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ORIGINAL RESEARCH article

Front. Endocrinol.
Sec. Reproduction
Volume 15 - 2024 | doi: 10.3389/fendo.2024.1442684
This article is part of the Research Topic Infertility and Endometriosis View all 19 articles

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

Provisionally accepted
Ayako Muraoka Ayako Muraoka *Akira Yokoi Akira Yokoi *Kosuke Yoshida Kosuke Yoshida Masami Kitagawa Masami Kitagawa Bayasula Bayasula Bayasula Bayasula Mayuko Murakami Mayuko Murakami Natsuki Miyake Natsuki Miyake Reina Sonehara Reina Sonehara Tomoko Nakamura Tomoko Nakamura Satoko Osuka Satoko Osuka Hiroaki Kajiyama Hiroaki Kajiyama
  • Nagoya University, Nagoya, Japan

The final, formatted version of the article will be published soon.

    Endometriosis 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. Serum 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 micro RNA (miRNA) profiles in the infertility patients with and without endometriosis to detect pregnancy-predicting biomarkers. Candidate 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. Further studies are required to examine the functional importance of these miRNAs to elucidate the pathological mechanisms of endometriosis and pregnancy.

    Keywords: extracellular vesicles, micro RNA, Serum, Pregnancy, Assisted Reproductive Technology, Endometriosis, noninvasive biomarker

    Received: 02 Jun 2024; Accepted: 18 Dec 2024.

    Copyright: © 2024 Muraoka, Yokoi, Yoshida, Kitagawa, Bayasula, Murakami, Miyake, Sonehara, Nakamura, Osuka and Kajiyama. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

    * Correspondence:
    Ayako Muraoka, Nagoya University, Nagoya, Japan
    Akira Yokoi, Nagoya University, Nagoya, Japan

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