THE EFFECTS OF THE ANTIHORMONES RU486 AND TAMOXIFEN ON FETOPLACENTAL DEVELOPMENT AND PLACENTAL BED VASCULARIZATION IN THE RAT - A MODEL FORINTRAUTERINE FETAL GROWTH-RETARDATION
S. Sadek et Sc. Bell, THE EFFECTS OF THE ANTIHORMONES RU486 AND TAMOXIFEN ON FETOPLACENTAL DEVELOPMENT AND PLACENTAL BED VASCULARIZATION IN THE RAT - A MODEL FORINTRAUTERINE FETAL GROWTH-RETARDATION, British journal of obstetrics and gynaecology, 103(7), 1996, pp. 630-641
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.