title: Ketoconazole-induced estrogen deficiency causes transient decrease in placental blood flow associated with hypoxia and later placental weight gain in rats.
abstract: This study investigated the relationship among estrogen, placental blood flow and placental weight gain in rats treated with ketoconazole. Oral administration of ketoconazole (25mg/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.
authors.affiliation: Drug Safety Research Laboratories, Pharmaceutical Research Division, Takeda Pharmaceutical Company Limited, Kanagawa 251-8555, Japan; Department of Advanced Pathobiology, Graduate School of Life and Environmental Sciences, Osaka Prefecture University, Osaka 598-8531, Japan.
authors.forename: Aoi
authors.initials: A
authors.lastname: Ichikawa
authors.affiliation: Department of Advanced Pathobiology, Graduate School of Life and Environmental Sciences, Osaka Prefecture University, Osaka 598-8531, Japan. Electronic address: tamada@vet.osakafu-u.ac.jp.
authors.forename: Hiromichi
authors.initials: H
authors.lastname: Tamada
mesh_terms: D000818:Animals; D000935:Antifungal Agents / Q000633:toxicity*; D004958:Estradiol / Q000097:blood / Q000172:deficiency*; D004967:Estrogens / Q000097:blood / Q000172:deficiency*; D005260:Female; D000860:Hypoxia / Q000139:chemically induced*; D007654:Ketoconazole / Q000633:toxicity*; D009929:Organ Size / Q000187:drug effects; D010920:Placenta / Q000098:blood supply / Q000187:drug effects*; D011247:Pregnancy; D051381:Rats; D012039:Regional Blood Flow / Q000187:drug effects*
chemical_list: D000935:Antifungal Agents; D004967:Estrogens; D004958:Estradiol; D007654:Ketoconazole
keywords: Blood flow; Estradiol-17β; Ketoconazole; Placenta; Rat