Identification the cause of and improvement of the low developmental potential of ROSI-derived zygotes

2020 Fiscal Year Final Research Report

• Project/Area Number: 19K16012
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 42030:Animal life science-related
• Research Institution: University of Yamanashi
• Principal Investigator: Ooga Masatoshi 山梨大学, 大学院総合研究部, 助教 (40644886)
• Project Period (FY): 2019-04-01 – 2021-03-31
• Keywords: ROSI / クロマチン構造

Outline of Final Research Achievements

The formation mechanism of abnormal chromatin structure in ROSI zygotes was clarified. It was found that sperm cause a compaction of chromatin structure in the zygotes, whereas round spermatids do not have this ability. Interestingly, sperm had resistance to this effect, causing a difference in the looseness level of the chromatin structure between male and female pronuclei. However, the round spermatids did not have this resistance and therefore could not form a difference in the looseness of the chromatin structure between the male and female pronuclei, unlike the case when the sperm fertilized the oocytes. Thus, male germ cells acquired the specific ability to condense chromatin structure during spermiogenesis.
In order to get a complete overview of the abnormalities in loose chromatin structure in ROSI zygotes, we also performed ATAC-seq and clarified the differences in open chromatin between ICSI and ROSI embryos.

Free Research Field

発生工学

Academic Significance and Societal Importance of the Research Achievements

精子の前駆細胞である円形精子細胞を使った受精卵作成法であるROSIは、精子形成能を持たない男性不妊治療患者の最後の頼みの綱と言える。これまでその普及を阻む低産仔率の原因の候補として、ROSI胚に関して様々なエピジェネティックな異常が報告されてきた。だが、それらは円形精子細胞に由来する雄性前核におけるものばかりであった。本研究では初めて、ROSI胚における雌性前核のエピジェネティックな異常を見出し、さらに、精子に由来する活性の欠損がその形成の原因であることが明らかとなり、雌雄ゲノムの相互作用と精子成熟過程の新しい関係を見出すことができた。本知見は、ROSI胚の低産仔率改善のために貢献するだろう。