Retinoic acid (RA) is an active metabolite of vitamin A that is terato
genic when present in excess during mammalian embryogenesis. We have i
nvestigated the effect of embryonic exposure to nonphysiological level
s of all-trans RA on the development of the mouse inner ear. Dysmorpho
genesis of both vestibular and auditory portions of the inner ear, and
abnormal formation of the surrounding capsule are produced by exposur
e to teratogenic levels of RA at on embryonic age of 9 days (E9). Ther
e was no observable teratogenic effect of RA when administered at earl
ier (i.e., E7 or E8) or later (i.e., E10) stages of otic morphogenesis
. We hypothesize that exposure to high levels of RA during a critical
period of early otic morphogenesis interferes with the inductive tissu
e interactions required for inner ear development. (C) 1996 Wiley-Liss
, Inc.