Genome-wide DNA methylation analysis of sperm to explore the mechanism of hepatin tumor augmentation in the F2 by gestational arsenite exposure of F0 pregnant mice

2016 Fiscal Year Final Research Report

• Project/Area Number: 15K15246
• Research Category: Grant-in-Aid for Challenging Exploratory Research
• Allocation Type: Multi-year Fund
• Research Field: Hygiene and public health
• Research Institution: National Institute for Environmental Studies
• Principal Investigator: Nohara Keiko 国立研究開発法人国立環境研究所, 環境リスク・健康研究センター, フェロー (50160271)
• Co-Investigator(Renkei-kenkyūsha): Nakabayashi Kazuhiko 国立研究開発法人国立成育医療研究センター, 周産期病態研究部, 室長 (10415557) ; Okamura Kazuyuki 国立研究開発法人国立環境研究所, 環境リスク・健康研究センター, 研究員 (50736064) ; Suzuki Takehiro 国立研究開発法人国立環境研究所, 環境リスク・健康研究センター, 主任研究員 (60425494) ; Udagawa Osamu 国立研究開発法人国立環境研究所, 環境リスク・健康研究センター, 研究員 (50738466)
• Research Collaborator: Matsushita Junya 東京理科大学, 大学院薬学研究科, 大学院生
• Project Period (FY): 2015-04-01 – 2017-03-31
• Keywords: 無機ヒ素 / 妊娠期曝露 / F2影響 / DNAメチル化 / 精子

Outline of Final Research Achievements

The F2 pups born to F1 males which are gestationally exposed to inorganic arsenic develop hepatic tumors at higher rates compared to the control mice. In order to seek the mechanism of how the effects of developmental exposure of F1 male are transmitted to F2 and cause tumor increases in F2, we investigated DNA methylation changes in F1 sperm by the reduced representation bisulfite sequencing (RRBS) method. We succeeded in identifying differentially methylated cytosines (DMCs) and regions (DMRs) by comparing the control and arsenite-F1 sperm DNA. We also identified DMRs around transcription start sites (promoter-DMRs), which closely associate with gene expression regulation. These data enable us to further analyze DNA methylation and gene expression changes involved in the transmission of parentally acquired epigenetic effects.

Free Research Field

分子毒性学