Cyclosporin A-induced embryopathy in embryo culture is mediated through inhibition of the arachidonic acid pathway. Proc Soc Exp Biol Med 1993 Mar;202(3):307-14
Date
03/01/1993Pubmed ID
8437986DOI
10.3181/00379727-202-43540Scopus ID
2-s2.0-0027396914 (requires institutional sign-in at Scopus site) 8 CitationsAbstract
Embryos from Swiss Webster mice were grown in culture for 24 hr starting at Day 8.5 of gestation to study the effects of cyclosporin A (CsA) on the developing embryo. The embryos exposed to concentrations of CsA from 0.1 microgram/ml to 10.0 micrograms/ml developed a significant increase in the incidence of malformations from 28.6% to 78.6%, as compared with the 6.8% incidence of malformations in the control embryos. These malformations included defects in the neural tubes, head folds, and facial arches. In addition, inhibition of embryonic growth in CsA-exposed embryos was shown by a lower somite number, crown-rump length, and protein content than those of the control embryos. Supplementation of the culture medium with arachidonic acid or prostaglandin E2 decreased the incidence of CsA-induced malformations by 50% to 70% and prevented the CsA-induced inhibition of growth. We conclude that CsA causes abnormal embryonic development in mouse embryo culture and that the mechanism of CsA-induced embryopathy involves inhibition of the arachidonic acid pathway.
Author List
Uhing MR, Goldman AS, Goto MPMESH terms used to index this publication - Major topics in bold
Abnormalities, Drug-InducedAnimals
Arachidonic Acid
Culture Techniques
Cyclosporine
Dinoprostone
Dose-Response Relationship, Drug
Embryo, Mammalian
Embryonic and Fetal Development
Head
Mice
Neural Tube Defects
Proteins
Regression Analysis
