Moustafa Gihan Gamal, Ibrahim Zein Shaban, Hashimoto Yoshiharu, Alkelch Alkelch M, Sakamoto Kentaro Q, Ishizuka Mayumi, Fujita Shoichi
Laboratory of Toxicology, Department of Environmental Veterinary Sciences, Graduate School of Veterinary Medicine, Hokkaido University, N18, W9, Kita-ku, Sapporo, 060-0818, Japan.
Arch Toxicol. 2007 Dec;81(12):875-81. doi: 10.1007/s00204-007-0217-2. Epub 2007 Jun 14.
To investigate the effect of the phosphorothoate insecticide profenofos on male specific gene expression on rat testis, 16-week-old Wistar rats were orally administered at dose of 17.8 mg/kg twice weekly for 65 days. Gene expression in the testes was monitored by DNA microarray analysis and real-time RT-PCR, which revealed that genes related to steroidogenesis including cytochrome P450 17A1 (CYP17A1), steroidogenic acute regulatory protein (StAR) and CYP11A1 were significantly increased. Besides the testes were histopathologicaly examined, which revealed testicular destruction and degeneration represented by a layer of columnar epithelium, oedematous changes surrounding the seminiferous tubules besides vacuolated spermatogonial cells and more elongated Leydig cells. These data suggest that profenofos considered as one of the male reproductive toxicants. Furthermore, we propose that the above three steroidogenic-related genes and the gene of acrosomal reaction as potential biomarkers of testicular toxicity.
为研究硫代磷酸酯杀虫剂丙溴磷对大鼠睾丸雄性特异性基因表达的影响,将16周龄的Wistar大鼠每周两次口服给予17.8mg/kg的剂量,持续65天。通过DNA微阵列分析和实时逆转录聚合酶链反应监测睾丸中的基因表达,结果显示与类固醇生成相关的基因,包括细胞色素P450 17A1(CYP17A1)、类固醇生成急性调节蛋白(StAR)和CYP11A1显著增加。此外,对睾丸进行了组织病理学检查,结果显示睾丸破坏和变性,表现为一层柱状上皮、生精小管周围的水肿变化、空泡化的精原细胞以及更长的睾丸间质细胞。这些数据表明丙溴磷被认为是雄性生殖毒物之一。此外,我们提出上述三个与类固醇生成相关的基因和顶体反应基因作为睾丸毒性的潜在生物标志物。