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Breast Cancer Resistance Protein (BCRP/ ABCG2 ) Inhibits Extra Villous Trophoblast Migration: The Impact of Bacterial and Viral Infection.
- Source :
-
Cells [Cells] 2019 Sep 26; Vol. 8 (10). Date of Electronic Publication: 2019 Sep 26. - Publication Year :
- 2019
-
Abstract
- 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.
- Subjects :
- Cell Line
Cell Movement
Cell Proliferation
Down-Regulation
Female
Humans
Placentation
Pregnancy
Trophoblasts metabolism
Trophoblasts microbiology
Trophoblasts virology
ATP Binding Cassette Transporter, Subfamily G, Member 2 genetics
ATP Binding Cassette Transporter, Subfamily G, Member 2 metabolism
Lipopolysaccharides adverse effects
Neoplasm Proteins genetics
Neoplasm Proteins metabolism
RNA, Viral adverse effects
Trophoblasts cytology
Subjects
Details
- Language :
- English
- ISSN :
- 2073-4409
- Volume :
- 8
- Issue :
- 10
- Database :
- MEDLINE
- Journal :
- Cells
- Publication Type :
- Academic Journal
- Accession number :
- 31561453
- Full Text :
- https://doi.org/10.3390/cells8101150