Abstract
Moderate invasion of trophoblast cells into endometrium is essential for the placental development and normal pregnancy. Electric field (EF)-induced effects on cellular behaviors have been observed in many cell types. This study was to investigate the effect of physiological direct current EF (dc EF) on cellular responses such as elongation, orientation and motility of trophoblast cells. Immortalized first trimester extravillous trophoblast cells (HTR-8/SVneo) were exposed to the dc EF at physiological magnitude. Cell images were recorded and analyzed by image analyzer. Cell lysates were used to detect protein expression by Western blot. Cultured in the dc EFs the cells showed elongation, orientation and enhanced migration rate compared with non-EF stimulated cells at field strengths of 100 mV/mm to 200 mV/mm. EF exposure increased focal adhesion kinase (FAK) phosphorylation in a time-dependent manner and increased expression levels of MMP-2. Pharmacological inhibition of FAK impaired the EF-induced responses including motility and abrogated the elevation of MMP-2 expression. However, the expression levels of integrins like integrin α1, α5, αV and β1 were not affected by EF stimulation. Our results demonstrate the importance of FAK activation in migration/motility of trophobalst cells driven by EFs. In addition, it raises the feasibility of using applied EFs to promote placentation through effects on trophoblast cells.
Highlights
Physiological electric fields (EFs) occur in embryonic development [1] and during wound healing [2,3]
Trophoblast cells exposed to direct current EF (dc EF) showed enhanced migration rate compared with non-EF stimulated cells at field strengths of 0 mV/mm, 100 mV/mm and 200 mV/mm [(0.1260.02) mm/h, (2.4760.25) mm/h and (2.9060.28) mm/h, respectively] (Fig. 1)
Cells cultured with no EF showed no such response (Fig. 2A)
Summary
Physiological electric fields (EFs) occur in embryonic development [1] and during wound healing [2,3]. A variety of cells respond to EFs with migration, elongation and orientation These include epithelial cells, chondrocytes, bone cells, fibroblasts, smooth muscle cells and endothelial cells [4,5,6,7,8]. Extravillous cytotrophoblasts (EVTs) invade the underlying maternal tissue and migrate into the wall of the uterine spiral arteries, which results in the remodeling of uterine vasculature. This process plays an important role in the mammalian placental development and is stringently regulated to ensure a successful pregnancy. Poor invasion of EVTs was believed to be associated with insufficient remodeling of the spiral arteries, which was typical pathological alterations in miscarriage [9], preeclampsia [10], and intrauterine growth restriction [11]
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