Global Gene Expression Analysis Reveals Pathway Differences Between Teratogenic and Non-Teratogenic Exposure Concentrations of Bisphenol A and 17ß-Estradiol in Embryonic Zebrafish
Saili KS, SC Tilton, KM Waters, and R Tanguay. 2013. "Global Gene Expression Analysis Reveals Pathway Differences Between Teratogenic and Non-Teratogenic Exposure Concentrations of Bisphenol A and 17ß-Estradiol in Embryonic Zebrafish." Reproductive Toxicology 38:89-101. doi:10.1016/j.reprotox.2013.03.009
Transient developmental exposure to 0.1μM bisphenol A (BPA) results in larval zebrafish hyperactivity and learning impairments in the adult, while exposure to 80μM 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, 17β-estradiol (E2), based on previously determined behavioral or teratogenic phenotypes. Functional analysis of differentially expressed genes revealed distinct expression profiles at 24h post fertilization for 0.1μM versus 80μM BPA and 0.1μM versus 15μM E2 exposure, identification of prothrombin activation as a top canonical pathway impacted by both 0.1μM BPA and 0.1μM E2 exposure, and suppressed expression of several genes involved in nervous system development and function following 0.1μM BPA exposure.