Induction of fetal meiotic oocytes from embryonic stem cells in cynomolgus monkeys

2023 Fiscal Year Final Research Report

• Project/Area Number: 22K15380
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 48040:Medical biochemistry-related
• Research Institution: Kyoto University
• Principal Investigator: Motani Sayuri 京都大学, 高等研究院, 助教 (30792428)
• Project Period (FY): 2022-04-01 – 2024-03-31
• Keywords: 試験管内再構成 / ES細胞 / 卵母細胞 / 減数分裂 / カニクイザル

Outline of Final Research Achievements

In previous study, I have established “2-step xenogenic reconstituted ovary (xrOvary) culture system” which enabled to induce cynomolgus monkey oocyte-like cells at meiosis I (OC(I)LCs) in vitro. According to single cell RNA-seq analysis, it was revealed that OC(I)LCs showed the similar gene expression patterns to cynomolgus oocytes in vivo. Also, from genome-wide DNA methylome analysis, it was indicated that genomic DNA was demethylated in fetal oocyte development in primate species. To complete meiosis I in vitro, xrOvary was cultured in several, modified conditions. However, any of them did not lead to further progression of meiosis I. In the future study, the completion of meiosis I will be accompanied by finding optimal culture conditions referring to transcriptome data of OC(I)LC.

Free Research Field

分子生物学

Academic Significance and Societal Importance of the Research Achievements

サル成熟卵子発生過程を忠実に再現することができれば、ヒトの雌性生殖細胞の発生過程を再現できると期待される。また、これまで困難であった減数分裂時のエピゲノムリプログラミングの様相が解析可能になり、ヒトの発生過程のより深い理解につながる。そして、各段階の生殖細胞を用いた分子生物学的、生化学的解析によりヒト生殖細胞発生機構が完全に理解された暁には、新たな不妊治療技術の開発にも寄与すると期待される。