Investigation of the pathogenesis of imprinting disorders in ART patients and search for risk factors in ART

2020 Fiscal Year Final Research Report

• Project/Area Number: 18K09215
• 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: Tokyo University of Agriculture (2019-2020); Tohoku University (2018)
• Principal Investigator: HIURA Hitoshi 東京農業大学, 生命科学部, 准教授 (70451523)
• Project Period (FY): 2018-04-01 – 2021-03-31
• Keywords: 生殖補助医療（ART） / インプリント疾患 / DNAメチル化

Outline of Final Research Achievements

In this study, we compared comprehensive DNA methylation in peripheral blood with assisted reproductive technologies (ART)-conceived and spontaneously conceived imprinting disorders (Silver-Russell syndrome and Beckwith-Wiedemann syndrome) patients to evaluate risk factors for ART. We found that ART-conceived patients had incomplete and more widespread DNA methylation variations (DMVs) than spontaneously conceived patients, especially in sperm-specific methylated regions. These results suggest that the imprinting disorders related to ART might tend to take place just after fertilization at a time when the epigenome is most vulnerable and might be affected by the techniques of manipulation used for in vitro fertilization or intracytoplasmic sperm injection and the culture medium of the fertilized egg.

Free Research Field

分子生物学

Academic Significance and Societal Importance of the Research Achievements

晩婚化の社会情勢に伴い、生殖補助医療（ART）が急速に普及してきた。しかし、これまで非常に稀であったゲノムインプリンティング（GI）異常症の発症頻度が増加していることが世界中で報告されている。本研究では、ART由来のGI異常症と非ART由来の患者末梢血のDNAメチル化を比較し、ARTのリスク要因について評価した。その結果、DNAメチル化可変領域はARTにおける体外受精または顕微授精操作、体外培養に用いられる培養液等によって影響される可能性が示唆された。本研究成果はARTにおける疾患発症予防に繋がることが期待できる。