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Rebecca Klaper,¹ Christopher B. Rees,¹ Paul Drevnick,² Daniel Weber,³ Mark Sandheinrich,⁴ and Michael J. Carvan¹

¹Great Lakes WATER Institute, University of Wisconsin–Milwaukee, Milwaukee, Wisconsin, USA; ²Department of Zoology, Miami University, Oxford, Ohio, USA; ³Marine and Freshwater Biomedical Sciences Center, University of Wisconsin–Milwaukee, Milwaukee, Wisconsin, USA; ⁴River Studies Center and Department of Biology, University of Wisconsin–La Crosse, La Crosse, Wisconsin, USA

Abstract
Background: Methylmercury (MeHg) is a known neurotoxic agent, but the mechanisms by which MeHg 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 MeHg exposure.

Objectives: The purpose of this study was to identify alterations in gene expression associated with MeHg 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 MeHg in the diets of wild invertivorous and piscivorous fish. We used a commercial macroarray in conjunction with quantitative polymerase chain reaction to examine gene expression in fish in relation to exposure to these environmentally relevant doses of MeHg.

Results: Expression of genes commonly associated with endocrine disruption was altered with Hg exposure. Specifically, we observed a marked up-regulation in vitellogenin mRNA in individual Hg-exposed males and a significant decline in vitellogenin gene expression in female fish with increasing Hg concentrations. Other genes identified by the macroarray experiment included those associated with egg fertilization and development, sugar metabolism, apoptosis, and electron transport. We also observed differences in expression patterns between male and female fish not related to genes specifically associated with reproduction, indicating a potential physiological difference in the reaction of males and females to MeHg.

Conclusion: Gene expression data may provide insight into the mechanisms by which MeHg affects reproduction in fish and indicate how MeHg differs in its effect from other heavy metals and endocrine-disrupting compounds.

Key words: endocrine disruption, gene expression, mercury, methylmercury, microarray, Pimephales promelas, reproduction, toxicogenomics, vitellogenin. Environ Health Perspect 114: 1337–1343 (2006) . doi:10.1289/ehp.8786 available via http://dx.doi.org/ [Online 30 May 2006]

Address correspondence to R. Klaper, Great Lakes WATER Institute, 600 East Greenfield Ave., Milwaukee, WI 53204. Telephone: (414) 382-1713. Fax: (414) 382-1705. E-mail: rklaper@uwm.edu

Supplemental Material is available online at http://www.ehponline.org/members/2006/8786/supplemental.pdf

We thank three anonymous reviewers that contributed suggestions to improve the manuscript.

This is paper 476 of the Great Lakes WATER Institute, University of Wisconsin–Milwaukee.

This research was supported by a pilot project grant from the National Institute of Environmental Health Sciences (NIEHS) Marine and Freshwater Biomedical Sciences Center (supported by NIEHS ES04184) at the University of Wisconsin–Milwaukee (R.K.) , a grant from the Wisconsin Sea Grant College Program (M.S.) , and a National Institutes of Health, Indian Health Service, Native American Research Centers for Health grant (M.J.C.) .

The authors declare they have no competing financial interests.

Received 29 October 2005 ; accepted 30 May 2006.