Combined effects of an antidepressant (fluoxetine) and hypoxia on Mytilus edulis reproduction and metabolism

Eutrophication and chemical pollution often co-occur in coastal ecosystems, where their combined effects impact model sentinel sessile organisms like bivalves. We investigated the interactive effects of the serotonin re-uptake inhibitor fluoxetine (FLX) and hypoxia on metabolic and reproductive processes in the blue mussel Mytilus edulis . Given the central role of serotonin in regulating bivalve metabolism and reproduction, we hypothesized that FLX, alone and combined with hypoxia, will disrupt these functions. Mussels were exposed for three weeks to environmentally relevant FLX concentrations (targets 20 and 200 ng/L, “low” and “high”) under normoxia (8.8 mg O 2 /L) or hypoxia (0.9 mg O 2 /L). Metabolic and reproductive status were evaluated using histological indicators of tissue condition and gonadal development, supported by biochemical and molecular markers. FLX exposure reduced egg density and promoted digestive gland atrophy. Hypoxia accelerated gonadal development, reduced sperm density and stimulated the electron transport system activity, indicating metabolic compensation for reduced oxygen availability, while energy reserves remained stable. Molecular and metabolite responses to FLX were dependent on concentration and oxygen regime: FLX-induced changes in catecholamine (low FLX) and nucleotide metabolism (high FLX) in normoxia were absent under hypoxia condition. Hypoxia also impacted catecholamine and tricarboxylic acid cycle metabolism, but only at the low FLX concentration. Low FLX reduced mussel β-catenin expression in the gonad, but expression patterns of genes related to gonad development or apoptosis did not consistently align with histological changes, reflecting complex interactions between FLX, oxygen regime, and sex. These findings show that pharmaceutical pollution exerts context-dependent effects through interactions with hypoxia in a habitat-forming marine species. • Fluoxetine and hypoxia impaired sex-specific reproductive traits in mussels • Fluoxetine showed linear and non-monotonic concentration-dependent effects • Reproduction was more affected than metabolism and digestive health • Hypoxia has antagonistic effects on the FLX-induced metabolic changes • Further studies are needed to clarify mechanisms of interactions