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Embryonic stem cell- and transcriptomics-based in vitro analyses reveal that bisphenols A, F and S have similar and very complex potential developmental toxicities

胚胎干细胞 生物 干细胞 转录组 祖细胞 胚状体 细胞生物学 发育毒性 神经干细胞 细胞分化 诱导多能干细胞 遗传学 基因 基因表达 妊娠期 怀孕
作者
Nuoya Yin,Xiaoxing Liang,Shengxian Liang,Siwei Liang,Renjun Yang,Bowen Hu,Zhanwen Cheng,Shuyu Liu,Hengzhi Dong,Sijin Liu,Francesco Faiola
出处
期刊:Ecotoxicology and Environmental Safety [Elsevier]
卷期号:176: 330-338 被引量:46
标识
DOI:10.1016/j.ecoenv.2019.03.115
摘要

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.
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