Combining Transcriptomic and Metabolomic Analyses to Investigate the Acute Effects of Microcystin-LR and Nanoplastics of Asian Clams

In agricultural and fishery production, the occurrence of cyanobacterial blooms and the contamination of freshwater systems with microplastics have become increasingly important research focuses. However, the individual and combined toxic mechanisms of these two pollutants are not yet fully understood. Therefore, in this study, we analyzed the effects of these two stressors, microcystins (MC) and nanoplastics (NP), on the transcriptome and metabolome of the hepatopancreas of river clams. RNA and metabolites extracted from river clams treated with MC, NP, and a combination of MC and NP were used to construct standardized cDNA libraries, which were then subjected to integrated analysis. Significant enrichment of 49 pathways, 34 pathways, and 44 pathways was observed in the MC group compared to the control group, NP group compared to the control group, and NP-MC group compared to the control group, respectively. In these three experimental groups, we found that the lysosome pathway, which affects immune function and cell apoptosis, was enriched with numerous differentially expressed genes and metabolites. Changes in ATP6N and ADP may impair lysosomal acidification and disrupt normal lysosomal degradation processes, indicating interference with the hepatopancreatic metabolism of pollutants. Interestingly, we observed significant alterations in the cathepsin family, and the downregulation of cathepsin genes, along with the downregulation of ATP6N, implies a potential disruption in lysosomal proteolysis. In the NP-MC group, the downregulation of purine expression levels suggests an impact on the immune system of river clams by NP-MC. In conclusion, while there is some overlap in the damage caused to the hepatopancreas of river clams by MCs, MPs, and the combination of NP-MC, further research is necessary to fully understand their effects.