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首页> 外文期刊>Reproductive toxicology >Early effects of ovotoxicity induced by 4-vinylcyclohexene diepoxide in rats and mice.
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Early effects of ovotoxicity induced by 4-vinylcyclohexene diepoxide in rats and mice.

机译:4-乙烯基环己烯二环氧化合物在大鼠和小鼠中引起的卵毒性的早期作用。

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The industrial chemical 4-vinylcyclohexene diepoxide (VCD) causes specific destruction of oocyte-containing small preantral follicles (primordial and primary) in ovaries of rats and mice. The mouse seems more susceptible to ovotoxic effects of VCD than the rat. The purpose of this study was to better understand these species differences in susceptibility to VCD by comparing the initial rates of VCD-induced follicle damage and loss in response to dosing in both species. Female Fischer 344 rats and B6C3F1 mice (age, Day 28) were dosed daily (vehicle or 80 mg/kg, i.p.) for 6, 8, 10, or 12 d. Ovaries collected after the final dose were prepared for histologic evaluation. Primordial and primary follicles in ovarian slices were counted and classified as healthy or atretic. A VCD-dependent increase (P < 0.05) in percent atretic primordial follicles was first observed 4 h after the final dose in mice on Day 8 (VCD-treated, 44.4 +/- 3.1% vs. control, 26.9 +/- 5.4%). Conversely, in rats, this significant increase was not seen until Day 10 (VCD-treated, 44.3 +/- 1.3% vs. control, 23.1 +/- 4.0%). A VCD-dependent increase in percent atretic primary follicles was not observed in either species before Day 12. There was no significant effect on growing or preantral follicles on any day in either species. Significant loss of primordial and primary follicles (P < 0.05) was first measured on day 12 in both rats and mice. However, when compared with controls, follicle loss on that day was greater (P < 0.05) in mice (64.2 +/- 4.5%) than in rats (34.7 +/- 4.9%). Once VCD-dependent follicle loss was observed, the rate of follicle damage was similar in rats and mice, and was fairly constant in response to each dose. VCD-induced follicle damage in mice, as with rats, also displayed morphologic characteristics of atresia (apoptosis). In summary, follicle destruction seems to be similar in rats and mice; however, follicle damage is initiated earlier and to a greater extent in mice than in rats. Additionally, ovotoxic effects of VCD seem to initially directly target primordial follicles. These results provide temporal evidence that mice are more susceptible to VCD-induced ovotoxicity than rats.
机译:工业化学4-乙烯基环己烯二环氧化物(VCD)会导致大鼠和小鼠卵巢中卵母细胞小的前窦卵泡(原始和初级)发生特异性破坏。老鼠似乎比老鼠更容易受到VCD的卵毒性作用。本研究的目的是通过比较两种物种中VCD引起的卵泡损伤和损失的初始比率,从而更好地了解这些物种对VCD的敏感性。每天给雌性Fischer 344只大鼠和B6C3F1小鼠(年龄,第28天)给药(车辆或80 mg / kg,腹腔注射)6、8、10或12天。准备最终剂量后收集的卵巢用于组织学评估。计数卵巢切片中的原始卵泡和初级卵泡,并将其分类为健康或闭锁的。在第8天对小鼠进行最终剂量给药后4小时,首次观察到VCD依赖性的闭锁性原始原始卵泡百分比增加(P <0.05)(VCD处理的对照组为44.4 +/- 3.1%,对照组为26.9 +/- 5.4% )。相反,在大鼠中,直到第10天才观察到这种显着增加(VCD治疗,相对于对照组,为44.3 +/- 1.3%,为23.1 +/- 4.0%)。在第12天之前,在任何一个物种中都没有观察到依赖VCD的闭锁性初级卵泡百分比的增加。在任何一个物种中,任何一天的生长或窦前卵泡都没有显着影响。在第12天,在大鼠和小鼠中首次测量了原始和初级卵泡的显着损失(P <0.05)。但是,当与对照组相比时,小鼠(64.2 +/- 4.5%)当天的卵泡损失大于大鼠(34.7 +/- 4.9%)(P <0.05)。一旦观察到依赖VCD的卵泡丧失,在大鼠和小鼠中,卵泡损伤的速率是相似的,并且对每个剂量的响应都相当恒定。与大鼠一样,VCD诱发的小鼠卵泡损伤也表现出闭锁(细胞凋亡)的形态特征。总之,大鼠和小鼠的卵泡破坏似乎是相似的。然而,与大鼠相比,小鼠中的卵泡损伤更早开始,并且程度更大。另外,VCD的卵毒性作用最初似乎直接针对原始卵泡。这些结果提供了暂时的证据,表明小鼠比大鼠更容易受到VCD诱导的卵毒性的影响。

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