Effects of cyclophosphamide treatment before implantation on the development of rat embryos after implantation.

After treatment of pregnant rats 24 h before implantation with a single injection of cyclophosphamide (20--80 mg/kg), a dose-dependent increase in resorption was observed at term but no malformed fetuses could be found. The lowest cyclophosphamide dose that caused 100% resoprtion was 60 mg/kg. Somite number and wet weight indicated retardation of about 24 h during organogenesis. Determination of the time of implantation revealed that the developmental retardation in treated embryos was not due to delayed implantation. At implantation, 24 h after cyclophosphamide treatment, a significant and dose-dependent decrease of the cell number of blastocysts was found. Embryo transplantation experiments showed that early cyclophosphamide treatment interfered with the subsequent development of both the embryo and the mother. The decidual reaction seemed to be more affected by the treatment than the embryos. Most teratologists hold that mouse embryos after treatment in the preimplantation period either die before implantation or survive to term without being malformed. The present study, however, proves that the reaction of drugs at this early stage of pregnancy is more complex than is generally assumed.