Cyclosporin-induced embryotoxicity in mice

Pregnant ICR mice were injected daily with 30 mg cyclosporin (CS)/kg body weight on days 6-8 or 10-12 of gestation. In parallel, control mice were administered saline injections on the same gestational days. The mice were sacrificed on days 12, 15, 17 or 19 of gestation. The number of resorption sites counted, the embryos and placentae were carefully separated, weighed and examined macro- and microscopically, along with various other maternal organs. It was found that 30 mg CS/kg body weight, when administered to pregnant ICR mice in 3 successive injections, did not raise the maternal mortality rate. Histological examination of maternal organs revealed pathological alterations in the thymus, liver, kidney and spleen; most changes had disappeared by 1 week following the last injection. CS reduced the number of viable embryos and increased the number of embryos resorbed. Microscopic examination of the embryos showed that organogenesis was not affected by the drug. However, CS, in the administered dose, had a clear embryotoxic effect.