Dose-response of retinoic acid induced stress protein synthesis and teratogenesis in mice

Stress proteins are synthesized in response to a variety of stressors, including several teratogenic agents. However, their role, if any, in the teratogenic process is unknown. We have previously demonstrated that all-trans-retinoic acid administered to pregnant CD-1 mice on gestational day 11 or 13...

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Bibliographic Details
Published in:Reproductive toxicology (Elmsford, N.Y.) N.Y.), 2001, Vol.15 (1), p.31-41
Main Authors: HANSEN, Deborah K, LABORDE, James B, WALL, Kelly S, HINSON, William G, PIPKIN, James L, SHADDOCK, Joe, LYN-COOK, Lascelles, YOUNG, John F
Format: Article
Language:English
Subjects:
Abnormalities, Drug-Induced
Animals
Biological and medical sciences
Dose-Response Relationship, Drug
Embryology: invertebrates and vertebrates. Teratology
Female
Fundamental and applied biological sciences. Psychology
Heat-Shock Proteins - biosynthesis
Mice
Pregnancy
stress proteins
Teratology. Teratogens
Tretinoin - toxicity
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Summary:Stress proteins are synthesized in response to a variety of stressors, including several teratogenic agents. However, their role, if any, in the teratogenic process is unknown. We have previously demonstrated that all-trans-retinoic acid administered to pregnant CD-1 mice on gestational day 11 or 13 produced limb defects and cleft palate near term in a dose-responsive manner. This chemical also induced the synthesis of several nuclear stress proteins in embryonic tissues within several hours of dosing. The stress proteins were only observed in tissues that eventually became malformed and not in tissues that appeared normal at term. In the current work, we examined the stress response in embryonic target tissues after several different doses of retinoic acid. The nuclear stress proteins were synthesized in a dose-related manner and at a lower retinoic acid dose than doses producing malformations in the corresponding tissue at birth. Each individual stress protein and the total stress protein response were highly correlated, across dose, with the respective malformations observed at term.
ISSN:0890-6238
1873-1708