University of Wisconsin Milwaukee

Marine and Freshwater Biomedical Sciences Center

David H Petering, Ph.D.
petering@uwm.edu
http://www.uwm.edu/Dept/MFB/

Project Description

The unifying theme of the Marine and Freshwater Biomedical Sciences Center of the University of Wisconsin- Milwaukee is the development and exploitation of aquatic biomedical model systems for the study of significant human environmental health problems. To advance this theme, the overall Center objectives include, (1) providing a multifaceted array of support for investigators that enhances innovative, multidisciplinary, and interactive research with aquatic organisms on significant problems related to human environmental health, (2) compacting scientists and their research with the public in order to enrich the community's understanding of environmental health and its importance. Among key specific aims of the Centers cores are the following: (1) Administration (a) to assemble a first rate group of Center investigators from a variety of complementary disciplines who interact and collaborate with one another on important research problems in the area of environmental health, (b) to provide Center investigators with a stimulating environment that fosters innovative, cooperative research and communication, and (c) to continue to find additional sources of funding to support the development of the Center's program; (2) Facility and Service Cores (a) to provide increasingly sophisticated staff and facilities support to investigators in the design and implementation of experiments, (b) to expand the support services including techniques in fish research and molecular biology and microscopy which otherwise would be unavailable to researchers, and (c) to offer expert technical support for outreach and education projects; (3) Research Cores (a) to continue to develop excellent, interacting groups in Metals/Neurobehavioral Toxicology and in Signal Transduction/Endocrine Disruption Toxicology and (b) to build the premier program in zebrafish toxicology; (4) Community Outreach and Education Program (a) to increase science and environmental health literacy among precollege youth, (b) To offer research opportunities to minority college students in environmental health science disciplines, (c) to increase the knowledge and involvement of minority communities in environmental health issues, (d) to increase competency of nurses and public health practitioners in environmental health practice.

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Program Highlights

Effects of Methylmercury on Genomic Response Associated with Reproduction in Fathead Minnows

Methylmercury is a known neurotoxic agent, however the mechanisms by which methylmercury may act on reproductive pathways are relatively unknown. Several studies have indicated potential changes in hormone levels as well as declines in vertebrates with increasing dietary methylmercury exposure. The purpose of this study was to identify alterations in gene expression associated with methylmercury exposure, specifically those associated with previously observed changes in reproduction and reproductive biomarkers. Fathead minnows, Pimephales promelas, were fed one of three diets that were similar to documented concentrations of methylmercury in the diets of wild invertivorous and piscivorous fish. We used a commercial macroarray in conjunction with quantitative PCR (QPCR) to examine gene expression in relationship to exposure in fish exposed to one of three environmentally relevant doses of methylmercury. Expression of genes commonly associated with endocrine disruption was altered with mercury exposure. Specifically, we observed a marked upregulation in vitellogenin mRNA in individual mercury-exposed males and a significant decline in vitellogenin gene expression in female fish with increasing mercury concentrations. Other genes, identified by the macroarray experiment included those associated with egg fertilization and development, sugar metabolism, apoptosis, and electron transport. Differences in expression patterns between male and female fish were also observed not related to genes specifically associated with reproduction, indicating a potential physiological difference in the reaction of males and females to methylmercury.

The results demonstrate that at environmentally relevant concentrations, methylmercury acts as an endocrine disruptor. Thus, besides concern for its potent neurotoxic effects, it is important to consider its potential to exert deletarious effects on the reproductive system.

Gene expression changes related to endocrine function and decline in reproduction in fathead minnow (Pimephales promelas) after dietary methylmercury exposure. Klaper, Rebecca, Rees, C.B., Drevnick, P., Weber, D., Sandheinrich. M., Carvan, M.J. (2006) Environ Health Perspect., 14:1337 43.)¹

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Dioxin and Heart Development in the Embryonic Zebrafish

Dioxin exposure at the time of fertilization causes heart malformation as well as functional defects that lead to circulatory collapse. Measurements have been made of cell number, heart size, and cardiac output in the developing zebrafish hearts. The present work demonstrates that the developing heart is exquisitely sensitive to aryl hydrocarbon receptor (AHR) agonists during a critical window of heart development. Recently, methods were developed to isolate sufficient numbers of synchronously developing embryonic hearts to conduct microarray experiments. The findings reveal that the heart is a unique target for dioxin toxicity. The pattern of gene expression shows that dioxin immediately triggers the upregulation of a group of mRNAs associated with cellular signaling pathways. This is followed by the massive down regulation of a cluster of genes involved in promoting cell division. This latter change coincides with a cessation of cardiomyocyte growth. These results show great promise in leading us towards a better understanding of the risks that AHR agonists pose towards developing vertebrates.

This work points towards specific pathways that may be altered by exposure to environmental contaminants. The zebrafish has become a robust model system for studying the developing vertebrate heart. This research underscores the utility of the model to study the impact of environmental factors upon cardiac development.

Carney, S.A., Chen, J., Burns, C.G., Xiong, K.M., Peterson, R.E., Heideman, W. (2006) Aryl hydrocarbon receptor activation produces heart specific transcriptional and toxic responses in developing zebrafish, Mol. Pharmacol., 70:549 61.

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