Wang Z et al. (2024), Exposure to High Concentrations of Tetrabromobi...

ECB-ART-53421

Genes (Basel) 2024 Nov 09;1511:. doi: 10.3390/genes15111448.

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Exposure to High Concentrations of Tetrabromobisphenol A Slows the Process of Tissue Regeneration and Induces an Imbalance of Metabolic Homeostasis in the Regenerated Intestines of Apostichopus japonicus.

Wang Z , Song X , Yin W , Shi K , Lin Y , Liu J , Li X , Tan J , Rong J , Xu K , Wang G .

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BACKGROUND: Tissue regenerative capacity following evisceration, potentially influenced by environmental contaminants and intestinal microflora, is essential for the financial success of Apostichopus japonicus farming. However, the morphological structure, gut microbiome composition, and genes expression pattern of the regenerated gut after exposure to high levels of TBBPA remain poorly unclear. METHODS: In this research, the effect of TBBPA exposure on tissue regeneration in A. japonicus was investigated through a comprehensive multi-omics approach. RESULTS: Our results showed that the integrity, the intestinal wall thickness, and the villi length of the regenerated intestines in A. japonicus decreased after treatment with high levels of TBBPA. The findings from PCoA and NMDS analyses revealed that the microbial community composition was significantly altered following exposure to high concentrations of TBBPA in the regenerated intestines of A. japonicus. The KEGG pathway enrichment analysis indicated that the DEGs (differentially expressed genes) were predominantly enriched on metabolism and immunity-related signaling pathways after exposure to high levels of TBBPA. These included pathways involved in the PPAR signaling pathway, ECM receptor interaction, glycerolipid metabolism, and fatty acid degradation. Interestingly, the results have demonstrated that there are 77 transcript factors that were significantly different after exposure to TBBPA. CONCLUSIONS: These results suggested that high levels of exposure to TBBPA induces an imbalance of the metabolic homeostasis by regulating the expression levels of transcription factors in the regenerated intestines of A. japonicus.

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	Figure 1. Morphological structure of the regenerated intestines in A. japonicus after exposure to different levels of TBBPA. There are three replications for each level. Red arrows indicate the regenerated intestines, gray arrows indicate the wound for evisceration.
	Figure 2. The intestinal wall thickness and the villi length of the regenerated intestine decreased after 11 days of exposure to different levels of TBBPA. (A–C) The effects of TBBPA exposure on the regenerated intestine were examined at concentrations of 0 nmol/L (A), 3 nmol/L (B), and 5 nmol/L (C) using hematoxylin-eosin (HE) staining. (D) The intestinal wall thickness of the regenerated intestines was measured following exposure to TBBPA at concentrations of 0 nmol/L, 3 nmol/L, and 5 nmol/L. (E) The villi length of the regenerated intestines was measured following exposure to TBBPA at concentrations of 0 nmol/L, 3 nmol/L, and 5 nmol/L.
	Figure 3. The coelomic fluid enzymatic activity of SOD (A), LZM (B), and AKP (C) in A. japonicus after exposure to TBBPA. * Presents p < 0.05.
	Figure 4. The alpha diversity indexes of gut microbiome in the regenerated intestines of A. japonicus after exposure to different levels of TBBPA. (A) ACE index, (B) Chao1 index, (C) Shannon index, and (D) Simpson index of gut microbiome in the regenerated intestines of A. japonicus after exposure to different levels of TBBPA.
	Figure 5. The gut microbiome composition at the phylum level in the regenerated intestines of A. japonicus was evaluated after exposure to TBBPA. (A) The microbial community composition at the phylum level in the regenerated intestines of A. japonicus after exposure to TBBPA. (B–F) The relative abundance of Bacteroidota (B), Firmicutes (C), Myxococcota (D), Bdellovibrionota (E), and Dadabacteria (F) after exposure to TBBPA. * Means p < 0.05; means p < 0.01; * means p < 0.001.
	Figure 6. The diversity of the microbial community in the regenerated intestines of A. japonicus was analyzed following exposure to TBBPA. (A) The sample clustering heatmap analysis between the TBBPA exposure groups and the control. (B–D) The analysis of PCoA (B), NMDS (C), and taxonomic composition (D) demonstrated the diversity of gut microbiome in the regenerated intestines of A. japonicus after exposure to TBBPA. TBBPA-0, TBBPA-3, and TBBPA-5 means the 0 nmol/L TBBPA exposure group, the 3 nmol/L TBBPA exposure group, and the 5 nmol/L TBBPA exposure group, respectively.
	Figure 7. The DEGs analysis of the regenerated intestines following exposure to TBBPA. (A) PCA analysis revealed differences of gene expression in the regenerated intestines of A. japonicus between the TBBPA exposure groups and the control group. (B–D) Volcanic plots illustrate the distribution of DEGs in the regenerated gut between control and TBBPA-3 (B), control and TBBPA-5 (C), and TBBPA-3 and TBBPA-5 (D). TBBPA-0, TBBPA-3 and TBBPA-5 means the 0 nmol/L TBBPA exposure group, the 3 nmol/L TBBPA exposure group, and the 5 nmol/L TBBPA exposure group, respectively. (E,F) The qRT-PCR was employed to assess the expression levels of randomly selected genes.
	Figure 8. KEGG pathway enrichment analysis of DEGs in the regenerated intestines between the control (TBBPA-0) group and the TBBPA-3 group. (A) The top 20 pathways of KEGG pathways were revealed. (B) The KEGG classification and proportion of pathways. (C) The heatmap of DEGs in the regenerated intestines between the control and the TBBPA-3 groups. (D) The number of KEGG pathways in the first category in the regenerated intestines of A. japonicus between the control and TBBPA-3 groups. (E) The number of KEGG pathways for metabolism in the second category in the regenerated intestine of A. japonicus between the control and TBBPA-3 groups. TBBPA-0 and TBBPA-3 means the 0 nmol/L TBBPA exposure group and the 3 nmol/L TBBPA exposure group, respectively.
	Figure 9. KEGG pathway enrichment analysis of DEGs in the regenerated intestines between the control (TBBPA-0) group and the TBBPA-5 group. (A) The top 20 pathways of KEGG pathways were revealed. (B) The KEGG classification and proportion of KEGG pathways. (C) The heatmap of DEGs in the regenerated intestines between the control group and the TBBPA-5 group. (D) The number of KEGG pathways in the first category in the regenerated intestine of A. japonicus between the control and the TBBPA-5 groups. (E) The number of KEGG pathways for metabolism in the second category in the regenerated intestine of A. japonicus between the control and the TBBPA-5 groups. TBBPA-0 and TBBPA-5 means the 0 nmol/L TBBPA exposure group and the 5 nmol/L TBBPA exposure group, respectively.
	Figure 10. The composition and expression levels of transcription factors in the regeneration of A. japonicus after exposure to TBBPA. (A) The transcription factors found in the transcriptome of the regenerated intestines. (B) The DEGs of transcript factors in the regenerated intestines after exposure to TBBPA. (C) The expression levels of gene-BSL78_08697 (C2H2 family), gene-BSL78_00076 (HMG family), gene-BSL78_28882 (STE_STE20-Fray family), gene-BSL78_27935 (C2H2 family), and gene-BSL78_29739 (TKL-Pl-4 family) in the regeneration after exposure to TBBPA. TBBPA-0, TBBPA-3, and TBBPA-5 means the 0 nmol/L TBBPA exposure group, the 3 nmol/L TBBPA exposure group, and the 5 nmol/L TBBPA exposure group, respectively. * Means p < 0.05.