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ALTERED SENSITIVITY OF THE MOUSE FETUS TO IMPAIRED PROSTATIC BUD FORMATION BY DIOXIN: INFLUENCE OF GENETIC BACKGROUND AND NULL EXPRESSION OF TGF-ALFA AND EGF
Citation:
Rasmussen, N. T., T. M. Lin, S E. Fenton, B D. Abbott, AND R. E. Peterson. ALTERED SENSITIVITY OF THE MOUSE FETUS TO IMPAIRED PROSTATIC BUD FORMATION BY DIOXIN: INFLUENCE OF GENETIC BACKGROUND AND NULL EXPRESSION OF TGF-ALFA AND EGF. Presented at Society of Toxicology, Nashville, TN, March 17-21, 2002.
Description:
Altered sensitivity of the mouse fetus to impaired prostatic bud formation by dioxin: Influence of genetic background and null expression of TGF and EGF.
Rasmussen, N.T., Lin T-M., Fenton, S.E., Abbott, B.D. and R.E. Peterson.
2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD) inhibits prostatic bud formation from the urogenital sinus in the C57Bl/6J mouse fetus. Knock-out EGF (EGFKO), TGF (TGF KO) and EGF+TGF (EGF/TGF KO) mice were used to investigate the roles of EGF and TGF in the impairment of prostatic budding by TCDD. The EGFKO and EGFKO/TGF KO mice share a "mixed" genetic background of the 129 and C57Bl/6J strain; whereas genetic background of the TGF KO mice resembles the C57Bl/6J strain. Compared to the wild-type C57Bl/6J strain (WT), wild-type mice of the "mixed" genetic background (WT-m) required about 100 times more TCDD to produce an equivalent inhibitory effect on prostatic budding following in utero TCDD exposure. Dams were dosed with TCDD or vehicle on gestation day (GD) 12 and budding was examined on GD 17.5. Dams producing WT and TGF KO offspring were dosed with 0, 0.2, 1 or 5 g TCDD/kg, while dams producing WT-m, EGFKO and EGFKO/TGF KO offspring were dosed with 0, 1, 10, 50, 100 or 150 g/kg. Essentially complete agenesis of ventral buds (VBs) and a reduction in dorsolateral bud (DLB) numbers were observed in 1 g/kg TCDD-exposed WT and TGF KO fetuses, suggesting that the absence of TGF does not affect responsiveness to TCDD. WT-m fetuses showed no inhibition of budding at 1 g TCDD/kg, but at 50 g/kg and higher doses of TCDD there were dose-related reductions in VB and DLB number. The 10 g TCDD/kg EGFKO group showed an inhibition of VB and DLB formation similar to the 150 g TCDD/kg WT-m group. EGFKO and EGFKO/TGF KO groups treated with 150 g TCDD/kg showed agenesis of VBs and nearly complete agenesis of DLBs. Sensitivity to TCDD-induced impairment of prostatic budding is enhanced in EGFKO and EGFKO/TGF KO fetuses. Thus, null expression of EGF appears to increase sensitivity of prostatic bud formation to inhibition by TCDD. (Supported by USEPA and NIH grant ES01332).