A risk assessment of autism caused by environmental chemicals using epigenetic information

Research Project

Project/Area Number	18K11679
Research Category	Grant-in-Aid for Scientific Research (C)
Allocation Type	Multi-year Fund
Section	一般
Review Section	Basic Section 64010:Environmental load and risk assessment-related
Research Institution	University of Miyazaki
Principal Investigator	ARAI YOSHIKAZU 宮崎大学, 農学部, 助教 (90614769)
Project Period (FY)	2018-04-01 – 2021-03-31
Project Status	Completed (Fiscal Year 2020)
Budget Amount *help	¥4,420,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥1,020,000) Fiscal Year 2020: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000) Fiscal Year 2019: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000) Fiscal Year 2018: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
Keywords	エピジェネティクス / iPS細胞 / 自閉症 / 神経分化 / 化学物質 / DNAメチル化 / 神経幹細胞 / 環境化学物質 / 神経
Outline of Final Research Achievements	Autism spectrum disorder is a neurological disease that has been increasing in recent years and has become a major social problem. In this study, we focused on the effects of harmful chemicals in the environment and elucidated the pathogenic mechanism of autism based on epigenetic regulation. As a result of analysis using neural differentiation system of human iPS cells, some of the chemicals detected in the maternal environment disturbed the neural differentiation at the concentration in the biological exposure range. In addition, chemical exposure disrupted epigenetics, the regulatory mechanism of gene expression, confirming the effects of chemicals over a wide range of genome. The results indicate that environmental chemicals adversely affect the epigenetic regulation and neural differentiation in vitro.
Academic Significance and Societal Importance of the Research Achievements	これまでに自閉症の原因遺伝子が多数報告されているが、遺伝子変異のみでは疾患の発症機序を説明できないのが現状である。本研究は自閉症発症について、環境要因として母体環境中に含まれる有害な化学物質の影響に着目し、遺伝子の発現記憶装置であるエピジェネティクスをもとに、自閉症の発症機序解明に向けた新たな試みである。本研究結果は、従来の遺伝子変異の特定とともに、環境要因による遺伝子発現制御への影響を検証することの重要性を示すものである。今後、化学物質の影響を受けた遺伝子の詳細な解析によって、遺伝子変異のみでは説明が困難であった自閉症の新たな原因究明に繋がることが期待される。