2,3,7,8-Tetrachlorodibenzo-p-dioxin differentially suppresses angiogenic responses in human placental vein and artery endothelial cells.
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 10 nM 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 10 nM 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.
Department of Obstetrics and Gynecology, Perinatal Research Laboratories, University of Wisconsin-Madison, Madison, WI 53715, USA.
Yan
Y
Li
Shanghai First Maternity and Infant Hospital, Tongji University School of Medicine, Shanghai 200040, PR China.
Kai
K
Wang
Department of Obstetrics and Gynecology, Perinatal Research Laboratories, University of Wisconsin-Madison, Madison, WI 53715, USA.
Qing-Yun
QY
Zou
Department of Obstetrics and Gynecology, Perinatal Research Laboratories, University of Wisconsin-Madison, Madison, WI 53715, USA; Departments of Pediatrics, University of Wisconsin-Madison, Madison, WI 53715, USA; Department of Animal Sciences, University of Wisconsin-Madison, Madison, WI 53715, USA.
Ronald R
RR
Magness
Department of Obstetrics and Gynecology, Perinatal Research Laboratories, University of Wisconsin-Madison, Madison, WI 53715, USA; Department of Cardiovascular Medicine, Affiliated Hospital of Guangdong Medical College, Zhanjiang 524001, Guangdong, PR China. Electronic address: jzheng@wisc.edu.
Jing
J
Zheng
D002453:Cell Cycle / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D004730:Endothelium, Vascular / Q000187:drug effects*; D005260:Female; D006801:Humans; D018919:Neovascularization, Physiologic / Q000187:drug effects*; D010920:Placenta / Q000098:blood supply / Q000187:drug effects*; D000072317:Polychlorinated Dibenzodioxins / Q000633:toxicity*; D011247:Pregnancy; D014469:Umbilical Arteries / Q000166:cytology / Q000187:drug effects*; D014471:Umbilical Veins / Q000166:cytology / Q000187:drug effects*
D000072317:Polychlorinated Dibenzodioxins
Angiogenesis; Aryl hydrocarbon receptor; Endothelial cells; Placenta; TCDD