Regulation And Function Of Ndrg1 During Mouse Decidualization

Decidualization is a process in which stromal cells turn into the decidual cells after implantation.The decidual cells provide nutrition and immune protection for embryos.These roles are important for embryo implantation,pregnancy maintenance and birth onset.Ndrg1 is a member of the Ndrg family and highly expressed in the mouse uterus.Ndrg1,as a tumor suppressor gene,has an important role in cell proliferation,differentiation,lipid biosynthesis,stress response and immune.Although Ndrg1 is involved in embryogenesis and development,it is not clear how Ndrg1 is regulated in the process of decidualization.In order to investigate the regulation mechanism of Ndrg1 in early pregnancy,in situ hybridization and Western blot were used to analyze Ndrg1 expression in mouse uterus during early pregnancy.We found that Ndrg1 has a high expression in uterineepithelial cells on day 1 of pregnancy.Ndrg1 is undetected from D2 to D4.On day 5,Ndrg1 is strongly expressed in the subluminal stromal cells at implantation site.The signal of Ndrg1 in the uterine mesometrial side increases gradually with the continuous enlargement of the decidua area from D5 to D8.Westrn blot results showed that Ndrg1 protein increases gradually in mouse uterus from pregnancy D5 to D8.Under in vitro decidualization,the expression of Ndrg1 is markedly enhanced in different times of decidualization and reached a high levele.Instromal cells,progesterone significantly increases Ndrg1 expression.DFO is one of iron-chelating agent.It can stimulate the expression of Ndrg1 to affect the migration and proliferation of tumor cells,as an effective drug for tumors.DFO can increase the expression of Ndrg1 in a dose-dependentmanner in stromal cells.As the marker of the mouse decidua,Dtprp is significantly increased when stromal cells were treatedwith DFO for 12 h and 24 h.But Dtprp expression is downreguted after stromal cells are treated with DFO for 48 h and 72 h.As an Iron chelating agent,DFO can reduce the intracellular iron level and thus affect many physiological processes.To explore the effect of intracellular iron level on Ndrg1 expression,stromal cells are treated with FAC and FeSO4.However,either FAC or FeSO4 has no effect on Ndrg1 expression.As a member of the TGF-β family,BMP2 plays an important role in the process of decidualization.Because the expression pattern of Bmp2 in the mouse uterus is similar to Ndrg1,we assume that there is a certain link between Bmp2 and Ndrg1.When stromal cells are treated with recombinant BMP2,BMP2 promotes Ndrg1 expression with the significantly increase of Ptgs2 and Mmp9.When the expression of Ndrg1 is silenced,the expression of Dtprp is induced.The expression of Ptgs2 and Mmp9 is also downregulated.DFO may induce the expression of Ndrg1 via Bmp2.