Chen Xiaojiao, Xu Bo, Han Xiumei, Mao Zhilei, Chen Minjian, Du Guizhen, Talbot Prue, Wang Xinru, Xia Yankai
State Key Laboratory of Reproductive Medicine, Nanjing Maternity and Child Health Hospital, Nanjing Medical University, Nanjing, 210029, China.
Arch Toxicol. 2015 Apr;89(4):635-46. doi: 10.1007/s00204-014-1270-2. Epub 2014 May 31.
Triclosan (TCS) poses potential risks to reproduction and development due to its endocrine-disrupting properties. However, the mechanism of TCS's effects on early embryonic development is little known. Embryonic stem cells (ESC) and zebrafish embryos provide valuable models for testing the toxic effects of environmental chemicals on early embryogenesis. In this study, mouse embryonic stem cells (mESC) were acutely exposed to TCS for 24 h, and general cytotoxicity and the effect of TCS on pluripotency were then evaluated. In addition, zebrafish embryos were exposed to TCS from 2- to 24-h post-fertilization (hpf), and their morphology was evaluated. In mESC, alkaline phosphatase staining was significantly decreased after treatment with the highest concentration of TCS (50 μM). Although the expression levels of Sox2 mRNA were not changed, the mRNA levels of Oct4 and Nanog in TCS-treated groups were significantly decreased compared to controls. In addition, the protein levels of Oct4, Sox2 and Nanog were significantly reduced in response to TCS treatment. MicroRNA (miR)-134, an expression inhibitor of pluripotency markers, was significantly increased in TCS-treated mESC. In zebrafish experiments, after 24 hpf of treatment, the controls had developed to the late stage of somitogenesis, while embryos exposed to 300 μg/L of TCS were still at the early stage of somitogenesis, and three genes (Oct4, Sox2 and Nanog) were upregulated in treated groups when compared with the controls. The two models demonstrated that TCS may affect early embryonic development by disturbing the expression of the pluripotency markers (Oct4, Sox2 and Nanog).
三氯生(TCS)因其内分泌干扰特性对生殖和发育构成潜在风险。然而,TCS对早期胚胎发育的影响机制尚不清楚。胚胎干细胞(ESC)和斑马鱼胚胎为测试环境化学物质对早期胚胎发生的毒性作用提供了有价值的模型。在本研究中,将小鼠胚胎干细胞(mESC)急性暴露于TCS 24小时,然后评估一般细胞毒性以及TCS对多能性的影响。此外,将斑马鱼胚胎在受精后2至24小时(hpf)暴露于TCS,并评估其形态。在mESC中,用最高浓度的TCS(50μM)处理后,碱性磷酸酶染色显著降低。虽然Sox2 mRNA的表达水平没有变化,但与对照组相比,TCS处理组中Oct4和Nanog的mRNA水平显著降低。此外,响应TCS处理,Oct4、Sox2和Nanog的蛋白质水平显著降低。多能性标志物的表达抑制剂微小RNA(miR)-134在TCS处理的mESC中显著增加。在斑马鱼实验中,处理24 hpf后,对照组已发育到体节发生后期,而暴露于300μg/L TCS的胚胎仍处于体节发生早期,与对照组相比,处理组中有三个基因(Oct4、Sox2和Nanog)上调。这两种模型表明,TCS可能通过干扰多能性标志物(Oct4、Sox2和Nanog)的表达来影响早期胚胎发育。