The effect on sperm production in adult Sprague-Dawley rats exposed by gavage to bisphenol a between postnatal days 91-97
The effect on sperm production in adult Sprague-Dawley rats exposed by gavage to bisphenol a between postnatal days 91-97
复制标题
DOI：
10.1093/toxsci/kfg093
复制
发表时间：
2003-07-01
影响因子：
3.8
通讯作者：
Haseman, J
中科院分区：
文献类型：
--
作者：
Ashby, J;Tinwell, H;Haseman, J
M. Sakaue et al. (2001，J。Occup。健康vol. 43, pp. 185-190)描述了性成熟雄性大鼠在出生后91-97天（PND）之间口服双酚A （BPA）如何导致5周（18周龄）后每日精子产量（DSP）减少。在20马克杯/千克-200毫克/千克BPA剂量范围内观察到活性，在2纳克/千克-2马克杯/千克BPA剂量范围内没有活性。没有证据表明在活性剂量范围（五个数量级范围）内存在剂量反应关系。如此低剂量的BPA对性成熟动物的内分泌干扰（ED）效应的观察是出乎意料的。因此，决定对他们的研究进行独立的重复。根据Sakaue等人使用的方案，共进行了四项独立研究。对PND 91-97的成年SD大鼠分别给予20杯/千克、2毫克/千克或200毫克/千克BPA，当大鼠年满18周龄时终止研究。采用3种不同的鼠粮（RM3、Purina 5002和CE2），最后一种是Sakaue等人使用的。BPA未能提供ED活性的任何证据，包括Sakaue等人2001年报道的DSP变化。在这些研究过程中，测试方案进行了调整，以更精确地与Sakaue等人使用的方案一致；这包括限制每个笼子的动物数量，从笼子里移走床上用品，并改为在笼子里使用玻璃水瓶。从我们的研究中出现的唯一有趣的事情是观察到我们的第一个和第二个研究的对照组之间DSP的显着差异。由于从RM3到Purina 5002的饮食变化是这两项研究之间的主要差异，我们对第二项研究进行了重复，但我们无法证实第一项研究和第二项研究之间的差异。在最后（第五）项研究中，在主要实验的条件下，比较了食用三种不同饮食的对照动物的精子参数，精子参数没有显著差异，这进一步加强了这些差异是偶然产生的，或者是研究间内在差异的结果。对于我们未能复制Sakaue等人报告的效应，没有明显的解释。本文对近期文献中报道的DSP值进行了回顾和讨论，并得出结论，使用术语DSP/g睾丸而不是DSP/睾丸可以提高DSP评估的敏感性。
M. Sakaue et al. (2001,J. Occup. Health vol. 43, pp. 185-190) have described how oral exposure of sexually mature male rats to bisphenol A (BPA) between postnatal days (PND) 91-97 led to a reduction in daily sperm production (DSP) 5 weeks later (18 weeks of age). Activity was observed over the dose range 20 mug/kg-200 mg/kg BPA, with an absence of activity over the dose range 2 ng/kg-2 mug/kg BPA. There was no evidence of a dose response relationship over the active dose range (five orders of magnitude range). The observation of endocrine disruption (ED) effects for BPA at such low doses, and in sexually mature animals, was unexpected. It was therefore decided to mount an independent repeat of their study. A total of four independent studies were conducted according to the protocol used by Sakaue et al. Doses of 20 mug/kg, 2 mg/kg, or 200 mg/kg BPA were administered to adult Sprague-Dawley (SD) rats over PND 91-97, and the studies were terminated when the rats reached the age of 18 weeks. Three different rodent diets were employed (RM3, Purina 5002, and CE2), the last of which had been used by Sakaue et al. BPA failed to give any evidence of ED activities, including the changes in DSP reported by Sakaue et al. 2001. During the course of these studies, the test protocol was adapted to coincide more precisely with that used by Sakaue et al.; this included restricting the number of animals per cage, removing bedding from the cages, and changing to the use of glass water bottles in the cages. The only thing of interest to emerge from our studies was the observation of a significant difference in DSP between the control groups of our first and second study. As the change in diet from RM3 to Purina 5002 was the major difference between those two studies, we conducted a repeat of the second study, but we were unable to confirm the differences seen between the first and second study. The probability that those differences arose either by chance, or as the result of intrinsic study-to-study variability, was strengthened by the absence of significant differences in the sperm parameters in a final (fifth) study where the sperm parameters for control animals maintained on the three different diets were compared under the conditions of the main experiments. No explanation for our failure to replicate the effects reported by Sakaue et al. is evident. A review of DSP values reported in the recent literature is provided and discussed, and it is concluded that use of the term DSP/g testis rather than DSP/testis could increase the sensitivity of DSP assessments.