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2018 Fiscal Year Final Research Report

Effects of prenatal exposure to nanoparticles on gene expression patterns in the brain of the second generation offspring via male germ cells

Research Project

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Project/Area Number 17K15854
Research Category

Grant-in-Aid for Young Scientists (B)

Allocation TypeMulti-year Fund
Research Field Hygiene and public health
Research InstitutionNational Institute of Health Sciences (2018)
Ohu University (2017)

Principal Investigator

Yokota Satoshi  国立医薬品食品衛生研究所, 毒性部, 主任研究官 (70706605)

Project Period (FY) 2017-04-01 – 2019-03-31
Keywordsナノマテリアル / DOHaD / 多世代・継世代影響 / 妊娠期曝露 / 精子形成 / エピゲノム
Outline of Final Research Achievements

The F2 offspring born to F1 sires which gestationally exposed to silver nanoparticles showed subtle changes in gene expressions related to behavior and acetylcholine signals compared to controls. To explore the mechanism of how the effects of F1 male pups were transmitted to F2 generation, we investigated changes in the expressions of one of the small non-coding RNA, microRNA, in the testes of F1 mice using microarray.
We observed significantly reduction of exposed F1 sperm motility and sperm number. We also identified some microRNA expression changes of exposed mice in a dose-dependent manner. These microRNA expressions were likely to be related to genes which were differentially expressed between exposed mice and controls in the F2 hippocampus. These data enable us to further investigate microRNA expression changes involved in the transgenerational effects of paternally acquired epigenetic effects.

Free Research Field

分子毒性学

Academic Significance and Societal Importance of the Research Achievements

ナノ粒子の妊娠期曝露により生じる多世代影響に関する報告は数少なく、そのメカニズムに関する報告は皆無である。このような状況下、私たちはマウス胎仔期曝露の実験により、F1 世代の脳神経および雄性生殖器に粒子が蓄積し健康影響が生じることを解明してきた。本研究は、妊娠期曝露の多世代影響に関する実験検証を行う良いモデルを構築することに成功し、曝露を直接受けていない F2 の脳神経系への影響を解明、ならびに、そのメカニズムとしてのF1 生殖系列のエピジェネティックな変化を捉えることができた。本研究の遂行による世代影響のバイオマーカー同定に向けた基礎的知見を付与した点に学術的・社会的意義があると考えている。

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Published: 2020-03-30  

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