The effects of the antihormones RU486 and tamoxifen on fetoplacental development and placental bed vascularisation in the rat: a model for intrauterine fetal growth retardation

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Abstract
Objective To examine the effect of administration of the antihormones RU486 and tamoxifen in early pregnancy during the period of maximal decidual development in the rat upon fetoplacental and placental bed development. Design Case-control study in an experimental animal model. Setting Academic department of obstetrics and gynaecology in a UK medical school. Animals Small laboratory animal—the rat—exhibiting haemochorial placentation. Intervention Administration of antiprogesterone or antioestrogen (RU486 and tamoxifen respectively) during early pregnancy. Main outcome measures Weight of the whole pregnancy implant, fetus, mesometrial decidua and placenta; incidence of intrauterine fetal death; and histological changes in the placental bed. Results RU486 produced resorption of all implants when administered above a threshold dose, below which it had no effect upon subsequent fetoplacental development. Tamoxifen treatment on days 9 to 11 resulted in significant reduction of decidual weight (35.1% on day 12 of pregnancy, P < 0.001). This was associated with a higher rate of implants or fetuses weighing below 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 higher rate of intrauterine fetal death (30.7% on day 16 compared with 4.5% in controls, P < 0001; 47.8% on day 20 compared to 0.83% in controls, P < 0.001). Histologically, the placental bed of treated animals failed to develop a dilated uteroplacental artery although trophoblast cells migrated endovascularly to a level equivalent to untreated animals. Conclusions RU486 had an all or none dose-dependent effect on fetoplacental development, resulting in either abortion or normal development of pregnancy. Tamoxifen produced significant impairment of decidual development, which was associated with altered blood vessel transformation in the placental bed, impaired fetoplacental development and higher incidence of growth retarded fetuses and fetal death.