Boekelheide K
Department of Pathology and Laboratory Medicine, Brown University, Providence, Rhode Island 02912.
Toxicol Appl Pharmacol. 1988 Jan;92(1):18-27. doi: 10.1016/0041-008x(88)90223-2.
The histopathology of the testicular injury induced by 2,5-hexanedione (2,5-HD) exposure was examined in the rat. Charles River CD rats (200 g) were intoxicated by consuming 1% 2,5-HD in the drinking water or by intraperitoneal injection of the toxicant. Both neurotoxic and subneurotoxic exposures were studied, the total dose ranging from 40 to 211 mmol/kg. The following results were obtained: (1) there was a time delay between administration of the toxicant and development of the testicular injury, (2) Sertoli cell vacuolation in stages associated with the meiotic metaphase was the first histological sign of cellular injury at all doses, (3) subneurotoxic doses produced selective defects in germ cells in stages I-VIII of the spermatogenic cycle, (4) both subneurotoxic and neurotoxic doses produced germ cell necrosis and generalized sloughing of germ cells, and (5) intensive intoxication followed by a 17-week recovery period resulted in an absence of all postspermatogonial germ cells from the seminiferous epithelium of three of five treated rats. These data demonstrate that 2,5-hexanedione-induced testicular atrophy occurs at exposure levels below those producing clinical neurotoxicity and that, within the time frame of this study, the testicular injury is at least partially irreversible.
在大鼠中研究了2,5 -己二酮（2,5 - HD）暴露所致睾丸损伤的组织病理学。将Charles River CD大鼠（200 g）通过饮用含1% 2,5 - HD的水或腹腔注射该毒物使其中毒。研究了神经毒性和亚神经毒性暴露，总剂量范围为40至211 mmol/kg。获得了以下结果：（1）毒物给药与睾丸损伤发展之间存在时间延迟；（2）在与减数分裂中期相关阶段的支持细胞空泡化是所有剂量下细胞损伤的首个组织学迹象；（3）亚神经毒性剂量在生精周期的I - VIII阶段的生殖细胞中产生选择性缺陷；（4）亚神经毒性和神经毒性剂量均导致生殖细胞坏死和生殖细胞广泛脱落；（5）重度中毒后经过17周的恢复期，五只接受治疗的大鼠中有三只的生精上皮中所有精原细胞后的生殖细胞均缺失。这些数据表明，2,5 -己二酮诱导的睾丸萎缩发生在产生临床神经毒性的暴露水平以下，并且在本研究的时间范围内，睾丸损伤至少部分是不可逆的。
