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

• Published in: Journal of toxicological sciences Vol. 36; no. 5; pp. 559 - 567
• Main Authors: Tainaka, Hitoshi, Takeda, Ken, Oshio, Shigeru, Nishimune, Yoshitake, Umezawa, Masakazu, Tanaka, Hiromitsu, Takahashi, Hikari
• Format: Journal Article
• Language: English
• Published: Japan The Japanese Society of Toxicology 2011; Japan Science and Technology Agency
• Subjects: Animals; Cell Count; Data processing; Databases, Genetic; DNA microarrays; Doxorubicin; Doxorubicin - toxicity; Enzyme-Linked Immunosorbent Assay; Gene expression; Gene Expression - drug effects; Gene Expression Profiling; Germ cells; Infertility; Male; Medical Subject Headings; Mice; Mice, Inbred ICR; Microarray; Mortality; Oligonucleotide Array Sequence Analysis; Organ Size - drug effects; Polymerase chain reaction; Reverse Transcriptase Polymerase Chain Reaction; Reviews; Seminiferous tubule; Sertoli cell; Sertoli cells; Sertoli Cells - cytology; Sertoli Cells - drug effects; Sperm; Sperm Motility - drug effects; Spermatogenesis; Spermatogenesis - drug effects; Spermatozoa - drug effects; Spermatozoa - pathology; Testes; Testis; Testis - drug effects; Testis - metabolism; Testis - pathology; Toxicity
• ISSN: 0388-1350; 1880-3989; 1880-3989
• DOI: 10.2131/jts.36.559

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.