Ketoconazole-induced estrogen deficiency causes transient decrease in placental blood flow associated with hypoxia and later placental weight gain in rats

This study investigated the relationship among estrogen, placental blood flow and placental weight gain in rats treated with ketoconazole. Oral administration of ketoconazole (25 mg/kg/day) on Days 12-14 of pregnancy induced reduction of plasma estradiol-17β (E2) concentration, transient decrease in placental blood flow and increased intensity of a hypoxia-related marker in the placenta on Day 14 of pregnancy. On Day 20 of pregnancy, placental weights of ketoconazole-treated rats increased when compared to controls. Histologically, maternal sinusoidal area of the placenta decreased on Day 14 of pregnancy and the total area of maternal and fetal sinusoids increased on Day 20. All the changes disappeared by concomitant subcutaneous infusion of E2. These results indicate that ketoconazole-induced E2 deficiency causes transient decrease in placental blood flow associated with hypoxia and later placental weight gain in rats.