Exposure of mouse oocytes to bisphenol A causes meiotic arrest but not aneuploidy
Exposure of mouse oocytes to bisphenol A causes meiotic arrest but not aneuploidy
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DOI：
10.1016/j.mrgentox.2007.10.014
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发表时间：
2008-03-12
影响因子：
1.9
通讯作者：
Parry, Jim
中科院分区：
文献类型：
--
作者：
Eichenlaub-Ritter, Ursula;Vogt, Edgar;Parry, Jim
从大窦卵泡中分离的小鼠卵母细胞在体外成熟过程中暴露于广泛浓度的双酚A（BPA）（培养基中BPA为50 ng/ml至10 μ g/ml）。暴露于高浓度的BPA（10 μ g/ml）影响纺锤体的形成，分布的pericentriolar材料和染色体上的纺锤体排列（称为congression失败），并引起显着的减数分裂停滞。然而，BPA在任何测试浓度下都不会增加减数分裂II的超倍性。一些但不是所有的减数分裂I停滞的卵母细胞在二价体染色体的着丝粒处具有MAD 2阳性灶，表明它们未能通过纺锤体检查点控制。在第二组实验中，青春期前小鼠亚慢性暴露于低BPA 7天，每天口服，然后在不存在BPA的情况下，将裸露的卵母细胞体外成熟至中期II，因为先前报道该处理方案诱导染色体聚集失败，因此怀疑其导致卵母细胞的非整倍性。亚慢性暴露微妙地影响纺锤体形态和卵母细胞成熟。然而，与体外暴露一样，没有证据表明低BPA剂量会增加减数分裂II时的超倍性。总之，这些数据表明，小鼠卵母细胞响应BPA诱导的纺锤体形成的减数分裂阻滞诱导的干扰。这种反应可能是由于一种有效的检查点机制，防止染色体异常分离和非整倍体的发生。在小鼠卵母细胞第一次减数分裂时，低水平的BPA体内长期暴露似乎不会引起染色体分离错误的诱导风险。除BPA外的其他因素可能导致了先前报道的小鼠中期II卵母细胞的高聚集失败率和超倍体的暂时增加。(c)2007 Elsevier B. V.保留所有权利。
Mouse oocytes isolated from large antral follicles were exposed to a wide range of concentrations of bisphenol A (BPA) during maturation in vitro (50 ng/ml to 10 mu g/ml BPA in medium). Exposure to high concentrations of BPA (10 mu g/ml) affected spindle formation, distribution of pericentriolar material and chromosome alignment on the spindle (termed congression failure), and caused a significant meiotic arrest. However, BPA did not increase hyperploidy at meiosis II at any tested concentration. Some but not all meiosis I arrested oocytes had MAD2-positive foci at centromeres of chromosomes in bivalents, suggesting that they had failed to pass the spindle checkpoint control.In a second set of experiments prepubertal mice were exposed sub-chronically for 7 days to low BPA by daily oral administration, followed by in vitro maturation of the denuded oocytes to metaphase II in the absence of BPA, as this treatment protocol was previously reported to induce chromosome congression failure and therefore suspected to cause aneuploidy in oocytes. The sub-chronic exposure subtly affected spindle morphology and oocyte maturation. However, as with the exposure in vitro, there was no evidence that low BPA doses increased hyperploidy at meiosis II. In conclusion, the data suggest that mouse oocytes from mice respond to BPA-induced disturbances in spindle formation by induction of meiotic arrest. This response might result from an effective checkpoint mechanism preventing the occurrence of chromosome malsegregation and aneuploidy. Low chronic BPA exposure in vivo as such does not appear to pose a risk for induction of errors in chromosome segregation at first meiosis in mouse oocytes. Additional factors besides BPA may have caused the high rate of congression failure and the temporary increase in hyperploidy in mouse metaphase II oocytes reported previously. (c) 2007 Elsevier B.V. All rights reserved.