Molecular mechanism of testicular dysfunction induced by titanium dioxide nanoparticles

2018 Fiscal Year Final Research Report

• Project/Area Number: 15H02829
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Risk sciences of radiation and chemicals
• Research Institution: National Institute of Occupational Safety and Health,Japan
• Principal Investigator: Miura Nobuhiko 独立行政法人労働者健康安全機構労働安全衛生総合研究所, 産業毒性・生体影響研究グループ, 部長代理 (20229644)
• Co-Investigator(Kenkyū-buntansha): 大谷 勝己 独立行政法人労働者健康安全機構労働安全衛生総合研究所, 産業疫学研究グループ, 統括研究員 (50333373) ; 吉岡 弘毅 金城学院大学, 薬学部, 助教 (30756606)
• Project Period (FY): 2015-04-01 – 2018-03-31
• Keywords: 二酸化チタン / ナノ粒子 / 精巣機能 / 精子運動能

Outline of Final Research Achievements

We found that titanium dioxide nanoparticles (TiNP) also possess acute testicular dysfunction in addition to subacute testicular dysfunction, since the sperm motility was reduced (by half) after only one day of single administration of TiNP. We also confirmed the decrease in sperm motility in ex vivo experiments in which sperm and TiNP were directly incubated, further, we observed the recuction of the fertility rate by TiNP administration by in vitro fertilization (IVF) assay. These results strongly indicate that TiNP directly attacks not only spermatogonia but also mature spermatozoa present in the cauda epididymis. Although quantitative changes in levels of hormones (testosterone, GnRH, FSH, LH) were not observed by TiNP administration, the results of microarray analysis indicated that TiNP might induce the cytoskeleton disruption by damaging microfilaments and microtubules.

Free Research Field

毒性学

Academic Significance and Societal Importance of the Research Achievements

我々はTiNPの反復曝露で精巣機能障害が生じることを報告してきたが、さらに急性障害も生じ得ること、これは成熟精子への直接的な障害であることを見出した。TiNPの工業的・商業的利用は多い。しかしTiNPのSDSには生殖障害について「情報がないため判断できない」と記載されておりTiNPの生殖影響を把握する必要がある。我々が得た結果は、特にTiNPの原材料を取り扱う男性労働者への精巣機能低下の危険性を示す基盤材料となり、取り扱い時において防護の重要性を促す基礎的知見となる。