Development of a new treatment for the deterioration of egg quality by aging based on mitochondrial quality control

• Project/Area Number: 16K11080
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Obstetrics and gynecology
• Research Institution: Fukushima Medical University
• Principal Investigator: Takahashi Toshifumi 福島県立医科大学, 公私立大学の部局等, 教授 (20302292)
• Co-Investigator(Kenkyū-buntansha): 菅沼 亮太 福島県立医科大学, 医学部, 講師 (30528211) ; 堤 誠司 山形大学, 医学部, 准教授 (50323168) ; 五十嵐 秀樹 山形大学, 医学部, 講師 (80333970)
• Project Period (FY): 2016-04-01 – 2019-03-31
• Project Status: Completed (Fiscal Year 2018)
• Budget Amount: ¥4,810,000 (Direct Cost: ¥3,700,000、Indirect Cost: ¥1,110,000); Fiscal Year 2018: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000); Fiscal Year 2017: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000); Fiscal Year 2016: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
• Keywords: 卵の加齢 / ミトコンドリア / マイトファジー / LC3 / Parkin / 加齢マウス / TFAM / 不妊症

Outline of Final Research Achievements

Compared with fresh oocytes, post-ovulatory aged oocytes had no change in the expression level of TFAM, but colocalization with TFAM and mitochondria was lost. Also, activation of autophagy and mitophagy might be activated in post-ovulatory aged oocytes compared to those in fresh oocytes. On the other hand, in maternal aged oocytes, the appearance of oocytes exhibiting an abnormal mitochondrial form was confirmed, but quantitative and spatial changes in TFAM could not be approved. Besides, activation of autophagy and mitophagy observed in the post-ovulatory aged oocytes was not found in maternal aged oocytes.

Academic Significance and Societal Importance of the Research Achievements

女性の加齢による妊孕力低下の原因として、卵の加齢による卵の質の低下が重要である。本研究では、ミトコンドリアの品質管理に着目し卵の質の低下のメカニズムを検討した。本研究では、卵の加齢とオートファジーによる選択的ミトコンドリア分解機構（マイトファジー）の変化を解析し、“卵の質の低下”に対する新しい予防・治療法の開発を目指す。

Research Products

• [Journal Article] Poor embryo development in post-ovulatory in vivo-aged mouse oocytes is associated with mitochondrial dysfunction, but mitochondrial transfer from somatic cells is not sufficient for rejuvenation. (2016)
  • Author(s): Igarashi H, Takahashi T, Abe H, Nakano H, Nakajima O, Nagase S
  • Journal Title: Human Reproduction Volume: 31 Pages: 23331-23338
  • DOI: 10.1093/humrep/dew203
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Presentation] MITOCHONDRIAL TRANSFER FROM SOMATIC CELLS IS NOT SUFFICIENT FOR REJUVENATION OF POSTOVULATORY IN VIVOAGED MOUSE OOCYTES (2017)
  • Author(s): Igarashi H, Takahashi T, Abe H, Nakano H, Nakajima O, Nagase S, Kyono K
  • Organizer: The 7th Congress of the Asia Pacific Initiative on Reproduction
  • Place of Presentation: Kuala Lumpur Convention Center, Kuala Lumpur, Malaysia
  • Year and Date: 2017-03-30
  • Int'l Joint Research