Exposure to nucleotides promotes fish larvae development: insights in zebrafish (Danio rerio) and gilthead seabream (Sparus aurata)

Nucleotide (NT) supplementation is an efficient practice for enhancing growth and immune performance in farmed aquatic species. However, the NT mode of use, optimal dosage and metabolic effects in different species remain poorly understood. This study investigated the effects of exposing zebrafish ( Danio rerio ) and gilthead seabream ( Sparus aurata ) embryos and larvae to different concentrations of a blend of NTs directly through the water. Embryos and larvae were exposed for 96 h, starting at 24 h post fertilisation. The developmental and physiological parameters assessed included survival, hatching rate, morphology, swimming behaviour, expression of growth-related genes, and macrophage cell status. In zebrafish, survival and hatching rate were unaffected up to 200 mg L −1 (>90%). Morphological analysis revealed that zebrafish exposed to NT at 20–40 mg L −1 exhibited the most significant enhancements in growth (+5% compared to controls), while behavioural tests and gene expression analysis indicated increased swimming activity and significant modulation of key growth-related genes at 10 mg L −1 . Furthermore, immunological assays demonstrated a significant increase in the prevalence of pro-healing M2 macrophages in the gut of larvae at this NT concentration. In gilthead seabream, NT-treated larvae at 10 mg L −1 exhibited a significant increase in standard body length (+4% compared to controls), with no adverse effects on survival or hatching rate up to this level (>75%). Overall, these findings demonstrate that NT exposure promotes larval growth and modulates immune and metabolic activity in zebrafish and gilthead seabream, supporting the application of NT blends as sustainable bioactive additives in aquaculture. • Waterborne nucleotide enhance zebrafish and gilthead seabream larval growth. • Nucleotide exposure boosts zebrafish swimming activity and expression of growth-related genes. • Nucleotides increase pro-healing M2 macrophages in the gut of transgenic zebrafish. • Zebrafish serves as an efficient model for testing bioactive compounds in aquaculture.