Transcriptional profile of ethylene glycol monomethyl ether-induced testicular toxicity in rats

Takuya Matsuyama, Koichi Yabe, Chiharu Kuwata, Kazumi Ito, Yosuke Ando, Hiroshi Iida, Kazuhiko Mori

研究成果: ジャーナルへの寄稿学術誌査読

7 被引用数 (Scopus)

抄録

To clarify the molecular mechanism of ethylene glycol monomethyl ether (EGME)-induced testicular toxicity, the potential for EGME-related changes in transcript levels of genes including spermatocyte-specific genes was evaluated in the testis of rats given single dosing of EGME at 200, 600, or 2000 mg/kg. Furthermore, the contribution of decreased testicular testosterone on EGME-induced spermatocyte toxicity was investigated by comparing to transcriptional profile due to a testosterone synthesis inhibitor, ketoconazole (KET), at 30 or 300 mg/kg. EGME at 600 mg/kg or more dose-dependently caused testicular toxicity characterized by degeneration and necrosis of spermatocytes at stage VII–XIV seminiferous tubules. The spermatocyte injury was well correlated with decreased spermatocyte-specific gene expression. Analysis of upstream regulators by the Ingenuity Pathways Analysis system suggested that up-regulation of oxidative stress, protein kinase activation, and histone acetylation was involved in EGME-induced spermatocyte toxicity. Interestingly, KET decreased testicular testosterone to a similar extent compared to the EGME treatment, but KET at up to 300 mg/kg did not show any histopathological abnormality or change in the expression of spermatocyte-specific genes. These results suggested that the decreased testicular testosterone have little impact on EGME-induced spermatocyte injury. In contrast, KET showed trends toward increases in Hsd3b2 and Hsd17b2 mRNAs, presumably resulting from inhibition of androgen synthesis. Transcriptome analysis clearly demonstrated the differential effects of EGME and KET on androgen synthesis. In conclusion, EGME caused spermatocyte toxicity correlated with decreased expression of spermatocyte-specific genes. Furthermore, oxidative stress, protein kinase activation, and histone acetylation were suggested to be involved in EGME-induced testicular toxicity.

本文言語英語
ページ(範囲)105-112
ページ数8
ジャーナルDrug and Chemical Toxicology
41
1
DOI
出版ステータス出版済み - 1月 2 2018

!!!All Science Journal Classification (ASJC) codes

  • 毒物学
  • 薬理学
  • 公衆衛生学、環境および労働衛生
  • 健康、毒物学および変異誘発
  • 化学的な安全衛生

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