Jove
Visualize
Contact Us
JoVE
x logofacebook logolinkedin logoyoutube logo
ABOUT JoVE
OverviewLeadershipBlogJoVE Help Center
AUTHORS
Publishing ProcessEditorial BoardScope & PoliciesPeer ReviewFAQSubmit
LIBRARIANS
TestimonialsSubscriptionsAccessResourcesLibrary Advisory BoardFAQ
RESEARCH
JoVE JournalMethods CollectionsJoVE Encyclopedia of ExperimentsArchive
EDUCATION
JoVE CoreJoVE BusinessJoVE Science EducationJoVE Lab ManualFaculty Resource CenterFaculty Site
Terms & Conditions of Use
Privacy Policy
Policies

Related Experiment Videos

9-cis-retinoic acid: a direct-acting dysmorphogen

J C Kraft1, M R Juchau

  • 1Department of Pharmacology, School of Medicine, University of Washington, Seattle 98195.

Biochemical Pharmacology
|August 17, 1993
PubMed
Summary

9-cis-retinoic acid (9-cis-RA) causes birth defects in rat embryos, including head and heart abnormalities. It converts to a less active form, but eventually to a potent dysmorphogen, all-trans-RA.

Related Concept Videos

You might also read

Related Articles

Articles linked to this work by shared authors, journal, and citation graph.

Sort by
Same author

Pharmacogenetics and anaesthesia: the value of genetic profiling.

Anaesthesia·2012
Same author

In vivo dopamine release and uptake impairments in rats treated with 3-nitropropionic acid.

Neuroscience·2009
Same author

Enzymic catalysis of the accumulation of acetaldehyde from ethanol in human prenatal cephalic tissues: evaluation of the relative contributions of CYP2E1, alcohol dehydrogenase, and catalase/peroxidases.

Alcoholism, clinical and experimental research·2000
Same author

Catalysis of the 4-hydroxylation of retinoic acids by cyp3a7 in human fetal hepatic tissues.

Drug metabolism and disposition: the biological fate of chemicals·2000
Same author

Patterns of CYP26 expression in human prenatal cephalic and hepatic tissues indicate an important role during early brain development.

Brain research. Developmental brain research·2000
Same author

Biosynthesis of all-trans-retinoic acid from all-trans-retinol: catalysis of all-trans-retinol oxidation by human P-450 cytochromes.

Drug metabolism and disposition: the biological fate of chemicals·2000

Area of Science:

  • Developmental biology
  • Toxicology
  • Teratology

Background:

  • Retinoids, including retinoic acid isomers, are crucial for embryonic development.
  • All-trans-retinoic acid (all-trans-RA) is a known teratogen, causing birth defects.
  • The specific role and teratogenic potential of 9-cis-retinoic acid (9-cis-RA) in embryonic development require further elucidation.

Purpose of the Study:

  • To investigate the teratogenic effects of 9-cis-RA on early embryonic development in vitro.
  • To compare the developmental toxicity of 9-cis-RA with all-trans-RA.
  • To explore the metabolic fate and potential conversion of 9-cis-RA to other retinoic acid isomers during embryogenesis.

Main Methods:

  • In vitro culture of rat conceptuses.
  • Intraamniotic microinjection of 9-cis-RA.
  • High-performance liquid chromatography (HPLC) for metabolite analysis.
  • Assessment of morphological defects in developing embryos.

Main Results:

  • 9-cis-RA induced branchial arch and somite defects, similar to all-trans-RA.
  • Higher concentrations of 9-cis-RA led to increased cephalic defects, including optic vesicle agenesis.
  • An unusual heart defect was observed following 9-cis-RA administration.
  • 9-cis-RA was converted to 13-cis-RA within 4 hours and to all-trans-RA after 6 hours in cultured conceptuses.
  • No detectable conversion of 13-cis-RA or all-trans-RA to 9-cis-RA was observed.
  • Endogenous 9-cis-RA levels were below detection limits in whole embryos.

Conclusions:

  • 9-cis-RA acts as a direct-acting dysmorphogen in rat embryonic development.
  • The teratogenic effects of 9-cis-RA are likely mediated through its conversion to all-trans-RA.
  • Specific target sites for 9-cis-RA's teratogenic action may exist.

Related Experiment Videos