Pathogenesis of cleft palate in mouse embryos exposed to 2,3,7, 8-tetrachlorodibenzo-p-dioxin (TCDD).

Abstract

2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) induces cleft palate in mouse embryos. It has been believed that TCDD inhibits palatal fusion by suppression of disappearance of medial edge epithelial (MEE) cells on palatal shelves. However, we found that exencephalic mouse embryos were resistant to the cleft palate-inducing action of TCDD. In the present study, we examined cell kinetics in MEE and palatal mesenchyme in embryos exposed to TCDD with or without exencephaly for elucidation of pathogenesis of cleft palate by TCDD. Pregnant Jcl:ICR mice were given TCDD orally at 40 microg/kg at gestation day (GD) 12.5. Embryos were harvested between GD 13.5 and GD 14.5 and examined for cell kinetics by bromodeoxyuridine (BrdU) and TUNEL methods. Exencephaly was induced by intraperitoneal injection of CdCl(2) at 6 mg/kg at GD 7.5. BrdU-positive cells were decreased in TCDD-treated embryos in MEE and mesenchymal cells. TUNEL-positive cells were detected in MEE both in TCDD-treated and untreated control embryos, as well as in embryos with or without exencephaly. We also measured the gap between shelves between GD 14. 0 and GD 14.5. There were no differences at GD 14.0 between control and TCDD-exposed embryos, but at GD 14.25 and GD 14.5, TCDD-exposed embryos had wider gaps than controls. These findings indicate that cleft palate by TCDD results from poor development of palatal shelves. Teratogenesis Carcinog. Mutagen. 20:73-86, 2000.