Spielmann H, Eibs H G, Merker H J
J Embryol Exp Morphol. 1977 Oct;41:65-78.
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.
在植入前24小时给怀孕大鼠单次注射环磷酰胺（20 - 80毫克/千克）后，足月时观察到吸收呈剂量依赖性增加，但未发现畸形胎儿。导致100%吸收的最低环磷酰胺剂量为60毫克/千克。体节数量和湿重表明在器官发生过程中发育迟缓约24小时。植入时间的测定表明，经处理胚胎的发育迟缓并非由于植入延迟。在环磷酰胺处理后24小时植入时，发现囊胚细胞数量显著且呈剂量依赖性减少。胚胎移植实验表明，早期环磷酰胺处理会干扰胚胎和母体的后续发育。蜕膜反应似乎比胚胎更受该处理的影响。大多数致畸学家认为，植入前期处理后的小鼠胚胎要么在植入前死亡，要么足月存活且无畸形。然而，本研究证明，药物在怀孕早期阶段的反应比一般认为的更为复杂。
