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2,3,7,8-TETRACHLORODIBENZO-P-DIOXIN (TCDD) DISRUPTS EARLY MORPHOGENETIC EVENTS THAT FORM THE LOWER REPRODUCTIVE TRACT IN FEMALE RAT FETUSES
Citation:
Hurst, C. H., B D. Abbott, J E. Schmid, AND L S. Birnbaum. 2,3,7,8-TETRACHLORODIBENZO-P-DIOXIN (TCDD) DISRUPTS EARLY MORPHOGENETIC EVENTS THAT FORM THE LOWER REPRODUCTIVE TRACT IN FEMALE RAT FETUSES. TOXICOLOGICAL SCIENCES 65:87-98, (2002).
Description:
In female rats, in utero exposure to 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) during critical periods of organogenesis causes a permanent thread of tissue across the vaginal opening, which consists of a core of mesenchyme surrounded by keratinized epithelia. The objective of the current study was to determine the earliest time during embryogenesis that morphological changes in the development of the lower reproductive tract could be detected. In addition, the spatio-temporal expression of several growth factors and DNA Array analysis of the developing reproductive tract was investigated to provide insight into the mechanism of action involved in TCDD-induced vaginal thread formation. Pregnant rats received a single oral dose of 1.0 ?g TCDD/kg on GD15. Dams were sacrificed on GD17, 18, 19 and 21 and individual reproductive tracts were isolated from female fetuses. As early as GD18, TCDD produced distinct abnormalities in the female reproductive tract. The width of mesenchyme separating the Mullerian ducts was significantly greater in TCDD-exposed female pups and the zone of unfused Mullerian ducts was substantially increased. TCDD induced alterations within the developing reproductive tract in the subcellular and temporal expression of TGF-$3, EGFR, and laminin and DNA array analysis suggested effects on several genes expressed on GD18 and 19.