Decidual changes in the rat following cyclophosphamide treatment before implantation

To explain the teratogenic action of cyclophosphamide treatment during the preimplantation period (day 3; 60 mg/kg), the decidual reaction of the uterus was studied in the rat by light microscopy and autoradiography on day 4 (preimplantation period) and on days 5 and 6 (implantation period). On day 4, 24 h after cyclophosphamide treatment, the 3H-thymidine labelling index of the stroma cells beneath the uterine epithelium was significantly increased (33.7 +/- 5.2%) as compared to untreated control animals (6.5 +/- 0.4%). In addition, the surface of the uterine lumina appeared smoother in treated animals than in controls. On day 5 of gestation no difference could be detected autoradiographically between the uteri and treated and untreated animals. Histologically, however, the decidual reaction in treated animals occupied a larger area than in controls. On day 6 of pregnancy the 3H-labelling index of stroma cells surrounding the implantation site of treated animals was considerably reduced (10.7 vs. 32.8% in controls) and necrotic stroma cells were found in the area around the implantation site. Mechanisms inducing the decidual changes in cyclophosphamide-treated animals are discussed.