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双酚 A 对小鼠胚胎干细胞多能性和小鼠胚体分化能力的影响。

Effect of bisphenol A on pluripotency of mouse embryonic stem cells and differentiation capacity in mouse embryoid bodies.

机构信息

State Key Laboratory of Reproductive Medicine, Nanjing Maternity and Child Health Hospital, Nanjing Medical University, Nanjing 210029, China; Key Laboratory of Modern Toxicology of Ministry of Education, School of Public Health, Nanjing Medical University, Nanjing 211166, China.

出版信息

Toxicol In Vitro. 2013 Dec;27(8):2249-55. doi: 10.1016/j.tiv.2013.09.018. Epub 2013 Sep 30.

Abstract

Bisphenol A (BPA) poses potential risks to reproduction and development. However, the mechanism of BPA's effects on early embryonic development is still unknown. Embryonic stem cells (ESC) and embryoid bodies (EB) provide valuable in vitro models for testing the toxic effects of environmental chemicals in early embryogenesis. In this study, mouse embryonic stem cells (mESC) were acutely exposed to BPA for 24h, and general cytotoxicity and the effect of BPA on pluripotency were then evaluated. Meanwhile, mouse embryoid bodies (mEB) were exposed to BPA up to 6 days and their differentiation capacity was evaluated. In mESC and mEB, we found that BPA up-regulated pluripotency markers (Oct4, Sox2 and Nanog) at mRNA and/or protein levels. Moreover, BPA increased the mRNA levels of endodermal markers (Gata4,Sox17) and mesodermal markers (Sma,Desmin), and reduced the mRNA levels of ectodermal markers (Nestin,Fgf5) in mEB. Furthermore, microRNA(miR)-134, an expression inhibitor of pluripotency markers including Oct4, Sox2 and Nanog, was decreased both in BPA-treated mESC and mEB. These results firstly indicate that BPA may disturb pluripotency in mESC and differentiation of mEB, and may inhibit ectodermal lineage differentiation of mEB while miR-134 may play a key role underlying this effect.

摘要

双酚 A (BPA) 对生殖和发育有潜在风险。然而,BPA 对早期胚胎发育影响的机制尚不清楚。胚胎干细胞 (ESC) 和类胚体 (EB) 为测试环境化学物质在早期胚胎发生中的毒性作用提供了有价值的体外模型。在这项研究中,将小鼠胚胎干细胞 (mESC) 急性暴露于 BPA 中 24 小时,然后评估其一般细胞毒性和对多能性的影响。同时,将小鼠类胚体 (mEB) 暴露于 BPA 中长达 6 天,并评估其分化能力。在 mESC 和 mEB 中,我们发现 BPA 在 mRNA 和/或蛋白水平上上调多能性标志物 (Oct4、Sox2 和 Nanog)。此外,BPA 增加了内胚层标志物 (Gata4、Sox17) 和中胚层标志物 (Sma、Desmin) 的 mRNA 水平,同时降低了 mEB 中外胚层标志物 (Nestin、Fgf5) 的 mRNA 水平。此外,miR-134,一种包括 Oct4、Sox2 和 Nanog 等多能性标志物的表达抑制剂,在 BPA 处理的 mESC 和 mEB 中均减少。这些结果首次表明,BPA 可能干扰 mESC 的多能性和 mEB 的分化,并且可能抑制 mEB 的外胚层谱系分化,而 miR-134 可能在这种作用中起关键作用。

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