A sustained elevation in retinoic acid receptor-beta 2 mRNA 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 dysmorphogenesis results in a rapid elevation in the mRNA of one specific isoform of the RA receptor-beta, RAR-beta 2, in susceptible embryonic regions. To further investigate the involvement of RAR-beta 2 mRNA in teratogenesis, we have examined its expression in mouse embryos exposed to marginal/nonteratogenic and teratogenic dosing regimens of both 13-cis RA and all-trans RA. We have found that the mere elevation in embryonic RAR-beta 2 mRNA levels and free retinoid levels is not sufficient to result in dysmorphogenesis. Rather, retinoid-induced dysmorphogenesis of embryos appears to occur only when RAR-beta 2 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 protein levels.
Department of Biochemistry, Temple University School of Medicine, Philadelphia, PA 19140.
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D000818:Animals; D002851:Chromatography, High Pressure Liquid; D005260:Female; D005333:Fetus / Q000002:abnormalities / Q000378:metabolism; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D009024:Morphogenesis; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism*; D018168:Receptors, Retinoic Acid / Q000235:genetics / Q000378:metabolism*; D013723:Teratogens / Q000494:pharmacology*; D014212:Tretinoin / Q000494:pharmacology*
D012333:RNA, Messenger; D018168:Receptors, Retinoic Acid; D013723:Teratogens; C082927:retinoic acid binding protein I, cellular; C082928:retinoic acid binding protein II, cellular; C082925:retinoic acid receptor beta; D014212:Tretinoin