Humans are exposed to Bisphenol A (BPA) from the consumer products and plastic substances. However, impacts of low levels of BPA exposure on placental developmental processes such as first trimester trophoblast cell growth, angiogenesis and epigenetic modifications are not well studied. Low concentration of BPA (1 nM) affected cell proliferation of human placental first trimester trophoblasts using a model cell, HTR8/SVneo. BPA abolished both basal- and vascular endothelial growth factor (VEGF)-stimulated tube formation in these cells. BPA significantly down regulated mRNA expression of VEGF, proliferating cell nuclear antigen, intercellular adhesion molecule 1 with concomitant upregulation of 11-β-hydroxysteroid dehydrogenase 2 mRNA and protein expression in HTR8/SVneo cells. BPA also lowered CpG methylation of gene promoter associated with metabolic and oxidative stress. This study demonstrated that BPA at 1 nM not only affected cellular growth, development and angiogenic activities but also affected DNA methylation of stress response and down-regulation of angiogenic growth factors in first trimester trophoblast cells.