Congenital anomalies induced by triamcinolone acetonide in murine embryos.
BACKGROUND
We have studied the morphogenesis of anorectal malformations in mice using retinoids. Several investigators have reported an interaction between glucocorticoids and retinoids. It was supposed that glucocorticoids had some effects on the morphogenesis of murine embryos similar to retinoids. Therefore, we investigated alterations in the morphogenesis of murine embryos after triamcinolone acetonide (TAC) administration.


METHODS
TAC was administered in a single dose (15 mg/kg or 30 mg/kg body weight) to pregnant ICR-SLC mice on embryonic day 7 (E7), 8, 9, and 10. They were sacrificed on E18, and fetuses were examined for internal and external malformations. Randomly chosen fetuses were embedded in paraffin for immunohistochemical staining of the glucocorticoid receptor (GR).


RESULTS
The groups given 15 mg/kg TAC had one peak in the incidence of cleft palate on E9 (100 %) and the groups given 30 mg/kg TAC showed a biphasic pattern in the incidence of cleft palate on E7 and E10. No other anomalies were found. GR expression was marked in the subepithelial layer of palatal processes in the treated specimens.


CONCLUSIONS
The group given 15 mg/kg TAC on E9 provided a good model of cleft palate in ICR-SLC mice, and cleft palate was probably induced by various factors including disturbance of the bone morphogenetic protein (BMP) signaling pathway, shown by GR overexpression.
Miyagi
H
H
Department of Pediatric Surgery, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, Kyoto, Japan.
Kubota
Y
Y
Tsuda
T
T
Sasaki
Y
Y
Ono
S
S
Kimura
O
O
Iwai
N
N
D000818:Animals; D002972:Cleft Palate / Q000139:chemically induced* / Q000378:metabolism / Q000473:pathology; D000013:Congenital Abnormalities / Q000209:etiology; D004195:Disease Models, Animal; D004622:Embryo, Mammalian / Q000187:drug effects; D005260:Female; D005938:Glucocorticoids / Q000009:adverse effects*; D051379:Mice; D008813:Mice, Inbred ICR; D011247:Pregnancy; D011965:Receptors, Glucocorticoid / Q000096:biosynthesis; D014222:Triamcinolone Acetonide / Q000009:adverse effects*
D005938:Glucocorticoids; D011965:Receptors, Glucocorticoid; D014222:Triamcinolone Acetonide