Untargeted Metabolomics Reveals Gonadal Metabolic Disruption in Mytilus Galloprovincialis Exposed to Cadmium and Microplastics

The contamination of marine ecosystems by heavy metals and microplastics poses a significant and escalating threat, carrying potential implications for biodiversity and food safety. Among marine invertebrates, Mytilus galloprovincialis is a widely utilized sentinel organism, owing to its filter-feeding behavior and pronounced capacity for bioaccumulation In this study, we applied an untargeted gas chromatography-mass spectrometry (GC-MS) metabolomics approach to investigate the gonadal metabolic responses of M. galloprovincialis following exposure to cadmium (Cd) alone (1, 10, 100 nM) and the same concentration of Cd conjugate with 1 µg/L microplastics of polystyrene 5µm (PS-MPs). While metabolomic profiling revealed that Cd exposure alone was able to induce dose-dependent alterations in the gonadal metabolomic composition, with major implications for carbohydrates metabolic pathways, the most striking metabolic disruptions were observed in the co-exposure groups (Cd+MPs). PLS-DA models revealed a sharply increased class separation across ascending Cd concentrations in the presence of MPs, indicating a synergistic interaction. VIP analysis identified key metabolites associated with altered ascorbate and aldarate metabolism, butanoate metabolism, the TCA cycle, inositol phosphate metabolism, and unsaturated fatty acid biosynthesis—suggesting enhanced oxidative stress, mitochondrial dysfunction, impaired phosphoinositide signaling, and altered membrane homeostasis specifically under co-exposure conditions. These findings highlight the amplified ecotoxicological burden of cadmium when combined with microplastics and call for future studies aimed at elucidating the molecular mechanisms underlying such synergistic interactions and their long-term impact on reproductive health in marine invertebrates.