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...
Main Authors: | , , , , , , , , |
---|---|
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 |
_version_ | 1797447782906200064 |
---|---|
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. |
first_indexed | 2024-03-09T14:00:55Z |
format | Article |
id | doaj.art-53352e9765b5447aabed917fbd41864d |
institution | Directory Open Access Journal |
issn | 2297-055X |
language | English |
last_indexed | 2024-03-09T14:00:55Z |
publishDate | 2023-11-01 |
publisher | Frontiers Media S.A. |
record_format | Article |
series | Frontiers in Cardiovascular Medicine |
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 |
work_keys_str_mv | AT toluwalaseawoyemi acrosssectionalanalysisofsyncytiotrophoblastmembraneextracellularvesiclesderivedtranscriptomicbiomarkersinearlyonsetpreeclampsia AT weizhang acrosssectionalanalysisofsyncytiotrophoblastmembraneextracellularvesiclesderivedtranscriptomicbiomarkersinearlyonsetpreeclampsia AT maryamrahbar acrosssectionalanalysisofsyncytiotrophoblastmembraneextracellularvesiclesderivedtranscriptomicbiomarkersinearlyonsetpreeclampsia AT adamcribbs acrosssectionalanalysisofsyncytiotrophoblastmembraneextracellularvesiclesderivedtranscriptomicbiomarkersinearlyonsetpreeclampsia AT prasannalogenthiran acrosssectionalanalysisofsyncytiotrophoblastmembraneextracellularvesiclesderivedtranscriptomicbiomarkersinearlyonsetpreeclampsia AT shuhanjiang acrosssectionalanalysisofsyncytiotrophoblastmembraneextracellularvesiclesderivedtranscriptomicbiomarkersinearlyonsetpreeclampsia AT gavincollett acrosssectionalanalysisofsyncytiotrophoblastmembraneextracellularvesiclesderivedtranscriptomicbiomarkersinearlyonsetpreeclampsia AT anasofiacerdeira acrosssectionalanalysisofsyncytiotrophoblastmembraneextracellularvesiclesderivedtranscriptomicbiomarkersinearlyonsetpreeclampsia AT manuvatish acrosssectionalanalysisofsyncytiotrophoblastmembraneextracellularvesiclesderivedtranscriptomicbiomarkersinearlyonsetpreeclampsia AT toluwalaseawoyemi crosssectionalanalysisofsyncytiotrophoblastmembraneextracellularvesiclesderivedtranscriptomicbiomarkersinearlyonsetpreeclampsia AT weizhang crosssectionalanalysisofsyncytiotrophoblastmembraneextracellularvesiclesderivedtranscriptomicbiomarkersinearlyonsetpreeclampsia AT maryamrahbar crosssectionalanalysisofsyncytiotrophoblastmembraneextracellularvesiclesderivedtranscriptomicbiomarkersinearlyonsetpreeclampsia AT adamcribbs crosssectionalanalysisofsyncytiotrophoblastmembraneextracellularvesiclesderivedtranscriptomicbiomarkersinearlyonsetpreeclampsia AT prasannalogenthiran crosssectionalanalysisofsyncytiotrophoblastmembraneextracellularvesiclesderivedtranscriptomicbiomarkersinearlyonsetpreeclampsia AT shuhanjiang crosssectionalanalysisofsyncytiotrophoblastmembraneextracellularvesiclesderivedtranscriptomicbiomarkersinearlyonsetpreeclampsia AT gavincollett crosssectionalanalysisofsyncytiotrophoblastmembraneextracellularvesiclesderivedtranscriptomicbiomarkersinearlyonsetpreeclampsia AT anasofiacerdeira crosssectionalanalysisofsyncytiotrophoblastmembraneextracellularvesiclesderivedtranscriptomicbiomarkersinearlyonsetpreeclampsia AT manuvatish crosssectionalanalysisofsyncytiotrophoblastmembraneextracellularvesiclesderivedtranscriptomicbiomarkersinearlyonsetpreeclampsia |