MicroRNA profiling in ethylene glycol monomethyl ether-induced monkey testicular toxicity model

• Sakurai Ken

  Medicinal Safety Research Laboratories, Daiichi Sankyo Co., Ltd.

• Mikamoto Kei

  Medicinal Safety Research Laboratories, Daiichi Sankyo Co., Ltd.

• Shirai Makoto

  Medicinal Safety Research Laboratories, Daiichi Sankyo Co., Ltd.

• Iguchi Takuma

  Medicinal Safety Research Laboratories, Daiichi Sankyo Co., Ltd.

• Ito Kazumi

  Translational Medicine & Clinical Pharmacology Department, Daiichi Sankyo Co., Ltd.

• Takasaki Wataru

  Medicinal Safety Research Laboratories, Daiichi Sankyo Co., Ltd.

• Mori Kazuhiko

  Medicinal Safety Research Laboratories, Daiichi Sankyo Co., Ltd.

書誌事項

タイトル別名

• MicroRNA profling in ethylene glycol monomethyl ether-induced monkey testicular toxicity model

抄録

To establish and characterize ethylene glycol monomethyl ether (EGME)-induced testicular toxicity model in cynomolgus monkeys, EGME at 0 or 300 mg/kg was administered orally to sexually mature male cynomolgus monkeys (n = 3/group) for 4 consecutive days. Circulating and testicular microRNA (miRNA) profiles in this model were investigated using miRNA microarray or real-time quantitative reverse transcription-PCR methods. EGME at 300 mg/kg induced testicular toxicity in all the monkeys, which was characterized histopathologically by decreases in pachytene spermatocytes and round spermatids, without any severe changes in general conditions or clinical pathology. In microarray analysis, 16 down-regulated and 347 up-regulated miRNAs were detected in the testis, and 326 down-regulated but no up-regulated miRNAs were detected in plasma. Interestingly, miR-1228 and miR-2861 were identified as abundant miRNAs in plasma and the testis of control animals, associated presumably with apoptosis and cell differentiation, respectively, and were prominently increased in the testis of EGME-treated animals, reflecting the recovery from EGME-induced testicular damages via stimulating cell proliferation and differentiation of sperm. Furthermore, down-regulation of miR-34b-5p and miR-449a, which are enriched in meiotic cells like pachytene spermatocytes, was obvious in the testis, suggesting that these spermatogenic cells were damaged by the EGME treatment. In conclusion, EGME-induced testicular toxicity in cynomolgus monkeys was shown, and this model would be useful for investigating the mechanism of EGME-induced testicular toxicity and identifying testicular biomarkers. Additionally, testicular miR-34b-5p and miR-449a were suggested to be involved in damage of pachytene spermatocytes.

収録刊行物

• Ｔｈｅ　Ｊｏｕｒｎａｌ　ｏｆ　Ｔｏｘｉｃｏｌｏｇｉｃａｌ　Ｓｃｉｅｎｃｅｓ

  Ｔｈｅ　Ｊｏｕｒｎａｌ　ｏｆ　Ｔｏｘｉｃｏｌｏｇｉｃａｌ　Ｓｃｉｅｎｃｅｓ 40 (3), 375-382, 2015

  一般社団法人　日本毒性学会

キーワード

• Testicular toxicity
• Ethylene glycol monomethyl ether
• Monkey
• miRNA

詳細情報

• CRID: 1390282679882167424
• NII論文ID: 130005068424
• NII書誌ID: AN00002808
• DOI: 10.2131/jts.40.375
• ISSN: 18803989
• ISSN: 03881350
• NDL書誌ID: 026522892
• PubMed: 25972197
• Web Site: https://ndlsearch.ndl.go.jp/books/R000000004-I026522892
• Web Site: https://www.jstage.jst.go.jp/article/jts/40/3/40_375/_pdf
• Web Site: https://search.jamas.or.jp/link/ui/2016026490
• 本文言語コード: en
• データソース種別:
  • JaLC
  • NDL
  • Crossref
  • PubMed
  • CiNii Articles
• 抄録ライセンスフラグ: 使用不可