Epigenetic mutation induced by environmental factors: a molecular mechanism elucidation of the DOHaD

2014 Fiscal Year Final Research Report

• Project/Area Number: 23310044
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Risk sciences of radiation/Chemicals
• Research Institution: The University of Tokyo
• Principal Investigator: OHSAKO Seiichiroh 東京大学, 医学(系)研究科(研究院), 准教授 (00274837)
• Co-Investigator(Kenkyū-buntansha): TOSHIYUKI Saito 国立研究開発法人放射線医学総合研究所, 重粒子医学センター, 主任研究員 (90205667)
• Co-Investigator(Renkei-kenkyūsha): TAKEDA Makio 一般財団法人残留農薬研究所, 毒性部, 室長
• Project Period (FY): 2011-04-01 – 2015-03-31
• Keywords: エピジェネティクス / 化学物質 / DOHaD

Outline of Final Research Achievements

An attempt of elucidation of molecular mechanism of the DOHaD in which fetal environmental factors are hypothesized to cause an epigenomic alteration and memory persisted in adulthood. Additionally we developed a new genome-wide methylation analysis (MSD-AFLP method). The Cyp1a1 promoter of the liver is hypomethylated from day 3 after birth when given TCDD to pregnant mice and the altered methylation level is maintained until after maturity. Because the Dnmt3b dissociation was found by ChIP assay, we assumed mechanistic possibility of passive demethylation. Whereas we tested whether this memory could happen in the adulthood. In the mouse liver of 10 weeks of age, it was found that hypomethylation was caused by the early point in time such as 24 hours after TCDD administration, suggesting that active demethylation should be considered.

Free Research Field

環境毒性学