Integrated MultiOmics Reveals Cadmium-Induced Hepatopancreatic Apoptosis and Dysregulated Metabolism in Penaeus vannamei

Cadmium (Cd), a pervasive heavy-metal pollutant, significantly threatens aquatic organisms. However, the molecular mechanisms underlying Cd-induced hepatopancreatic injury in Penaeus vannamei remain ambiguous. This study employed an integrated physiological, transcriptomic, and metabolomic approach to elucidate the hepatopancreatic response of P. vannamei during 48 h of acute exposure to 5.25 mg/L Cd. Cd accumulated prominently within the hepatopancreas, accompanied by elevated levels of reactive oxygen species, malondialdehyde, and caspase-3 activity, with a time-dependent change in total antioxidant capacity. Hepatopancreatic apoptosis was further supported by the Terminal Deoxynucleotidyl Transferase dUTP Nick End Labeling assay. At 48 h, integrated multiomics identified 1425 differentially expressed genes and 41 differentially expressed metabolites between the Cd-exposed and control groups. Regarding sulfur metabolism, sulfate-activation-related genes ( sat, papss ) and the H 2 S-oxidation-associated gene ( sqr ) were upregulated, whereas methylcysteine was markedly reduced. Concerning the annotation of phosphonate and phosphinate metabolism, the phospholipid-biosynthesis-related gene pcyt2 was downregulated, accompanied by increased lysophosphatidylcholine and platelet-activating factor levels. For glutathione (GSH) metabolism, the GSH catabolism-related gene ggt was upregulated, whereas the contents of glycine, ribulose-5-phosphate, and a glutathione-related disulfide metabolite (cysteinyl-glutathione disulfide) declined significantly. Collectively, these findings suggested that acute Cd exposure triggered oxidative stress and disrupted sulfur, phosphonate/phosphinate, and glutathione metabolic pathways, which likely contributed to hepatopancreatic apoptosis in P. vannamei . These results offered molecular insights into the toxicological mechanisms of Cd in crustaceans.