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Modulation by Dioxin of Reproductive Function of FishesEPA Grant Number: MA916290
Title: Modulation by Dioxin of Reproductive Function of Fishes
Investigators: Heiden, Tisha K.
Institution: University of Wisconsin - Milwaukee
EPA Project Officer: Zambrana, Jose
Project Period: January 1, 2004 through December 31, 2006
Project Amount: $78,436
RFA: GRO Fellowships for Graduate Environmental Study (2004) RFA Text | Recipients Lists
Research Category: Academic Fellowships , Aquatic Ecosystems , Fellowship - Aquatic Ecology and Ecosystems
Dioxins are prevalent within the environment and are formed as byproducts from several anthropogenic processes. 2,3,7,8-Tetrachloro-dibenzo-p-dioxin (TCDD), in particular, is especially toxic and has been shown to act as a teratogen, embryotoxin, carcinogen, immune system suppressor, and endocrine disruptor. TCDD has the potential to modulate several biological processes that impact growth and development, and fish are among the most sensitive vertebrates to its developmental toxic effects. Wild fish populations exposed to high levels of TCDD have reduced reproductive success, which is thought to be the result of impaired egg production and poor offspring survival. The objective of this project is to gain a better understanding of the mechanisms by which chronic exposure to sublethal concentrations of TCDD modulates reproductive function in fishes, using zebrafish (Danio rerio) as a model organism. This is essential for determining the realistic effects such toxins have on wild fish species and for the extrapolation of the similar dangers they pose to humans.
To assess the effects of chronic exposure to sublethal levels of TCDD on reproductive success, adult female zebrafish were fed food containing different concentrations of TCDD for several weeks and subsequently spawned with untreated males to determine effects of TCDD exposure on egg production and survival of offspring. Because the distribution of TCDD to different tissue types plays an important role in the tissue-specific response and toxicity, establishing the translocation and bioconcentration using 3H-TCDD will allow us to better understand the mechanisms by which TCDD exerts its toxicity. As it is often the disruption of normal cellular and molecular pathways that lead to a chemical’s toxic effect, we are using cDNA microarray technologies, with the aid of bioinformatics tools, for global analysis of changes in gene expression resulting from TCDD exposure. Patterns of gene expression from TCDD-treated and normal states will be compared to identify differentially expressed genes that may play a key role in the reproductive toxic effects of TCDD. Additionally, as it is known that TCDD disrupts serum estrogen levels and that the ovary is a major target site of TCDD toxicity, I will use real time RT-PCR to determine the effects of exposure to TCDD on the expression of genes important in estrogen biosynthesis. These results then will be compared to whole-body estradiol and vitellogenin concentrations to further characterize the mechanisms by which TCDD disrupts estrogen biosynthesis in zebrafish. These experiments provide the necessary framework for testing a number of emerging hypotheses regarding the mechanisms by which TCDD exerts its reproductive toxic effects through the integration of physiological hormonal endpoints with the global analysis of gene expression.
Physiologic effects of endocrine-disrupting contaminants range from morphologic anomalies to impaired immune systems to behavioral modifications. Because TCDD alters circulating estrogen concentrations, it is not surprising that TCDD has been shown to impede development and is associated with a decrease in egg production. By studying the effects of chronic exposure to sublethal concentrations of TCDD on fish reproductive function, I hope to complement and further support data previously collected using rat, human, and fish model systems to characterize the mechanisms by which TCDD alters estrogen biosynthesis and female reproductive function. It is imperative that we determine not only the kinds of chemicals that have such deleterious effects on fish species, but also the mechanisms by which these chemicals influence the reproductive physiology and success of fishes, so that we may identify ways to protect our wild fish populations.