Okamura Miwa, Watanabe Takao, Kashida Yoko, Machida Noboru, Mitsumori Kunitoshi
Laboratory of Veterinary Pathology, Tokyo University of Agriculture and Technology, 3-5-8 Saiwai-cho, Fuchu, Tokyo 183-8509, Japan.
Toxicol Pathol. 2004 Jan-Feb;32(1):1-8. doi: 10.1080/01926230490260655.
To clarify the mechanisms underlying the testicular toxicity of oxfendazole (OX), adult Wistar rats were orally administered a dose of 100 mg/kg/day for 3, 7, or 14 days. Assays of sex-related hormones showed a significant decrease in only the estradiol serum level at days 3 and 7, as compared with the control group. Histopathologically, marked degeneration of meiotic spermatocytes was observed in stage XIV-I seminiferous tubules from day 3 onwards, and these spermatocytes gave positive results on terminal deoxynucleotidyl transferase (TdT)-mediated dUTP nick end-labeling (TUNEL). Abnormalities of spermiogenesis such as megakaryospermatids and binucleated spermatids were also observed in the testes of OX-treated rats. Under the electron microscope, lipid accumulation and dilatation of the endoplasmic reticulum were frequently found in the cytoplasm of the Sertoli cells on day 3. These results strongly suggest that OX induces both apoptosis of meiotic spermatocytes, most probably due to disruption of the microtubules, and degeneration of the Sertoli cells, characterized by distended endoplasmic reticulum and prominent cytosolic lipid accumulation.
为阐明奥芬达唑（OX）睾丸毒性的潜在机制，将成年Wistar大鼠按100 mg/kg/天的剂量口服给药3天、7天或14天。性激素检测显示，与对照组相比，仅在第3天和第7天血清雌二醇水平显著降低。组织病理学检查发现，从第3天起，在第XIV-I期生精小管中观察到减数分裂期精母细胞明显退化，并且这些精母细胞在末端脱氧核苷酸转移酶（TdT）介导的dUTP缺口末端标记（TUNEL）检测中呈阳性结果。在接受OX处理的大鼠睾丸中还观察到精子发生异常，如巨核精子细胞和双核精子细胞。在电子显微镜下，第3天时在支持细胞的细胞质中经常发现内质网脂质积累和扩张。这些结果强烈表明，OX诱导减数分裂期精母细胞凋亡，最可能是由于微管破坏所致，同时还导致支持细胞退化，其特征为内质网扩张和胞质脂质积累明显。
