SPARCL1 impedes trophoblast migration and invasion by down-regulating ERK phosphorylation and AP-1 production and altering EMT-related molecule expression.

INTRODUCTION:Embryo implantation depends on trophoblast cells migration and invasion. Abnormal function of trophoblast cells could result in many pregnancy complications. Secreted protein acidic and rich in cysteine like-1 has been reported to inhibit cell migration and tumor invasion. This study aimed to explore the role of in trophoblast functions. METHODS:Villous specimens were obtained from 31 women with spontaneous abortion and 31 women with normal early pregnancy to determine the expression of HTR8/SVneo cells and JAR cells were transfected with vectors and control vectors. The proliferation assay and scratch-wound assay were performed. Quantitative polymerase chain reaction (qPCR) and western blotting were performed to assess epithelial mesenchymal transition (EMT)-related molecules including MMP2, MMP3, N-cadherin, E-cadherin and vimentin. Extracellular signal-regulated kinase (ERK) phosphorylation activity and AP-1 expression in HTR8/SVneo cells following multi-scratching were detected using above assays. RESULTS:The mRNA and protein levels of duanyu1842RCL1 were significantly higher in the abortion group than in the normal pregnancy group. After transfection, there was no difference of cell viability between the group and control vector group. However, the migration distance and area were reduced and the abundances of EMT related molecules were changed by duanyu1842RCL1 overexpression when compared with controls. Lower ERK phosphorylation activity and decreased Fos and Jun expressions were noted at high level of migration and invasion were noted in trophoblast cells with duanyu1842RCL1 overexpression, which might affect embryo implantation and placenta development. It could be involved in the pathogenesis of spontaneous abortion.

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