Intersex in Largemouth Bass Induced by Endocrine Disrupting Chemicals: A Time Course of Histopathology and Molecular Events along the Hypothalamic-Pituitary-Gonad (HPG) Axis
Funding Program: Contaminant Biology
Statement of Problem: Chemical disruption of endocrine systems in fish has been a topic of intense public interest over the past two decades. As a consequence of more intense research and monitoring, biologists have documented endocrine and reproductive dysfunction in wild populations of fish and wildlife across the country and across the world. In parallel, environmental chemists have documented the presence of endocrine disrupting chemicals (EDCs) in both ground and surface waters of the US (Kolpin et al. 2000). Through these efforts, EDCs have been observed in numerous locations, associated with municipal wastewaters, industry, agriculture, animal production operations, and urbanization. Measures of endocrine function in fish and EDCs in aquatic environments have both been important to document the potential for endocrine disruption in fish (and wildlife) from chemicals. Yet, the presence of these chemicals and the presence of endocrine-related disruption in fish, even together, do not provide the required evidence to establish causal linkages among these factors. The general measurements of endocrine disruption in fish (biomarkers) have been biochemical, physiological, and histological in nature. These include measurements of altered sex steroid, elevated plasma vitellogenin in males, and most notably ¿intersex¿ condition of fish gonads. Moreover, if endocrine-related effects in fish are attributable to EDCs, we must be able to understand the extent of adverse effects, particularly as they relate to population dynamics and our management strategies for fish populations. Thus, we need to understand what is natural for these populations of fish. Intersex in fish, for example, may be genetically based (ie. species-specific), related to environmental conditions (eg. temperature), or due to exposure to chemicals (eg. estrogen mimics). Thus, the natural occurrence of intersex in fish must be determined, as well as the mechanisms for development of intersex from these different factors. We must be able to distinguish if an intersex phenotype is due to a natural cause, such as species-related factors, or some unnatural factor, such as an EDC. Currently, our knowledge of intersex in fish, the causes of intersex, and the outcomes of intersex on fish populations does not allow us to know if it serves as a signal or warning for potential effects on humans. The investigations described below are designed to begin to address some of these fundamental questions regarding intersex in fish.
Objectives: The specific objectives for the studies are: 1) Induce intersex in largemouth bass with an endocrine disrupting chemical; 2) Monitor the development of the intersex in the gonads of the LMB over a chronic exposure period through histological examinations; 3) Measure global gene expression profiles in target tissues of the HPG-axis with a LMB-specific DNA microarray; 4) Select gene expression biomarkers indicative of the genotypic and phenotypic changes observed in intersex in largemouth bass; and 5) Develop testable hypotheses for potential biochemical pathways and cellular mechanisms leading to the condition of intersex in largemouth bass.