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

Abstract

The induction of abnormal palatal development by three glucocorticoids; prednisolone, triamcinolone acetonide and hydrocortisone was evaluated in rat fetuses.Pregnant rats were injected subcutaneously with either prednisolone (12.5-100 mgkgl day), triamcinolone acetonide (0.25-2 mg/kg/day) or hydrocortisone (1 00 mg/kg/day) on days 14 and 15 of gestation. These females were humanely killed on day 20 of gestation and viable fetuses were inspected for their palatal abnormalities. The frequencies of cleft palate were significantly higher in the group treated with 100 mg/kg/day prednisolone (10.6%), and in the groups treated with 0.5, 1 and 2 mg/kg/day triamcinolone acetonide (8.6%, 26.1% and 58.3%, respectively) than the control frequency of 0%. Triamcinolone acetonide was 70 times as potent as prednisolone in inducing palatal slit, with ED50 value of 1 .O mgkg/day and 70 mgkg/day, respectively. Hydrocortisone showed no potentiality for the induction of cleft palate and palatal slit. 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 normal development, the premaxilla fuses with the dorsal part of the palatal shelves, from the foremost to near the third ruga; palatal slit does not show such fusion and the oral cavity connected with the nasal cavity

NAEPP Expert Panel ReportManaging Asthma During Pregnancy: Recommendations for Pharmacologic Treatment—2004 Update

“…Nine experimental animal studies [38][39][40][41][42][43][44][45][46] and eight human studies were included. The animal studies do not change the previous understanding (Asthma and Pregnancy Report 1993) 5 of the steroid-mediated clefting or decreases in fetal growth in animals.…”