2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) disrupts early morphogenetic events that form the lower reproductive tract in female rat fetuses

Toxicol Sci. 2002 Jan;65(1):87-98. doi: 10.1093/toxsci/65.1.87.


In female rats, in uteroexposure to 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) during critical periods of organogenesis causes a permanent thread of tissue, consisting of a core of mesenchyme surrounded by keratinized epithelia, across the vaginal opening. The objective of the current study was to determine the earliest time after exposure to TCDD during fetal development that morphological changes in the development of the lower reproductive tract could be detected. In addition, the spatio-temporal expression of several growth factors within 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 microg TCDD/kg on gestation day (GD) 15. Dams were sacrificed on GD 17, 18, 19, and 21 and individual reproductive tracts were isolated from female fetuses. As early as GD 18, TCDD produced distinct abnormalities in the female reproductive tract. The width of mesenchyme separating the Mullerian ducts was significantly greater in TCDD-exposed female GD 18 and 19 fetuses and the zone of unfused Mullerian ducts was substantially increased on GD 19 and 21. TCDD induced alterations within the developing reproductive tract in the subcellular and temporal expression of transforming growth factor-beta3 (TGF-beta3) and epidermal growth factor receptor (EGFR). DNA array analysis suggested effects on several genes expressed on GD 18 and 19.

Publication types

  • Research Support, U.S. Gov't, Non-P.H.S.
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Abnormalities, Drug-Induced / etiology
  • Animals
  • Embryonic and Fetal Development / drug effects
  • Female
  • Gene Expression Regulation, Developmental
  • Genes, erbB-1 / genetics
  • Genitalia, Female / abnormalities*
  • Genitalia, Female / metabolism
  • Immunohistochemistry
  • Laminin / genetics
  • Laminin / metabolism
  • Maternal Exposure / adverse effects
  • Mesoderm / drug effects
  • Mesonephros / drug effects*
  • Mesonephros / embryology
  • Mullerian Ducts / drug effects*
  • Mullerian Ducts / embryology
  • Polychlorinated Dibenzodioxins / toxicity*
  • Pregnancy
  • Rats
  • Rats, Long-Evans
  • Time Factors
  • Transforming Growth Factor beta / metabolism
  • Transforming Growth Factor beta3
  • Urethra / drug effects*
  • Urethra / embryology


  • Laminin
  • Polychlorinated Dibenzodioxins
  • Tgfb3 protein, rat
  • Transforming Growth Factor beta
  • Transforming Growth Factor beta3