Microinjections of cultured rat conceptuses: studies with 4-oxo-all-trans-retinoic acid, 4-oxo-13-cis-retinoic acid and all-trans-retinoyl-beta-glucuronide

Teratology. 1992 Mar;45(3):259-70. doi: 10.1002/tera.1420450305.


4-Oxo-all-trans-retinoic acid, 4-oxo-13-cis-retinoic acid and all-trans-retinoyl-beta-glucuronide were intraamniotically microinjected in rat embryos on day 10 of gestation and cultured until day 11.5. A comparison of the concentration-effect relationships showed that the dysmorphogenic effects produced by these metabolites were qualitatively similar to those of parent all-trans-retinoic acid. Compared with all-trans-retinoic acid (300 ng/ml), the dysmorphogenic effects were elicited by a 2-fold higher concentration of 4-oxo-all-trans-retinoic acid, an approximately 10-fold higher concentration of 4-oxo-13-cis-retinoic acid and a 16-fold higher concentration of all-trans-retinoyl-beta-glucuronide. A surplus of uridine 5'-diphospho-glucuronic acid, microinjected together with 300 ng/ml all-trans-retinoic acid, decreased the observed embryo-toxicity of all-trans-retinoic acid, suggesting the possibility of glucuronidation in tissues of the conceptus per se. The results of the study provide further support for the hypothesis that 4-oxo-all-trans-retinoic acid and all-trans-retinoic acid are, in contrast to the corresponding cis-isomers and glucuronides, ultimate dysmorphogenic retinoids.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Amnion
  • Animals
  • Dose-Response Relationship, Drug
  • Embryo, Mammalian / drug effects
  • Microinjections*
  • Organ Culture Techniques
  • Rats
  • Rats, Inbred Strains
  • Teratogens / toxicity*
  • Tretinoin / administration & dosage
  • Tretinoin / analogs & derivatives*
  • Tretinoin / toxicity


  • Teratogens
  • 4-oxoretinoic acid
  • retinoyl glucuronide
  • Tretinoin