The Role Of SIRT1 In Endometrial Decidualization

Endometrium decidualization is an important event in mammalian embryo implantation,related to trophoblast cell invasion,immunity and nutritional supply,and preparation for blastocyst implantation in the early pregnancy[1].Decidual process involve complex cytokine network and signal transduction mechanism.As we known,cell apoptosis and oxidative stress are important molecular mechanism for endometrial decidual[2].The oxidation of maternal-fetal interface cell death includ recurrent miscarriage,fetal growth restriction and preeclampsia and other common pregnancy disease characteristics.So,focus on pregnancy early endometrial decidual mechanism has very important significance.SIRT1 is one member of the family of enzyme protein acetylation,regulating the cell cycle,metabolism,aging,and the function of oxidative stress,which be widely watched longevity genes.FOX transcription factor deacetylation by SIRT1 can regulate the disease process,such as in the process of aging,degenerative diseases,inflammation,and tumors[3].But the relevant functions in embryo implantation have not been reported.FOXO3a is a subtype of FOXO,and is a common substrate of histone deacetylase.FOXO3a can be deacetylated by the deacetylases SIRT1 and SIRT2 to control its transcriptional activity[3,4]Other studies found that in vitro knockdown of FOXO3a in decidualized stromal cells would lead to decidualization failure[5].At the same time,the spontaneous abortion FOXO3a level increased in uterine decidua may prevent the discharge of dead embryos,maintain the decidua,and increase the risk of oxidative stress[6].FOXO3a in the role of decidual proven.As a group of protein acetylation enzyme SIRT1 substrates,whether SIRT1 regulating the oxidative stress reaction through FOXO3a pathways.In turn,affect the decidual,yet to be confirmed.The purpose of this study was to confirm the function of SIRT1 in endometrium decidualization,and to preliminarily explore its mechanism.Methods:Cell model and animal model were used to induce decidualization.Protein expression was detected by WB and IHC staining,mRNA expression was detected by Q-PCR,The expression of SIRTI and FoxO3a and the landmarks of oxidative stress in decidualization model were observed by interfering with SIRTI inhibitor.Results:1.The high expression of SIRT1 in mouse decidua and human endometrial decidua cells during early pregnancy suggested that SIRT1 might be involved in mammalian endometrial decidua.2.In the cell model in vitro,SIRT1 inhibitor inhibited the expression of SIRT1 and F0XO3a in decidua cells,suggesting that SIRT1 may be involved in endometrial decidua through FOXO3a.3.In the cell model in vitro,SIRT1 inhibitors inhibited the expression of oxidative stress markers in decidua cells,suggesting that SIRT1 may be involved in the oxidative stress process of endometrium decidua.4.The expression of SIRT1 in uterine decidua of patients with recurrent abortion was significantly lower than that of normal pregnancy decidua,indicating that the loss of SIRT1 may affect the endometrial decidua process and cause spontaneous abortion.