Differential developmental effects and its potential mechanism of long-term exposure to TBBPA in two generations of marine medaka (Oryzias melastigma) during early life stages.

Tetrabromobisphenol A (TBBPA), a most widely used brominated flame retardant, has been detected in worldwide aquatic environments. However, the effects and mechanisms of TBBPA at environmentally realistic levels have not been well characterized in aquatic organisms. This study aims to investigate the impact of TBBPA on developmental toxicity and endocrine system in two generations of marine medaka (Oryzias melastigma) during early life stages. The results revealed that the embryos under exposure to environmentally relevant concentrations of TBBPA (0, 5, 50, and 500 μg/L) resulted in accelerated hatching and growth development in F0 generation. Conversely, delayed hatching, decreased hatch rate, and growth inhibition were observed in the F1 generation. Moreover, TBBPA disrupted the levels of THs (thyroid hormones), GH (growth hormone), and IGF (insulin growth factor). The gene transcriptional profiling implies modified gene expressions in the HPT axis, GH/IGF axis, and endoplasmic reticulum stress. The molecular docking analysis confirmed the binding affinity of TBBPA to key endocrine-related proteins, which partially elucidates the mechanism of endocrine disruption and developmental abnormalities. Endoplasmic reticulum stress may explain the developmental differences between the two generations. This was the first study to explore the multigenerational developmental toxicity of TBBPA to marine fish, which is essential for ecological risk assessment of this emerging pollutant.