Identification of Metabolic Pathways in <i>Daphnia magna</i> Explaining Hormetic Effects of Selective Serotonin Reuptake Inhibitors and 4‑Nonylphenol Using Transcriptomic and Phenotypic Responses

The molecular mechanisms explaining hormetic effects of selective serotonin reuptake inhibitors (SSRIs) and 4-nonylphenol in <i>Daphnia magna</i> reproduction were studied in juveniles and adults. Transcriptome analyses showed changes in mRNA levels for 1796 genes in juveniles and 1214 genes in adults (out of 15 000 total probes) exposed to two SSRIs (fluoxetine and fluvoxamine) or to 4-nonylphenol. Functional annotation of affected genes was improved by assuming the annotations of putatively homologous <i>Drosophila</i> genes. Self-organizing map analysis and partial least-square regression coupled with selectivity ratio procedures analyses allowed to define groups of genes with specific responses to the different treatments. Differentially expressed genes were analyzed for functional enrichment using Gene Ontology and Kyoto Encyclopaedia of Genes and Genomes databases. Serotonin metabolism, neuronal developmental processes, and carbohydrates and lipid metabolism functional categories appeared as selectively affected by SSRI treatment, whereas 4-nonylphenol deregulated genes from the carbohydrate metabolism and the ecdysone regulatory pathway. These changes in functional and metabolic pathways are consistent with previously reported SSRIs and 4-nonylphenol hormetic effects in <i>D. magna</i>, including a decrease in reserve carbohydrates and an increase in respiratory metabolism