Developmental priming increases copper-tolerance in a model fish species via epigenetic-and microbiome-mediated mechanisms

Pollution is a significant threat to aquatic ecosystems globally and, in order to survive, natural populations depend upon their ability to rapidly develop tolerance to chemical stressors. We examined whether early-life priming enhances life-long copper-tolerance in a model fish species via developmental plasticity. Stickleback ( Gasterosteus aculeatus ) embryos were pre-exposed to a low concentration of copper (10 µg/L) during early development, reared in clean water for nine months alongside a control group, and then exposed to copper (0,10 and 20 µg/L) for 96 h as adults. Priming markedly reduced evidence of copper-toxicity in adult gills at the transcriptional level (including reduced cellular stress response (CSR) and disruption of ion-homeostasis) and increased inducibility of the metal-binding protein, metallothionein. In parallel, we identified epigenetic and microbiome-mediated mechanisms likely contributing to this tolerance. Pre-exposure induced persistent DNA methylation changes, consistent with priming of CSR and ion-homeostasis pathways. We identified enhanced copper-tolerance in the gill microbiota of primed fish that likely also contributed to host tolerance. These findings provide critical evidence for developmental plasticity induced by chemical stressors in animals, highlight the importance of integrated microbiome and epigenetic responses, and enhance our understanding of how natural populations cope with pollution in their environment.