The Relationship Of Canonical Wnt Signal Pathway And Postpartum Endometrial Repair

Objective: To discuss if the activation of Wnt signal pathway involved in the process of postpartum endometrial recovery, and to observe the connection of the Wnt signal pathway activated cells with cell proliferation and apoptosis during the postpartum endometrial recovery process, also with the distribution of several types of stem cell markers.Exploring the possible regulating effect and mechanism of Wnt signal pathway on postpartum endometrial recovery and remodeling could provide new ideas for the study of endometrial recovery abnormalities related diseases.Methods:(1) Genetically bred Top-Gal tool mice were used to prepare β-catenin report mice.(2) We collected the postpartum β-catenin report mice uterus specimens at different time points, and observed the changes of location and volume report molecule β- galactosidase which is activated by the typical Wnt pathway core molecule β-catenin during the postpartum endometrial recovery process; Usage of TUNEL assay to detect apoptosis situation during the endometrium postpartum recovery process; use enzyme-linked immunosorbent assay(Elisa) was employed to detect postpartum β-galactosidase activity at different time points.(3) Through C57 female mice postpartum uterine tissue were stained by immunohistochemistry to detect the changes of stem cell related markers Ep CAM(marker for epithelium cell), CD146(marke for mesenchymal stem cells), PDGF-Rβ(marker for the sourse of vessel mesenchymal stem cells), and ABCG2(marker for side population cell) and the expression of proliferating antigen Ki67 during the postpartum recovery process; use Real-time PCR technology was used to analysis the expression and the possible significance of Wnt signal pathway related genes at postpartum different time points.Results:(1) During the postpartum recovery process of report mice endometrium, expression of x-gal-positive cells could express in a certain tissue-site specific and time specific way.(2) Results from Elisa showed the postpartum β- galactosidase activity decreasing gradiently, especially at postpartum 96 hours, which was a significant different(P <0.05) with the 0-hour and 12-hours group.(3) During the postpartum recovery process, the proliferation and apoptosis level of endometrial epithelial and stromal cell were coordinated. Ki67 staining showed the endometrial cell proliferation reached a peak at postpartum 72 h, Tunnel experiments showed that endometrial apoptosis reached a cell peak at postpartum 24 h. Ep CAM was expressed in all the luminal epithelium and glandular epithelium, rathee than in the strmmal cells; PDGF-Rβ was expressed only in the endometrial stromal cells, and was not expressed within 24h; CD146 was expressed both in endometrial epithelial and stromal cells, X-gal-positive cells and CD146-positive cells had the similar temporal and spatial expression pattern in the endometrial epithelial and stromal: the expression in epithelial cells showed a gradual decline within the postpartum recovery 72 h, the expression in stromal cells showed an upward trend within the postpartum recovery 72h; ABCG2 protein was expressed both in the postpartum endometrial epithelium and stromal cells, particularly in the stromal cells, and its expression could gradually increased with the duration postpartum recovery time(within 96h).(4) The expression of Wnt7 a significantly changed during the repairment of the endometrium postpartum: Compared with postpartum 0h, 12 h group postpartum 72 h,96h group increased significantly.Conclusions:(1) Wnt signal pathway core mediation molecule β-catenin could play a regulatory role during the repairment of the endometrium postpartum,The activation of Wnt/β-catenin signaling pathway could promote the differentiation of endometrial stem cells and the repairment of the endometrium.(2) During the repairment of the endometrium postpartum, there existed a recovery mode that the stromal stem cells would differentiate into epithelial cells.(3) Stem cells from the sourse of vessel mesenchymal coule differentiate into mesenchymal cells to repair the endometrium(4) Wnt7 a might participate in the repairment of the postpartum uterus.