Distribution of all-trans-, 13-cis- and 9-cis-retinoic acid to whole rat embryos and maternal serum following oral administration of a teratogenic dose of all-trans-retinoic acid. 1995

S J Ward, and G M Morriss-Kay
Department of Anatomy, Oxford, U.K.

Maternal administration of 200 mg/kg all-trans-retinoic acid to rat embryos at early limb stages of development (day 12 to day 13.5 post coitum) results in limb reduction defects. In order to determine the duration of exposure of the embryo to raised levels of all-trans-retinoic acid, we have used high performance liquid chromatography to measure retinoid levels at a series of time intervals following maternal administration on day 12.5 post coitum. Raised levels of all-trans-retinoic acid and 13-cis-retinoic acid were detectable in embryos after 30 min., reached a peak at 2 hr, and had fallen sharply by 4 hr. 13-cis-Retinoic acid levels were undetectable after 4 hr, and all-trans-retinoic acid levels after 8 hr. 9-cis-retinoic acid levels rose more slowly, were less elevated, and fell more gradually than the other two retinoids. The retinoid profiles in maternal serum were similar. The results indicate that induction of limb abnormalities by all-trans-retinoic acid in rat embryos is associated with a relatively short-term rise in embryonic retinoid levels.

UI MeSH Term Description Entries
D008431 Maternal-Fetal Exchange Exchange of substances between the maternal blood and the fetal blood at the PLACENTA via PLACENTAL CIRCULATION. The placental barrier excludes microbial or viral transmission. Transplacental Exposure,Exchange, Maternal-Fetal,Exposure, Transplacental,Maternal Fetal Exchange
D011247 Pregnancy The status during which female mammals carry their developing young (EMBRYOS or FETUSES) in utero before birth, beginning from FERTILIZATION to BIRTH. Gestation,Pregnancies
D004622 Embryo, Mammalian The entity of a developing mammal (MAMMALS), generally from the cleavage of a ZYGOTE to the end of embryonic differentiation of basic structures. For the human embryo, this represents the first two months of intrauterine development preceding the stages of the FETUS. Embryonic Structures, Mammalian,Mammalian Embryo,Mammalian Embryo Structures,Mammalian Embryonic Structures,Embryo Structure, Mammalian,Embryo Structures, Mammalian,Embryonic Structure, Mammalian,Embryos, Mammalian,Mammalian Embryo Structure,Mammalian Embryonic Structure,Mammalian Embryos,Structure, Mammalian Embryo,Structure, Mammalian Embryonic,Structures, Mammalian Embryo,Structures, Mammalian Embryonic
D005260 Female Females
D000284 Administration, Oral The giving of drugs, chemicals, or other substances by mouth. Drug Administration, Oral,Administration, Oral Drug,Oral Administration,Oral Drug Administration,Administrations, Oral,Administrations, Oral Drug,Drug Administrations, Oral,Oral Administrations,Oral Drug Administrations
D000818 Animals Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, Animalia was one of the kingdoms. Under the modern three domain model, Animalia represents one of the many groups in the domain EUKARYOTA. Animal,Metazoa,Animalia
D012176 Retinoids A group of tetraterpenes, with four terpene units joined head-to-tail. Biologically active members of this class are used clinically in the treatment of severe cystic ACNE; PSORIASIS; and other disorders of keratinization. Retinoid
D013723 Teratogens An agent that causes the production of physical defects in the developing embryo. Embryotoxins,Fetotoxins,Teratogen
D014212 Tretinoin An important regulator of GENE EXPRESSION during growth and development, and in NEOPLASMS. Tretinoin, also known as retinoic acid and derived from maternal VITAMIN A, is essential for normal GROWTH; and EMBRYONIC DEVELOPMENT. An excess of tretinoin can be teratogenic. It is used in the treatment of PSORIASIS; ACNE VULGARIS; and several other SKIN DISEASES. It has also been approved for use in promyelocytic leukemia (LEUKEMIA, PROMYELOCYTIC, ACUTE). Retinoic Acid,Vitamin A Acid,Retin-A,Tretinoin Potassium Salt,Tretinoin Sodium Salt,Tretinoin Zinc Salt,Vesanoid,all-trans-Retinoic Acid,beta-all-trans-Retinoic Acid,trans-Retinoic Acid,Acid, Retinoic,Acid, Vitamin A,Acid, all-trans-Retinoic,Acid, beta-all-trans-Retinoic,Acid, trans-Retinoic,Potassium Salt, Tretinoin,Retin A,Salt, Tretinoin Potassium,Salt, Tretinoin Sodium,Salt, Tretinoin Zinc,Sodium Salt, Tretinoin,Zinc Salt, Tretinoin,all trans Retinoic Acid,beta all trans Retinoic Acid,trans Retinoic Acid
D015474 Isotretinoin A topical dermatologic agent that is used in the treatment of ACNE VULGARIS and several other skin diseases. The drug has teratogenic and other adverse effects. 13-cis-Retinoic Acid,Accutane,Isotretinoin Zinc Salt, 13-cis-Isomer,Ro 4-3780,Roaccutane,13 cis Retinoic Acid,Isotretinoin Zinc Salt, 13 cis Isomer,Ro 4 3780,Ro 43780

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