Role of growth factor-induced epithelial-mesenchymal transition in embryo implantation and placentation: insight into implantation failure and pre-eclampcia
| Autor: | Chi-Hsiang Hung, 洪啟翔 |
|---|---|
| Rok vydání: | 2012 |
| Druh dokumentu: | 學位論文 ; thesis |
| Popis: | 100 Implantation and placentation are critical precesses in pregnancy. During implantation, trophoblast increases the ability of migration and invasion to invade deeply enough into the endometrium in order to secure the embryo. Previous studies have shown that implantation failure and pre-eclampcia are caused by weak migration and invasion during implantation and placentation. Epithelial-mesenchymal transition (EMT) is a process of cell type changing from epithelial to mesenchymal type, during which the epithelial cells lose cell-cell junctions and cell-basal adhesions such that their ability of migration is increased and eventually these cells are transformed into mesenchymal cells at last. In this study, we hypothesize that the trophoblasts increase migratory ability during implantation and placentation through EMT. Experimentally, I first detected the expression of protein markers in human normal delivery placenta, and found that E-cadherin in cell column of choronic villi was decreased, and vimentin in extravillus cytotrophoblasts was increased. This suggests that EMT indeed occurs in trophoblast cells. Because previous studies have reported that myriad growth factors exist in the microenvironment of implantation to maintain the process of pregnancy. Therefore, I used mouse blastocysts to test 5 different growth factors for the ability to promote trophoblasts expansion as well as to trigger EMT in trophoblast stem (TS) cells. I found that EGF and FGF-II could enhance blastocyst expansion and trigger EMT on TS cells. On the other hand, I used an animal model to functionally inhibit uterus EGF and FGF-II receptors in mouse fertilized 3 ~ 3.5 days, and found that implantation rate was significantly reduced. When the uterus was treated with the EGFR inhibitor; PD153035; to expression of EMT protein markers, we found that E-cadherin expressed in giant cells but vimentin did not detected in giant cells. It imply that EMT could be inhibited by blocking EGF receptors. This study demonstrates that during embryo implantation and placentation, EGF-induced EMT promoted the increase in trophoblasts increasing migratory ability. Although FGF-II was also important to embryo implantation and placentation, but it had no effect on EMT. These results may be help to women suffering from low implantation rate. |
| Databáze: | Networked Digital Library of Theses & Dissertations |
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