Epoxiconazole‐Induced Degeneration in Rat Placenta and the Effects of Estradiol Supplementation |
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Authors: | Maria Cecilia Rey Moreno Karma C. Fussell Sibylle Gröters Steffen Schneider Volker Strauss Stefan Stinchcombe Ivana Fegert Mariana Veras Bennard van Ravenzwaay |
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Affiliation: | 1. Department of Experimental Toxicology and Ecology, BASF SE, , Ludwigshafen, Germany;2. Department of Product Safety, Regulations, Toxicology and Ecology, BASF SE, , Ludwigshafen, Germany;3. LIM05‐Department of Pathology, Laboratory of Environmental Air Pollution, University of Sao Paulo School of Medicine, , Sao Paulo, Brazil |
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Abstract: | Epoxiconazole (CAS‐No. 133855‐98‐8) was recently shown to cause both a marked depletion of maternal estradiol blood levels and a significantly increased incidence of late fetal mortality when administered to pregnant rats throughout gestation (GD 7–18 or 21); estradiol supplementation prevented this epoxiconazole effect in rats (Stinchcombe et al., 2013), indicating that epoxiconazole‐mediated estradiol depletion is a critical key event for induction of late fetal resorptions in rats. For further elucidation of the mode of action, the placentas from these modified prenatal developmental toxicity experiments with 23 and 50 mg/kg bw/d epoxiconazole were subjected to a detailed histopathological examination. This revealed dose‐dependent placental degeneration characterized by cystic dilation of maternal sinuses in the labyrinth, leading to rupture of the interhemal membrane. Concomitant degeneration occurred in the trophospongium. Both placentas supporting live fetuses and late fetal resorptions were affected; the highest degree of severity was observed in placentas with late resorptions. Placental degeneration correlated with a severe decline in maternal serum estradiol concentration. Supplementation with 0.5 and 1.0 μg of the synthetic estrogen estradiol cyclopentylpropionate per day reduced the severity of the degeneration in placentas with live fetuses. The present study demonstrates that both the placental degeneration and the increased incidence of late fetal resorptions are due to decreased levels of estrogen, since estrogen supplementation ameliorates the former and abolishes the latter. Birth Defects Res (Part B) 98:208–221, 2013. © 2013 Wiley Periodicals, Inc. |
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Keywords: | epoxiconazole rat placenta histopathology placental degeneration |
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