Epigenomic cohort study in the ART-derived children

2019 Fiscal Year Final Research Report

• Project/Area Number: 17H04335
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Obstetrics and gynecology
• Research Institution: Tohoku University
• Principal Investigator: ARIMA TAKAHIRO 東北大学, 医学系研究科, 教授 (80253532)
• Co-Investigator(Kenkyū-buntansha): 岡江 寛明 東北大学, 医学系研究科, 准教授 (10582695)
• Project Period (FY): 2017-04-01 – 2020-03-31
• Keywords: 生殖補助医療（ART） / ゲノムインプリンティング / 胎盤 / DNAメチル化 / microRNA / 先天性インプリント異常症

Outline of Final Research Achievements

Assisted reproductive technology (ART) has become increasingly common due to late marriage and improvement of medical technology. However, the majority of recent studies published have suggested an increased incidence of normally very rare imprinting disorders in babies conceived after ART. The relationship between ART and aberrant genomic imprinting is still unclear. However, the major epigenetic events take place in the process of ART. The isolation and culture of early embryos may prevent the proper establishment and maintenance of genomic imprinting and cause imprinting disorders. 1) The risk of secondary sex ratio imbalance and increased monozygotic twinning after blastocyst transfer (BT) 2) Genome-wide microRNA expression profiling in placentae from frozen-thawed BT 3) Association of four congenital imprinting disorders and ART. These results help to clarity the necessity for new standards for reform in ART in order to increase safety and produce healthy babies.

Free Research Field

分子生物学、産婦人科学

Academic Significance and Societal Importance of the Research Achievements

生殖細胞および初期胚において、DNAメチル化などのエピジェネティクスが非常にダイナミックに変動する。DNAメチル化は、受精の際安定に維持されるGIを制御するため、配偶子や初期胚を扱うART操作の安全性とリスク評価には最適な指標である。本研究では、ART出生児の身体的特徴とエピゲノム解析を組み合わせ、リスクの一端を示した。また、先天性GI異常症におけるメチル化パターン分析は、疾患の病因、病態の解明にとどまらず、今後のART操作のリスク要因の発見に繋がり、安全性の高い標準化したART治療へ貢献できると予想される。