Palatal Slit and Cleft Palate in Rats Treated with a Glucocorticoid 1. Teratogenicity of Dexamethasone

Abstract

The sensitive period and the dose‐response characteristics for dexametha‐sone‐induced cleft palate and palatal slit in rats were examined. Pregnant rats were injected subcutaneously with dexamethasone in a single dose of 2–6 mg/kg on one day between day 8 and 16 of the gestational period or once each day for two successive days (days 14 and 15 of gestation). All animals were euthanized on day 20 of gestation and the palatal condition of their fetuses was inspected after fixation under a dissecting microscope. The sensitive stage of palatal slit and cleft palate induction was determined and the dose‐response relationship was analyzed by the log‐probit transformation method. No maternal lethality was elicited in any of the treatment groups. High frequencies of palatal slit and cleft palate were induced when dexamethasone was administered as a single dose on any individual day from day 12 to day 14 of gestation. Omphalocele and general edema were also found to be significantly more frequent in the high‐dose group treated on days 12–14 of gestation. All groups treated showed a reduction in fetal body weight. The response data for palatal slit and cleft palate after administration of dexamethasone fitted to similar linear regression slopes, suggesting a similarity in the underlying mechanisms for palatal slit and cleft palate induction in rats. ED50 values were 3.48 mg/kg for palatal slit and 6.64 mg/kg for cleft palate. These findings indicate that dexamethasone treatment is effective in inducing palatal slit and cleft palate in rats, as well as in mice. Key words: glucocorticoid, dexamethasone, palatal slit, cleft palate, sensitive stage, doseresponse, rats

Palatal Slit and Cleft Palate in Rats Treated with Glucocorticoids II. Comparative Teratogenicity of Prednisolone, Triamcinolone Acetonide and Hydrocortisone

“…Data from Ishizuka et al (1993) induction of palatal slit in rats, as well as in mice. However, palatal defects were not observed after treatment with 100 mg/kg/day hydrocortisone.…”

“…They were then fixed in 10% formalin solution for about 7 days and evaluated for palatal abnormalities under a dissecting microscope after cutting the region between the upper and lower jaws. Severe type of palatal slit; cone-shaped, triangular cleft was evaluated also in this study in order to compare with the potency of dexamethasone in inducing palatal slit (Ishizuka et al, 1993).…”

“…Other developmental abnormalities including omphalocele and general edema, late resorption, and growth retardation were induced by triamcinolone acetonide and prednisolone. These findings indicate that triamcinolone acetonide has a significantly higher potentiality for the induction of palatal slit in rats, as well as in mice, compared to prednisolone and hydrocortisone.In a previous study (Ishizuka et al, 1993), it was reported that dexamethasone produces palatal slits with an appreciable frequency in rat fetuses, as well as in mouse fetuses. Palatal slit involved a failure of fusion of the premaxilla and palatal shelves, corresponding to stage 7 in normal palatal closure (Biddle, 1980).…”

“…In a previous study (Ishizuka et al, 1993), it was reported that dexamethasone produces palatal slits with an appreciable frequency in rat fetuses, as well as in mouse fetuses. Palatal slit involved a failure of fusion of the premaxilla and palatal shelves, corresponding to stage 7 in normal palatal closure (Biddle, 1980).…”

“…Thus, in the present study, we studied induction of another palatal defect, palatal slit, by a few other glucocorticoids, prednisolone, triamcinolone acetonide and hydrocortisone in rat fetuses. Comparative evaluation with results of previous studies using dexamethasone (Ishizuka et al, 1993) was also carried out.…”