield Department of Women’s & Reproductive Health, University of Oxford, Oxford, United KingdomNuffield Department of Orthopaedics, Rheumatology and Musculoskeletal Sciences, University of Oxford, Oxford, United KingdomNuffield Department of Women’s & Reproductive Health, University of Oxford, Oxford, United KingdomNuffield Department of Women’s & Reproductive Health, University of Oxford, Oxford, United KingdomNuffield Department of Women’s & Reproductive Health, University of Oxford, Oxford, United KingdomNuffield Department of Women’s & Reproductive Health, University of Oxford, Oxford, United KingdomNuffield Department of Women’s & Reproductive Health, University of Oxford, Oxford, United KingdomBackgroundPreeclampsia (PE) is a pregnancy-specific hypertensive disorder affecting 2%–8% of pregnancies worldwide. Biomarker(s) for the disorder exists, but while these have excellent negative predictive value, their positive predictive value is poor. Extracellular vesicles released by the placenta into the maternal circulation, syncytiotrophoblast membrane extracellular vesicles (STB-EVs), have been identified as being involved in PE with the potential to act as liquid biopsies.ObjectiveThe objective of this study was to identify the difference in the transcriptome of placenta and STB-EVs between preeclampsia and normal pregnancy (NP) and mechanistic pathways.Methods/study designWe performed RNA-sequencing on placental tissue, medium/large and small STB-EVs from PE (n = 6) and NP (n = 6), followed by bioinformatic analysis to identify targets that could be used in the future for EV-based diagnostic tests for preeclampsia. Some of the identified biomarkers were validated with real-time polymerase chain reactions.ResultsOur analysis identified a difference in the transcriptomic STB-EV cargo between PE and NP. We then identified and verified the differential expression of FLNB, COL17A1, SLC45A4, LEP, HTRA4, PAPP-A2, EBI3, HSD17B1, FSTL3, INHBA, SIGLEC6, and CGB3. Our analysis also identified interesting mechanistic processes via an in silico prediction of STB-EV-based mechanistic pathways.ConclusionsIn this study, using comprehensive profiling of differentially expressed/carried genes of three linked sample subtypes in PE, we identified potential biomarkers and mechanistic gene pathways that may be important in the pathophysiology of PE and could be further explored in future studies.https://www.frontiersin.org/articles/10.3389/fcvm.2023.1291642/fulltranscriptomicssyncytiotrophoblast membrane extracellular vesicles (STB-EVs)preeclampsiabiomarkersplacenta EVsmechanisms
spellingShingle Toluwalase Awoyemi
Wei Zhang
Maryam Rahbar
Adam Cribbs
Prasanna Logenthiran
Shuhan Jiang
Gavin Collett
Ana Sofia Cerdeira
Manu Vatish
A cross-sectional analysis of syncytiotrophoblast membrane extracellular vesicles–derived transcriptomic biomarkers in early-onset preeclampsia
Frontiers in Cardiovascular Medicine
transcriptomics
syncytiotrophoblast membrane extracellular vesicles (STB-EVs)
preeclampsia
biomarkers
placenta EVs
mechanisms
title A cross-sectional analysis of syncytiotrophoblast membrane extracellular vesicles–derived transcriptomic biomarkers in early-onset preeclampsia
title_full A cross-sectional analysis of syncytiotrophoblast membrane extracellular vesicles–derived transcriptomic biomarkers in early-onset preeclampsia
title_fullStr A cross-sectional analysis of syncytiotrophoblast membrane extracellular vesicles–derived transcriptomic biomarkers in early-onset preeclampsia
title_full_unstemmed A cross-sectional analysis of syncytiotrophoblast membrane extracellular vesicles–derived transcriptomic biomarkers in early-onset preeclampsia
title_short A cross-sectional analysis of syncytiotrophoblast membrane extracellular vesicles–derived transcriptomic biomarkers in early-onset preeclampsia
title_sort cross sectional analysis of syncytiotrophoblast membrane extracellular vesicles derived transcriptomic biomarkers in early onset preeclampsia
topic transcriptomics
syncytiotrophoblast membrane extracellular vesicles (STB-EVs)
preeclampsia
biomarkers
placenta EVs
mechanisms
url https://www.frontiersin.org/articles/10.3389/fcvm.2023.1291642/full
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