Evaluation of testicular toxicology of doxorubicin based on microarray analysis of testicular specific gene expression

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概要

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• Testicular toxicity of chemical substances has been generally assessed by sperm properties and histology. However, the methods can provide only a few information of the mechanism of the toxicity. The aim of this study is to show a method that can evaluate an overview of testicular toxic mechanisms using a tissue-specific microarray and classification of genes using Medical Subject Headings (MeSH). Male ICR mice (6 weeks old) were treated with doxorubicin hydrochloride (0, 0.1, 0.3 mg/kg/time, three times per week) by subcutaneous injection for 6 weeks (until 11 weeks old). Six weeks after the final administration, tissue and blood samples were obtained. Testes were subjected to gene expression analysis using quantitative RT-PCR and cDNA microarray (testis2). To interpret the microarray data, genes were classified using MeSH related to the functions of testis and sperm. Doxorubicin (both 0.1 and 0.3 mg/kg group) induced a decrease in sperm normal morphology and mortality, daily sperm production, and the number of Sertoli cells in the seminiferous tubules. Quantitative RT-PCR and microarray analysis showed dysregulation of mRNA expression levels of genes related to Sertoli cells, germ cells and spermatogenesis. Analysis of microarray data showed a significant enrichment of a total of ten MeSH categories including Spermatogenesis, Sertoli cells, Germ cells and Male infertility. This article concluded that analysis using testicular specific microarray combined with MeSH showed a more comprehensive overview of testicular toxic mechanisms than existing methods; i.e., examination of sperm properties and the histological examinations.

• 日本トキシコロジー学会の論文

著者

• Umezawa Masakazu

  Department Of Hygienic Chemistry Faculty Of Pharmaceutical Sciences Tokyo University Of Science

• Oshio Shigeru

  Department Of Biology University Of Tokyo

• Takayama Hitoshi

  Department Of Urology Osaka University Graduate School Of Medicine

• TANAKA Hiromitsu

  Tanaka Project, Center for Advanced Science and Innovation, Osaka University

• Takeda Ken

  Department Of Hygiene Chemistry Faculty Of Pharmaceutical Science Tokyo University Of Science

• Hirai Toshiaki

  Tanaka Project Center For Advanced Science And Innovation Osaka University

• Takahashi Hikari

  Department of Hygienic Chemistry, Faculty of Pharmaceutical Sciences, Tokyo University of Science

• Tainaka Hitoshi

  Research Center for Health Sciences of Nanoparticles, Research Institute for Science and Technology,

• Nishimune Yoshitake

  Animal Resource Center for Infectious Diseases, Research Institute for Microbial Diseases, Osaka Uni

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