Perfluorobutane sulfonate exposure disrupted human placental cytotrophoblast cell proliferation and invasion involving in dysregulating preeclampsia related genes

Abstract

We reported that maternal PFBS, an emerging pollutant, exposure is positively associated with preeclampsia which can result from aberrant trophoblasts invasion and subsequent placental ischemia. In this study, we investigated the effects of PFBS on trophoblasts proliferation/invasion and signaling pathways. We exposed a human trophoblast line, HTR8/SVneo, to PFBS. Cell viability, proliferation, and cell cycle were evaluated by the MTS assay, Ki-67 staining, and flow cytometry, respectively. We assessed cell migration and invasion with live-cell imaging-based migration assay and matrigel invasion assay, respectively. Signaling pathways were examined by Western blot, RNA-seq, and qPCR. PFBS exposure interrupted cell proliferation and invasion in a dose-dependent manner. PFBS (100 μM) did not cause cell death but instead significant cell proliferation without cell cycle disruption. PFBS (10 and 100 μM) decreased cell migration and invasion, while PFBS (0.1 μM) significantly increased cell invasion but not migration. Further, RNA-seq analysis identified dysregulated HIF-1α target genes that are relevant to cell proliferation/invasion and preeclampsia, while Western Blot data showed the activation of HIF-1α, but not Notch, ERK1/2, (PI3K)AKT, and P38 pathways. PBFS exposure altered trophoblast cell proliferation/invasion which might be mediated by preeclampsia-related genes, suggesting a possible association between prenatal PFBS exposure and adverse placentation.