Environmental Concentrations of Contaminants Affect Morphological and Neuroendocrine Development in Zebrafish

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2015-07-31
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Abstract
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 with endocrine disruptive abilities, resulting in abnormal developmental rate, heart and eye morphology, and behavior that could not be explained by interaction with single hormone receptor pathways. To begin my thesis, I use a whole-organism approach to investigate morphological changes caused by exposure to the environmental contaminants, Bisphenol A (BPA), DEHP, nonylphenol, and fucosterol at concentrations measured in a local water body (Oldman River, AB), individually and in mixture. Here I report that exposure to nanomolar contaminant concentrations results in global developmental changes, abnormal pericardial development, and abnormal head development. These results support the hypothesis that adverse effects of contaminants were not mediated by single hormone receptor signaling. Furthermore, here I show that contaminant effects in mixture can not be consistently predicted by contaminant effects individually, based on an additive model. These findings provide a framework for better understanding of developmental toxicity of environmental contaminants in zebrafish and other vertebrate species. Given the well-established linkage between developmental BPA exposure and endocrine-related physiologies including obesity, cancers and neurodevelopmental disorders such as hyperactivity, in the second part of my thesis, I study the effects of BPA on neuroendocrine development. To start, I evaluate BPA effects on neuronal birth, or neurogenesis, within the hypothalamus, a small but powerful region of the brain linked to hyperactivity. Interestingly, exposure of embryonic zebrafish with the same environmental concentration of BPA and Bisphenol S (BPS), the primary analogue used in BPA-free products, resulted in 180% and 240% increases, respectively, in neurogenesis. Furthermore, restricted BPA and BPS exposure during the neurogenic window caused hyperactive behaviors later in life. Unexpectedly, BPA-mediated precocious neurogenesis was not dependent on predicted estrogen receptors, but relies on androgen receptor-mediated upregulation of aromatase. Given the emerging link between contaminant exposure and effects on early development, these studies open new avenues of research into how environmental contaminants may perturb neurodevelopment and reinforces that effects of environmental contaminants are complex and warrants further study.
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Physiology
Citation
Kinch, C. (2015). Environmental Concentrations of Contaminants Affect Morphological and Neuroendocrine Development in Zebrafish (Doctoral thesis, University of Calgary, Calgary, Canada). Retrieved from https://prism.ucalgary.ca. doi:10.11575/PRISM/25917