Kinch Cassandra D, Kurrasch Deborah M, Habibi Hamid R
Department of Biological Sciences, University of Calgary, 2500 University Dr. NW, Calgary, Alberta, T2N 1N4, Canada; Department of Medical Genetics, Cummings School of Medicine, University of Calgary, 3330 Hospital Dr. NW, Calgary, Alberta, T2N 4N1, Canada; Alberta Children's Hospital Research Institute, Heritage Medical Research Building, 3330 Hospital Dr. NW, Calgary, Alberta, T2N 4N1, Canada.
Department of Medical Genetics, Cummings School of Medicine, University of Calgary, 3330 Hospital Dr. NW, Calgary, Alberta, T2N 4N1, Canada; Alberta Children's Hospital Research Institute, Heritage Medical Research Building, 3330 Hospital Dr. NW, Calgary, Alberta, T2N 4N1, Canada.
Aquat Toxicol. 2016 Jun;175:286-98. doi: 10.1016/j.aquatox.2016.03.021. Epub 2016 Mar 29.
Exposure to environmental contaminants has been linked to developmental and reproductive abnormalities leading to infertility, spontaneous abortion, reduced number of offspring, and metabolic disorders. In addition, there is evidence linking environmental contaminants and endocrine disruption to abnormal developmental rate, defects in heart and eye morphology, and alterations in behavior. Notably, these effects could not be explained by interaction with a single hormone receptor. Here, using a whole-organism approach, we investigated morphological changes to developing zebrafish caused by exposure to a number of environmental contaminants, including bisphenol A (BPA), di(2-ethylhexyl)phthalate (DEHP), nonylphenol, and fucosterol at concentrations measured in a local water body (Oldman River, AB), individually and in mixture. Exposure to nanomolar contaminant concentrations resulted in abnormal morphological development, including changes to body length, pericardia (heart), and the head. We also characterize the spatiotemporal expression profiles of estrogen, androgen, and thyroid hormone receptors to demonstrate that localization of these receptors might be mediating contaminant effects on development. Finally, we examined the effects of contaminants singly and in mixture. Combined, our results support the hypothesis that adverse effects of contaminants are not mediated by single hormone receptor signaling, and adversity of contaminants in mixture could not be predicted by simple additive effect of contaminants. The findings provide a framework for better understanding of developmental toxicity of environmental contaminants in zebrafish and other vertebrate species.
接触环境污染物与发育和生殖异常有关，这些异常会导致不孕、自然流产、后代数量减少和代谢紊乱。此外，有证据表明环境污染物和内分泌干扰与发育速度异常、心脏和眼睛形态缺陷以及行为改变有关。值得注意的是，这些影响无法通过与单一激素受体的相互作用来解释。在这里，我们采用全生物体方法，研究了暴露于多种环境污染物（包括双酚A（BPA）、邻苯二甲酸二（2-乙基己基）酯（DEHP）、壬基酚和岩藻甾醇）对斑马鱼发育的形态学变化，这些污染物的浓度是在当地水体（阿尔伯塔省奥尔德曼河）中测得的，单独暴露和混合暴露均进行了研究。暴露于纳摩尔浓度的污染物会导致形态发育异常，包括体长、心包（心脏）和头部的变化。我们还对雌激素、雄激素和甲状腺激素受体的时空表达谱进行了表征，以证明这些受体的定位可能介导了污染物对发育的影响。最后，我们研究了污染物单独和混合时的影响。综合来看，我们的结果支持以下假设：污染物的不良影响不是由单一激素受体信号介导的，混合物中污染物的不利影响也不能通过污染物的简单加和效应来预测。这些发现为更好地理解斑马鱼和其他脊椎动物物种中环境污染物的发育毒性提供了一个框架。
