Cyclosporine-induced fetotoxicity in the rat

Female Lewis rats mated with DA male rats were given 25 or 10 mg/kg/day cyclosporine (CsA) from the time of mating to 20 days postcoitus when autopsies were performed. At the higher dose, characteristic drug-induced pathological changes in the mother were accompanied by a striking fetotoxic effect, resulting in a high incidence of fetal mortality or in runting. In addition, fetal kidneys that could be examined showed evidence of CsA-induced proximal tubular cell damage. These abnormalities were not found at the lower dosage of CsA. The fetotoxicity observed at 25 mg/kg did not appear to be dependent on major histocompatibility differences between parental strains, since it was also observed, at the same dosage, in syngeneically mated female Lewis rats.