Methanism of metabolic regulation and aging in mammalian eggs

• Project/Area Number: 26860184
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: General medical chemistry
• Research Institution: The University of Tokyo
• Principal Investigator: Kawamura Yumiko 東京大学, 医学(系)研究科(研究院), 研究員 (70599779)
• Research Collaborator: KURIHARA Hiroki 東京大学, 大学院医学系研究科, 教授 (20221947) ; WADA Yoichiro 東京大学, アイソトープセンター, 教授 (10322033) ; KURIHARA Yukiko 東京大学, 大学院医学系研究科, 講師 (80345040) ; UCHIJIMA Yasunobu 東京大学, 大学院医学系研究科, 助手 (90272426) ; OSATO Naoki 東京大学, 先端科学技術研究センター, 研究員 (50509536)
• Project Period (FY): 2014-04-01 – 2016-03-31
• Project Status: Completed (Fiscal Year 2015)
• Budget Amount: ¥3,900,000 (Direct Cost: ¥3,000,000、Indirect Cost: ¥900,000); Fiscal Year 2015: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000); Fiscal Year 2014: ¥2,340,000 (Direct Cost: ¥1,800,000、Indirect Cost: ¥540,000)
• Keywords: Mitochondria / Sirtuin / Aging / 老化 / 初期胚発生 / 活性酸素種

Outline of Final Research Achievements

In this project, we aimed to unveil the relation between the alteration in metabolism and gene expression and the deterioration of oocyte quality with increasing maternal age. For this purpose, we focused on Sirt3, which regulates mitochondrial functions in mouse early embryos. We used Sirt3 knockout, Sirt3 overexpression and wild type mice of varying age and compared the aging related phenotypes in oocytes and zygotes. During the study period, although we could not reveal the metabolic and transcriptional alterations by originally intended methods because of the limitation of sample number, nonetheless we found that mitochondrial functions declined with aging but excessive Sirt3 could compensate the decline and keep the oocyte quality with high developmental competency even after getting older. We revealed also a part of Sirt3 expression regulation mechanisms. These results would help us understand oocyte physiology and contribute to improving reproductive technology.

Research Products

• [Journal Article] Distinct effects of Hoxa2 overexpression in cranial neural crest populations reveal that the mammalian hyomandibular-ceratohyal boundary maps within the styloid process. (2015)
  • Author(s): Kitazawa T, Fujisawa K, Narboux-Neme N, Arima Y, Kawamura Y, Inoue T, Wada Y, Kohro T, Aburatani H, Kodama T, Kim KS, Sato T, Uchijima Y, Maeda K, Miyagawa-Tomita S, Minoux M, Rijli FM, Levi G, Kurihara Y, Kurihara H
  • Journal Title: Developmental Biology Volume: 15 Issue: 2 Pages: 162-174
  • DOI: 10.1016/j.ydbio.2015.04.007
  • Peer Reviewed / Open Access
• [Journal Article] SIRT3 positively regulates the expression of folliculogenesis- and luteinization-related genes and progesterone secretion by manipulating oxidative stress in human luteinized granulosa cells. (2014)
  • Author(s): Fu H, Wada-Hiraike O, Hirano M, Kawamura Y, Sakurabashi A, Shirane A, Morita Y, Isono W, Oishi H, Koga K, Oda K, Kawana K, Yano T, Kurihara H, Osuga Y, Fujii T.
  • Journal Title: Endocrinology Volume: 155 Issue: 8 Pages: 3079-3087
  • DOI: 10.1210/en.2014-1025
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Presentation] Role of Sirt3 in early embryogenesis (2015)
  • Author(s): Hiroki Kurihara and Yumiko Kawamura
  • Organizer: IFFS/JSRM International Meetinf 2015
  • Place of Presentation: パシフィコ横浜 (神奈川県横浜市)
  • Year and Date: 2015-04-25
  • Int'l Joint Research / Invited