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
Metrics: PDF 713 views | HTML 1059 views | ?
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
Yu-Bin Ding, email: email@example.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
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.
All site content, except where otherwise noted, is licensed under a Creative Commons Attribution 3.0 License.