title: Cyclosporin A-induced embryopathy in embryo culture is mediated through inhibition of the arachidonic acid pathway.
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.
authors.affiliation: Division of Neonatology, University of Illinois College of Medicine, Chicago 60612.
authors.forename: M R
authors.initials: MR
authors.lastname: Uhing
authors.forename: A S
authors.initials: AS
authors.lastname: Goldman
authors.forename: M P
authors.initials: MP
authors.lastname: Goto
mesh_terms: D000014:Abnormalities, Drug-Induced; D000818:Animals; D016718:Arachidonic Acid / Q000378:metabolism* / Q000494:pharmacology; D046508:Culture Techniques; D016572:Cyclosporine / Q000633:toxicity*; D015232:Dinoprostone / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004622:Embryo, Mammalian / Q000187:drug effects* / Q000502:physiology; D005314:Embryonic and Fetal Development / Q000187:drug effects*; D006257:Head / Q000002:abnormalities / Q000196:embryology; D051379:Mice; D009436:Neural Tube Defects / Q000139:chemically induced; D011506:Proteins / Q000378:metabolism; D012044:Regression Analysis
chemical_list: D011506:Proteins; D016718:Arachidonic Acid; D016572:Cyclosporine; D015232:Dinoprostone