Center for Excellence in Regional Atmospheric Environment, Institute of Urban Environment, Chinese Academy of Sciences, Xiamen 361021, China; Key Lab of Urban Environment and Health, Institute of Urban Environment, Chinese Academy of Sciences, Xiamen 361021, China; College of Resources and Environment, University of Chinese Academy of Sciences, Beijing 100049, China.
Department of Clinical Laboratory, Tianjin Key Laboratory of Cerebral Vessels and Neurodegenerative Diseases, Tianjin Huanhu Hospital, Tianjin 300350, China.
Reprod Toxicol. 2019 Apr;85:26-33. doi: 10.1016/j.reprotox.2019.01.008. Epub 2019 Jan 16.
Benzo[a]pyrene (B[a]P) is one of the most common polycyclic aromatic hydrocarbons. In utero B[a]P exposure exerts multiple adverse effects on embryo development, although the underlying molecular mechanisms have still not been clearly elucidated. In the present study, we used human embryonic stem cell derived embryoid body (EB) as an in vitro model to investigate the embryotoxicity effects of B[a]P. EBs were exposed to B[a]P for 14 days, and the morphology, viability and differentiation of the cells were analyzed, in addition to the molecular changes. The results showed that B[a]P exposure repressed cell growth, impaired the morphology, and triggered apoptosis in the EBs. In addition, B[a]P reduced the gene expression levels of the ectoderm, mesoderm and endoderm biomarkers. Finally, B[a]P inhibited the epithelial-mesenchymal transition (EMT) process and the Akt/GSK-3β signaling pathway. Taken together, B[a]P-induced aberrant EB development and apoptosis were related to EMT process and the Akt/GSK-3β signaling pathway modulation.
苯并[a]芘（B[a]P）是最常见的多环芳烃之一。母体 B[a]P 暴露对胚胎发育有多种不良影响，但其潜在的分子机制尚未阐明。在本研究中，我们使用人胚胎干细胞衍生的类胚体（EB）作为体外模型来研究 B[a]P 的胚胎毒性作用。将 EBs 暴露于 B[a]P 中 14 天，分析细胞的形态、活力和分化以及分子变化。结果表明，B[a]P 暴露抑制细胞生长、破坏形态，并诱导 EBs 凋亡。此外，B[a]P 降低了外胚层、中胚层和内胚层生物标志物的基因表达水平。最后，B[a]P 抑制了上皮-间充质转化（EMT）过程和 Akt/GSK-3β信号通路。综上所述，B[a]P 诱导的异常 EB 发育和凋亡与 EMT 过程和 Akt/GSK-3β信号通路的调节有关。
