State Key Laboratory of Environmental Chemistry and Ecotoxicology, Research Center for Eco-Environmental Sciences, Chinese Academy of Sciences, Beijing, 100085, China; College of Resources and Environment, University of Chinese Academy of Sciences, Beijing, 100049, China.
State Key Laboratory of Environmental Chemistry and Ecotoxicology, Research Center for Eco-Environmental Sciences, Chinese Academy of Sciences, Beijing, 100085, China; College of Resources and Environment, University of Chinese Academy of Sciences, Beijing, 100049, China; Wellcome Trust/CRUK Gurdon Institute, Department of Pathology, University of Cambridge, Cambridge CB2 1QN, UK.
Ecotoxicol Environ Saf. 2019 Jul 30;176:330-338. doi: 10.1016/j.ecoenv.2019.03.115. Epub 2019 Apr 2.
Bisphenol A (BPA) is a very versatile industrial chemical. Many reports have associated BPA with several health effects. Some bisphenol alternatives have been introduced to replace BPA in its many applications. However, comprehensive toxicological evaluations for these replacements are still lacking. In this study, we examined the potential effects of BPA, bisphenol F (BPF) and bisphenol S (BPS), on embryonic development with an in vitro stem cell toxicology system and transcriptomics analyses. Mouse embryonic stem cells (mESCs) were differentiated via embryoid body formation, either globally towards the three primary germ layers and their lineages, or specifically into neuroectoderm/neural progenitor cells. During the differentiation, cells were treated with BPA, BPF, BPS, or DMSO control. Samples were collected at different time points, for qRT-PCR and RNA-seq analyses. BPA, BPF and BPS disrupted many processes, during mESC global and neural differentiations, in very similar manners. In fact, at each time point the three chemicals differentially regulated analogous gene categories, particularly the ones involved in cell-matrix and cell-cell adhesion, signal transduction pathways, and medical conditions such as cardiovascular diseases and cancer. Our findings demonstrate once more then BPA substitutes may not be very safe. They potentially have a very complex developmental toxicity, similarly to BPA, and seem more toxic than BPA itself. In addition, our results reveal that stem cell-based developmental toxicity assays can be very comprehensive.
双酚 A（BPA）是一种用途广泛的工业化学品。许多报告将 BPA 与多种健康影响联系起来。已经引入了一些双酚替代品来替代其许多应用中的 BPA。然而，这些替代品的全面毒理学评价仍然缺乏。在这项研究中，我们使用体外干细胞毒理学系统和转录组学分析，研究了 BPA、双酚 F（BPF）和双酚 S（BPS）对胚胎发育的潜在影响。通过胚状体形成将小鼠胚胎干细胞（mESCs）分化为三个原始胚层及其谱系的整体，或专门分化为神经外胚层/神经祖细胞。在分化过程中，用 BPA、BPF、BPS 或 DMSO 对照处理细胞。在不同时间点收集样品，进行 qRT-PCR 和 RNA-seq 分析。BPA、BPF 和 BPS 以非常相似的方式干扰 mESC 整体和神经分化过程中的许多过程。事实上，在每个时间点，这三种化学物质都以不同的方式调节类似的基因类别，特别是那些涉及细胞-基质和细胞-细胞黏附、信号转导途径以及心血管疾病和癌症等医学状况的基因类别。我们的研究结果再次表明，BPA 替代品可能并不安全。它们可能具有与 BPA 非常相似的复杂发育毒性，并且似乎比 BPA 本身更具毒性。此外，我们的结果表明，基于干细胞的发育毒性测定可以非常全面。
