Retinoid homeostasis of an oviparous fish
The central hypothesis addressed in this dissertation is that exposure of fish to toxic dioxin-like compounds (DLCs) alters homeostatic processes that regulate local concentrations of retinoids, derivatives of vitamin A. The basis for this hypothesis is that DLCs bind the Aryl hydrocarbon (Ah) receptor activating a signal transduction pathway that affects the regulation of enzymes that metabolize certain endo- and xeno-biotic compounds. Therefore, it was proposed specifically that DLC exposure changes local concentrations of biologically active retinoids by affecting their rates of formation and degradation. Populations of the estuarine fish species Fundulus heteroclitus (mummichogs) that vary in their sensitivity to DLCs provided unique and environmentally-relevant models to test components of this hypothesis. ^ To characterize DLC variation among F. heteroclitus embryos, a novel method was developed that quantifies the activity of an enzyme regulated by the Ah receptor pathway. Results demonstrated that Ah receptor agonists affect embryonic metabolism at earlier developmental stages than previously demonstrated in this or other fish species. Using these methods, it was also shown that populations of mummichogs from a highly DLC-contaminated site were dramatically less responsive to DLC exposure than those from the reference site. Although no specific mechanism for this inherited resistance was investigated, results were consistent with altered responsiveness in the Ah receptor signaling pathway. Consistent with other results documenting their insensitivity to certain DLC effects, retinoid stores in adult mummichogs from the contaminated site were shown to be minimally affected by indigenous chemical exposures. ^ Results also showed that DLC exposure producing toxic effects during embryonic development altered retinoid processes. Specifically, DLC exposure affected the rate of retinoic acid metabolism in DLC-responsive embryos but not in those embryos with diminished responsiveness of the Ah receptor pathway. These results are consistent with the hypothesis that the Ah receptor pathway regulates the activities of some enzymes involved in retinoid homeostasis during the development of fish. Similarly, alterations in the Ah receptor pathway that reduced the effects of retinoid disruption in DLC-resistant embryos may provide one mechanism by which these fish are protected in the wild from contaminant-mediated developmental toxicity. ^
Biology, Ecology|Biology, Oceanography|Biology, Zoology
Diane Ellen Nacci,
"Retinoid homeostasis of an oviparous fish"
Dissertations and Master's Theses (Campus Access).