Development of human retinal organoid models for bisphenol toxicity assessment

作者：Minghui Li, Jing Gong, Lingling Ge, Hui Gao, Junling Yang, Yang Cao, Jiahui Kang, Yajie Fang, Haiwei Xu · 发表于：Ecotoxicology and Environmental Safety · 年份：2022 · DOI：10.1016/j.ecoenv.2022.114094 · 被引用次数：43 · 研究领域：Effects and risks of endocrine disrupting chemicals、Animal testing and alternatives、Pluripotent Stem Cells Research

Bisphenols, including Bisphenol A (BPA), Tetrabromobisphenol A (TBBPA), and Tetrabromobisphenol S (TBBPS), have been widely applied in the production of polycarbonate plastics and epoxy resins and have been detected in the environment worldwide. The frequent detection of bisphenols in maternal and fetal samples has raised concerns about their toxic effects on human embryonic development, especially on the development of the central nervous system. However, the effect of bisphenols on human retinal development is still unknown. In this study, to evaluate the toxicity of bisphenols on early retinal development, human embryonic stem cells were induced to differentiate into retinal organoids that responded to BPA, TBBPA, and TBBPS, at human exposure relevant concentrations. The global gene expression of retinal organoids was analyzed by RNA sequencing (RNA-seq). A set of retinal development-related biological processes, including neuron differentiation, phototransduction, axon guidance, and retina layer formation, were identified in retinal organoids corresponding to different developmental stages. The RNA-seq data also showed that BPA, TBBPA, and TBBPS influenced retinal development by interfering with the Cytokine-cytokine receptor interaction pathway. HSPA6, HIF1A-AS3, CDC20B, IL19, OAS1, HSPA7, and RN7SK were dysregulated by these chemicals. Additionally, BPA, TBBPA, and TBBPS exhibited different toxic effects on neural retina development, with TBBPA appearing to exert more t...