Environmental Concentrations of Contaminants Affect Morphological and Neuroendocrine Development in Zebrafish

atmire.migration.oldid3421
dc.contributor.advisorHabibi, Hamid
dc.contributor.advisorKurrasch, Deborah
dc.contributor.authorKinch, Cassandra
dc.date.accessioned2015-07-31T16:11:46Z
dc.date.available2015-11-20T08:00:34Z
dc.date.issued2015-07-31
dc.date.submitted2015en
dc.description.abstractExposure 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.en_US
dc.identifier.citationKinch, 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/25917en_US
dc.identifier.doihttp://dx.doi.org/10.11575/PRISM/25917
dc.identifier.urihttp://hdl.handle.net/11023/2375
dc.language.isoeng
dc.publisher.facultyGraduate Studies
dc.publisher.institutionUniversity of Calgaryen
dc.publisher.placeCalgaryen
dc.rightsUniversity of Calgary graduate students retain copyright ownership and moral rights for their thesis. You may use this material in any way that is permitted by the Copyright Act or through licensing that has been assigned to the document. For uses that are not allowable under copyright legislation or licensing, you are required to seek permission.
dc.subjectPhysiology
dc.subject.classificationBisphenol Aen_US
dc.subject.classificationBisphenol Sen_US
dc.subject.classificationbrain developmenten_US
dc.subject.classificationneurogenesisen_US
dc.subject.classificationaromataseen_US
dc.subject.classificationandrogen receptoren_US
dc.subject.classificationzebrafishen_US
dc.subject.classificationmorphologyen_US
dc.titleEnvironmental Concentrations of Contaminants Affect Morphological and Neuroendocrine Development in Zebrafish
dc.typedoctoral thesis
thesis.degree.disciplineBiological Sciences
thesis.degree.grantorUniversity of Calgary
thesis.degree.nameDoctor of Philosophy (PhD)
ucalgary.item.requestcopytrue
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