Emodin induces embryonic toxicity in mouse blastocysts through apoptosis
Emodin induces embryonic toxicity in mouse blastocysts through apoptosis
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DOI：
10.1016/j.tox.2012.05.006
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发表时间：
2012-09-04
期刊：
影响因子：
4.5
通讯作者：
Chan, Wen-Hsiung
中科院分区：
文献类型：
--
作者：
Chang, Mei-Hui;Huang, Fu-Jen;Chan, Wen-Hsiung
大黄素（1,3,8-三羟基-6-甲基蒽醌）是大黄的主要成分，具有广泛的治疗应用。先前的研究已证实大黄素可抑制细胞增殖并诱导 caspase 3 依赖性细胞凋亡。然而，其副作用，特别是对胚胎发育的副作用，尚未得到很好的表征。在目前的研究中，我们检查了大黄素对囊胚期小鼠胚胎、随后胚胎附着和体外生长以及通过胚胎移植体内植入的细胞毒性作用。用25-75μM大黄素处理的囊胚表现出显着增加的细胞凋亡和相应的总细胞数减少。值得注意的是，用大黄素预处理的囊胚的着床成功率低于对照囊胚。此外，用25-75μM大黄素进行体外处理与植入后胚胎的吸收增加和胎儿体重减轻有关。借助体内小鼠模型，我们发现饮用含有大黄素的饮用水会导致细胞凋亡和细胞增殖减少，并抑制早期胚胎发育至囊胚阶段。我们的研究结果支持用大黄素处理的囊胚中视黄酸受体有一定程度的选择性抑制。此外，大黄素似乎通过内在的细胞凋亡信号传导过程诱导小鼠囊胚损伤，从而损害随后的胚胎发育。这些结果共同表明大黄素具有诱导胚胎细胞毒性的潜力。 (c) 2012 Elsevier Ireland Ltd. 保留所有权利。
Emodin (1,3,8-trihydroxy-6-methylanthraquinone), a major constituent of rhubarb, has a wide range of therapeutic applications. Previous studies have established that emodin inhibits cell proliferation and induces caspase 3-dependent apoptosis. However, its side-effects, particularly those on embryonic development, have not been well characterized as yet. In the current study, we examined the cytotoxic effects of emodin on mouse embryos at the blastocyst stage, subsequent embryonic attachment and outgrowth in vitro, and in vivo implantation by embryo transfer. Blastocysts treated with 25-75 mu M emodin exhibited significantly increased apoptosis and a corresponding decrease in total cell number. Notably, the implantation success rate of blastocysts pretreated with emodin was lower than that of their control counterparts. Moreover, in vitro treatment with 25-75 mu M emodin was associated with increased resorption of post-implantation embryos and decreased fetal weight. With the aid of an in vivo mouse model, we showed that consumption of drinking water containing emodin led to apoptosis and decreased cell proliferation, and inhibited early embryonic development to the blastocyst stage. Our findings support a degree of selective inhibition of retinoic acid receptors in blastocysts treated with emodin. In addition, emodin appears to induce injury in mouse blastocysts through intrinsic apoptotic signaling processes to impair sequent embryonic development. These results collectively indicate that emodin has the potential to induce embryonic cytotoxicity. (c) 2012 Elsevier Ireland Ltd. All rights reserved.