Challenges in overcoming sex-determining epigenomic mutations by in vitro culture conditions

2022 Fiscal Year Final Research Report

• Project/Area Number: 20K09596
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 56040:Obstetrics and gynecology-related
• Research Institution: Osaka University
• Principal Investigator: Okashita Naoki 大阪大学, 大学院生命機能研究科, 助教 (10757933)
• Project Period (FY): 2020-04-01 – 2023-03-31
• Keywords: 性決定 / 体外受精 / エピゲノム / DNAのメチル化

Outline of Final Research Achievements

XY Jmjd1a-deficient mice are generated by natural mating showed an intermediate phenotype between male and female. On the other hand, when these mice were generated by in vitro fertilization, the male-female balance tilted toward females, causing complete sex reversal in all individuals.
These results indicated that exposure of fertilized eggs and early embryos to IVF culture media and embryo culture media may affect sex determination.
Therefore, we attempted to challenge whether the effects of existing in vitro culture conditions on the fetus could be modified by applying the CRISPR/Cas9 system to epigenome editing and the administration of drugs to the culture medium in this study. As a result, it was found that the promotion of sex reversal could be repaired by decreasing DNA methylation of the Sry promoter in the embryo before implantation.

Free Research Field

発生生物学

Academic Significance and Societal Importance of the Research Achievements

本研究は、エピゲノムの観点から性決定メカニズムを理解する独自のテーマであり、遺伝要因だけでなく環境要因による性の攪乱を定量的にアプローチする点に特色がある。本研究結果は性決定の仕組みの解明に繋がる非常に意義のある成果である。さらに、本研究成果は学術的価値だけでなく医学的な意義も大きい。本研究では、体外受精がエピゲノム変化を起こすことで胎児の性決定に影響を及ぼすことを明らかにしており、生殖補助医療によるエピゲノム修飾の異常を起因とした疾患の発症メカニズム解明やその治療を目的とした研究の道標になることが期待される。