Serum-derived small extracellular vesicles as biomarkers for predicting pregnancy and delivery on assisted reproductive technology in patients with endometriosis

IntroductionEndometriosis can cause of infertility, and evaluation methods for predicting clinical pregnancy outcomes are desired. Extracellular vesicles (EVs) exist in blood and it contains small non-coding RNAs (ncRNAs) that may reflect disease severity. In this study, we investigated small ncRNAs...

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Main Authors: Ayako Muraoka, Akira Yokoi, Kosuke Yoshida, Masami Kitagawa, Bayasula, Mayuko Murakami, Natsuki Miyake, Reina Sonehara, Tomoko Nakamura, Satoko Osuka, Hiroaki Kajiyama
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Language:English
Published: Frontiers Media S.A. 2025-01-01
Series:Frontiers in Endocrinology
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Online Access:https://www.frontiersin.org/articles/10.3389/fendo.2024.1442684/full
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author Ayako Muraoka
Akira Yokoi
Akira Yokoi
Akira Yokoi
Kosuke Yoshida
Kosuke Yoshida
Masami Kitagawa
Bayasula
Mayuko Murakami
Natsuki Miyake
Reina Sonehara
Tomoko Nakamura
Satoko Osuka
Hiroaki Kajiyama
author_facet Ayako Muraoka
Akira Yokoi
Akira Yokoi
Akira Yokoi
Kosuke Yoshida
Kosuke Yoshida
Masami Kitagawa
Bayasula
Mayuko Murakami
Natsuki Miyake
Reina Sonehara
Tomoko Nakamura
Satoko Osuka
Hiroaki Kajiyama
author_sort Ayako Muraoka
collection DOAJ
description IntroductionEndometriosis can cause of infertility, and evaluation methods for predicting clinical pregnancy outcomes are desired. Extracellular vesicles (EVs) exist in blood and it contains small non-coding RNAs (ncRNAs) that may reflect disease severity. In this study, we investigated small ncRNAs in serum EVs to identify specific biomarkers for predicting clinical pregnancy.MethodsSerum samples were collected from 48 patients who underwent assisted reproductive technology (ART). EVs were successfully isolated from serum samples and characterized using nanoparticle tracking assays, electron microscopy, and western blotting of EV’s markers. We performed small RNA sequencing and analyzed microRNA (miRNA) profiles in the infertility patients with and without endometriosis to detect pregnancy-predicting biomarkers.ResultsCandidate miRNAs in serum EVs were selected by comparing patients without endometriosis who became pregnant (n = 13) with those who did not (n = 21). A total of 241 miRNAs were detected; however, no trends separated the two groups. Next, EVs from patients with endometriosis were analyzed and divided into pregnant (n = 4) and non-pregnant (n = 10) cases. Among the 224 candidate miRNAs, miRNA profiles of pregnant women with endometriosis were separated from those of non-pregnant women by receiver-operating characteristics (ROC) curve analysis (area under the curve [AUC] > 0.8). In patients with endometriosis, serum EVs may be useful for predicting possible pregnancy before infertility treatment. Finally, we used small RNA sequencing of the tissue to demonstrate that pregnancy-predicting miRNAs in serum EVs were produced from endometriosis lesions. Although no predictors were found from miRNAs in serum EVs without endometriosis, miRNAs in serum EVs of patients with endometriosis could provide novel noninvasive biomarkers to predict pregnancy and have potential clinical applicability in ART.DiscussionFurther studies are required to examine the functional importance of these miRNAs to elucidate the pathological mechanisms of endometriosis and pregnancy.
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spelling doaj-art-bfaba82e6e9a451dabd49563f9ed813a2025-01-17T05:10:43ZengFrontiers Media S.A.Frontiers in Endocrinology1664-23922025-01-011510.3389/fendo.2024.14426841442684Serum-derived small extracellular vesicles as biomarkers for predicting pregnancy and delivery on assisted reproductive technology in patients with endometriosisAyako Muraoka0Akira Yokoi1Akira Yokoi2Akira Yokoi3Kosuke Yoshida4Kosuke Yoshida5Masami Kitagawa6 Bayasula7Mayuko Murakami8Natsuki Miyake9Reina Sonehara10Tomoko Nakamura11Satoko Osuka12Hiroaki Kajiyama13Department of Obstetrics and Gynecology, Nagoya University Graduate School of Medicine, Nagoya, JapanDepartment of Obstetrics and Gynecology, Nagoya University Graduate School of Medicine, Nagoya, JapanNagoya University Institute for Advanced Research, Nagoya, JapanJapan Science and Technology Agency (JST), FOREST, Saitama, JapanDepartment of Obstetrics and Gynecology, Nagoya University Graduate School of Medicine, Nagoya, JapanNagoya University Institute for Advanced Research, Nagoya, JapanBell Research Center for Reproductive Health and Cancer, Nagoya University Graduate School of Medicine, Nagoya, JapanBell Research Center for Reproductive Health and Cancer, Nagoya University Graduate School of Medicine, Nagoya, JapanDepartment of Obstetrics and Gynecology, Nagoya University Graduate School of Medicine, Nagoya, JapanDepartment of Obstetrics and Gynecology, Nagoya University Graduate School of Medicine, Nagoya, JapanDepartment of Obstetrics and Gynecology, Nagoya University Graduate School of Medicine, Nagoya, JapanDepartment of Obstetrics and Gynecology, Nagoya University Graduate School of Medicine, Nagoya, JapanDepartment of Obstetrics and Gynecology, Nagoya University Graduate School of Medicine, Nagoya, JapanDepartment of Obstetrics and Gynecology, Nagoya University Graduate School of Medicine, Nagoya, JapanIntroductionEndometriosis can cause of infertility, and evaluation methods for predicting clinical pregnancy outcomes are desired. Extracellular vesicles (EVs) exist in blood and it contains small non-coding RNAs (ncRNAs) that may reflect disease severity. In this study, we investigated small ncRNAs in serum EVs to identify specific biomarkers for predicting clinical pregnancy.MethodsSerum samples were collected from 48 patients who underwent assisted reproductive technology (ART). EVs were successfully isolated from serum samples and characterized using nanoparticle tracking assays, electron microscopy, and western blotting of EV’s markers. We performed small RNA sequencing and analyzed microRNA (miRNA) profiles in the infertility patients with and without endometriosis to detect pregnancy-predicting biomarkers.ResultsCandidate miRNAs in serum EVs were selected by comparing patients without endometriosis who became pregnant (n = 13) with those who did not (n = 21). A total of 241 miRNAs were detected; however, no trends separated the two groups. Next, EVs from patients with endometriosis were analyzed and divided into pregnant (n = 4) and non-pregnant (n = 10) cases. Among the 224 candidate miRNAs, miRNA profiles of pregnant women with endometriosis were separated from those of non-pregnant women by receiver-operating characteristics (ROC) curve analysis (area under the curve [AUC] > 0.8). In patients with endometriosis, serum EVs may be useful for predicting possible pregnancy before infertility treatment. Finally, we used small RNA sequencing of the tissue to demonstrate that pregnancy-predicting miRNAs in serum EVs were produced from endometriosis lesions. Although no predictors were found from miRNAs in serum EVs without endometriosis, miRNAs in serum EVs of patients with endometriosis could provide novel noninvasive biomarkers to predict pregnancy and have potential clinical applicability in ART.DiscussionFurther studies are required to examine the functional importance of these miRNAs to elucidate the pathological mechanisms of endometriosis and pregnancy.https://www.frontiersin.org/articles/10.3389/fendo.2024.1442684/fullextracellular vesiclesmicroRNAserumpregnancyassisted reproductive technologyendometriosis
spellingShingle Ayako Muraoka
Akira Yokoi
Akira Yokoi
Akira Yokoi
Kosuke Yoshida
Kosuke Yoshida
Masami Kitagawa
Bayasula
Mayuko Murakami
Natsuki Miyake
Reina Sonehara
Tomoko Nakamura
Satoko Osuka
Hiroaki Kajiyama
Serum-derived small extracellular vesicles as biomarkers for predicting pregnancy and delivery on assisted reproductive technology in patients with endometriosis
Frontiers in Endocrinology
extracellular vesicles
microRNA
serum
pregnancy
assisted reproductive technology
endometriosis
title Serum-derived small extracellular vesicles as biomarkers for predicting pregnancy and delivery on assisted reproductive technology in patients with endometriosis
title_full Serum-derived small extracellular vesicles as biomarkers for predicting pregnancy and delivery on assisted reproductive technology in patients with endometriosis
title_fullStr Serum-derived small extracellular vesicles as biomarkers for predicting pregnancy and delivery on assisted reproductive technology in patients with endometriosis
title_full_unstemmed Serum-derived small extracellular vesicles as biomarkers for predicting pregnancy and delivery on assisted reproductive technology in patients with endometriosis
title_short Serum-derived small extracellular vesicles as biomarkers for predicting pregnancy and delivery on assisted reproductive technology in patients with endometriosis
title_sort serum derived small extracellular vesicles as biomarkers for predicting pregnancy and delivery on assisted reproductive technology in patients with endometriosis
topic extracellular vesicles
microRNA
serum
pregnancy
assisted reproductive technology
endometriosis
url https://www.frontiersin.org/articles/10.3389/fendo.2024.1442684/full
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