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 (10-100μM) 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.postprin

Human chorionic gonadotropin stimulates spheroid attachment on fallopian tube epithelial cells through the mitogen-activated protein kinase pathway and down-regulation of olfactomedin-1

OBJECTIVE: To study the effect of human chorionic gonadotropin (hCG) on olfactomedin-1 (Olfm1) expression and spheroid attachment in human fallopian tube epithelial cells in vitro. DESIGN: Experimental study. SETTING: Reproductive biology laboratory. PATIENT(S): Healthy non-pregnant women. INTERVENTION(S): No patient interventions. MAIN OUTCOME MEASURE(S): Luteinizing hormone/chorionic gonadotropin receptor (LHCGR) and Olfm1 expression in fallopian tube epithelium cell line (OE-E6/E7 cells). OE-E6/E7 cells treated with hCG, U0126 extracellular signal-regulated kinase (ERK) inhibitor, or XAV939 Wnt/β-catenin inhibitor were analyzed by Western blotting, real-time polymerase chain reaction, and in vitro spheroid attachment assay. RESULT(S): Human chorionic gonadotropin increased spheroid attachment on OE-E6/E7 cells through down-regulation of Olfm1 and activation of Wnt and mitogen-activated protein kinase (MAPK) signaling pathways. U0126 down-regulated both MAPK and Wnt/β-catenin signaling pathways and up-regulated Olfm1 expression. XAV939 down-regulated only the Wnt/β-catenin signaling pathway but up-regulated Olfm1 expression. CONCLUSION(S): Human chorionic gonadotropin activated both ERK and Wnt/β-catenin signaling pathways and enhanced spheroid attachment on fallopian tube epithelial cells through down-regulation of Olfm1 expression.postprin