Bisphenol A impairs the double-strand break repair machinery in the germline and causes chromosome abnormalities
Bisphenol A impairs the double-strand break repair machinery in the germline and causes chromosome abnormalities
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DOI：
10.1073/pnas.1010386107
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发表时间：
2010-11-23
影响因子：
11.1
通讯作者：
Colaiacovo, Monica P.
中科院分区：
文献类型：
--
作者：
Allard, Patrick;Colaiacovo, Monica P.
双酚A（BPA）是塑料中非常普遍的成分，与糖尿病，心血管疾病和人类流产风险增加有关。在小鼠中，BPA暴露会破坏减数分裂过程;然而，对受影响的分子途径的分析是滞后的，特别具有挑战性。在这里，我们表明，暴露的线虫秀丽隐杆线虫BPA，在内部浓度与哺乳动物模型一致，导致不育和胚胎致死率增加。BPA暴露导致染色体突触受损和减数分裂双链断裂修复（DSBR）进程中断。BPA在种系中具有抗雌激素活性，导致DSBR基因的种系特异性下调，从而损害减数分裂期间基因组完整性的维持。C.因此，线虫构成了一个与哺乳动物显著相关的模型，可以用来评估我们的化学景观如何影响生殖细胞和减数分裂。
Bisphenol A (BPA) is a highly prevalent constituent of plastics that has been associated with diabetes, cardiovascular disease, and an increased risk of miscarriages in humans. In mice, BPA exposure disrupts the process of meiosis; however, analysis of the affected molecular pathways is lagging and has been particularly challenging. Here we show that exposure of the nematode Caenorhabditis elegans to BPA, at internal concentrations consistent with mammalian models, causes increased sterility and embryonic lethality. BPA exposure results in impaired chromosome synapsis and disruption of meiotic double-strand break repair (DSBR) progression. BPA carries an anti-estrogenic activity in the germline and results in germline-specific down-regulation of DSBR genes, thereby impairing maintenance of genomic integrity during meiosis. C. elegans therefore constitutes a model of remarkable relevance to mammals with which to assess how our chemical landscape affects germ cells and meiosis.