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

Research Project

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
Project Status	Completed (Fiscal Year 2015)
Budget Amount *help	¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000) Fiscal Year 2015: ¥650,000 (Direct Cost: ¥500,000、Indirect Cost: ¥150,000) Fiscal Year 2014: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000) Fiscal Year 2013: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
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 / 選択的スプライシング異常 / エピゲノム異常 / 大脳皮質 / 環境エピゲノム
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.