T6 PM Immune and Endocrine Disruption: Detection and Implication
Tuesday, 15 November 2005: 1:50 PM - 5:30 PM in 324-326

(KIN-1117-726211) 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD): Impacts of an endocrine disruptor on reproduction of fish.

King Heiden, T^{1, 2}, Hessner, M³, Hutz, R^{1, 2}, Carvan, III, M¹, ¹ UWM Great Lakes WATER Inst, Milwaukee, WI, USA² Dept of Biological Sciences UW-Milwaukee, Milwaukee, WI, USA³ Medical College of Wisconsin, Milwaukee, WI, USA

ABSTRACT- TCDD is a reproductive toxicant and endocrine disruptor in nearly all vertebrates, yet the mechanisms by which TCDD induces these reproductive alterations have not been fully characterized. Fish are among the most sensitive vertebrates to the toxic effects of TCDD, and even subtle physiologic changes induced by TCDD can lead to altered gonadogenesis and impaired fertility. Following chronic, sublethal exposure to TCDD, zebrafish show a significant decrease in the ovosomatic index, and egg production is reduced by greater than 50%. Such TCDD-induced effects on reproduction may reflect AHR-mediated alterations in ovarian gene expression with specific impacts on steroidogenesis. Here we investigate the impact of TCDD exposure on gene expression as they relate to the suppression of estradiol biosynthesis or to the alteration of oogenesis or vitellogenesis. Female zebrafish were exposed to dietary TCDD over a period of four weeks, and were spawned weekly with untreated males. Changes in serum estradiol and vitellogenin concentrations in response to TCDD were compared, as were modulation of ovarian development. Alterations in gene expression and molecular pathways in the ovary caused by TCDD exposure were identified using Affymetrix microarray analysis. Several genes were identified as being dysregulated at least 2-fold including those involved in glucose and lipid metabolism, mitochondrial transport, regulation of transcription, and immune function. Gene expression profiles suggest that TCDD suppresses core functional genes that are necessary for ovarian development. Exposure to TCDD may induce ovarian quiescence, which in turn may account for the observed down-stream effects on ovarian development and egg production. On-going analyses will provide additional information regarding the molecular targets and cellular pathways that are affected. This constitutes the first step in understanding the mechanisms that underlie the reproductive toxic effects of TCDD.

Key words: endocrine disruption, reproduction, zebrafish, microarray