title: Increased glycogen content and glucose transporter 3 mRNA level in the placenta of Holtzman rats after exposure to 2,3,7,8-tetrachlorodibenzo-p-dioxin.
abstract: Exposure to a low dose of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) produces a variety of toxic manifestations, including fetal death. In order to evaluate the effects of low-dose TCDD on placental function in this study, pregnant Holtzman rats were given a single oral dose of 800 or 1600 ng TCDD/kg body wt or an equivalent volume of vehicle (control) on gestation day (GD) 15 and the results were observed on GD16 and GD20. The number of fetal deaths increased in the animals exposed to TCDD. Although fetal and placental weight did not differ significantly between the control group and the TCDD groups, histological differences from the control rats were clearly observed in the junctional zone (JZ) of the placentas of the TCDD-exposed rats. In the control placenta, glycogen cells occupied the majority of the JZ on GD16, but then decreased in number and almost disappeared by GD20, whereas on GD20 the placenta of the TCDD-exposed rats exhibited a larger area occupied by the glycogen cells and cysts filled with eosinophilic material surrounded by glycogen cells in the JZ than that of the control group. Glycogen assay revealed that the glycogen content of the placentas from the TCDD-exposed rats was higher than in the control rats. Semiquantitative RT-PCR analysis was performed to assess the expression of glucose transporter 1 (GLUT1) and GLUT3, the two major placental glucose transporter isoforms. On GD20 the level of expression of GLUT1 mRNA in the placentas was not different between the control and TCDD groups, whereas the level of expression of GLUT3 mRNA approximately doubled in both the 800 and 1600 ng/kg TCDD groups. GLUT3 mRNA expression was restricted to the labyrinth zone of placenta, where zone-specific expression of mRNA arylhydrocarbon receptor and induction of cytochrome P450 1A1 mRNA by TCDD were observed, and none was detected in the JZ. These results, including the increase of glycogen content and GLUT3 mRNA level in TCDD-exposed placentas, provide the first evidence of alteration of glucose kinetics in the placenta by TCDD.
authors.affiliation: Environmental Health Sciences Division, Endocrine Disruptors and Dioxin Research Project, National Institute for Environmental Studies, 16-2 Onogawa, Tsukuba 305-8506, Japan.
authors.forename: Ryuta
authors.initials: R
authors.lastname: Ishimura
authors.forename: Seiichiroh
authors.initials: S
authors.lastname: Ohsako
authors.forename: Yuichi
authors.initials: Y
authors.lastname: Miyabara
authors.forename: Motoharu
authors.initials: M
authors.lastname: Sakaue
authors.forename: Takashige
authors.initials: T
authors.lastname: Kawakami
authors.forename: Yasunobu
authors.initials: Y
authors.lastname: Aoki
authors.forename: Junzo
authors.initials: J
authors.lastname: Yonemoto
authors.forename: Chiharu
authors.initials: C
authors.lastname: Tohyama
mesh_terms: D000818:Animals; D004305:Dose-Response Relationship, Drug; D004785:Environmental Pollutants / Q000633:toxicity*; D005260:Female; D005313:Fetal Death / Q000139:chemically induced; D008401:Gas Chromatography-Mass Spectrometry; D006003:Glycogen / Q000378:metabolism*; D008297:Male; D009004:Monosaccharide Transport Proteins / Q000187:drug effects*; D010920:Placenta / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D000072317:Polychlorinated Dibenzodioxins / Q000633:toxicity*; D011247:Pregnancy; D012333:RNA, Messenger / Q000187:drug effects; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D004785:Environmental Pollutants; D009004:Monosaccharide Transport Proteins; D000072317:Polychlorinated Dibenzodioxins; D012333:RNA, Messenger; D006003:Glycogen