Function Of Furin And PC7 On Mouse Embryo Implantation And Human Trophoblast Invasion

Implantation of the embryo into the uterine endometrium is a highly regulated event critical for the establishment of pregnancy. A series of morphological and physiological changes involved in embryo implantation include decidualization of uterine stromal cells, development of the blastocyst and the invasion of trophoblast cells. Proprotein convertases (PCs), a key family of enzymes with the function of processing protein precursor into their mature forms, plays an important role in development, tumorigenesis and many kind of diseases. The expression and regulatory mechanisms of Furin and PC7 during embryo implantation are not clear. Accordingly, the current study was designed to investigate the expression and function of Furin and PC7 in mouse embryo implantation via immunohistochemistry, immunofluorescence and an in vitro embryo-endometrial epithelial cell co-culture system, and the expression and function of Furin and PC7 in human trophoblast invasion, via immunohistochemistry, immunofluorescence, RT-PCR and a matrigel invasion model.Results from mice showed that Furin and PC7 were mainly detected in the glandular epithelial cells from D1 to D4 of pregnancy and in both decidual cells and glandular epithelium on Days 5-7 of pregnancy. Expression of PC7 was hardly detectable in embryos at 2-cell and 4-cell stages, but was significantly upregulated in 8-cell stage and the expression level of PC7 was the highest at blastocyst stage, with strong PC7 positive signal in trophectoderm. Dec-RVKR-CMK, a Furin inhibitor, significantly inhibited adhesion and outgrowth of embryos in the co-culture system. The above results suggest that Furin plays an important role in embryonic adhesion and outgrowth. Furin and PC7 may also be involved in mouse endometrial decidualization and early embryonic development.Furthermore, Furin and PC7 were both detected in the human placenta villi, and the expression of Furin during 6-9 weeks were higher than what was in the placental villi of the second and third trimesters, PC7 levels did not changed significantly during pregnancy. All the PCs, but not PC1 and PC2, were detected in HTR8/Svneo cells, a human invasive extravillous trophoblast cell line. Transfection of Furin siRNA into HTR8/Svneo cells significantly decreased invasive nature of these cells.Taken together, our data, for the first time, illustrates a role of Furin in adhesion and outgrowth of embryos during embryo implantation and invasion of trophoblast cells during early placentation.