Effects of estradiol administration on feto-placental growth in rat.

Background: To clarify the effect of estradiol benzoate on placental structure and its consequences for fetal survival and fetoplacental growth. Study design: Estradiol benzoate (0, 0.1, 1, 10, 100 μg/day) was infused intraperitoneally into pregnant Wistar rats from 12 to 19 days' gestation. Survival rate, weight of pups and placentas at 20 days' gestation, and plasma levels of estrogen and progesterone were measured. Pathological changes in the placenta were also examined. Results: Estradiol benzoate reduced fetal survival (1 μg/day: 100%, 10 μg/day: 70%, 100 μg/day: 14.6%) and the weights of the pups and placentas in a dose-dependent manner. Maternal estradiol concentration was raised 23-fold with 100μg/day of estradiol benzoate. Trophoblast degeneration, including apoptosis and destruction of placental labyrinth was induced but the structures of the maternal kidney and liver were not affected. Conclusions: In pregnant rats, estradiol benzoate causes fetal mortality at a pharmacological dose (more than 10 μg/day) and fetoplacental growth retardation via trophoblastic degeneration and destruction of the placental labyrinth even at a physiological dose (1 μg/day).