Mitochondria quality control in aged sperm and egg

• Project/Area Number: 18K09224
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 56040:Obstetrics and gynecology-related
• Research Institution: University of Fukui
• Principal Investigator: orisaka makoto 福井大学, 学術研究院医学系部門(附属病院部), 講師 (80324143)
• Project Period (FY): 2018-04-01 – 2022-03-31
• Project Status: Completed (Fiscal Year 2021)
• Budget Amount: ¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000); Fiscal Year 2020: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000); Fiscal Year 2019: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000); Fiscal Year 2018: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
• Keywords: 不妊治療 / 体外受精 / ミトコンドリア / 精子 / 卵子 / 酸化ストレス / 胚 / 品質管理 / 加齢

Outline of Final Research Achievements

Mitochondrial quality control (MQC) is critical in controlling the quality of mitochondrial function and maintaining cellular health. We investigated the role of Mieap, one of the proteins that control MQC, on sperm and egg functions. Mieap-knockout induced sperm oxidative stress and markedly reduced sperm function. Mieap-knockout sperm induced embryonic growth arrest during in vitro fertilization. These results indicate that MQC is essential for sperm function and embryonic development. Unfortunately, we could not prove the association between the MQC impairment and aged-related fertility decline in sperm/egg.

Academic Significance and Societal Importance of the Research Achievements

生殖細胞におけるミトコンドリア品質管理（MQC）システムは精子と卵子で異なり、特に精子ではMieapタンパクが重要な役割を担うことが明らかになった。MQC機能が低い精子は、体外受精の胚発育に悪影響を及ぼす可能性が示唆された。「生殖細胞の質とミトコンドリア機能」のコンセプトを体外受精に応用する場合、ターゲットは卵子でなく精子になると思われる。

Research Products

• [Journal Article] The role of pituitary gonadotropins and intraovarian regulators in follicle development: A mini-review (2021)
  • Author(s): M.Orisaka, Y.Miyazaki, A.Shirafuji, C.Tamamura, H.Tsuyoshi, B.K. Tsang, Y.Yoshida
  • Journal Title: Reprod Med Biol Volume: 20 Issue: 2 Pages: 169-175
  • DOI: 10.1002/rmb2.12371
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Profiles of 5α-Reduced Androgens in Humans and Eels: 5α-Dihydrotestosterone and 11-Ketodihydrotestosterone Are Active Androgens Produced in Eel Gonads (2021)
  • Author(s): Yazawa Takashi、Inaba Hiroyuki、Imamichi Yoshitaka、Sekiguchi Toshio、Uwada Junsuke、Islam Mohammad Sayful、Orisaka Makoto、Mikami Daisuke、Ida Takanori、Sato Takahiro、Miyashiro Yoshimichi、Takahashi Satoru、Khan Md. Rafiqul Islam、Suzuki Nobuo、Umezawa Akihiro、Kitano Takeshi
  • Journal Title: Frontiers in Endocrinology Volume: 12 Pages: 1-10
  • DOI: 10.3389/fendo.2021.657360
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Prognostic impact of Dynamin related protein 1 (Drp1) in epithelial ovarian cancer (2020)
  • Author(s): Tsuyoshi Hideaki、Orisaka Makoto、Fujita Yuko、Asare-Werehene Meshach、Tsang Benjamin K.、Yoshida Yoshio
  • Journal Title: BMC Cancer Volume: 20 Issue: 1 Pages: 467-467
  • DOI: 10.1186/s12885-020-06965-4
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Bone morphogenetic protein‐2 enhances gonadotropin‐independent follicular development via sphingosine kinase 1 (2020)
  • Author(s): Ito Masami、Yoshino Osamu、Ono Yosuke、Yamaki‐Ushijima Akemi、Tanaka Tomoko、Shima Tomoko、Orisaka Makoto、Iwase Akira、Nakashima Akitoshi、Saito Shigeru
  • Journal Title: American Journal of Reproductive Immunology Volume: 85 Issue: 5
  • DOI: 10.1111/aji.13374
  • Peer Reviewed / Open Access
• [Journal Article] 子宮内膜症と不妊症 (2019)
  • Author(s): 折坂誠、白藤文
  • Journal Title: 日本生殖内分泌学会雑誌 Volume: 24 Pages: 27-30
  • Peer Reviewed
• [Presentation] Bridging Basic Research and Reproductive Medicine ～基礎研究と生殖医療の橋渡しを目指して～ (2021)
  • Author(s): 折坂 誠
  • Organizer: 第56回 北陸生殖医学会総会・学術講演会
  • Invited
• [Presentation] Mitochondria-eating protein is essential for sperm function, but not oocyte quality, in in vitro fertilization (2019)
  • Author(s): Orisaka M, Nakamura Y, Arakawa H, Yoshida Y
  • Organizer: 52nd Annual conference of the Society for the Study of Reproduction
  • Int'l Joint Research
• [Presentation] Mitochondria-eating protein is essential for sperm function, but not oocyte quality, in in vitro fertilization (2018)
  • Author(s): Makoto Orisaka
  • Organizer: 第70回日本産科婦人科学会学術講演会
• [Presentation] Mitochondria-eating protein (Mieap) は精子機能に必須だが、卵子の質には影響しない (2018)
  • Author(s): 折坂 誠
  • Organizer: 第23回日本生殖内分泌学会
• [Book] 生殖生理 (2019)
  • Author(s): 折坂 誠（大須賀 穣、藤井知行 編）
  • Total Pages: 330
  • Publisher: 中山書店
  • ISBN: 9784521747613
• [Book] 不妊症・不育症診療 : その伝承とエビデンス (2019)
  • Author(s): 折坂 誠（柴原 浩章 編）
  • Total Pages: 780
  • Publisher: 中外医学社
  • ISBN: 9784498160002