Bisphenol A exposure causes meiotic aneuploidy in the female mouse
Bisphenol A exposure causes meiotic aneuploidy in the female mouse
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DOI：
10.1016/s0960-9822(03)00189-1
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发表时间：
2003-04-01
期刊：
影响因子：
9.2
通讯作者：
Hassold, TJ
中科院分区：
文献类型：
--
作者：
Hunt, PA;Koehler, KE;Hassold, TJ
背景资料：人们越来越担心，暴露于模仿内源性激素的人造物质可能会对哺乳动物的生殖产生不利影响。虽然各种生殖并发症已被归因于具有雄激素或雌激素特性的化合物，但很少有人关注这种暴露对配子遗传质量的潜在后果。结果：减数分裂紊乱的突然自发增加，包括非整倍体，在我们实验室对对照雌性小鼠的卵母细胞进行的研究中，与我们的动物意外暴露于双酚A（BPA）的环境源相吻合，. BPA是一种雌激素化合物，广泛用于聚碳酸酯塑料和环氧树脂的生产。我们将损坏的笼材料确定为暴露源，因为我们能够通过故意损坏笼和水瓶重现减数分裂异常。在随后对雌性小鼠的研究中，我们每天口服一定剂量的BPA，以直接检验低水平BPA破坏雌性减数分裂的假设。我们的研究结果表明，减数分裂的影响是剂量依赖性的，可以诱导环境相关剂量的BPA.Conclusions：无论是最初的无意中暴露和随后的实验研究表明，BPA是一个强大的减数分裂非整倍体。具体而言，在雌性小鼠中，在卵母细胞生长的最后阶段短期低剂量暴露足以引起可检测的减数分裂效应。这些结果提供了哺乳动物减数分裂非整倍性和意外的环境暴露之间的第一个明确的联系，并建议卵母细胞和它的减数分裂纺锤体将提供一个敏感的检测系统的研究生殖毒素。
Background: There is increasing concern that exposure to man-made substances that mimic endogenous hormones may adversely affect mammalian reproduction. Although a variety of reproductive complications have been ascribed to compounds with androgenic or estrogenic properties, little attention has been directed at the potential consequences of such exposures to the genetic quality of the gamete.Results: A sudden, spontaneous increase in meiotic disturbances, including aneuploidy, in studies of oocytes from control female mice in our laboratory coincided with the accidental exposure of our animals to an environmental source of bisphenol A (BPA). BPA is an estrogenic compound widely used in the production of polycarbonate plastics and epoxy resins. We identified damaged caging material as the source of the exposure, as we were able to recapitulate the meiotic abnormalities by intentionally damaging cages and water bottles. In subsequent studies of female mice, we administered daily oral doses of BPA to directly test the hypothesis that low levels of BPA disrupt female meiosis. Our results demonstrated that the meiotic effects were dose dependent and could be induced by environmentally relevant doses of BPA.Conclusions: Both the initial inadvertent exposure and subsequent experimental studies suggest that BPA is a potent meiotic aneugen. Specifically, in the female mouse, short-term, low-dose exposure during the final stages of oocyte growth is sufficient to elicit detectable meiotic effects. These results provide the first unequivocal link between mammalian meiotic aneuploidy and an accidental environmental exposure and suggest that the oocyte and its meiotic spindle will provide a sensitive assay system for the study of reproductive toxins.