OBJECTIVE: BPA is a reproductive hazard able to affect implantation, trophoblast endocrine activity, differentiation and fetal development. Nothing is known about BPA effects on Placental-derived Mesenchymal Stromal Cells (PDMSCs), a unique cellular population with pro-angiogenic and immunomodulatory abilities. The aim of our work was to determine BPA activity on primary PDMSCs by characterizing the expression of pro-angiogenic Vascular Endothelial Growth Factor (VEGF), Placental Growth Factor (PlGF), anti-angiogenic soluble Fms-like tyrosine kinase-1 (sFlt1), immnomodulatory Indoleamine 2,3-dioxygenase 1 (IDO1) and Lipoprotein Receptor-related Protein-1 (LRP1) in BPA-treated PDMSCs.
METHODS: Placental tissue were collected from physiological pregnant women and PDMSCs were isolated. At passage 5, PDMSCs were plated (1x105 cells/ml) in DMEM without FBS and next treated with 1nM and 1µM BPA. Untreated cells were used as controls. After 48h, CM were collected and PDMSCs viability was assessed by Lactate Dehydrogenase Cytotoxicity (LDH) assay. VEGF, sFlt-1, PlGF, IDO1 and LRP1 gene expression were evaluated by Real Time PCR.
RESULTS: 1nM and 1µM BPA did not affect PDMSCs viability. Decreased VEGF and sFtl1 and increased IDO1 gene expression levels were reported in PDMSCs treated with 1nM BPA relative to control and 1uM BPA-treated PDMSCs. No differences were found in PlGF and LRP1 in 1nM BPA-treated PDMSCs. After treatment with 1µM BPA, we found increased VEGF, sFlt-1, PlGF, IDO1 and LRP1 levels relative to control and 1nM BPA-treated PDMSCs
CONCLUSION: Our data suggest that both 1nM and 1µM BPA stimulate angiogenesis by sFlt1 downregulation and by VEGF and PlGF up-regulation, respectively. Moreover, BPA treatment induced the activation of immunemodulatory pathways mediated by IDO1 and/or LRP1. Indeed, our findings indicate that BPA exposure result in changes in angiogenic factors and immunemodulatory factors indicative of altered PDMSCs abilities, with potential adverse consequences for pregnancy.