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2,3,7,8-Tetrachlorodibenzo-p-dioxin differentially suppresses angiogenic responses in human placental vein and artery endothelial cells

Author:
Li, Yan, Wang, Kai, Zou, Qing-Yun, Magness, Ronald R., Zheng, Jing
Source:
Toxicology 2015 v.336 pp. 70-78
ISSN:
0300-483X
Subject:
angiogenesis, apoptosis, blood serum, cell cycle, cell viability, culture media, endothelial cells, growth retardation, humans, models, pregnancy outcome, small interfering RNA, tetrachlorodibenzo-p-dioxin, umbilical cord
Abstract:
Placental angiogenesis is dramatically increased during pregnancy in association with the elevated placental blood flows to support the rapidly growing fetus. 2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD) is an environmental toxicant and a ligand of aryl hydrocarbon receptor (AhR). Herein, we investigated the effects of TCDD on proliferation, migration, and viability of fetoplacental endothelial cells in response to a complete growth medium which contained serum and growth supplement using human umbilical cord vein (HUVECs) and artery (HUAECs) cells as models. We found that TCDD dose- and time-dependently inhibited (p<0.05) proliferation of HUVECs and HUAECs. Treatment with TCDD at 10nM for 6 days inhibited (p<0.05) migration (by ∼30%) of HUAECs, but not HUVECs. TCDD at 10nM also decreased (p<0.05) viability of HUVECs and HUAECs. Interestingly, specific AhR siRNA blocked (p<0.05) the TCDD-inhibited cellular responses in HUAECs, but not HUVECs. Nonetheless, TCDD at 10nM neither affected the cell cycle progression, nor did it induce cell apoptosis in HUVECs and HUAECs. In addition, TCDD at 10nM also did not alter activation of ERK1/2 and AKT1 in HUVECs and HUAECs. Collectively, TCDD suppresses proliferation and/or migration (two key steps of angiogenesis) of HUVECs and HUAECs independent and dependent of AhR, respectively. These data suggest that TCDD inhibited growth of HUVECs and HUAECs via decreasing cell viability. Thus, TCDD may inhibit fetoplacental angiogenesis, leading to negative pregnancy outcomes.
Agid:
5461952