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首页> 外文期刊>The Journal of toxicological sciences >Effects of male reproductive toxicants on gene expression in rat testes.
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Effects of male reproductive toxicants on gene expression in rat testes.

机译：雄性生殖有毒物质对大鼠睾丸基因表达的影响。

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摘要

Predictive biomarkers of testicular toxicity are needed for an efficient development of drugs. The purpose of the present study was to obtain further insight into the toxicity mechanisms of various male reproductive toxicants and to detect genomic biomarkers for rapid screening of testicular toxicity. Four reproductive toxicants, 2,5-hexanedione (Sertoli cells toxicant), ethylene glycol monomethyl ether (EGME; spermatocytes toxicant), cyclophosphamide (spermatogonia toxicant) and sulfasalazine, were orally administered to male rats once. Six hours after the single dosing, gene expression in the testes was monitored by cDNA microarray and real-time RT-PCR and the testes were histopathologically examined. No histopathological abnormality was detected except for slight degeneration of spermatocytes in the EGME-treated testes. cDNA microarray analysis revealed differential gene expression profiles, and it was possible based on the profiles to characterize the action of the compounds in the testes. Interestingly, 3 spermatogenesis-related genes - heat shock protein 70-2, insulin growth factor binding protein 3 and glutathione S transferase pi - were affected by all the compounds. The above changes of gene expression were detectable within a short period after the dosing prior to the appearance of obvious pathological changes. These data suggest that cDNA microarray is a useful technique for evaluation of primary testicular toxicity. Furthermore, we propose the above 3 spermatogenesis-related genes as potential biomarkers of testicular toxicity.
机译：为了有效开发药物，需要睾丸毒性的预测性生物标志物。本研究的目的是进一步了解各种男性生殖毒物的毒性机制，并检测基因组生物标记物以快速筛选睾丸毒性。雄性大鼠一次口服了两种生殖毒物：2,5-己二酮（Sertoli细胞毒物），乙二醇单甲醚（EGME;精细胞毒物），环磷酰胺（精原细胞毒物）和柳氮磺胺吡啶。单次给药后六小时，通过cDNA微阵列和实时RT-PCR监测睾丸中的基因表达，并进行组织病理学检查。除了在EGME处理的睾丸中精细胞的轻微变性外，未检测到组织病理学异常。 cDNA微阵列分析揭示了差异基因表达谱，并且有可能基于这些谱图表征化合物在睾丸中的作用。有趣的是，三个与精子生成相关的基因-热休克蛋白70-2，胰岛素生长因子结合蛋白3和谷胱甘肽S转移酶pi-都受所有化合物的影响。在给药后短时间内，在出现明显病理变化之前，可以检测到上述基因表达的变化。这些数据表明，cDNA微阵列是评估原发性睾丸毒性的有用技术。此外，我们提出上述3个与精子发生有关的基因作为睾丸毒性的潜在生物标记。

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