Teratogenesis by retinoic acid analogs positively correlates with elevation of retinoic acid receptor-β2 mRNA levels in treated embryos
| Autor: | Michael Gyda, D. M. Kochhar, Dianne Robert Soprano, Kenneth J. Soprano, Roshantha A.S. Chandraratna, Heng Jiang, Douglas C. Harnish |
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| Rok vydání: | 1994 |
| Předmět: |
Embryology
medicine.medical_specialty Ectromelia Receptors Retinoic Acid medicine.drug_class Health Toxicology and Mutagenesis Retinoic acid Tretinoin Biology Toxicology Benzoates Mice Retinoids chemistry.chemical_compound Isomerism Internal medicine Gene expression medicine Animals RNA Messenger Retinoid Mice Inbred ICR Messenger RNA Embryogenesis Abnormalities Drug-Induced Embryo Retinoic acid receptor Endocrinology Mechanism of action chemistry embryonic structures Fatty Acids Unsaturated Female medicine.symptom Developmental Biology |
| Zdroj: | Teratology. 50:38-43 |
| ISSN: | 1096-9926 0040-3709 |
| DOI: | 10.1002/tera.1420500106 |
| Popis: | Retinoic acid (RA) plays an important role during normal embryogenesis, however high doses of RA are teratogenic. Retinoic acid receptor-beta 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 variety of chemical structures and which differ in their teratogenic potencies, on RAR-beta 2 mRNA levels in mouse embryos 6 hr after treatment. Retinoid treatments which result in a high incidence of limb defects elevated RAR-beta 2 mRNA levels similarly (10-14 fold in the limb buds, 4-8 fold in the head, and 2-4 fold in the remainder of the body). On the other hand, retinoid treatments which cause a low or no incidence of limb defects resulted in minor changes in RAR-beta 2 mRNA levels in each embryonic region. Therefore, a strong positive correlation was found between the elevation 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. |
| Databáze: | OpenAIRE |
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