Possible mechanisms underlying the testicular toxicity of oxfendazole in rats.
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.
Okamura
Miwa
M
Laboratory of Veterinary Pathology, Tokyo University of Agriculture and Technology, 3-5-8 Saiwai-cho, Fuchu, Tokyo 183-8509, Japan. mokamura@cc.tuat.ac.jp
Watanabe
Takao
T
Kashida
Yoko
Y
Machida
Noboru
N
Mitsumori
Kunitoshi
K
D000284:Administration, Oral; D000818:Animals; D000871:Anthelmintics / Q000008:administration & dosage / Q000633:toxicity*; D017209:Apoptosis / Q000187:drug effects; D001562:Benzimidazoles / Q000008:administration & dosage / Q000633:toxicity*; D004958:Estradiol / Q000097:blood; D020287:In Situ Nick-End Labeling; D008297:Male; D008540:Meiosis / Q000187:drug effects; D008854:Microscopy, Electron; D051381:Rats; D017208:Rats, Wistar; D012708:Sertoli Cells / Q000187:drug effects / Q000648:ultrastructure; D013090:Spermatocytes / Q000187:drug effects / Q000473:pathology; D013733:Testicular Diseases / Q000097:blood / Q000139:chemically induced* / Q000473:pathology; D013737:Testis / Q000187:drug effects* / Q000473:pathology; D013997:Time Factors
D000871:Anthelmintics; D001562:Benzimidazoles; D004958:Estradiol; C011030:oxfendazole