Embryonic exposure to prednisone induces bone developmental toxicity in zebrafish: Characteristics and molecular...

As a synthetic glucocorticoid, prednisone has been widely used in autoimmune diseases, recurrent abortion and asthma during pregnancy. Although studies suggested that glucocorticoid exposure during pregnancy have developmental toxicity, systematic research on the characteristics of the developmental toxicity of prednisone is lacking. This study intends to construct embryonic prednisone exposure (EPE) model to observe its bone developmental toxicity characteristics of prednisone and explore the mechanism. The results showed that EPE can shortened body and head length, reduced eye and head area, decreased operculum mineralization area, reduced mineralized vertebrae number, shortened ceratohyal and palatoquadrate cartilage length, and decreased expression of key osteogenic differentiation and cartilage development genes. The toxicity to osteogenesis is more severe than chondrogenesis. The toxicity caused by exposure in the middle and terminal stages of embryogenesis is more serious and shows a concentration-effect relationship. We confirmed that Gr/Hdac6 signaling activation mediates prednisone-induced inhibition of osteoblast differentiation by epigenetically regulating the Postnb/Wnt/β-catenin signaling pathway. The results of this study systematically demonstrate the characteristics of prednisone-induced systemic, bone, and cartilage developmental toxicity, and clarify the epigenetic mechanism of its osteogenic developmental toxicity. This provides theoretical and experimental evidence for the safe use of prednisone during pregnancy and the determination of early monitoring targets for bone developmental toxicity.