Abstract
Bisphenol A (BPA), an endocrine-disrupting chemical, is present in everyday-used consumables and common household products. Although the side effects of BPA have been sufficiently explored, little is known the effects of environmentally relevant low levels of BPA on chondrogenesis in skeletal development. Here we used a morphological approach to investigate whether exposure to BPA (0, 0.0038, 0.05, 0.1, 1.0 μM) could affect craniofacial cartilage development of zebrafish embryo. Furthermore, we sought to determine receptor-mediated BPA induced chondrogenesis toxicity by co-exposing developing embryos to BPA and various inhibitors. Low-dose BPA affected heart rate and induced body and head elongation of larvae. Quantitative morphometric and histopathological analysis revealed that BPA exposure changed the angle and length of craniofacial cartilage elements and disrupted chondrocytes. BPA induced pharyngeal cartilage defects via multiple cellular pathways, including estrogen receptor, androgen receptor, and estrogen-related receptors. Our findings demonstrate that BPA alters the normal development of cartilage and craniofacial structures in zebrafish embryos. Furthermore, in this study we find multiple cellular pathways mediating the effects of BPA-induced craniofacial chondrogenesis toxicity. Further experiments will allow for establishing a connection between BPA and increased risk of congenital malformation of the facial cranium in BPA-exposed populations.