Global gene expression analysis reveals pathway differences between teratogenic and non-teratogenic exposure concentrations of bisphenol A and 17β-estradiol in embryonic zebrafish

Transient developmental exposure to 0.1 mu M bisphenol A (BPA) results in larval zebrafish hyperactivity and learning impairments in the adult, while exposure to 80 mu M BPA results in teratogenic responses, including craniofacial abnormalities and edema. The mode of action underlying these effects is unclear. We used global gene expression analysis to identify candidate genes and signaling pathways that mediate BPA's developmental toxicity in zebrafish. Exposure concentrations were selected and anchored to the positive control, 17 beta-estradiol (E2), based on previously determined behavioral or teratogenic phenotypes. Functional analysis of differentially expressed genes revealed distinct expression profiles at 24 h post fertilization for 0.1 mu M versus 80 mu M BPA and 0.1 mu M versus 15 mu M E2 exposure, identification of prothrombin activation as a top canonical pathway impacted by both 0.1 mu M BPA and 0.1 mu M E2 exposure, and suppressed expression of several genes involved in nervous system development and function following 0.1 mu M BPA exposure. (c) 2013 Elsevier Inc. All rights reserved.