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Cyclosporin-induced embryotoxicity in mice
A Fein1, M Vechoropoulos, L Nebel
1Department of Embryology and Teratology, Tel-Aviv University Medical School, Tel-Hashomer, Israel.
Abstract:
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.
Insights
Cyclosporin (CS) administration during pregnancy in mice did not increase maternal death but caused significant embryotoxicity. The drug reduced viable embryos and increased resorptions, indicating a clear adverse effect on fetal development.
Area of Science:
- Toxicology
- Developmental Biology
- Immunology
Background:
- Cyclosporin (CS) is an immunosuppressive drug with potential effects on pregnancy.
- Understanding CS's impact on embryonic development is crucial for risk assessment.
Purpose of the Study:
- To investigate the embryotoxic effects of cyclosporin (CS) in pregnant ICR mice.
- To evaluate the impact of CS on maternal organs and embryonic development at various gestational stages.
Main Methods:
- Pregnant ICR mice received daily injections of 30 mg/kg cyclosporin (CS) on gestational days 6-8 or 10-12.
- Control groups received saline injections.
- Mice were sacrificed at different time points (days 12, 15, 17, 19) for analysis.
- Embryos, placentae, and maternal organs were examined macroscopically and microscopically.
Main Results:
- Cyclosporin (CS) administration did not increase maternal mortality.
- Histological examination revealed transient pathological alterations in maternal thymus, liver, kidney, and spleen.
- CS significantly reduced the number of viable embryos and increased embryo resorptions.
- Microscopic examination indicated no adverse effects on embryonic organogenesis.
Conclusions:
- Cyclosporin (CS) at 30 mg/kg exhibits clear embryotoxic effects in ICR mice.
- The drug impacts pregnancy outcomes by reducing viable fetuses and increasing resorptions.
- While maternal organs showed transient changes, the primary concern is the drug's adverse effect on embryonic development.