Comparison of dexamethasone-induced embryotoxicity in vitro in mouse and rat embryos.
Previous work demonstrated that rat embryos were more susceptible to the growth retardation effect of the synthetic glucocorticoid dexamethasone (DEX) in vivo than were mouse embryos. The purpose of this study was to examine this species difference using an in vitro system. Embryos of CD rats and CD-1 mice were cultured in a whole embryo culture system with concentrations of DEX from 5 to 250 micrograms/ml. Rat embryos were explanted on day 9 of gestation (GD 9: plug day = GD 0), while mouse embryos were removed on GD 8. After 48 h in culture, each viable embryo was evaluated for morphological score, and the number of somite pairs, crown-rump, and head lengths, as well as DNA and protein concentrations were determined. A reduced morphological score was observed for mouse embryos at 5 micrograms DEX/ml, but a significant decrease in this parameter was only observed at DEX concentrations of > or = 100 micrograms/ml in rat embryos. Significant reductions in the number of somite pairs were observed at 25 micrograms/ml for mouse embryos and 100 micrograms/ml for rat embryos. Crown-rump and head lengths as well as DNA and protein concentrations were significantly decreased at 100 micrograms/ml in mouse embryos and 150 micrograms/ml in rat embryos. Therefore, in vitro mouse embryos were adversely affected by lower concentrations of DEX than were rat embryos for each of the six end points examined in this study. This species sensitivity in vitro could be due to inherent genetic differences or to the slightly different developmental stages evaluated using the culture system.(ABSTRACT TRUNCATED AT 250 WORDS)
Hansen
D K
DK
Department of Health and Human Services, Food and Drug Administration, Jefferson, Arkansas.
Grafton
T F
TF
D000014:Abnormalities, Drug-Induced / Q000209:etiology*; D000704:Analysis of Variance; D000818:Animals; D046508:Culture Techniques; D003907:Dexamethasone / Q000633:toxicity*; D005314:Embryonic and Fetal Development / Q000187:drug effects; D051379:Mice / Q000196:embryology*; D051381:Rats / Q000196:embryology*; D013045:Species Specificity
D003907:Dexamethasone