Oncotarget

Research Papers:

Bisphenol A exposure promotes HTR-8/SVneo cell migration and impairs mouse placentation involving upregulation of integrin-β1 and MMP-9 and stimulation of MAPK and PI3K signaling pathways

Xi Lan, Li-Juan Fu, Jun Zhang, Xue-Qing Liu, Hui-Jie Zhang, Xue Zhang, Ming-Fu Ma, Xue-Mei Chen, Jun-Lin He, Lian-Bing Li, Ying-Xiong Wang and Yu-Bin Ding _

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Oncotarget. 2017; 8:51507-51521. https://doi.org/10.18632/oncotarget.17882

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Abstract

Xi Lan1, Li-Juan Fu1,2, Jun Zhang3, Xue-Qing Liu1, Hui-Jie Zhang4, Xue Zhang1, Ming-Fu Ma5, Xue-Mei Chen1, Jun-Lin He1, Lian-Bing Li5, Ying-Xiong Wang1 and Yu-Bin Ding1

1Department of Reproductive Biology, School of Public Health, Chongqing Medical University, Chongqing, 400016, P.R. China

2Department of Immunology, School of Medicine, University of Pittsburgh, Pittsburgh, Pennsylvania, 15260, USA

3Center of Molecular Diagnostic Medicine, Life Science Institute, Chongqing Medical University, Chongqing, 400016, P.R. China

4Ministry of Education Key Laboratory of Diagnostic Medicine, College of Laboratory Medicine, Chongqing Medical University, Chongqing, 400016, P.R. China

5The Key Laboratory of Birth Defects and Reproductive Health of the National Health and Family Planning Commission, Chongqing Population and Family Planning Science and Technology Research Institute, Chongqing, 401147, P.R. China

Correspondence to:

Yu-Bin Ding, email: 178384198@qq.com

Keywords: bisphenol A, extravillous trophoblasts, cell migration, placentation, MAPK/PI3K signaling pathway

Received: September 28, 2016    Accepted: April 19, 2017    Published: May 16, 2017

ABSTRACT

In this study, we investigated the effect of Bisphenol A (BPA), an endocrine-disrupting chemical, on the migration of human trophoblasts and mouse placentation by using the primary extravillous trophoblast (EVT) and its cell line HTR-8/SVneo, villous explant cultures, and pregnant mice. BPA increased EVT motility and the outgrowth of villous explants in a dose-dependent manner. BPA also increased the protein levels of integrin-β1 and matrix metalloproteinase (MMP)-9 in human EVTs. Low-dose BPA (≤50 mg) increased the protein levels of MMP-9 and MMP-2 as well as integrin-β1 and integrin-α5 in mouse placenta and decreased the proportion of the labyrinth and spongiotrophoblast layers. Inhibitors of mitogen-activated protein kinase (MAPK) U0126 and phosphatidylinositol-3-kinases (PI3K) LY294002 reversed the protein levels of integrin-β1 and MMP-9 as well as the migratory ability induced by BPA. In conclusion, these results indicated that BPA can enhance trophoblast migration and impair placentation in mice by a mechanism involving upregulation of integrin(s) and MMP(s) as well as the stimulation of MAPK and PI3K/Akt (protein kinase B) signaling pathways.


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