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Relationship between embryo-derived substances in culture supernatant and human embryo developmental dynamics: Development of new biomarkers for embryo selection to be transplanted

Research Project

Project/Area Number 18H02942
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section一般
Review Section Basic Section 56040:Obstetrics and gynecology-related
Research InstitutionAkita University

Principal Investigator

TERADA Yukihiro  秋田大学, 医学系研究科, 教授 (10260431)

Co-Investigator(Kenkyū-buntansha) 白澤 弘光  秋田大学, 医学系研究科, 助教 (60598019)
高橋 和政  秋田大学, 医学部附属病院, 技術系スタッフ (60791910)
Project Period (FY) 2018-04-01 – 2021-03-31
Project Status Completed (Fiscal Year 2020)
Budget Amount *help
¥15,470,000 (Direct Cost: ¥11,900,000、Indirect Cost: ¥3,570,000)
Fiscal Year 2020: ¥4,420,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥1,020,000)
Fiscal Year 2019: ¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000)
Fiscal Year 2018: ¥6,890,000 (Direct Cost: ¥5,300,000、Indirect Cost: ¥1,590,000)
Keywords体外受精 / バイオマーカー / NGS / NaK ATPase / miRNA / NGS
Outline of Final Research Achievements

In the analysis of embryonic chromosomal status using NGS, the results showed that the biopsy sample did not necessarily reflect the chromosomal status of the entire embryo. In the study of the relationship between cell free DNA(cfDNA) present in the spent culture media of blastocysts and the chromosomal status of long-term cultured embryos, it was found that the cfDNA in the culture medium well reflected the chromosomal status of the long-term cultured embryo(10dpf). This finding was published in an international journal(PLoS ONE Shitara,Terada 2021). The expression of NaK ATPase, which is essential for blastocyst development, was analyzed using immunostaining and qRT-PCR. NaK ATPase in human blastocysts is composed of α1 and β3, and it was found that the relative amount of β3 detected in biopsy cells is related to the behavior of embryo expansion / contraction. It has been shown that β3 may be a biomarker of development. These results are currently being prepared for submission.

Academic Significance and Societal Importance of the Research Achievements

生殖補助医療技術の向上にはヒト胚の細胞生物学・細胞遺伝学的知見が必要不可欠である。胚移植において胚の客観的基準が求められている。本研究では、胚の一部を使用して染色体状態を調べるPGT-Aの信頼性は必ずしも完全ではないことを示した、非侵襲的な培養液中のバイオマーカーについてはcfDNAが長期培養後の胚の染色体状態をよく反映していることを示した。胚盤胞の機能的タンパク質の解析については、NaK ATPaseのβ3が重要な重要であることを示し、バイオマーカーとなり得る可能性を示した。これらの知見により、移植胚の効率的選択が可能となり、生殖補助医療における患者の負担の軽減に寄与することが期待される。

Report

(4 results)
  • 2020 Annual Research Report   Final Research Report ( PDF )
  • 2019 Annual Research Report
  • 2018 Annual Research Report
  • Research Products

    (20 results)

All 2021 2020 2019 2018

All Journal Article (8 results) (of which Peer Reviewed: 8 results,  Open Access: 8 results) Presentation (12 results)

  • [Journal Article] Cell-free DNA in spent culture medium effectively reflects the chromosomal status of embryos following culturing beyond implantation compared to trophectoderm biopsy.2021

    • Author(s)
      Shitara A, Takahashi K, Goto M, Takahashi H, Iwasawa T, Onadera Y, Makino K, Miura H, Shirasawa H, Sato W, Kumazawa Y, Terada Y
    • Journal Title

      PLoS ONE

      Volume: 16 Issue: 2 Pages: e0246438-e0246438

    • DOI

      10.1371/journal.pone.0246438

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Live visualisation of electrolytes during mouse embryonic development using electrolyte indicators2021

    • Author(s)
      Fujishima A, Takahashi K, Goto M, Hirakawa T, Iwasawa T, Togashi K, Maeda E, Shirasawa H, Miura H, Sato W, Kumazawa Y, Terada Y
    • Journal Title

      PLoS ONE

      Volume: 16 Issue: 1 Pages: e0246337-e0246337

    • DOI

      10.1371/journal.pone.0246337

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Human frozen-thawed blastocyst morphokinetics observed using time-lapse cinematography reflects the number of trophectoderm cells2019

    • Author(s)
      Iwasawa Takuya、Takahashi Kazumasa、Goto Mayumi、Anzai Mibuki、Shirasawa Hiromitsu、Sato Wataru、Kumazawa Yukiyo、Terada Yukihiro
    • Journal Title

      PLOS ONE

      Volume: 14 Issue: 1 Pages: e0210992-e0210992

    • DOI

      10.1371/journal.pone.0210992

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Associations of environmental exposures to methylmercury and selenium with female infertility: A case-control study2019

    • Author(s)
      Maeda Eri、Murata Katsuyuki、Kumazawa Yukiyo、Sato Wataru、Shirasawa Hiromitsu、Iwasawa Takuya、Izumo Kimiko、Tatsuta Nozomi、Sakamoto Mineshi、Terada Yukihiro
    • Journal Title

      Environmental Research

      Volume: 168 Pages: 357-363

    • DOI

      10.1016/j.envres.2018.10.007

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Oocyte collection and in vitro maturation after train transportation of human follicular fluid aspirated from resected non‐stimulated ovaries of patients with endometrial adenocarcinoma2019

    • Author(s)
      Shirasawa Hiromitsu、Ono Natsuki、Kumazawa Yukiyo、Sato Wataru、Sato Naoki、Ihara Motomasa、Yaegashi Nobuo、Terada Yukihiro
    • Journal Title

      Reproductive Medicine and Biology

      Volume: 18 Issue: 2 Pages: 180-189

    • DOI

      10.1002/rmb2.12265

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Adenomatoid tumour of the uterus is frequently associated with iatrogenic immunosuppression2018

    • Author(s)
      Tamura Daisuke、Maeda Daichi、Halimi Sultan Ahmad、Okimura Masato、Kudo-Asabe Yukitsugu、Ito Satoru、Sato Naoki、Shibahara Junji、Nanjo Hiroshi、Terada Yukihiro、Goto Akiteru
    • Journal Title

      Histopathology

      Volume: 73 Issue: 6 Pages: 1013-1022

    • DOI

      10.1111/his.13726

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Leaflets and continual educational offerings led to increased coverage rate of newborn hearing screening in Akita.2018

    • Author(s)
      Sato Teruyuki,Nakazawa Misao,Takahashi Shin,Mizuno Tomomi,Sato Akira,Noguchi Atsuko,Sato Megumi,Katagiri Sadako,Yamada Takechiyo
    • Journal Title

      Auris Nasus Larynx

      Volume: 45 Issue: 4 Pages: 673-679

    • DOI

      10.1016/j.anl.2017.11.014

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] MED12 is frequently mutated in ovarian and other adnexal leiomyomas2018

    • Author(s)
      Li Zhuo、Maeda Daichi、Kudo-Asabe Yukitsugu、Tamura Daisuke、Nanjo Hiroshi、Hayashi Akimasa、Ikemura Masako、Fukayama Masashi、Goto Akiteru
    • Journal Title

      Human Pathology

      Volume: 81 Pages: 89-95

    • DOI

      10.1016/j.humpath.2018.06.013

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Open Access
  • [Presentation] ヒト胚延長培養における挙動と細胞分化及び遺伝学的検討.2020

    • Author(s)
      設楽明宏
    • Organizer
      第72回日本産科婦人科学会学術講演会
    • Related Report
      2020 Annual Research Report
  • [Presentation] ヒト胚延長培養における細胞分化,発育挙動の観察.2020

    • Author(s)
      設楽明宏
    • Organizer
      第61回日本卵子学会学術集会
    • Related Report
      2020 Annual Research Report
  • [Presentation] NGSによるPGT-Aの結果はヒト胚盤胞全細胞の状態をどの程度反映しているのか2019

    • Author(s)
      3)高橋玄徳,髙橋和政,安西実武貴,岩澤卓也,尾野夏紀,白澤弘光,佐藤亘,熊澤由紀代,寺田幸弘
    • Organizer
      第60回日本卵子学会
    • Related Report
      2019 Annual Research Report
  • [Presentation] NGS による PGT-A の結果はヒト胚盤胞全細胞の状態をどの程度反映しているのか?2019

    • Author(s)
      髙橋玄徳,高橋和政,岩澤卓也,尾野夏紀,白澤弘光,佐藤亘,熊澤由紀代,寺田幸弘
    • Organizer
      第64回日本生殖医学会
    • Related Report
      2019 Annual Research Report
  • [Presentation] ヒト胚盤胞の発育動態は栄養外胚葉を構成する細胞数に依存する2018

    • Author(s)
      岩澤卓也,高須賀緑,白澤弘光,佐藤亘,金森恭子,熊澤由紀代,兒玉英也,寺田幸弘
    • Organizer
      第70回日本産科婦人科学会
    • Related Report
      2018 Annual Research Report
  • [Presentation] 形態的評価を考慮した、当院における40歳以上の患者に対する移植個数の検討2018

    • Author(s)
      白澤弘光,熊澤由紀代,佐藤亘,高須賀緑,金森恭子,兒玉英也,寺田幸弘
    • Organizer
      第70回日本産科婦人科学会
    • Related Report
      2018 Annual Research Report
  • [Presentation] タイムラプス観察による前核期持続時間と胚盤胞到達率の関係2018

    • Author(s)
      安西実武貴,髙橋和政,吉川諒子,白澤弘光,佐藤亘,熊澤由紀代,寺田幸弘
    • Organizer
      第59回日本卵子学会
    • Related Report
      2018 Annual Research Report
  • [Presentation] 妊孕性温存を目的とする術中卵子回収・IVM・卵子凍結における、極体放出過程のタイムラプス観察意義.2018

    • Author(s)
      白澤弘光,熊澤由紀代,佐藤亘,髙橋和政,安西実武貴,吉川諒子,岩澤卓也,寺田幸弘
    • Organizer
      第59回日本卵子学会
    • Related Report
      2018 Annual Research Report
  • [Presentation] ヒト胚盤胞の発育挙動よりアシステッドハッチが有効な胚を抽出できる可能性: TLC による挙動観察と免疫染色による ICM,TE 細胞数の計測より.2018

    • Author(s)
      岩澤卓也,髙橋和政,後藤真由美,安西実武貴,吉川諒子,白澤弘光,佐藤亘,熊澤由紀代,寺田幸弘
    • Organizer
      第59回日本卵子学会
    • Related Report
      2018 Annual Research Report
  • [Presentation] ヒト未成熟卵子に対するIVM後の第1極体放出のタイミングに着目した,単為発生過程のタイムラプス解析2018

    • Author(s)
      白澤弘光,熊澤由紀代,佐藤亘,岩澤卓也,高橋和政,安西実武貴,寺田幸弘
    • Organizer
      第63回日本生殖医学会
    • Related Report
      2018 Annual Research Report
  • [Presentation] Blastomere Movementと胚盤胞到達率および胚の形態学的評価の関連性2018

    • Author(s)
      安西実武貴、高橋和政、岩澤卓也、尾野夏紀、白澤弘光、佐藤亘、熊澤由紀代、寺田幸弘
    • Organizer
      第56回東北生殖医学会
    • Related Report
      2018 Annual Research Report
  • [Presentation] NGSによるPGT-Aの結果はヒト胚盤胞全細胞の状態をどの程度反映しているのか?2018

    • Author(s)
      髙橋玄徳、高橋和政、岩澤卓也、尾野夏紀、白澤弘光、佐藤亘、熊澤由紀代、寺田幸弘
    • Organizer
      第56回東北生殖医学会
    • Related Report
      2018 Annual Research Report

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Published: 2018-04-23   Modified: 2022-01-27  

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