Faculty Collaboration Database

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

03/01/1993

Pubmed ID

8437986

DOI

10.3181/00379727-202-43540

Scopus ID

2-s2.0-0027396914 (requires institutional sign-in at Scopus site)   8 Citations

Abstract

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 MP

Author

Michael R. Uhing MD Professor in the Pediatrics department at Medical College of Wisconsin

MESH terms used to index this publication - Major topics in bold

Abnormalities, Drug-Induced
Animals
Arachidonic Acid
Culture Techniques
Cyclosporine
Dinoprostone
Dose-Response Relationship, Drug
Embryo, Mammalian
Embryonic and Fetal Development
Head
Mice
Neural Tube Defects
Proteins
Regression Analysis