A SUSTAINED ELEVATION IN RETINOIC ACID RECEPTOR-BETA-2 MESSENGER-RNA AND PROTEIN OCCURS DURING RETINOIC ACID-INDUCED FETAL DYSMORPHOGENESIS

We have previously shown that oral treatment of pregnant mice with all -trans retinoic acid (RA) at doses which cause 100% fetal dysmorphogen esis results in a rapid elevation in the mRNA of one specific isoform of the RA receptor-beta, RAR-beta2, in susceptible embryonic regions. To further investigate the involvement of RAR-beta2 mRNA in teratogene sis, we have examined its expression in mouse embryos exposed to margi nal/nonteratogenic and teratogenic dosing regimens of both 13-cis RA a nd all-trans RA. We have found that the mere elevation in embryonic RA R-beta2 mRNA levels and free retinoid levels is not sufficient to resu lt in dysmorphogenesis. Rather, retinoid-induced dysmorphogenesis of e mbryos appears to occur only when RAR-beta2 mRNA and unbound retinoid levels remain elevated for at least 6-9 h following retinoid treatment resulting in a significant and prolonged elevation in RAR-beta protei n levels.