Comprehensive explore for morphokinetic biomarkers expressed in association with chromosomal abnormalities in fertilized embryos

• Project/Area Number: 21K19184
• Research Category: Grant-in-Aid for Challenging Research (Exploratory)
• Allocation Type: Multi-year Fund
• Review Section: Medium-sized Section 42:Veterinary medical science, animal science, and related fields
• Research Institution: Tokyo University of Agriculture and Technology
• Principal Investigator: Satoshi Sugimura 東京農工大学, (連合)農学研究科(研究院), 教授 (00728454)
• Project Period (FY): 2021-07-09 – 2023-03-31
• Project Status: Completed (Fiscal Year 2022)
• Budget Amount: ¥6,500,000 (Direct Cost: ¥5,000,000、Indirect Cost: ¥1,500,000); Fiscal Year 2022: ¥3,250,000 (Direct Cost: ¥2,500,000、Indirect Cost: ¥750,000); Fiscal Year 2021: ¥3,250,000 (Direct Cost: ¥2,500,000、Indirect Cost: ¥750,000)
• Keywords: 染色体異数性 / 形態動態 / 受精卵 / ウシ / 受精胚 / 染色体 / 発生カイネティクス / 自動定量

Outline of Research at the Start

ウシIVF胚の約半数が染色体異常を有しており、これが低受胎率の一因となっている。したがって、染色体異常を有する胚を移植に先駆け予測可能になれば、ウシIVF胚の移植後の受胎率が向上することが期待される。本研究では、ウシIVF胚の染色体異常に関連して発現する動的特徴を自動定量システム搭載タイムラプスイメージングにより網羅的に解析することで、染色体異常を予測する新たなバイオマーカーの同定を目指す。

Outline of Final Research Achievements

In this study, by analyzing the relationship between the developmental kinetics of bovine IVF embryos and chromosomal aneuploidy in blastocysts, I try to identify for biomarkers that predict chromosomal abnormalities. As a result, no relationship between morphokinetics such as pronuclear morphological dynamics, first cleavage patern, and duration of each cell cycle and chromosomal aneuploidy in blastocysts was observed. As a result of live cell imaging, the relationship between abnormal chromosomal segregation at early cleavage and developmental kinetics was demonstrated. Hence, it was suggested that morphokinetics are related to chromosomal aneuploidy in early cleavage rather than to blastocysts. In the future, it will be necessary to search for biomarkers other than morphokinetics related to chromosomal aneuploidy in blastocysts.

Academic Significance and Societal Importance of the Research Achievements

本研究成果は、哺乳動物の発生カイネティクスと染色体異数性との関係性を理解するうえで重要な知見となる。また、本研究成果は家畜生産のみならず、生殖補助医療といった医学分野への応用が期待される。

Research Products

• [Journal Article] Direct cleavage during the first mitosis is a sign of abnormal fertilization in cattle. (2022)
  • Author(s): Suzuki R, Yao T, Okada M, Nagai H, Khurchabilig A, Kobayashi J, Yamagata K, Sugimura S.
  • Journal Title: Theriogenology Volume: 200 Pages: 96-105
  • DOI: 10.1016/j.theriogenology.2023.01.028
  • Peer Reviewed / Open Access
• [Journal Article] Micronucleus formation during early cleavage division is a potential hallmark of preimplantation embryonic loss in cattle (2022)
  • Author(s): Yao Tatsuma、Ueda Akane、Khurchabilig Atchalalt、Mashiko Daisuke、Tokoro Mikiko、Nagai Hiroki、Sho Tei、Matoba Satoko、Yamagata Kazuo、Sugimura Satoshi
  • Journal Title: Biochemical and Biophysical Research Communications Volume: 617 Pages: 25-32
  • DOI: 10.1016/j.bbrc.2022.05.075
  • Peer Reviewed / Open Access
• [Journal Article] Changes in ovarian morphology and hormone concentrations associated with reproductive seasonality in wild large Japanese field mice ( Apodemus speciosus) (2021)
  • Author(s): Komatsu K, Murata K, Iwasaki T, Tokita S, Yonekura S, Sugimura S, Fujishima Y, Nakata A, Miura T, Yamashiro H.
  • Journal Title: Anim Reprod Volume: 18 Issue: 4
  • DOI: 10.1590/1984-3143-ar2021-0067
  • Peer Reviewed / Open Access
• [Presentation] ウシ体外受精卵における前核の形態動態と染色体異数性との関係 (2022)
  • Author(s): 鈴木亮祐，小林淳一，杉村智史
  • Organizer: 日本生殖医学会
• [Presentation] 異常卵割のウシ胚の自己修復への関与 (2022)
  • Author(s): 長井博紀 、岡田真依 、長井陽子 、桜庭喜行、岡江寛明、鈴木亮祐、杉村智史
  • Organizer: 第5回日本胚移植技術研究会