Tompsett Amber R, Higley Eric, Pryce Sara, Giesy John P, Hecker Markus, Wiseman Steve
Toxicology Centre, University of Saskatchewan, 44 Campus Drive, Saskatoon, SK, S7N 5B3, Canada.
Ecotoxicology. 2015 Mar;24(2):321-9. doi: 10.1007/s10646-014-1380-x. Epub 2014 Nov 27.
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 17α-ethynylestradiol (EE2) throughout their early development. Specifically, transcriptional responses of X. laevis exposed to 0.09, 0.84, or 8.81 µg 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 α, and vitellogenin A2 was significantly greater (>2-fold) than in controls while expression of farnesoid x-activated receptors α and β 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.
尽管在过去二十年里,研究雌激素类化学物质对两栖动物影响的研究数量显著增加,但迄今为止,对于发育中的两栖动物,雌激素与下丘脑 - 垂体 - 性腺 - 肝轴的具体分子相互作用仍知之甚少。在此,我们对非洲爪蟾在其早期发育过程中暴露于17α - 乙炔基雌二醇(EE2)的情况进行了评估,这些基因功能集是先前从暴露于内分泌活性化学物质的鱼类研究中获得的组织特异性功能基因集。具体而言,在性分化期间(孵化后31天,dph)以及幼体阶段变态完成后(89 dph),对暴露于0.09、0.84或8.81 μg EE2/L的非洲爪蟾的转录反应进行了表征。虽然在31 dph时,EE2对转录本丰度没有一致的影响,但在89 dph时,非洲爪蟾在参与类固醇信号传导和代谢、胆固醇合成以及卵黄生成的基因表达上出现了显著变化。具体来说,雄激素受体、法呢基二磷酸合酶、雌激素受体α和卵黄蛋白原A2的表达显著高于对照组(>2倍),而法尼醇X激活受体α和β的表达显著低于对照组(>2倍降低)。这些结果支持了这样一种假设,即源自硬骨鱼类研究的基因集可外推用于两栖动物的幼体阶段,但不适用于性未分化个体。此外,在性分化后采样的动物中,这里使用的基因集转录本丰度的变化与平行研究中报道的发育效应和性腺组织学改变一致。这组基因可能有助于预测后期生命阶段的潜在不良后果。