ABSTRACT
2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD), a highly toxic halogenated aromatic hydrocarbon, is a teratogen to induce cleft palate when exposed during the pregnancy. There are inter-strain differences in the sensitivity to cleft palate induced by TCDD and other chemicals including polychlorinated terphenyls (PCTs). The C57BL/6 mouse and the ddY mouse had been shown to be different in the induction of cleft palate following the treatment of PCTs, which attempts us to evaluate the TCDD-induced cleft palate in two mouse strains to understand the mechanism through which TCDD and PCTs induce cleft palate. This study evaluated the induction of cleft palate in the fetuses of ddY and C57BL/6 mice after subcutaneous treatment of TCDD on gestation day (GD) 10.5-14.5 or oral treatment on GD 8.5-13.5. Our results clearly showed that ddY mice, a susceptible strain to PCTs-induced cleft palate, are resistant to the induction of cleft palate by TCDD comparably to the high susceptibility of C57BL/6 mice, suggesting a different teratological mechanism between TCDD and PCTs. In addition, at the low doses, our study supported the concept of "window effect" of TCDD on around GD 12 for the induction of cleft palate in C57BL/6 and ddY mice.
Subject(s)
Animals , Female , Male , Mice , Pregnancy , Administration, Oral , Cleft Palate/chemically induced , Fetal Diseases/chemically induced , Incidence , Injections, Subcutaneous , Mice, Inbred C57BL , Polychloroterphenyl Compounds/toxicity , Rodent Diseases/chemically induced , Teratogens/toxicity , Polychlorinated Dibenzodioxins/administration & dosageABSTRACT
The aim of this study was to identify possible candidate genes for the susceptibility to cleft palate. We studied hyaluronic and glycoprotein levels with morphometric and histochemical techniques, in palatine process of 13 and 14 days old mouse embryos of strains A/Sn and C/57 BL, that are respectively susceptible and resistant to glucocorticoid and non steroid anti-inflammatory drug induced cleft palate. At 13 days, in palatine process of the resistant strain and when these are still vertical, there was a significantly higher amount of extracellular matrix, constituted principally by hyaluronic acid. These differences disappeared at 14 days, when the processes became horizontal. The basal membrane of the medial palatine epithelium of the susceptible strain, showed interruptions due to a lower amount of glycoproteins. It is concluded that the observed differences in the amount and quality of these molecules, are a consequence of genetic differences that could determine the susceptibility to cleft palate