Reproductive toxicity of low level bisphenol A exposures in a two-generation zebrafish assay: Evidence of male-specific effects.

Reproductive toxicity of low level bisphenol A exposures in a two-generation zebrafish assay: Evidence of male-specific effects.
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DOI:
10.1016/j.aquatox.2015.10.020
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发表时间:
2015-12
期刊:
Aquatic toxicology (Amsterdam, Netherlands)
影响因子:
--
通讯作者:
Dong Q
Dong Q
中科院分区:
其他
文献类型:
--
作者:
Chen J;Xiao Y;Gai Z;Li R;Zhu Z;Bai C;Tanguay RL;Xu X;Huang C;Dong Q

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双酚A(BPA)是生产聚碳酸酯塑料和环氧树脂的大容量化学品,是环境和人体中普遍存在的污染物。为了研究长期接触低浓度双酚A对斑马鱼繁殖的影响,对斑马鱼进行了两代研究。结果表明,连续两代暴露于1 NM(0.228μg/L)双酚A可导致F1和F2成年群体性别比偏向女性,精子密度下降,精子活力、速度、三磷酸腺苷含量和脂质过氧化水平下降。雌性对双酚A暴露的敏感性低于雄性,因为雌性性腺或配子中没有发现不良影响。双酚A暴露的F2代后代48hpf孵化延迟,畸形率和死亡率增加,而F1代则没有。最重要的是,双酚A暴露的F2亲本对幼虫发育和存活的不利影响是父本特有的,主要是由于双酚A暴露的雄性。随后对F2雄性腺的转录分析显示,线粒体生物发生异常,非规范的Wnt/平面细胞极性和Wnt/钙信号通路显著激活。双酚A暴露的F2亲本幼虫的基因表达分析显示,DNA甲基转移酶如DNMT1、dnmt3和dnmt5的表达显著降低。总之,连续两代低水平的BPA暴露不仅影响F1和F2成虫的性别比例和精子数量/质量,影响F2代后代的生殖成功,而且还扰乱了可能导致这些BPA诱导的男性特异性生殖缺陷的各种分子途径。
Bisphenol A (BPA), a high-volume chemical used to make polycarbonate plastic and epoxy resins, is a ubiquitous contaminant in environment and human body. To investigate the reproductive effects of long-term exposure to low concentrations of BPA, a two-generation study was conducted using the aquatic model species of zebrafish. Our findings revealed that exposure to 1 nM (0.228 μg/L) BPA for continuous two generations resulted in female-biased sex ratio in both F1 and F2 adult population, decreased sperm density, and decreased sperm quality as measured by motility, velocity, ATP content and lipid peroxidation in F1 and F2 males. Females were less sensitive to BPA exposures than males as no adverse effects were found in female gonads or gametes. Delayed hatching at 48 hpf and increased malformation and mortality were found in the offspring from BPA exposed F2, but not F1 parents. Most importantly, the adverse effect on larval development and survival from BPA exposed F2 parents was paternal-specific, resulting mainly from BPA exposed males. Subsequent transcription analysis of F2 male gonads revealed dysregulated mitochondrial biogenesis and significant activation of non-canonical Wnt/planar cell polarity and Wnt/Calcium signaling pathways. Gene expression analysis of larvae from BPA exposed F2 parents showed significant reduced expression of DNA methyltransferases such as dnmt1, dnmt3, and dnmt5. In conclusion, low level BPA exposures for continuous two generations not only affects sex ratio and sperm quantity/quality in F1 and F2 adults, reproductive success in offspring from F2 parents, but also perturbs various molecular pathways potentially contributing to these BPA induced male-specific reproductive defects.
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