Histopathological Effect of Ketoconazole on Rat Placenta

Abstract

ABSTRACT. In order to investigate the morphological effects of ketoconazole on hypertrophied placentas, we examined the sequential histopathological changes in the placenta from rats exposed to ketoconazole. Ketoconazole was administered orally at 0 and 25 mg/kg/day during gestation days (GDs) 12 to 14, and the placentas were sampled on GDs 15, 17 and 21. All dams showed neither effect on body weight nor any abnormal clinical signs during the experimental period. In the treated group, the placentas appeared more hypertrophic with increases in the weight, diameter and thickness on GD 21. Histopathologically, increased thickness was noted in the labyrinth zone and basal zone on GDs 17 and 21, while on GD 15 the change had been already evident in the former zone. In the labyrinth zone, the mitotic figures of the trophoblasts were significantly elevated on GD 15. A multiple cystic dilatation of maternal sinusoids was observed in some placentas on GDs 15, 17 and 21. In the basal zone, an increase in spongiotrophoblasts and clusters of glycogen cells were detected on GDs 17 and 21. In the decidua basalis, there were no significant changes in either histology or thickness between the control and treated group during GDs 15 to 21. In conclusion, ketoconazole increased the population of composed cells in the labyrinth and basal zone, leading to placental hypertrophy in pregnant rats.

Chromium VI − Induced developmental toxicity of placenta is mediated through spatiotemporal dysregulation of cell survival and apoptotic proteins

“…The current study shows that CrVI induces toxic lesions in the LZ and BZ of the placenta. Several EDCs have been reported to cause lesions in the placenta such as ketoconazole (hypertrophy) [68], cadmium and lead (necrosis) [69], 6-mercaptopurine (cystic degeneration of glycogen cells) [70], and busulfan (apoptosis of trophoblasts and endothelial cells) [22] [71]. CrVI increased hypertrophy of the BZ and induced hem- orrhagic lesions in BZ above the decidual bed (Fig.…”

Effect of PPARβ/δ Agonist on the Placentation and Embryo‐Fetal Development in Rats

“…Especially, basal zone is the site of production of steroids and peptide hormones that play an important role for maintaining pregnancy (Davies and Glasser, ). In the normal placental development, the basal zone is composed of small cytotrophoblastic elements on GD 12 (Furukawa et al, ). The cytotrophoblastic elements differentiate into glycogen cells after GD 14, and the size of the basal zone consequently becomes smaller in accordance with development of placenta after GD 15, and then finally glycogen cells will disappear until GD 21 (Furukawa et al, ; Furukawa et al, ).…”

Toxicological Pathology in the Rat Placenta

“…Thirdly, placental hypertrophy is induced as a hormone imbalance reaction, such as estrogen deficiency 43,44 and ovariectomy with estrogen and progesterone treatment 45 . Pathological sequential changes of ketoconazoleinduced placental hypertrophy were recently investigated in rats 46 , as described below.…”