Dose the fetal exposure to environmental chemicals have a impact on the alternative splicing profiles in post weaning brain via its epigenetic changes ?

2015 Fiscal Year Final Research Report

• Project/Area Number: 25550039
• Research Category: Grant-in-Aid for Challenging Exploratory Research
• Allocation Type: Multi-year Fund
• Research Field: Risk sciences of radiation and chemicals
• Research Institution: Kyoto Prefectural University of Medicine
• Principal Investigator: YAOI Takeshi 京都府立医科大学, 医学(系)研究科(研究院), 助教 (40311914)
• Project Period (FY): 2013-04-01 – 2016-03-31
• Keywords: 環境化学物質 / 選択的スプライシング / エピゲノム / 天然変性アミノ酸配列領域

Outline of Final Research Achievements

Bisphenol A (BPA) is used mainly in the production of polycarbonate plastics and epoxy resins. BPA was detected in the serum of pregnant women as well as fetuses. The prenatal exposure to BPA at low doses has been demonstrated to affect brain development in mice. During vertebrate development it has been postulated that dynamic changes in epigenome are able to regulate tissue- and cell type-specific gene expression. We reported the genome-wide effect of maternal exposure to BPA on the epigenome and transcriptome in fetal mouse forebrain. The perturbated epigenetic states seemed to underlie the changed gene expression levels. The present study reveals that such levels was mostly restored in the post weaning mouse cerebral cortex maternally exposed to BPA. The exposure changed the selection efficiency of alternatively spliced exons encoding protein isoform. We also detected the changes of epigenetic marks around such representative alternatively spliced exons.

Free Research Field

分子神経生物学、分子生物学