Perfluorooctanoate suppresses spheroid attachment on endometrial epithelial cells through peroxisome proliferator-activated receptor alpha and down-regulation of Wnt signaling

Exposure of animals to perfluorooctanoic acid (PFOA), a surfactant used in emulsion polymerization processes causes early pregnancy loss, delayed growth and development of fetuses. The mechanisms of action are largely unknown. We studied the effect of PFOA on implantation using an in vitro spheroid-endometrial cell co-culture model. PFOA (10-100 μM) significantly reduced Jeg-3 spheroid attachment on RL95-2 endometrial cells. PFOA also suppressed β-catenin expression in Jeg-3 cells. The Wnt agonist Wnt3a stimulated β-catenin expression in Jeg-3 cells and reversed the PFOA suppression of the spheroid attachment. The putative PFOA receptors (PPARα, β, γ) present in both cell lines were not affected by PFOA (0.01-100 μM). The PPARα antagonist MK886 restored the β-catenin and E-cadherin expression levels in Jeg-3 cells and reversed the suppression of the spheroid attachment caused by PFOA. Taken together, PFOA suppresses spheroid attachment through PPARα and Wnt signaling pathways via down-regulation of β-catenin and E-cadherin expression.