Morphological and immunohistochemical studies on cleft palates induced by 2,3,7,8-tetrachlorodibenzo-p-dioxin in mice.

Morphological and immunohistological examinations were performed to reveal the mechanisms of cleft palate induction by 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD). ICR strain mice 8-10 weeks of age were used in the study. TCDD was administered in olive oil on gestation day (GD) 12.5 with gastric tubes at 40 microg/kg. From GD 13.5 to 16.5, palates were examined by scanning electron microscopy (SEM), hematoxyline-eosin (HE) staining, and immunohistochemical staining of FGFR1/2, TGF-beta3, MSX1 and LHX8. In the control group, both of the palatal shelves began elevating on GD 14.0 and finished within 6 h. After the elevation, all of the shelves had completely fused with each other on GD 14.5. In the TCDD-treated group, palatal shelves elevated 1 day later than in the control group. However, all palates had elevated by GD 15.0. After the elevation, the shelves contacted each other and fused; however, they were separated on GD16.0. HE staining showed that medial edge epithelium (MEE) was thinner in the TCDD group than in the control group. MEE observed under a high magnification (x2500) exhibited filopodia-like filaments and the cells were bulged in the control group. In contrast, in the TCDD group, no filaments were observed and the cells were flat with unclear boundaries. Immunohistologically, there were no characteristic findings except for FGFR1. FGFR1 was not expressed in the TCDD group after the fusion phase (GD 14.5). TCDD induces many morphological and molecular changes to MEE cells and causes cleft palates.