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Breast Cancer Resistance Protein (BCRP/ABCG2) Inhibits Extra Villous Trophoblast Migration: The Impact of Bacterial and Viral Infection

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Department of Physiology, University of Toronto, Toronto, ON M5S 1A8, Canada
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Department of Morphology, Federal University of Minas Gerais, Belo Horizonte 31270-901, Brazil
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Lunenfeld-Tanenbaum Research Institute, Mount Sinai Hospital, Toronto, ON M5G 1X5, Canada
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Department of Biology, York University, Toronto, ON M3J 1P3, Canada
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Department of Obstetrics & Gynaecology, University of Ottawa, Ottawa, ON K1H 8L6, Canada
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Department of Cellular & Molecular Medicine, University of Ottawa, Ottawa, ON K1H 8M5, Canada
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Laboratory of Translational Endocrinology, Biophysics Institute Carlos Chagas Filho, Federal University of Rio de Janeiro, Rio de Janeiro 21941-902, Brazil
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Department of Obstetrics & Gynaecology, University of Toronto, Toronto, ON M5G 1E2, Canada
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Department of Medicine, Faculty of Medicine, University of Toronto, Toronto, ON M5S 1A8, Canada
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Author to whom correspondence should be addressed.
Cells 2019, 8(10), 1150; https://doi.org/10.3390/cells8101150
Received: 26 August 2019 / Revised: 18 September 2019 / Accepted: 24 September 2019 / Published: 26 September 2019
(This article belongs to the Section Cell Motility and Adhesion)
Extravillous trophoblasts (EVT) migration into the decidua is critical for establishing placental perfusion and when dysregulated, may lead to pre-eclampsia (PE) and intrauterine growth restriction (IUGR). The breast cancer resistance protein (BCRP; encoded by ABCG2) regulates the fusion of cytotrophoblasts into syncytiotrophoblasts and protects the fetus from maternally derived xenobiotics. Information about BCRP function in EVTs is limited, however placental exposure to bacterial/viral infection leads to BCRP downregulation in syncitiotrophoblasts. We hypothesized that BCRP is involved in the regulation of EVT function and is modulated by infection/inflammation. We report that besides syncitiotrophoblasts and cytotrophoblasts, BCRP is also expressed in EVTs. BCRP inhibits EVT cell migration in HTR8/SVneo (human EVT-like) cells and in human EVT explant cultures, while not affecting cell proliferation. We have also shown that bacterial—lipopolysaccharide (LPS)—and viral antigens—single stranded RNA (ssRNA)—have a profound effect in downregulating ABCG2 and BCRP levels, whilst simultaneously increasing the migration potential of EVT-like cells. Our study reports a novel function of BCRP in early placentation and suggests that exposure of EVTs to maternal infection/inflammation could disrupt their migration potential via the downregulation of BCRP. This could negatively influence placental development/function, contribute to existing obstetric pathologies, and negatively impact pregnancy outcomes and maternal/neonatal health. View Full-Text
Keywords: Breast cancer resistance protein (BCRP/ABCG2); extra villous trophoblast; first trimester placenta; migration; infection Breast cancer resistance protein (BCRP/ABCG2); extra villous trophoblast; first trimester placenta; migration; infection
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Lye, P.; Bloise, E.; Nadeem, L.; Peng, C.; Gibb, W.; Ortiga-Carvalho, T.M.; Lye, S.J.; Matthews, S.G. Breast Cancer Resistance Protein (BCRP/ABCG2) Inhibits Extra Villous Trophoblast Migration: The Impact of Bacterial and Viral Infection. Cells 2019, 8, 1150.

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