Transcriptional Changes in African Clawed Frogs (Xenopus laevis) Exposed to 17α-ethinylestradiol During Development. Ecotoxicol

Abstract Although the past two decades have witnessed a significant increase in the number of studies investigating effects of estrogenic chemicals on amphibians, to date little is known about specific molecular interactions of estrogens with the hypothalamus-pituitary-gonadal-hepatic axis in developing amphibians. Here, tissue-specific functional sets of genes, derived previously from studies of fishes exposed to endocrine active chemicals, were evaluated in Xenopus laevis exposed to 17a-ethynylestradiol (EE2) throughout their early development. Specifically, transcriptional responses of X. laevis exposed to 0.09, 0.84, or 8.81 lg EE2/L were characterized during sexual differentiation [31 day post hatch (dph)] and after completion of metamorphosis during the juvenile stage (89 dph). While at 31 dph there were no consistent effects of EE2 on abundances of transcripts,at 89 dph X. laevis exhibited significant alterations in expression of genes involved in steroid signaling and metabolism, synthesis of cholesterol, and vitellogenesis. Specifically, expression of androgen receptor, farnesyl diphosphate synthase, estrogen receptor a, and vitellogenin A2 was significantly greater ([2-fold) than in controls while expression of farnesoid x-activated receptors a and b was significantly less ([2-fold reduction) than in controls. These results support the hypothesis that sets of genes derived from studies in teleost fish can be extrapolated for use in amphibians during the juvenile stage but not in sexually undifferentiated individuals. Furthermore, changes in abundances of transcripts of the here utilized sets of genes in animals sampled post sexual differentiation were in accordance with developmental effects and alterations of gonadal histology reported in a parallel study. This set of genes might be useful for predicting potential adverse outcomes at later life-stages