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

• Published in: Reproductive toxicology (Elmsford, N.Y.) N.Y.), 2013-12, Vol.42, p.164-171
• Main Authors: Tsang, Hilda, Cheung, Tsz-Yan, Kodithuwakku, Suranga P., Chai, Joyce, Yeung, William S.B., Wong, Chris K.C., Lee, Kai-Fai
• Format: Article
• Language: English
• Subjects: Attachment; Caprylates - toxicity; Cell Adhesion - drug effects; Cell Line, Tumor; Coculture Techniques; Down-Regulation; Endocrine Disruptors - toxicity; Endometrium; Endometrium - cytology; Epithelial Cells - drug effects; Epithelial Cells - physiology; Female; Fluorocarbons - toxicity; Humans; PFOA; PPAR; PPAR alpha - metabolism; Spheroid; Spheroids, Cellular - drug effects; Spheroids, Cellular - physiology; Tumor Cells, Cultured; Wnt signaling; Wnt Signaling Pathway - drug effects
• ISSN: 0890-6238; 1873-1708
• DOI: 10.1016/j.reprotox.2013.08.001

•PFOA suppresses β-catenin and E-cadherin expression in trophoblastic cells.•PFOA suppresses spheroids attachment onto endometrial cells partly through the PPARα.•Activation of Wnt-signaling pathway reverses the suppressive effect of PFOA on β-catenin expression and spheroid attachment. 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 (10–100μM) 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 (0.01–100μM). 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.