Tris(1,3-dichloro-2-propyl) Phosphate Exposure During the Early-Blastula Stage Alters the Normal Trajectory of Zebrafish Embryogenesis.
Tris(1,3-dichloro-2-propyl) Phosphate Exposure During the Early-Blastula Stage Alters the Normal Trajectory of Zebrafish Embryogenesis.
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DOI：
10.1021/acs.est.8b03730
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发表时间：
2018-09-18
影响因子：
11.4
通讯作者：
Volz DC
中科院分区：
文献类型：
--
作者：
Dasgupta S;Cheng V;Vliet SMF;Mitchell CA;Volz DC
三（1,3-二氯-2-丙基）磷酸盐（TDCIPP）是一种世界范围内使用的有机磷酸盐阻燃剂。在斑马鱼中，我们之前的研究表明，在卵裂期间（受精后0.75 h, hpf）开始暴露TDCIPP会导致6 hpf的表观代谢中断，导致24 hpf的胚胎dorsorphin （DMP）的作用-这种表型模仿dorsomorphin （DMP）的作用，DMP是一种骨形态发生蛋白（BMP）拮抗剂，在没有表观代谢缺陷的情况下使胚胎dorsorphin。本研究的目的是：1)研究BMP信号在tdcipp诱导的早期胚胎发生毒性中的作用；2)确定TDCIPP靶向的其他途径和过程；3)描述早期发育缺陷的下游影响。以斑马鱼为模型，我们首先确定了在0.75 hpf暴露后TDCIPP诱导效应的敏感窗口。然后，我们利用mRNA和扩增子测序研究了TDCIPP在发育的前24小时对转录组的影响。最后，我们依靠全坐骑免疫组织化学、染料标记和形态学评估来研究胚胎发育后期的异常。总的来说，我们的数据表明，在囊胚早期暴露于TDCIPP，通过诱导原肠胚发育缺陷和异常胚层形成，改变了早期胚胎发生的正常轨迹，导致胚胎内组织和器官发育异常。
Tris(1,3-dichloro-2-propyl) phosphate (TDCIPP) is an organophosphate flame retardant used around the world. Within zebrafish, we previously showed that initiation of TDCIPP exposure during cleavage (0.75 h post-fertilization, hpf) results in epiboly disruption at 6 hpf, leading to dorsalized embryos by 24 hpf – a phenotype that mimics the effects of dorsomorphin (DMP), a bone morphogenetic protein (BMP) antagonist that dorsalizes embryos in the absence of epiboly defects. The objective of this study was to 1) investigate the role of BMP signaling in TDCIPP-induced toxicity during early embryogenesis; 2) identify other pathways and processes targeted by TDCIPP; and 3) characterize downstream impacts of early developmental defects. Using zebrafish as a model, we first identified a sensitive window for TDCIPP induced effects following exposure initiation at 0.75 hpf. We then investigated the effects of TDCIPP on the transcriptome during the first 24 h of development using mRNA and amplicon sequencing. Finally, we relied on whole mount immunohistochemistry, dye based labeling, and morphological assessments to study abnormalities later in embryonic development. Overall, our data suggest that initiation of TDCIPP exposure during early blastula alters the normal trajectory of early embryogenesis by inducing gastrulation defects and aberrant germ layer formation, leading to abnormal tissue and organ development within the embryo.
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影响因子：
10.9
作者：
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