Sato Makoto, Kitaura Keisuke, Minami Takanori, Matsumoto Satoshi, Fukuda Meiko
Department of Toxicology, Drug Safety Research Center, Tokushima Research Institute, Otsuka Pharmaceutical Co., Ltd., 463-10 Kagasuno, Kawauchi-cho, Tokushima 771-0192, Japan.
Exp Toxicol Pathol. 2007 Nov;59(3-4):187-95. doi: 10.1016/j.etp.2007.05.006. Epub 2007 Sep 24.
Local cooling of the testis was reported to cause testicular abnormality, but there is no information regarding the effect of whole body cooling, such as hypothermia on spermatogenesis. We investigated whether hypothermia would cause testicular toxicity in mice. Male mice were administered with a single intraperitoneal dose of 100mg/kg of reserpine. The rectal temperature decreased to 29 degrees C 6h post dosing and thereafter sustained at lower values (24-25 degrees C) until 96 h post dosing. The histopathological examination of the testis showed nuclear vacuolation of round spermatids at stages I-V in mice examined 24, 48, 72 and 96 h post dosing. The lesions were more severe in the groups examined 72 and 96 h post dosing than in the groups examined 24 and 48 h post dosing. These results suggested that hypothermia condition at lower than 30 degrees C and sustained for more than 18 h could induce nuclear vacuolation of round spermatids at stages I-V in the testis. In order to demonstrate that the testicular lesion in the reserpine-treated mice was induced by hypothermia, mice were given a single intraperitoneal dose of 100mg/kg of reserpine, and each dosed group was housed under different environmental conditions for 72 h; one consisted of housing the mice individually at room temperature, and the other consisted of housing the mice individually under heated condition. In the mice administered with reserpine and housed at room temperature, hypothermia below 30 degrees C with a minimal of 26 degrees C was observed for 66 h. In contrast, the mice administered with reserpine and housed under heated condition maintained the rectal temperature of 33-36 degrees C. Nuclear vacuolation of round spermatids at stages I-V in the testis was observed in reserpine-treated mice maintained at room temperature, but not in reserpine-treated mice kept under heated condition. These data strongly indicated that nuclear vacuolation of round spermatids at stages I-V observed in reserpine-treated mice was related to hypothermia.
据报道，睾丸局部冷却会导致睾丸异常，但关于全身冷却（如低温）对精子发生的影响尚无相关信息。我们研究了低温是否会对小鼠造成睾丸毒性。给雄性小鼠腹腔注射单次剂量100mg/kg的利血平。给药后6小时直肠温度降至29摄氏度，此后一直维持在较低水平（24 - 25摄氏度）直至给药后96小时。给药后24、48、72和96小时检查的小鼠睾丸组织病理学检查显示，I - V期圆形精子细胞出现核空泡化。给药后72和96小时检查的组中的病变比给药后24和48小时检查的组更严重。这些结果表明，低于30摄氏度并持续超过18小时的低温条件可诱导睾丸中I - V期圆形精子细胞核空泡化。为了证明利血平处理的小鼠中的睾丸病变是由低温诱导的，给小鼠腹腔注射单次剂量100mg/kg的利血平，每个给药组在不同环境条件下饲养72小时；一组是在室温下单独饲养小鼠，另一组是在加热条件下单独饲养小鼠。在腹腔注射利血平并在室温下饲养的小鼠中，观察到低于30摄氏度且最低为26摄氏度的低温持续了66小时。相比之下，腹腔注射利血平并在加热条件下饲养的小鼠直肠温度维持在33 - 36摄氏度。在室温下饲养的利血平处理小鼠的睾丸中观察到I - V期圆形精子细胞核空泡化，而在加热条件下饲养的利血平处理小鼠中未观察到。这些数据有力地表明，在利血平处理的小鼠中观察到的I - V期圆形精子细胞核空泡化与低温有关。
