Advanced understanding of the neurotoxicity of brominated flame retardants: Integrating human neural organoids with multi-omics

cells). Moreover, PBDE exposure disrupted cell differentiation and neuronal distribution. PBDEs exerted comparable neurotoxic effects on both cortical and retinal development. Toxic effects of PBDEs depended on the exposure dose and the developmental stage at which exposure occurred. mRNA profiling of hCOs and hROs demonstrated that PBDE-induced common neurotoxicity may be mediated by disrupting anatomical structure morphogenesis, neurogenesis, the generation of neurons, and axon guidance. miRNA profiling of BDE-exposed organoids showed that PBDE exposure was closely associated with the neuron apoptotic process and neuron death. The integration analysis of mRNA-miRNA showed that hsa-let-7a-3p, hsa-let-7a-5p, and hsa-let-7b-5p play vital roles in PBDE-induced neurotoxicity. This study is expected to provide additional evidence to substantiate the neurotoxicity of PBDEs to humans based on neural organoids.