Dataset Information

Syncytiotrophoblast extracellular microvesicle profiles in maternal circulation for noninvasive diagnosis of preeclampsia.

ABSTRACT: Preeclampsia is the most common placental pathology in pregnant females, with increased morbidity and mortality incurred on the mother and the fetus. There is a need for improved biomarkers for diagnosis and monitoring of this condition. Placental syncytiotrophoblasts at the maternal-fetal interface release nanoparticles, including extracellular microvesicles, into the maternal blood during pregnancy. Syncytiotrophoblast extracellular microvesicles (STEVs) are being studied for their diagnostic potential and for their potential physiologic role in preeclampsia. We hypothesized that STEV profiles in maternal circulation would be altered under conditions of preeclampsia compared to normal pregnancy. Extracellular vesicles (EVs) released by BeWo cells in vitro showed high expression of syncytin-1, but no plac1 expression, demonstrating that trophoblast cell EVs express syncytin-1 on their surface. Placental alkaline phosphatase also showed high expression on BeWo EVs, but due to concern for cross reactivity to highly prevalent isoforms of intestinal and bone alkaline phosphatase, we utilized syncytin-1 as a marker for STEVs. In vivo, syncytin-1 protein expression was confirmed in maternal plasma EVs from Control and Preeclampsia subjects by Western blot, and overall, lower expression was noted in samples from patients with preeclampsia (n?=?8). By nanoparticle analysis, EV profiles from Control and Preeclampsia groups showed similar total plasma EV quantities (p?=?0.313) and size distribution (p?=?0.415), but STEV quantitative signal, marked by syncytin-1 specific EVs, was significantly decreased in the Preeclampsia group (p?=?2.8 × 10-11). Receiver operating characteristic curve demonstrated that STEV signal threshold cut-off of <0.316 was 95.2% sensitive and 95.6% specific for diagnosis of preeclampsia in this cohort (area under curve = 0.975 ± 0.020). In conclusion, we report that the syncytin-1 expressing EV profiles in maternal plasma might serve as a placental tissue specific biomarker for preeclampsia.

SUBMITTER: Levine L

PROVIDER: S-EPMC7156695 | biostudies-literature | 2020 Apr

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Syncytiotrophoblast extracellular microvesicle profiles in maternal circulation for noninvasive diagnosis of preeclampsia.

Levine Lisa L Habertheuer Andreas A Ram Chirag C Korutla Laxminarayana L Schwartz Nadav N Hu Robert W RW Reddy Sanjana S Freas Andrew A Zielinski Patrick D PD Harmon Joey J Molugu Sudheer Kumar SK Parry Samuel S Vallabhajosyula Prashanth P

Scientific reports 20200414 1

Preeclampsia is the most common placental pathology in pregnant females, with increased morbidity and mortality incurred on the mother and the fetus. There is a need for improved biomarkers for diagnosis and monitoring of this condition. Placental syncytiotrophoblasts at the maternal-fetal interface release nanoparticles, including extracellular microvesicles, into the maternal blood during pregnancy. Syncytiotrophoblast extracellular microvesicles (STEVs) are being studied for their diagnostic ...[more]

PMID: 32286341

Similar Datasets

Project description:Preeclampsia (PE), defined as new-onset hypertension and multi-organ systemic complication during pregnancy, is the leading cause of maternal and neonatal mortality and morbidity. With extracellular vesicles research progresses, current data refers to the possibility that ferroptosis may play a role in exosomal effects. Evidence has suggested that ferroptosis may contribute to the pathogenesis of preeclampsia by bioinformatics analyses. The purpose of the current study is to identify the potential ferroptosis-related genes in syncytiotrophoblast-derived extracellular vesicles (STB-EVs) of preeclampsia using bioinformatics analyses. Clinical characteristics and gene expression data of all samples were obtained from the NCBI GEO database. The differentially expressed mRNAs (DE-mRNAs) in STB-EVs of preeclampsia were screened and then were intersected with ferroptosis genes. Functional and pathway enrichment analyses of ferroptosis-related DE-mRNAs in STB-EVs were performed. Ferroptosis-related hub genes in STB-EVs were identified by Cytoscape plugin CytoHubba with a Degree algorithm using a protein-protein interaction network built constructed from the STRING database. The predictive performance of ferroptosis-related hub genes was determined by a univariate analysis of receiver operating characteristic (ROC). The miRNA-hub gene regulatory network was constructed using the miRwalk database. A total of 1976 DE-mRNAs in STB-EVs were identified and the most enriched item identified by gene set enrichment analysis was signaling by G Protein-Coupled Receptors (normalized enrichment score = 1.238). These DE-mRNAs obtained 26 ferroptosis-related DE-mRNAs. Ferroptosis-related DE-mRNAs of gene ontology terms and Encyclopedia of Genes and Genomes pathway enrichment analysis were enriched significantly in response to oxidative stress and ferroptosis. Five hub genes (ALB, NOX4, CDKN2A, TXNRD1, and CAV1) were found in the constructed protein-protein interaction network with ferroptosis-related DE-mRNAs and the areas under the ROC curves for ALB, NOX4, CDKN2A, TXNRD1, and CAV1 were 0.938 (CI: 0.815-1.000), 0.833 (CI: 0.612-1.000), 0.875 (CI: 0.704-1.000), 0.958 (CI: 0.862-1.000), and 0.854 (CI: 0.652-1.000) in univariate analysis of ROC. We constructed a regulatory network of miRNA-hub gene and the findings demonstrate that hsa-miR-26b-5p, hsa-miR-192-5p, hsa-miR-124-3p, hsa-miR-492, hsa-miR-34a-5p and hsa-miR-155-5p could regulate most hub genes. In this study, we identified several central genes closely related to ferroptosis in STB-EVs (ALB, NOX4, CDKN2A, TXNRD1, and CAV1) that are potential biomarkers related to ferroptosis in preeclampsia. Our findings will provide evidence for the involvement of ferroptosis in preeclampsia and improve the understanding of ferroptosis-related molecular pathways in the pathogenesis of preeclampsia.

Dataset Information

Syncytiotrophoblast extracellular microvesicle profiles in maternal circulation for noninvasive diagnosis of preeclampsia.

Publications

Syncytiotrophoblast extracellular microvesicle profiles in maternal circulation for noninvasive diagnosis of preeclampsia.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets