The environmental toxicant 2,3,7,8-tetrachlorodibenzo-p-dioxin disrupts morphogenesis of the rat pre-implantation embryo.
The environmental toxicant 2,3,7,8-tetrachlorodibenzo-p-dioxin disrupts morphogenesis of the rat pre-implantation embryo.
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DOI：
10.1186/1471-213x-8-1
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发表时间：
2008-01-02
影响因子：
--
通讯作者：
Petroff BK
中科院分区：
文献类型：
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作者：
Hutt KJ;Shi Z;Albertini DF;Petroff BK
环境毒物的作用通常通过芳烃受体途径介导，对包括人类在内的接触物种的健康和福祉构成风险。特别令人关切的是，在发育的最早阶段受到的辐射虽然不能消除胚胎发生，但可能对新生儿或成年人产生长期影响。本研究的目的是评估母体暴露于AhR特异性配体2，3，7，8-四氯二苯并-p-二恶英（TCDD）对大鼠植入前胚胎发育的影响，包括核和细胞骨架结构以及细胞谱系分配。我们进行了系统的三维（3D）共聚焦显微镜分析大鼠植入前胚胎后，母体暴露于环境相关剂量的TCDD。慢性（50 ng/kg/wk，持续3个月）和急性（50 ng/kg和1 μg/kg，在发情前期）母体TCDD暴露破坏了致密阶段（8-16细胞）的形态发生，缺陷包括单极纺锤体形成、f-肌动蛋白帽化和由于异常胞质分裂而导致的片段化。此外，在从处理的动物收集的致密化阶段植入前胚胎中，细胞核的大小、形状和位置被改变。值得注意的是，母体TCDD暴露并不影响囊胚的存活率，除了核的形状，在形态上与对照囊胚相似。我们已经确定植入前胚胎发生的致密化阶段对TCDD的影响非常敏感，而胚泡阶段的存活率不受影响。据我们所知，这是第一个体内研究，以证明一个关键的窗口植入前哺乳动物的发展是脆弱的破坏AhR配体在环境相关剂量。
Environmental toxicants, whose actions are often mediated through the aryl hydrocarbon receptor (AhR) pathway, pose risks to the health and well-being of exposed species, including humans. Of particular concern are exposures during the earliest stages of development that while failing to abrogate embryogenesis, may have long term effects on newborns or adults. The purpose of this study was to evaluate the effect of maternal exposure to the AhR-specific ligand 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) on the development of rat pre-implantation embryos with respect to nuclear and cytoskeletal architecture and cell lineage allocation. We performed a systematic 3 dimensional (3D) confocal microscopy analysis of rat pre-implantation embryos following maternal exposure to environmentally relevant doses of TCDD. Both chronic (50 ng/kg/wk for 3 months) and acute (50 ng/kg and 1 μg/kg at proestrus) maternal TCDD exposure disrupted morphogenesis at the compaction stage (8–16 cell), with defects including monopolar spindle formation, f-actin capping and fragmentation due to aberrant cytokinesis. Additionally, the size, shape and position of nuclei were modified in compaction stage pre-implantation embryos collected from treated animals. Notably, maternal TCDD exposure did not compromise survival to blastocyst, which with the exception of nuclear shape, were morphologically similar to control blastocysts. We have identified the compaction stage of pre-implantation embryogenesis as critically sensitive to the effects of TCDD, while survival to the blastocyst stage is not compromised. To the best of our knowledge this is the first in vivo study to demonstrate a critical window of pre-implantation mammalian development that is vulnerable to disruption by an AhR ligand at environmentally relevant doses.