Bisphenol A (BPA) is a kind of environmental endocrine disruptors (EEDs) that interfere embryo implantation. Trophoblast invasion plays a crucial role during embryo implantation. In this study, the effects of BPA on invasion ability of human trophoblastic Jeg-3 spheroids and regulation of endothelial and stromal cells on trophoblastic spheroids invasion, and its possible mechanism were investigated. The results showed that BPA at 10 and 100 mu M can inhibit the attachment of Jeg-3 spheroid onto Ishikawa cells. BPA at 1-100 mu M also activate ERE-Luc reporter expression in the transfected cells, which was through the ER alpha, but not ER beta or GPR30 binding. Endothelial receptivity ability was harmed by BPA treatment since receptivity markers of LIF, EGF, MUC1 and integrin alpha V beta 3 were decreased after BPA treatment. The invasion ability of trophoblastic spheroids generated from Jeg-3 cell line was inhibited by BPA and this effect was mediated through canonical ERs pathway and MMP2/MMP9 down-regulation and TIMP1 /PAI-1 up-regulation. Besides, BPA treated decidualized stromal cells suppressed Jeg-3 spheroid outgrowth and invasion in co-culture assay. Our study would give a better understanding on the possible mechanism of BPA effect on human embryo implantation process. (C) 2019 Elsevier Inc. All rights reserved.