Yin Jun, Sun Kaiwen, Chen Bing
Comparative Medicine Center, Yangzhou University Yangzhou 225009, Jiangsu, PR China ; College of Veterinary Medicine, Yangzhou University Yangzhou 225009, Jiangsu, PR China.
College of Veterinary Medicine, Yangzhou University Yangzhou 225009, Jiangsu, PR China.
Int J Clin Exp Pathol. 2015 Feb 1;8(2):1830-43. eCollection 2015.
N-ethyl-N-nitrosourea (ENU), a well known alkylating agent, is a powerful mutagen in mouse spermatogonia that is frequently used to generate mutant mice for the study of gene function. The present study was performed to investigate the toxic effects of a suggested ENU treatment protocol (100 mg/kg ENU once a week for three consecutive weeks) on the C57BL/6J mouse testis using light and transmission electron microscopy, with reference to testis weight and sperm count. Time-dependent changes in the weight of the testes, sperm counts and testicular morphology were observed, following an injury and recovery pattern; the most severe damage was observed in week four after the first injection of ENU, and then the testis gradually recovered. By the end of the experiment (week 12), the testis weights and sperm counts of the ENU-treated mice had restored to around 80% of the respective values in the control group. Histopathological alterations in the testis were identified by light and electron microscopy, which revealed that ENU led to a temporary depletion in the number of spermatogenic cells via direct and indirect toxic effects, including apoptosis and growth arrest in spermatogonia, Sertoli cell damage and peritubular cell injury. The results of this study complement the existing basic information on the toxicity of ENU in the testis, and provide scientific information for selecting the appropriate mating time for ENU-treated male mice.
N-乙基-N-亚硝基脲（ENU）是一种著名的烷化剂，是小鼠精原细胞中的一种强大诱变剂，常用于生成突变小鼠以研究基因功能。本研究旨在使用光学显微镜和透射电子显微镜，参考睾丸重量和精子计数，研究一种建议的ENU处理方案（连续三周每周一次给予100 mg/kg ENU）对C57BL/6J小鼠睾丸的毒性作用。观察到睾丸重量、精子计数和睾丸形态随时间的变化呈现损伤和恢复模式；在首次注射ENU后的第四周观察到最严重的损伤，然后睾丸逐渐恢复。到实验结束时（第12周），ENU处理组小鼠的睾丸重量和精子计数已恢复到对照组相应值的约80%。通过光学显微镜和电子显微镜鉴定了睾丸的组织病理学改变，结果显示ENU通过直接和间接毒性作用导致生精细胞数量暂时减少，包括精原细胞凋亡和生长停滞、支持细胞损伤和睾丸间质细胞损伤。本研究结果补充了关于ENU对睾丸毒性的现有基础信息，并为选择ENU处理的雄性小鼠的合适交配时间提供了科学依据。
