TERATOGENESIS BY RETINOIC ACID ANALOGS POSITIVELY CORRELATES WITH ELEVATION OF RETINOIC ACID RECEPTOR-BETA-2 MESSENGER-RNA LEVELS IN TREATED EMBRYOS

Retinoic acid (RA) plays an important role during normal embryogenesis , however high doses of RA are teratogenic. Retinoic acid receptor-bet a 2 (RAR-beta 2) mRNA and protein levels were previously demonstrated to undergo rapid elevation in susceptible tissues after treatment with teratogenic doses of RA. In this report we compared the effects of a number of retinoids, which represent a wide va rie?l of chemical struc tures and which differ in their teratogenic potencies, on RAR-beta 2 m RNA levels in mouse embryos 6 hr after treatment. Retinoid treatments which result in a high incidence of limb defects elevated RAR-beta 2 m RNA levels similarly (10-14 fold in the limb buds, 4-8 fold in the hea d, and 2-4 fold in the remainder of the body). On the other hand, reti noid treatments which cause a low or no incidence of limb defects resu lted in minor changes in RAR-beta 2 mRNA levels in each embryonic regi on. Therefore, a strong positive correlation was found between the ele vation of RAR-beta 2 mRNA levels and the retinoids which produce limb defects. This provides further evidence that an elevation of RAR-beta 2 mRNA levels, and subsequently protein levels, is an important event involved in mediating the effects of RA during dysmorphogenesis. (C) 1 994 Wiley-Liss, Inc.