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ToxSci Advance Access originally published online on February 22, 2006
Toxicological Sciences 2006 91(1):265-274; doi:10.1093/toxsci/kfj138
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© The Author 2006. Published by Oxford University Press on behalf of the Society of Toxicology. All rights reserved. For Permissions, please email: journals.permissions@oxfordjournals.org

Suppressive Effect of 2,3,7,8-Tetrachlorodibenzo-p-dioxin on Vascular Remodeling That Takes Place in the Normal Labyrinth Zone of Rat Placenta during Late Gestation

Ryuta Ishimura*,1, Takashige Kawakami*,{dagger}, Seiichiroh Ohsako*,{ddagger}, Keiko Nohara* and Chiharu Tohyama*,{ddagger},2

* Molecular and Cellular Toxicology Section, Environmental Health Sciences Division, National Institute for Environmental Studies, Onogawa, Tsukuba 305-8506, Japan; {dagger} Department of Hygiene-Chemistry, Faculty of Pharmaceutical Sciences, Tokyo University of Science, Yamazaki, Noda 278-8510, Japan; and {ddagger} Division of Environmental Health Sciences, Center for Disease Biology and Integrative Medicine, Graduate School of Medicine, The University of Tokyo, Tokyo 113-0033, Japan

Received December 9, 2005; accepted February 13, 2006

The maintenance of the placental vasculature is essential for sustaining normal fetal growth. On the basis of our previous observation that fetal death was accompanied by placental hypoxia upon exposure to 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) (R. Ishimura et al., 2002a, Toxicol. Appl. Pharmacol. 185, 197–206), we here investigated the effects of TCDD on the placenta, focusing on the development of the labyrinth zone. Holtzman rats were administered a single oral dose of 1.6 µg of TCDD/kg body weight or an equivalent volume of vehicle (control) on gestation day (GD) 15, and placental tissues were analyzed on GD20. Immunohistochemical staining showed that the exposure to TCDD decreased the size of maternal blood sinusoids and caused the constriction of fetal capillaries in the placenta. In contrast, we found that vascular remodeling occurred in the labyrinth zone of normal rat placenta; that is, the vascular development in the normal labyrinth zone during the late gestation (from GD16 to GD20) showed dilated maternal blood sinusoids and fetal capillaries accompanied by a decrease in thickness and the apoptosis of trophoblasts. The present results demonstrate that this remodeling is suppressed by TCDD, which is further supported by the decreased expression level of Tie2 mRNA, the gene which is associated with vascular remodeling, and also by the decrease in the number of apoptotic trophoblasts in TCDD-exposed rats. The present study provided a new finding on the development of the vasculature in the labyrinth zone during the late gestation under normal conditions and showed the inhibition of vascular remodeling in TCDD-exposed rats.

Key Words: apoptosis; placenta; rat; Tie2; TCDD; trophoblasts; vascular remodeling.


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