Effects of the Ay gene on susceptibility to hydrocortisone fetotoxicity and teratogenicity in mice.
Effects of the Ay gene, a coat color gene, on susceptibility to hydrocortisone fetotoxicity and teratogenicity were investigated by using the congenic strain of C57BL/6-Ay (Ay/a) which had been maintained by repeated back-crosses of the Ay gene to the C57BL/6 (a/a) background. Matings were conducted as follows (female x male): group I, a/a; group II, a/a x Ay/a; and group III, Ay/a x a/a. Pregnant females were subcutaneously given daily doses of 0, 12.5, 25, or 50 mg/kg of hydrocortisone on days 10-13 of pregnancy. On day 18 of pregnancy, fetuses were sexed, weighed, and examined for external abnormalities. In group I, the mean fetal weight was significantly decreased at a dose of 25 mg/kg or more. The incidences of cleft palate were 3.2 and 22.7% at 25 and 50 mg/kg, respectively. In group II, in which half of the fetuses were expected to carry the Ay gene, the mean fetal weight was decreased significantly at 12.5 mg/kg or more. The incidence of cleft palate in group II at 50 mg/kg was 44.2%, which was significantly higher than that in group I. In group III, in which maternal mice as well as half of their fetuses carried the Ay gene, a decrease in the mean fetal weight was greater than in group II. In addition, the mean percentage of fetal resorptions was significantly increased at 50 mg/kg. The incidence of cleft palate in group III was significantly increased at 25 mg/kg (10.5%) when compared with those in groups I and II. These results indicate that the Ay gene may be associated with susceptibility to hydrocortisone fetotoxicity and teratogenicity in mice.
Teramoto
S
S
Mitsukaida Laboratories, Institute of Environmental Toxicology, Ibaraki, Japan.
Hatakenaka
N
N
Shirasu
Y
Y
D000014:Abnormalities, Drug-Induced / Q000196:embryology / Q000235:genetics*; D000818:Animals; D002972:Cleft Palate / Q000196:embryology / Q000235:genetics*; D004198:Disease Susceptibility / Q000196:embryology; D005314:Embryonic and Fetal Development / Q000187:drug effects; D005260:Female; D005799:Genes, Dominant / Q000235:genetics*; D020022:Genetic Predisposition to Disease; D006854:Hydrocortisone / Q000633:toxicity*; D008431:Maternal-Fetal Exchange / Q000502:physiology*; D051379:Mice; D008810:Mice, Inbred C57BL; D011247:Pregnancy
D006854:Hydrocortisone