Methylmercury is both a potent neurotoxin and putative non-steroidal endocrine disruptor. Laboratory studies have provided evidence of reproductive impairment in many fish species after mercury exposure. Effects have been observed at every level of the reproductive axis including degeneration of neurons in the hypothalamus, decreased activity of gonadotrophs in the pituitary, and reduced steroidogenesis in the gonads. Despite the growing amount of research linking methylmercury exposure to reproductive impairment, the target tissues and mechanisms of action involved are still largely unknown. This thesis extends the body of evidence supporting the hypothesis that methylmercury is an endocrine disruptor in fish. To my knowledge, this is the first study to compare the effects of sub-chronic methylmercury exposure on adult goldfish at two different periods within the annual spawning cycle. The effects of endocrine disrupting toxins may differ depending on the season of exposure as goldfish exhibit seasonal fluctuations in gonad size, circulating sex steroids, and luteinizing hormone (LH). The present study demonstrates that ovarian steroidogenesis is impaired by methylmercury in both pre- and post-spawning fish. Analyses of pituitary and serum LH levels suggest that reductions in sex steroid levels are independent of alterations in LH. The possibility that reduced sex steroid levels in fish exposed to dietary methylmercury may be secondary to hypothalamic dysfunction remains to be addressed. Microarray analysis identified 59 genes differentially expressed in the hypothalamus after methylmercury accumulation. These candidate genes were categorized into discrete functional groups including apoptosis and stress response, calcium binding and transport, and protein synthesis, degradation, and transport. In addition, several neuroendocrine-related genes were differentially regulated including transcripts encoding peptides involved in stimulating the production and release of gonadotropin releasing hormone, secretion of LH, and gonadal steroidogenesis. This thesis demonstrates changes in the endocrine system linked to methylmercury exposure and provides the first step towards identifying the mechanistic relationship between changes in reproductive biomarkers and gene expression.
| Identifer | oai:union.ndltd.org:uottawa.ca/oai:ruor.uottawa.ca:10393/27674 |
| Date | January 2008 |
| Creators | Crump, Kate |
| Publisher | University of Ottawa (Canada) |
| Source Sets | Université d’Ottawa |
| Language | English |
| Detected Language | English |
| Type | Thesis |
| Format | 117 p. |
Page generated in 0.0013 seconds