Glucocorticoid teratogenesis in mouse whole embryo culture.
Glucocorticoids, such as triamcinolone acetonide (TAC-A) and triamcinolone hexacetonide (TAC-HA), are potent inducers of cleft palate in vivo in various mouse strains when administered on day 11 of gestation, whereas they are poor or ineffective inducers of cleft lip when given on day 7. The purpose of the present study was to determine whether glucocorticoids are capable of interfering with early embryonic development in culture. CD-1 mouse embryos were cultured for 48 hours starting either on day 8 (plug day 0) with the embryo inside the yolk sac, or on day 10 with the embryo exteriorized from its functional yolk sac. At the end of the culture period, embryos were examined grossly for malformations and biochemically for altered DNA and protein levels. With the day 8 cultures, TAC-A produced a dose-dependent inhibition of growth along with malformations consisting of cardiac irregularities, abnormal rotation, and irregular neural tube closure. With the day 10 cultures, these malformations were not observed, presumably due to the advanced stage of development when the embryos were exposed to TAC-A; however, TAC-A did produce growth inhibition along with cleft lip. When TAC-HA was administered in vivo to pregnant donor females on day 7, in combination with TAC-A added on day 10 to the culture medium, there was a dramatic increase in the frequency of cleft lip along with other alterations in craniofacial appearance. Our results demonstrate that glucocorticoids are capable of directly affecting embryonic growth and development during the early stages of organogenesis.
D000014:Abnormalities, Drug-Induced; D000818:Animals; D002971:Cleft Lip / Q000139:chemically induced; D002972:Cleft Palate / Q000139:chemically induced; D046508:Culture Techniques; D005314:Embryonic and Fetal Development / Q000187:drug effects; D005145:Face / Q000002:abnormalities; D005865:Gestational Age; D006330:Heart Defects, Congenital / Q000139:chemically induced; D051379:Mice; D014222:Triamcinolone Acetonide / Q000031:analogs & derivatives* / Q000633:toxicity*
D014222:Triamcinolone Acetonide; C005900:triamcinolone hexacetonide