Ying Chen1,2, Yi Zhang3, Qinyin Deng1,2, Nan Shan1,2, Wei Peng1,2, Xin Luo1,2, Hua Zhang1,2, Philip N Baker2,4, Chao Tong1,2, Hongbo Qi1,2. 1. a Department of Obstetrics and Gynecology , The First Affiliated Hospital of Chongqing Medical University , Yuzhong District , Chongqing , China . 2. b Canada-China-New Zealand Joint Laboratory of Maternal and Fetal Medicine, Chongqing Medical University , Yuzhong District , Chongqing , China . 3. c Key Laboratory of Birth Defects and Reproductive Health of National Health and Family Planning Commission, Chongqing Population and Family Planning Science and Technology Research Institute , Jiangbei District , Chongqing , China , and. 4. d Liggins Institute, University of Auckland , Grafton , Auckland , New Zealand.
Abstract
OBJECTIVE: Wnt5a and Wnt signaling play potential roles in human placental and fetal development. The objective of this study is to explore the role of Wnt5a in the invasion of the human trophoblast cell line HTR8/SVneo and the probable mechanism of early placentation and preeclampsia in which Wnt5a is involved. METHODS: Human first trimester villous tissues from normal pregnancies and third trimester placentas from pregnancies with or without preeclampsia (PE) were used in the detection of the expression and subcellular location of Wnt5a. The human trophoblast cell line HTR8/SVneo was treated with 0-400 ng/ml recombinant Wnt5a to investigate the role of Wnt5a in human trophoblast invasion. RESULTS: Human first trimester villous is accompanied by the decreased expression of Wnt5a compared with term placenta. Upregulated Wnt5a was detected in PE placenta compared with the normal control. Wnt5a inhibited the migration and invasion of HTR8/SVneo cells with decreased integrin β1, α5 and N-cadherin. Moreover, Wnt5a downregulated β-catenin in HTR8/SVneo cells. CONCLUSIONS: These findings strongly suggest that Wnt5a inhibits the invasion of HTR8/SVneo cells. Decreased Wnt5a facilitates early placentation, whereas increased Wnt5a contributes to the pathogenesis of PE with insufficient trophoblast invasion. Aberrant Wnt5a may function by impairing Wnt non-canonical/β-catenin signaling pathway in trophoblasts.
OBJECTIVE:Wnt5a and Wnt signaling play potential roles in human placental and fetal development. The objective of this study is to explore the role of Wnt5a in the invasion of the human trophoblast cell line HTR8/SVneo and the probable mechanism of early placentation and preeclampsia in which Wnt5a is involved. METHODS:Human first trimester villous tissues from normal pregnancies and third trimester placentas from pregnancies with or without preeclampsia (PE) were used in the detection of the expression and subcellular location of Wnt5a. The human trophoblast cell line HTR8/SVneo was treated with 0-400 ng/ml recombinant Wnt5a to investigate the role of Wnt5a in human trophoblast invasion. RESULTS:Human first trimester villous is accompanied by the decreased expression of Wnt5a compared with term placenta. Upregulated Wnt5a was detected in PE placenta compared with the normal control. Wnt5a inhibited the migration and invasion of HTR8/SVneo cells with decreased integrin β1, α5 and N-cadherin. Moreover, Wnt5a downregulated β-catenin in HTR8/SVneo cells. CONCLUSIONS: These findings strongly suggest that Wnt5a inhibits the invasion of HTR8/SVneo cells. Decreased Wnt5a facilitates early placentation, whereas increased Wnt5a contributes to the pathogenesis of PE with insufficient trophoblast invasion. Aberrant Wnt5a may function by impairing Wnt non-canonical/β-catenin signaling pathway in trophoblasts.