ITE and TCDD differentially regulate the vascular remodeling of rat placenta via the activation of AhR.
Vascular remodeling in the placenta is essential for normal fetal development. The previous studies have demonstrated that in utero exposure to 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD, an environmental toxicant) induces the intrauterine fetal death in many species via the activation of aryl hydrocarbon receptor (AhR). In the current study, we compared the effects of 2-(1'H-indole-3'-carbonyl)-thiazole-4-carboxylic acid methyl ester (ITE) and TCDD on the vascular remodeling of rat placentas. Pregnant rats on gestational day (GD) 15 were randomly assigned into 5 groups, and were exposed to a single dose of 1.6 and 8.0 mg/kg body weight (bw) ITE, 1.6 and 8.0 µg/kg bw TCDD, or an equivalent volume of the vehicle, respectively. The dams were sacrificed on GD20 and the placental tissues were gathered. The intrauterine fetal death was observed only in 8.0 µg/kg bw TCDD-exposed group and no significant difference was seen in either the placental weight or the fetal weight among all these groups. The immunohistochemical and histological analyses revealed that as compared with the vehicle-control, TCDD, but not ITE, suppressed the placental vascular remodeling, including reduced the ratio of the placental labyrinth zone to the basal zone thickness (at least 0.71 fold of control), inhibited the maternal sinusoids dilation and thickened the trophoblastic septa. However, no marked difference was observed in the density of fetal capillaries in the labyrinth zone among these groups, although significant differences were detected in the expression of angiogenic growth factors between ITE and TCDD-exposed groups, especially Angiopoietin-2 (Ang-2), Endoglin, Interferon-γ (IFN-γ) and placenta growth factor (PIGF). These results suggest ITE and TCDD differentially regulate the vascular remodeling of rat placentas, as well as the expression of angiogenic factors and their receptors, which in turn may alter the blood flow in the late gestation and partially resulted in intrauterine fetal death.
Clinical and Translational Research Center, Shanghai First Maternity and Infant Hospital, Tongji University School of Medicine, Shanghai, P.R. China.
Yanming
Y
Wu
Clinical and Translational Research Center, Shanghai First Maternity and Infant Hospital, Tongji University School of Medicine, Shanghai, P.R. China.
Xiao
X
Chen
Clinical and Translational Research Center, Shanghai First Maternity and Infant Hospital, Tongji University School of Medicine, Shanghai, P.R. China.
Qian
Q
Zhou
Department of Pathology, Shanghai First Maternity and Infant Hospital, Tongji University School of Medicine, Shanghai, P.R. China.
Qizhi
Q
He
Clinical and Translational Research Center, Shanghai First Maternity and Infant Hospital, Tongji University School of Medicine, Shanghai, P.R. China ; Shanghai Key Laboratory of Signaling and Disease Research, School of Life Science and Technology, Tongji University, Shanghai, P.R. China.
Jiuhong
J
Kang
Department of Ob/Gyn, University of Wisconsin, Madison, Wisconsin, United States of America.
Jing
J
Zheng
Clinical and Translational Research Center, Shanghai First Maternity and Infant Hospital, Tongji University School of Medicine, Shanghai, P.R. China.
Kai
K
Wang
Clinical and Translational Research Center, Shanghai First Maternity and Infant Hospital, Tongji University School of Medicine, Shanghai, P.R. China ; Department of Obstetrics, Shanghai First Maternity and Infant Hospital, Tongji University School of Medicine, Shanghai, P.R. China.
Tao
T
Duan
D042702:Angiopoietin-2 / Q000235:genetics / Q000378:metabolism; D000818:Animals; D000071063:Endoglin; D004785:Environmental Pollutants / Q000633:toxicity*; D005260:Female; D005313:Fetal Death; D005333:Fetus / Q000098:blood supply / Q000187:drug effects* / Q000378:metabolism; D015870:Gene Expression / Q000187:drug effects; D007211:Indoles / Q000633:toxicity*; D007371:Interferon-gamma / Q000235:genetics / Q000378:metabolism; D047908:Intracellular Signaling Peptides and Proteins / Q000235:genetics / Q000378:metabolism; D010920:Placenta / Q000098:blood supply / Q000187:drug effects* / Q000378:metabolism; D000072483:Placenta Growth Factor; D000072317:Polychlorinated Dibenzodioxins / Q000031:analogs & derivatives* / Q000633:toxicity; D011247:Pregnancy; D011257:Pregnancy Proteins / Q000235:genetics / Q000378:metabolism; D051381:Rats; D018336:Receptors, Aryl Hydrocarbon / Q000819:agonists / Q000235:genetics / Q000378:metabolism; D013844:Thiazoles / Q000633:toxicity*; D066253:Vascular Remodeling / Q000187:drug effects
C548651:2-(1'H-indole-3'-carbonyl)thiazole-4-carboxylic acid methyl ester; D042702:Angiopoietin-2; D000071063:Endoglin; C501740:Eng protein, rat; D004785:Environmental Pollutants; D007211:Indoles; D047908:Intracellular Signaling Peptides and Proteins; C000608038:Pgf protein, rat; D000072317:Polychlorinated Dibenzodioxins; D011257:Pregnancy Proteins; D018336:Receptors, Aryl Hydrocarbon; D013844:Thiazoles; D000072483:Placenta Growth Factor; C049089:2-hydroxy-1,3,7,8-tetrachlorodibenzo-4-dioxin; D007371:Interferon-gamma