TDCPP is a flame retardant which has nervous and reproductive toxicity. Although there is a close association between nervous and reproductive system, the exact toxic mechanism of TDCPP in these systems is still seldom, especially in a genome scale. In this study, we explored the transcriptomic landscape of TDCPP in PC12 and GC2 cells using RNAseq method. A total of 465 co-differential expressed genes were found. These genes were mainly enriched in extra-cellular matrix, cell adhesion, cell cycle arrest, oxidoreductase activity GO terms, and PI3K/AKT, focal adhesion, ECM-receptor interaction KEGG pathways. Hub genes (ANXA1, COL27A1, GAS6, GNB4 and THBS1) were extracted using STRING and confirmed by qPCR experiment. Vimentin, HSPA5 and Caspase3 were proved to be responsible to TDCPP in GC2 and PC12 cells. Knockdown assay in PC12 cells showed that these hub genes could also affect the protein expression of vimentin, HSPA5 and Caspase3. In summary, TDCPP might exert its toxic effect through disturbing focal adhesion, ECM-receptor interaction and PI3K/Akt pathways. One of the mechanisms could be influence on the cytoskeleton (vimentin), ER stress (HSPA5) and apoptosis (Caspase3). The sequence data in this study might be a useful resource for future TDCPP related researches.

TDCPP是一种具有神经和生殖毒性的阻燃剂。尽管神经系统和生殖系统之间存在密切关联，但 TDCPP 在这些系统中的确切毒性机制仍然很少，尤其是在基因组规模上。在这项研究中，我们使用 RNAseq 方法探索了 PC12 和 GC2 细胞中 TDCPP 的转录组学景观。共发现465个共差异表达基因。这些基因主要富集在细胞外基质、细胞粘附、细胞周期停滞、氧化还原酶活性GO术语和PI3K/AKT、粘着斑、ECM-受体相互作用KEGG通路中。使用 STRING 提取 Hub 基因（ANXA1、COL27A1、GAS6、GNB4 和 THBS1）并通过 qPCR 实验确认。波形蛋白、HSPA5 和 Caspase3 被证明对 GC2 和 PC12 细胞中的 TDCPP 负责。PC12 细胞中的敲低试验表明，这些中枢基因也可以影响波形蛋白、HSPA5 和 Caspase3 的蛋白质表达。总之，TDCPP 可能通过干扰粘着斑、ECM-受体相互作用和 PI3K/Akt 通路发挥其毒性作用。其中一种机制可能是对细胞骨架（波形蛋白）、ER 应激（HSPA5）和细胞凋亡（Caspase3）的影响。本研究中的序列数据可能是未来 TDCPP 相关研究的有用资源。