Cyclosporin A-induced embryopathy in embryo culture is mediated through inhibition of the arachidonic acid pathway.
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| 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.
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| Authors | M R Uhing, A S Goldman, M P Goto |
| Journal | Proceedings of the Society for Experimental Biology and Medicine. Society for Experimental Biology and Medicine (New York, N.Y.) (Proc Soc Exp Biol Med) Vol. 202 Issue 3 Pg. 307-14 (Mar 1993) ISSN: 0037-9727 [Print] United States |
| PMID | 8437986 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't) |
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