Transient and permanent reproductive dysfunction in fish has been linked to chemicals that disrupt the endocrine system, but the mechanisms involved are unclear. Many endocrine-disrupting chemicals (EDCs) interact with sex hormone receptors by acting as agonists to induce gene expression at inappropriate times or act as antagonists to prevent the normal functioning of the receptors. Other EDCs may act indirectly by altering the processes involved in regulating sex steroid synthesis and metabolism. Poor reproduction and altered plasma hormone levels have been observed in largemouth bass living in ecosystems polluted with organochlorine pesticides (OCPs), including the Superfund site at Lake Apopka and its surrounding muck farms, suggesting that OCP exposure has adversely affected their reproduction. In past research, we have identified three estrogen receptors (a, pi, and (32) in largemouth bass, which exhibit tissue specific expression and respond differently to 17-p-estradiol at the message and activity level. These differences are important to control normal reproductive function. We have evidence that EDCs can alter their normal expression and activity patterns, possibly disrupting reproduction. In addition, we have preliminary evidence that expression of enzymes involved in the synthesis and metabolism of EDCs is affected by the OCPs. The proposed studies will test the central hypothesis that exposure of largemouth bass to concentrations of OCPs found in the Lake Apopka region disrupts endocrine system function by sex hormone receptor mediated and sex hormone receptor independent mechanisms. In this proposal, we have designed a set of interrelated experiments from the organismal level where pleiotropic effects of OCPs can be measured to the cellular level where specific molecular mechanisms of action can be assessed. We are exposing largemouth bass to methoxychlor (and its metabolites), p,p'DDE, dieldrin and toxaphene.
Our specific aims i nclude 1: Develop biomarkers of exposure to organochlorinated pesticides in vivo, via the use of microarrays and novel proteomics methodologies;2: Determine the effect of in vivo OCP exposure on LME steroid synthesis and metabolism;and 3: Evaluate the effects of OCPs on the molecular mechanisms of action of the three estrogen receptors. We plan on using exposures to compounds with known modes of action as controls to determine mode of action specific gene expression patterns against which we will compare the patterns of gene expression changes induced by the OCPs. We will check these pattern changes against reproductive endpoints including the ability of eggs to mature (germinal vesicle breakdown) and sperm function (sperm motility). Fish are useful as sentinels of environmental quality and are perfect models to monitor adverse effects in reproduction caused by contaminants in superfund sites. By extrapolation fish can report on the potential of OCPs to harm human health.

National Institute of Health (NIH)
National Institute of Environmental Health Sciences (NIEHS)
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Special Emphasis Panel (ZES1-SET-A (P9))
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Henry, Heather F
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University of Florida
Schools of Veterinary Medicine
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Dominguez, Gustavo A; Bisesi Jr, Joseph H; Kroll, Kevin J et al. (2014) Control of transcriptional repression of the vitellogenin receptor gene in largemouth bass (Micropterus salmoides) by select estrogen receptors isotypes. Toxicol Sci 141:423-31
Colli-Dula, Reyna-Cristina; Martyniuk, Christopher J; Kroll, Kevin J et al. (2014) Dietary exposure of 17-alpha ethinylestradiol modulates physiological endpoints and gene signaling pathways in female largemouth bass (Micropterus salmoides). Aquat Toxicol 156:148-60
Mehinto, Alvine C; Prucha, Melinda S; Colli-Dula, Reyna C et al. (2014) Gene networks and toxicity pathways induced by acute cadmium exposure in adult largemouth bass (Micropterus salmoides). Aquat Toxicol 152:186-94
Martyniuk, Christopher J; Prucha, Melinda S; Doperalski, Nicholas J et al. (2013) Gene expression networks underlying ovarian development in wild largemouth bass (Micropterus salmoides). PLoS One 8:e59093
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Martyniuk, Christopher J; Denslow, Nancy D (2012) Exploring androgen-regulated pathways in teleost fish using transcriptomics and proteomics. Integr Comp Biol 52:695-704
Martyniuk, Christopher J; Popesku, Jason T; Chown, Brittany et al. (2012) Quantitative proteomics in teleost fish: insights and challenges for neuroendocrine and neurotoxicology research. Gen Comp Endocrinol 176:314-20
Martyniuk, Christopher J; Alvarez, Sophie; Denslow, Nancy D (2012) DIGE and iTRAQ as biomarker discovery tools in aquatic toxicology. Ecotoxicol Environ Saf 76:3-10
Dominguez, Gustavo A; Quattro, Joseph M; Denslow, Nancy D et al. (2012) Identification and transcriptional modulation of the largemouth bass, Micropterus salmoides, vitellogenin receptor during oocyte development by insulin and sex steroids. Biol Reprod 87:67
Doperalski, Nicholas J; Martyniuk, Christopher J; Prucha, Melinda S et al. (2011) Cloning and expression of the translocator protein (18 kDa), voltage-dependent anion channel, and diazepam binding inhibitor in the gonad of largemouth bass (Micropterus salmoides) across the reproductive cycle. Gen Comp Endocrinol 173:86-95

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