THE EFFECTS OF THE ANTIHORMONES RU486 AND TAMOXIFEN ON FETOPLACENTAL DEVELOPMENT AND PLACENTAL BED VASCULARIZATION IN THE RAT - A MODEL FORINTRAUTERINE FETAL GROWTH-RETARDATION

Objective To examine the effect of administration of the antihormones RU486 and tamoxifen in early pregnancy during the period of maximal de cidual development in the rat upon fetoplacental and placental bed dev elopment. Design Case-control study in an experimental animal model. S etting Academic department of obstetrics and gynaecology in a UK medic al school. Animals Small laboratory animal-the rat-exhibiting haemocho rial placentation. Intervention Administration of antiprogesterone or antioestrogen (RU486 and tamoxifen respectively) during early pregnanc y. Main outcome measures Weight of the whole pregnancy implant, fetus, mesometrial decidua and placenta; incidence of intrauterine fetal dea th; and histological changes in the placental bed. Results RU486 produ ced resorption of all implants when administered above a threshold dos e, below which it had no effect upon subsequent fetoplacental developm ent. Tamoxifen treatment on days 9 to 11 resulted in significant reduc tion of decidual weight (35.1% on day 12 of pregnancy, P < 0.001). Thi s was associated with a higher rate of implants or fetuses weighing be low the 10th centile (59.6% and 5.7% on day 12, P < 0.001; 42.9% and 7 % on day 16, P < 0.001; 25.4% and 7.6% on day 20, P < 0.001 in treated and control animals, respectively). This was also associated with a h igher rate of intrauterine fetal death (30.7% on day 16 compared with 4.5% in controls, P < 0.001; 47.8% on day 20 compared to 0.83% in cont rols, P < 0.001). Histologically, the placental bed of treated animals failed to develop a dilated uteroplacental artery although trophoblas t cells migrated endovascularly to a level equivalent to untreated ani mals. Conclusions RU486 had an all or none dose-dependent effect on fe toplacental development, resulting in either abortion or normal develo pment of pregnancy. Tamoxifen produced significant impairment of decid ual development, which was associated with altered blood vessel transf ormation in the placental bed, impaired fetoplacental development and higher incidence of growth retarded fetuses and fetal death.