Tetrabromobisphenol A acts a neurodevelopmental disruptor in early larval stages of Mytilus galloprovincialis

Highlights: • Tetrabromobisphenol A-TBBPA affects early larval development in Mytilus. • Effects on shell formation, organic matrix and CaCO3 deposition • Altered expression pattern of genes involved in shell biogenesis from 28 hpf • From 24 hpf impairment of serotonin, GABA and dopamine systems • TBBPA acts as a neurodevelopmental disruptor in mussel early larval stages. Tetrabromobisphenol A-TBBPA, a widely used brominated flame retardant detected in aquatic environments, is considered a potential endocrine disruptor-ED for its reproductive/developmental effects in vertebrates. In aquatic invertebrates, the modes of action of most EDs are largely unknown, due to partial knowledge of the mechanisms controlling neuroendocrine functions. In the marine bivalve Mytilus galloprovincialis, TBBPA has been previously shown to affect larval development in the 48 h larval toxicity assay at environmental concentrations. In this work, the effects of TBBPA were further investigated at different times post-fertilization. TBBPA, from 1 μg/L, affected shell biogenesis at 48 hours post fertilization-hpf, as shown by phenotypic and SEM analysis. The mechanisms of action of TBBPA were investigated at concentrations of the same order of magnitude as those found in highly polluted coastal areas (10 μg/L). At 28–32 hpf, TBBPA significantly affected deposition of both the organic matrix and CaCO₃ in the shell. TBBPA also altered expression of shell-related genes from 24 to 48 hpf, in particular of tyrosinase, a key enzyme in shell matrix remodeling. At earlier stages (24 hpf), TBBPA affected the development of dopaminergic, serotoninergic and GABAergic systems, as shown by in situ hybridization-ISH and immunocytochemistry. These data contribute draw adverse outcome pathways-AOPs, where TBBPA affects the synthesis of neutrotransmitters involved in key events (neurodevelopment and shell biogenesis), resulting in phenotypic changes on individuals (delayed or arrested development) that might lead to detrimental consequences on populations.