Serum exosomal microRNA pathway activation in placenta accreta spectrum: pathophysiology and detectionAJOG Global Reports at a Glance
BACKGROUND: Placenta accreta spectrum disorders are a complex range of placental pathologies that are associated with significant maternal morbidity and mortality. A diagnosis of placenta accreta spectrum relies on ultrasonographic findings with modest positive predictive value. Exosomal microRNAs a...
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| Format: | Article |
| Language: | English |
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Elsevier
2024-02-01
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| Series: | AJOG Global Reports |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S2666577824000133 |
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| author | Jessian L. Munoz, MD, PhD, MPH Brett D. Einerson, MD Robert M. Silver, MD Sureshkumar Mulampurath, PhD Lauren S. Sherman, PhD Pranela Rameshwar, PhD Egle Bytautiene Prewit, PhD Patrick S. Ramsey, MD, MSPH |
| author_facet | Jessian L. Munoz, MD, PhD, MPH Brett D. Einerson, MD Robert M. Silver, MD Sureshkumar Mulampurath, PhD Lauren S. Sherman, PhD Pranela Rameshwar, PhD Egle Bytautiene Prewit, PhD Patrick S. Ramsey, MD, MSPH |
| author_sort | Jessian L. Munoz, MD, PhD, MPH |
| collection | DOAJ |
| description | BACKGROUND: Placenta accreta spectrum disorders are a complex range of placental pathologies that are associated with significant maternal morbidity and mortality. A diagnosis of placenta accreta spectrum relies on ultrasonographic findings with modest positive predictive value. Exosomal microRNAs are small RNA molecules that reflect the cellular processes of the origin tissues. OBJECTIVE: We aimed to explore exosomal microRNA expression to understand placenta accreta spectrum pathology and clinical use for placenta accreta spectrum detection. STUDY DESIGN: This study was a biomarker analysis of prospectively collected samples at 2 academic institutions from 2011 to 2022. Plasma specimens were collected from patients with suspected placenta accreta spectrum, placenta previa, or repeat cesarean deliveries. Exosomes were quantified and characterized by nanoparticle tracking analysis and western blotting. MicroRNA were assessed by polymerase chain reaction array and targeted single quantification. MicroRNA pathway analysis was performed using the Ingenuity Pathway Analyses software. Placental biopsies were taken from all groups and analyzed by polymerase chain reaction and whole cell enzyme-linked immunosorbent assay. Receiver operating characteristic curve univariate analysis was performed for the use of microRNA in the prediction of placenta accreta spectrum. Clinically relevant outcomes were collected from abstracted medical records. RESULTS: Plasma specimens were analyzed from a total of 120 subjects (60 placenta accreta spectrum, 30 placenta previa, and 30 control). Isolated plasma exosomes had a mean size of 71.5 nm and were 10 times greater in placenta accreta spectrum specimens (20 vs 2 particles/frame). Protein expression of exosomes was positive for intracellular adhesion molecule 1, flotilin, annexin, and CD9. MicroRNA analysis showed increased detection of 3 microRNAs (mir-92, -103, and -192) in patients with placenta accreta spectrum. Pathway interaction assessment revealed differential regulation of p53 signaling in placenta accreta spectrum and of erythroblastic oncogene B2 or human epidermal growth factor 2 in control specimens. These findings were subsequently confirmed in placental protein analysis. Placental microRNA paralleled plasma exosomal microRNA expression. Biomarker assessment of placenta accreta spectrum signature microRNA had an area under the receiver operating characteristic curve of 0.81 (P<.001; 95% confidence interval, 0.73–0.89) with a sensitivity and specificity of 89.2% and 80%, respectively. CONCLUSION: In this large cohort, plasma exosomal microRNA assessment revealed differentially expressed pathways in placenta accreta spectrum, and these microRNAs are potential biomarkers for the detection of placenta accreta spectrum. |
| first_indexed | 2024-03-07T19:08:38Z |
| format | Article |
| id | doaj.art-ac427b22c4b34dc6ae6ae5a08897dabd |
| institution | Directory Open Access Journal |
| issn | 2666-5778 |
| language | English |
| last_indexed | 2024-04-24T17:28:27Z |
| publishDate | 2024-02-01 |
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| series | AJOG Global Reports |
| spelling | doaj.art-ac427b22c4b34dc6ae6ae5a08897dabd2024-03-28T06:38:56ZengElsevierAJOG Global Reports2666-57782024-02-0141100319Serum exosomal microRNA pathway activation in placenta accreta spectrum: pathophysiology and detectionAJOG Global Reports at a GlanceJessian L. Munoz, MD, PhD, MPH0Brett D. Einerson, MD1Robert M. Silver, MD2Sureshkumar Mulampurath, PhD3Lauren S. Sherman, PhD4Pranela Rameshwar, PhD5Egle Bytautiene Prewit, PhD6Patrick S. Ramsey, MD, MSPH7Division of Maternal Fetal Medicine, Department of Obstetrics and Gynecology, Baylor College of Medicine, Houston, TX (Dr Munoz); Division of Fetal Intervention, Department of Obstetrics and Gynecology, Texas Children's Hospital, Houston, TX (Dr Munoz); Corresponding author: Jessian L. Munoz, MD, PhD, MPH, FACOG.Department of Obstetrics and Gynecology, University of Utah Health, Salt Lake City, UT (Dr Einerson and Dr Silver)Department of Obstetrics and Gynecology, University of Utah Health, Salt Lake City, UT (Dr Einerson and Dr Silver)Department of Obstetrics & Gynecology, University of Texas Health Sciences Center at San Antonio and the University Health System, San Antonio, TX (Dr Mulampurath, Dr Prewit, and Dr Ramsey)Department of Medicine, Rutgers New Jersey Medical School, Newark, NJ (Dr Sherman and Dr Rameshwar)Department of Medicine, Rutgers New Jersey Medical School, Newark, NJ (Dr Sherman and Dr Rameshwar)Department of Obstetrics & Gynecology, University of Texas Health Sciences Center at San Antonio and the University Health System, San Antonio, TX (Dr Mulampurath, Dr Prewit, and Dr Ramsey)Department of Obstetrics & Gynecology, University of Texas Health Sciences Center at San Antonio and the University Health System, San Antonio, TX (Dr Mulampurath, Dr Prewit, and Dr Ramsey)BACKGROUND: Placenta accreta spectrum disorders are a complex range of placental pathologies that are associated with significant maternal morbidity and mortality. A diagnosis of placenta accreta spectrum relies on ultrasonographic findings with modest positive predictive value. Exosomal microRNAs are small RNA molecules that reflect the cellular processes of the origin tissues. OBJECTIVE: We aimed to explore exosomal microRNA expression to understand placenta accreta spectrum pathology and clinical use for placenta accreta spectrum detection. STUDY DESIGN: This study was a biomarker analysis of prospectively collected samples at 2 academic institutions from 2011 to 2022. Plasma specimens were collected from patients with suspected placenta accreta spectrum, placenta previa, or repeat cesarean deliveries. Exosomes were quantified and characterized by nanoparticle tracking analysis and western blotting. MicroRNA were assessed by polymerase chain reaction array and targeted single quantification. MicroRNA pathway analysis was performed using the Ingenuity Pathway Analyses software. Placental biopsies were taken from all groups and analyzed by polymerase chain reaction and whole cell enzyme-linked immunosorbent assay. Receiver operating characteristic curve univariate analysis was performed for the use of microRNA in the prediction of placenta accreta spectrum. Clinically relevant outcomes were collected from abstracted medical records. RESULTS: Plasma specimens were analyzed from a total of 120 subjects (60 placenta accreta spectrum, 30 placenta previa, and 30 control). Isolated plasma exosomes had a mean size of 71.5 nm and were 10 times greater in placenta accreta spectrum specimens (20 vs 2 particles/frame). Protein expression of exosomes was positive for intracellular adhesion molecule 1, flotilin, annexin, and CD9. MicroRNA analysis showed increased detection of 3 microRNAs (mir-92, -103, and -192) in patients with placenta accreta spectrum. Pathway interaction assessment revealed differential regulation of p53 signaling in placenta accreta spectrum and of erythroblastic oncogene B2 or human epidermal growth factor 2 in control specimens. These findings were subsequently confirmed in placental protein analysis. Placental microRNA paralleled plasma exosomal microRNA expression. Biomarker assessment of placenta accreta spectrum signature microRNA had an area under the receiver operating characteristic curve of 0.81 (P<.001; 95% confidence interval, 0.73–0.89) with a sensitivity and specificity of 89.2% and 80%, respectively. CONCLUSION: In this large cohort, plasma exosomal microRNA assessment revealed differentially expressed pathways in placenta accreta spectrum, and these microRNAs are potential biomarkers for the detection of placenta accreta spectrum.http://www.sciencedirect.com/science/article/pii/S2666577824000133abnormal placentationbiomarkercesarean hysterectomyexosomemicroRNAplacenta accreta |
| spellingShingle | Jessian L. Munoz, MD, PhD, MPH Brett D. Einerson, MD Robert M. Silver, MD Sureshkumar Mulampurath, PhD Lauren S. Sherman, PhD Pranela Rameshwar, PhD Egle Bytautiene Prewit, PhD Patrick S. Ramsey, MD, MSPH Serum exosomal microRNA pathway activation in placenta accreta spectrum: pathophysiology and detectionAJOG Global Reports at a Glance AJOG Global Reports abnormal placentation biomarker cesarean hysterectomy exosome microRNA placenta accreta |
| title | Serum exosomal microRNA pathway activation in placenta accreta spectrum: pathophysiology and detectionAJOG Global Reports at a Glance |
| title_full | Serum exosomal microRNA pathway activation in placenta accreta spectrum: pathophysiology and detectionAJOG Global Reports at a Glance |
| title_fullStr | Serum exosomal microRNA pathway activation in placenta accreta spectrum: pathophysiology and detectionAJOG Global Reports at a Glance |
| title_full_unstemmed | Serum exosomal microRNA pathway activation in placenta accreta spectrum: pathophysiology and detectionAJOG Global Reports at a Glance |
| title_short | Serum exosomal microRNA pathway activation in placenta accreta spectrum: pathophysiology and detectionAJOG Global Reports at a Glance |
| title_sort | serum exosomal microrna pathway activation in placenta accreta spectrum pathophysiology and detectionajog global reports at a glance |
| topic | abnormal placentation biomarker cesarean hysterectomy exosome microRNA placenta accreta |
| url | http://www.sciencedirect.com/science/article/pii/S2666577824000133 |
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