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Identification of labor related microRNAs and their clinical significance

Research Project

Project/Area Number 21K09497
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Review Section Basic Section 56040:Obstetrics and gynecology-related
Research InstitutionNagasaki University

Principal Investigator

三浦 清徳  長崎大学, 医歯薬学総合研究科(医学系), 教授 (00363490)

Project Period (FY) 2021-04-01 – 2025-03-31
Project Status Granted (Fiscal Year 2023)
Budget Amount *help
¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000)
Fiscal Year 2023: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
Fiscal Year 2022: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000)
Fiscal Year 2021: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
Keywords産婦人科学 / 陣痛発来 / 分子マーカー / microRNA / mRNA / 母体血 / 陣痛 / 環状RNA / エクソソーム / 間葉系幹細胞 / 胎盤 / RNA / circRNA / 妊娠 / 発現量 / 産科婦人科
Outline of Research at the Start

陣痛発来のメカニズムは未だ不明な点が多く、その分子機構の解明は安全な妊娠・分娩管理につながるため、周産期医療における最重要課題の一つである。本研究では、母体血漿中に流入しているエクソソームに内包されている胎盤、胎児ならびに羊膜特異的mRNA/microRNAに着目し、陣痛と関連するmRNA/microRNAを同定し、その臨床的意義と陣痛発来の分子メカニズムの解明を目指す。

Outline of Annual Research Achievements

本研究では、母体血漿中に流入している胎盤、胎児ならびに羊水特異的mRNA/microRNAに着目し、陣痛と関連するRNA分子プロファイルを同定し、その臨床応用と陣痛発来の分子メカニズムの解明を目指し、安全な妊娠・分娩管理の確立に貢献する。長崎大学病院を受診した妊婦のうち、妊娠中経時的(妊娠12-16週、妊娠20-24週、妊娠30-32週、妊娠35-36週、陣痛発来時、分娩後1日目、分娩後4日目、および産後1ヶ月健診時)に母体血漿を集積保存した。血漿以外にも胎盤組織、臍帯の残余検体を集積した。ハウスキーピング遺伝子、U6 snRNA、SNORD48、RNU6-2などを含む内部コントロール用のTaqManプローブセット(ライフテクノロジー)を用いて、胎児・胎盤・羊膜におけるmRNA/microRNA発現量を比較検討し、最も発現量の変化が少ないものを最適な内部コントロールとして選択した。陣痛発来と関連する胎盤特異的microRNAの候補としてC19MCに存在するmiR-515-3p、miR-517a、miR-517cおよびmiR-518を、陣痛発来と関連する胎児特異的miRNAの候補としてC14MCに存在するmiR-323-3p、miR-411およびmiR-433を選択した。また、陣痛発来と関連するmRNAの候補としてCLCN3およびMOB1Bを選択した。現在集積している検体数は、陣痛発来し経腟分娩した症例では妊娠30-32週のものが72検体、妊娠35-36週が74検体、陣痛発来時は31検体、分娩後1日目は38検体、分娩後4日目は15検体、および産後1ヶ月健診のものは102検体の集積がある。

Current Status of Research Progress
Current Status of Research Progress

3: Progress in research has been slightly delayed.

Reason

陣痛発来と関連するmicroRNAおよびmRNAのスクリーニング、内部コントロールの選択、および研究に用いる検体集積に時間を要してしまった。とくに、microRNAおよびmRNAのスクリーニングでは、想定よりも多くのmicroRNAおよびmRNAが陣痛は辛いと関連するmicroRNAおよびmRNAの候補として選択されてきたため、文献検索でターゲットを絞る作業を行ったため遅延が生じた。定量的RT-PCRの条件設定では、相対定量法ではなかなか安定した定量系を設定することができなくて、絶対定量で用いる内部コントロールの選択をやり直したので遅延が生じた。研究に用いる検体集積については、より正確に陣痛は辛いと関連する分子マーカーを同定するため、同一例で妊娠経時的にサンプリングされている検体を用いる方針としたたため、検体集積に時間がかかり遅延が生じた。

Strategy for Future Research Activity

現在までに妊娠30-32週の母体血が72検体、妊娠35-36週が74検体、陣痛発来時は31検体、分娩後1日目は38検体、分娩後4日目は15検体、および産後1ヶ月健診のものは102検体の集積があるので、母体血中microRNA(miR-515-3p、miR-517a、miR-517cおよびmiR-518)およびmRNA(CLCN3およびMOB1B)の変化を経時的に解析する。そして、分娩予定日より早く陣痛発来した症例と予定日超過した陣痛が遅く発来した症例で比較し、陣痛発来を予測できる分子マーカーを同定することで、R6年度中に研究の目的を達成する。

Report

(3 results)
  • 2023 Research-status Report
  • 2022 Research-status Report
  • 2021 Research-status Report
  • Research Products

    (31 results)

All 2024 2023 2022 2021 Other

All Journal Article (25 results) (of which Int'l Joint Research: 1 results,  Peer Reviewed: 23 results,  Open Access: 10 results) Presentation (2 results) (of which Invited: 2 results) Remarks (2 results) Patent(Industrial Property Rights) (2 results)

  • [Journal Article] Establishment of a novel human T-cell leukemia virus type 1 infection model using cell-free virus2024

    • Author(s)
      Nagata Koh、Tezuka Kenta、Kuramitsu Madoka、Fuchi Naoki、Hasegawa Yuri、Hamaguchi Isao、Miura Kiyonori
    • Journal Title

      Journal of Virology

      Volume: 98 Issue: 2

    • DOI

      10.1128/jvi.01862-23

    • Related Report
      2023 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Performance evaluation of Espline HTLV-I/II, a newly developed rapid immunochromatographic antibody test for different diagnostic situations2023

    • Author(s)
      Kuramitsu M, Momose H, Uchida Y, Ishitsuka K, Kubota R, Tokunaga M, Utsunomiya A, Umekita K, Hashikura Y, Nosaka K, Koh K-R, Nakamura H, Sagara Y, Sobata R, Satake M, Nagata K, Hasegawa Y, Sasaki D, Hasegawa H, Sato T, Yamano Y, Hiraga K, Tezuka K, Ikebe E, Matsuoka S, Okuma K, Watanabe T, Miura K, Hamaguchi I.
    • Journal Title

      Microbiology Spectrum

      Volume: 11 Issue: 6 Pages: 1-10

    • DOI

      10.1128/spectrum.02078-23

    • Related Report
      2023 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Simultaneous bilateral mastectomy and RRSO for BRCA2-positive non-invasive breast cancer in Japan: a case report and analysis of initial experience2023

    • Author(s)
      Tanaka Aya、Matsumoto Megumi、Takao Mami、Miura Shoko、Hasegawa Yuri、Otsubo Ryota、Hayashi Hiroko、Isomoto Ichiro、Miura Kiyonori、Nagayasu Takeshi
    • Journal Title

      Hereditary Cancer in Clinical Practice

      Volume: 21 Issue: 1 Pages: 23-23

    • DOI

      10.1186/s13053-023-00268-y

    • Related Report
      2023 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Four conserved amino acids on human papillomavirus E6 predict clinical high‐risk types2023

    • Author(s)
      Niiya Akari、Hamaguchi Yo、Mishima Hiroyuki、Miura Shoko、Komatsu Nahoko、Nagata Koh、Hasegawa Yuri、Miura Kiyonori、Yoshiura Koh‐ichiro
    • Journal Title

      Journal of Medical Virology

      Volume: 95 Issue: 8 Pages: 106844-106844

    • DOI

      10.1002/jmv.29049

    • Related Report
      2023 Research-status Report
    • Peer Reviewed
  • [Journal Article] Drug-induced interstitial lung disease caused by olaparib: three case reports and review of the Japanese Adverse Drug Event Report database and literature2023

    • Author(s)
      Ishimoto Hiroshi、Sakamoto Noriho、Kido Takashi、Ozasa Mutsumi、Tsutsui Shin、Mori Mayako、Setoguchi Daichi、Takemoto Shinnosuke、Obase Yasushi、Ishimatsu Yuji、Tomonaga Chiharu、Matsumoto Kanako、Morisaki Sachiko、Miura Kiyonori、Mukae Hiroshi
    • Journal Title

      BMC Pulmonary Medicine

      Volume: 23 Issue: 1 Pages: 289-289

    • DOI

      10.1186/s12890-023-02569-3

    • Related Report
      2023 Research-status Report
    • Peer Reviewed
  • [Journal Article] AMH producing purely cystic virilizing adult granulosa cell tumor in 17 years old girl: a case report and review of literatures2023

    • Author(s)
      Kitajima Michio、Kajimura Itsuki、Kitajima Yuriko、Murakami Naoko、Matsumura Asako、Matsumoto Kanako、Harada Ayumi、Hasegawa Yuri、Miura Kiyonori
    • Journal Title

      Journal of Ovarian Research

      Volume: 16 Issue: 1 Pages: 52-52

    • DOI

      10.1186/s13048-023-01134-0

    • Related Report
      2022 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Dysgerminoma of the Left Ovary in a Patient with Balanced Translocation 46X, t(X:1) (q22;q21): A Case Report2023

    • Author(s)
      Nagata Koh、Shimada Takako、Eishi Chiaki、Nishi Masaki、Murakami Toru、Ohashi Kazuaki、Kajimura Itsuki、Miura Kiyonori
    • Journal Title

      International Medical Case Reports Journal

      Volume: Volume 16 Pages: 117-122

    • DOI

      10.2147/imcrj.s395511

    • Related Report
      2022 Research-status Report
    • Peer Reviewed
  • [Journal Article] 合併増大号 今月の臨床 産婦人科医が知っておきたい臨床遺伝学のすべて 周産期 羊水検査・絨毛検査の適応と実施法2022

    • Author(s)
      三浦 生子、長谷川 ゆり、三浦 清徳
    • Journal Title

      臨床婦人科産科

      Volume: 76 Issue: 1 Pages: 62-68

    • DOI

      10.11477/mf.1409210564

    • ISSN
      0386-9865, 1882-1294
    • Year and Date
      2022-01-10
    • Related Report
      2021 Research-status Report
  • [Journal Article] Frequency of HTLV-1 seroconversion between pregnancies in Nagasaki, Japan, 2011-20182022

    • Author(s)
      Komatsu Nahoko、Iwanaga Masako、Hasegawa Yuri、Miura Shoko、Fuchi Naoki、Moriuchi Hiroyuki、Yanagihara Katsunori、Miura Kiyonori
    • Journal Title

      Frontiers in Microbiology

      Volume: 13 Pages: 1036955-1036955

    • DOI

      10.3389/fmicb.2022.1036955

    • Related Report
      2022 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] “Welcome to OBGYN World!” A novel recruitment event for medical students organized by the Japan Society of Obstetrics and Gynecology2022

    • Author(s)
      Miyake Ryuta and Miura Kiyonori.
    • Journal Title

      Journal of Obstetrics and Gynaecology Research

      Volume: 49 Issue: 2 Pages: 487-492

    • DOI

      10.1111/jog.15504

    • Related Report
      2022 Research-status Report
    • Peer Reviewed
  • [Journal Article] Association of online activities with obstetrics and gynecology specialty choice: a nationwide online survey2022

    • Author(s)
      Maeda Yuto、Hasegawa Akihiro、Miyake Ryuta、Dofutsu Mihoko、Higuchi Yayoi、Osaku Daiken、Suemitsu Tokumasa、Onodera Yohei、Shozu Makio、Miura Kiyonori、Yoshida Yoshio、Komatsu Hiroaki、Watari Hidemichi
    • Journal Title

      International Journal of Medical Education

      Volume: 13 Pages: 261-266

    • DOI

      10.5116/ijme.6320.36eb

    • Related Report
      2022 Research-status Report
    • Peer Reviewed
  • [Journal Article] Pathological features of biopsied myocardium in patients clinically diagnosed with peripartum cardiomyopathy2022

    • Author(s)
      Kawano Hiroaki、Kawamura Koichi、Ishijima Mitsuaki、Abe Kuniko、Hayashi Tomayoshi、Eguchi Masamichi、Miura Kiyonori、Maemura Koji
    • Journal Title

      Medical Molecular Morphology

      Volume: 56 Issue: 1 Pages: 58-68

    • DOI

      10.1007/s00795-022-00340-x

    • Related Report
      2022 Research-status Report
    • Peer Reviewed
  • [Journal Article] Retained products of conception (RPOC) following delivery without placenta previa: Which patients with RPOC show postpartum hemorrhage?2022

    • Author(s)
      Takahashi Hironori、Tanaka Hiroaki、Osuga Yutaka、Miura Kiyonori、Saito Shigeru、Sato Shoji、Sugawara Junichi、Ide Sanae、Koh Iiji、Yamauchi Keiko、Okuyama Ayumi、Okuno Kentaro、Kuwata Tomoyuki、Fujieda Satoko、Ikeda Tomoaki
    • Journal Title

      Placenta

      Volume: 124 Pages: 12-17

    • DOI

      10.1016/j.placenta.2022.05.004

    • Related Report
      2022 Research-status Report 2021 Research-status Report
    • Peer Reviewed
  • [Journal Article] Challenges facing workstyle reform for Japanese obstetricians and gynecologists revealed from time studies2022

    • Author(s)
      Sekine Masayuki、Nishijima Koji、Nakagawa Satoshi、Suzuki Yukio、Murakami Takashi、Kato Yasuhito、Umazume Takeshi、Tanaka Hiroaki、Komatsu Hiroaki、Doi Koutaro、Miura Kiyonori、Kudo Yoshiki、Unno Nobuya、Kimura Tadashi、Enomoto Takayuki
    • Journal Title

      Journal of Obstetrics and Gynaecology Research

      Volume: 48 Issue: 7 Pages: 1580-1590

    • DOI

      10.1111/jog.15230

    • Related Report
      2022 Research-status Report 2021 Research-status Report
    • Peer Reviewed
  • [Journal Article] Biological Differences Between Ovarian Cancer-associated Fibroblasts and Contralateral Normal Ovary-derived Mesenchymal Stem Cells2022

    • Author(s)
      OHASHI KAZUAKI、LI TAO-SHENG、MIURA SHOKO、HASEGAWA YURI、MIURA KIYONORI
    • Journal Title

      Anticancer Research

      Volume: 42 Issue: 4 Pages: 1729-1737

    • DOI

      10.21873/anticanres.15649

    • Related Report
      2022 Research-status Report 2021 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Prevalence of common aneuploidy in twin pregnancies.2022

    • Author(s)
      Konishi Akiko, Kamei Yoshimasa(18番目/60), et al.
    • Journal Title

      J Hum Genet

      Volume: 65 Issue: 5 Pages: 261-265

    • DOI

      10.1038/s10038-021-01001-0

    • Related Report
      2022 Research-status Report 2021 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Accumulation of fibrosis and altered perifollicular stromal differentiation in vitrified‐thawed human ovarian tissue xenografted to nude mice.2022

    • Author(s)
      Kitajima Michio、Murakami Naoko、Kitajima Yuriko、Kajimura Itsuki、Matsumura Asako、Matsumoto Kanako、Harada Ayumi、Miura Kiyonori
    • Journal Title

      Reproductive Medicine and Biology

      Volume: 21 Issue: 1

    • DOI

      10.1002/rmb2.12451

    • Related Report
      2021 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Placental chronic villitis in biliary atresia in dizygotic twins: A case report2022

    • Author(s)
      Kosaka Seitaro、Muraji Toshihiro、Ohtani Haruo、Toma Miki、Miura Kiyonori
    • Journal Title

      Pediatrics International

      Volume: 64 Issue: 1

    • DOI

      10.1111/ped.15101

    • Related Report
      2021 Research-status Report
    • Peer Reviewed
  • [Journal Article] Large deletion in 6q containing the TNFAIP3 gene associated with autoimmune lymphoproliferative syndrome2022

    • Author(s)
      Endo Yushiro、Funakoshi Yasutomo、Koga Tomohiro、Ohashi Hirofumi、Takao Mami、Miura Kiyonori、Yoshiura Koh-ichiro、Matsumoto Tadashi、Moriuchi Hiroyuki、Kawakami Atsushi
    • Journal Title

      Clinical Immunology

      Volume: 235 Pages: 108853-108853

    • DOI

      10.1016/j.clim.2021.108853

    • Related Report
      2021 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] 増刊号 産婦人科患者説明ガイド-納得・満足を引き出すために 周産期 出生前診断の検査と処置 絨毛検査を行うにあたっての患者説明2021

    • Author(s)
      三浦 生子、三浦 清徳
    • Journal Title

      臨床婦人科産科

      Volume: 75 Issue: 4 Pages: 36-41

    • DOI

      10.11477/mf.1409210291

    • ISSN
      0386-9865, 1882-1294
    • Year and Date
      2021-04-20
    • Related Report
      2021 Research-status Report
  • [Journal Article] Long-term culture of rat hepatocytes using human amniotic membrane as a culture substrate2021

    • Author(s)
      Maekawa Kyoichiro、Natsuda Koji、Hidaka Masaaki、Uematsu Masafumi、Soyama Akihiko、Hara Takanobu、Takatsuki Mitsuhisa、Nagai Kazuhiro、Miura Kiyonori、Eguchi Susumu
    • Journal Title

      Regenerative Therapy

      Volume: 18 Pages: 384-390

    • DOI

      10.1016/j.reth.2021.09.002

    • NAID

      120007175560

    • Related Report
      2021 Research-status Report
    • Peer Reviewed
  • [Journal Article] Evaluation of the clinical performance of noninvasive prenatal testing at a Japanese laboratory2021

    • Author(s)
      Sasaki Yuna, Kamei Yoshimasa(16番目/79), et al.
    • Journal Title

      J Obstet Gynaecol Res

      Volume: 47 Issue: 10 Pages: 3437-3446

    • DOI

      10.1111/jog.14954

    • Related Report
      2021 Research-status Report
    • Peer Reviewed
  • [Journal Article] Mesenchymal stem cell-derived extracellular vesicles as probable triggers of radiation-induced heart disease2021

    • Author(s)
      Luo Lan、Yan Chen、Fuchi Naoki、Kodama Yukinobu、Zhang Xu、Shinji Goto、Miura Kiyonori、Sasaki Hitoshi、Li Tao-Sheng
    • Journal Title

      Stem Cell Research & Therapy

      Volume: 12 Issue: 1 Pages: 422-422

    • DOI

      10.1186/s13287-021-02504-5

    • NAID

      120007172281

    • Related Report
      2021 Research-status Report
    • Peer Reviewed
  • [Journal Article] Nationwide survey (Japan) on spontaneous hemoperitoneum in pregnancy2021

    • Author(s)
      Hagimoto Miki、Tanaka Hiroaki、Osuga Yutaka、Miura Kiyonori、Saito Shigeru、Sato Shoji、Sugawara Junichi、Ikeda Tomoaki
    • Journal Title

      Journal of Obstetrics and Gynaecology Research

      Volume: 47 Issue: 8 Pages: 2646-2652

    • DOI

      10.1111/jog.14819

    • Related Report
      2021 Research-status Report
    • Peer Reviewed
  • [Journal Article] Bihormonal dysregulation of insulin and glucagon contributes to glucose intolerance development at one year post-delivery in women with gestational diabetes: a prospective cohort study using an early postpartum 75-g glucose tolerance test2021

    • Author(s)
      Shigeno Riyoko、Horie Ichiro、Miwa Masaki、Ito Ayako、Haraguchi Ai、Natsuda Shoko、Akazawa Satoru、Nagata Ai、Hasegawa Yuri、Miura Shoko、Miura Kiyonori、Kawakami Atsushi、Abiru Norio
    • Journal Title

      Endocrine Journal

      Volume: 68 Issue: 8 Pages: 919-931

    • DOI

      10.1507/endocrj.EJ20-0795

    • NAID

      130008079308

    • ISSN
      0918-8959, 1348-4540
    • Related Report
      2021 Research-status Report
    • Peer Reviewed / Open Access
  • [Presentation] HTLV-1母子感染2021

    • Author(s)
      三浦清徳
    • Organizer
      第37回日本生殖免疫学会学術集会
    • Related Report
      2021 Research-status Report
    • Invited
  • [Presentation] 産科手術におけるひと工夫2021

    • Author(s)
      三浦清徳
    • Organizer
      第8回北陸周産期生殖医学研究会
    • Related Report
      2021 Research-status Report
    • Invited
  • [Remarks] 長崎大学産婦人科ホームページ

    • URL

      https://www.med.nagasaki-u.ac.jp/gyneclgy/

    • Related Report
      2023 Research-status Report 2022 Research-status Report
  • [Remarks] 長崎大学産婦人科

    • URL

      https://www.med.nagasaki-u.ac.jp/gyneclgy/

    • Related Report
      2021 Research-status Report
  • [Patent(Industrial Property Rights)] 凍結融解胚移植において着床率の高いヒト受精胚を選別する方法およびキット2023

    • Inventor(s)
      三浦清徳、三浦生子、永田 幸、永田 愛、長谷川ゆり
    • Industrial Property Rights Holder
      長崎大学
    • Industrial Property Rights Type
      特許
    • Industrial Property Number
      2023-146934
    • Filing Date
      2023
    • Related Report
      2023 Research-status Report
  • [Patent(Industrial Property Rights)] ヒトパピローマウイルスの子宮頸がんの発がんリスクを評価する方法およびキット2023

    • Inventor(s)
      吉浦孝一郎、三嶋博之、三浦清徳
    • Industrial Property Rights Holder
      長崎大学
    • Industrial Property Rights Type
      特許
    • Industrial Property Number
      2023-128496
    • Filing Date
      2023
    • Related Report
      2023 Research-status Report

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Published: 2021-04-28   Modified: 2024-12-25  

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