The Physiological Fuction In Of MCM2during Uterine Decidualization In Mice

Blastocyst implantation and uterine decidualization are two critical events during mammalian pregnancy. Implantation involves an intricate discourse between the embryo and the receptive uterus. The process of implantation is consisted of three stages:apposition, attachment (adhesion) and penetration. Uterine stromal cells undergo proliferation, differentiation, polyploidization to form decidual cells (decidualization) following attachment. The deciduum provides nutrients and immune protection for the developing embryo before the establishment of a functional placenta and the apoptosis of stromal cells creates space for growing embryos. Abnormal decidualiaztion would cause pregnancy related desease, including placental defects, intrauterine growth retardation and preterm birth. Proliferation of stromal cells is essetional for uterine decidualization. Although previous studies have shown that many molecules and signalling pathways are involved in uterine decidualiaiton, the underlying mechanism of cell proliferation and differentiation during decidualization still remains unknown.MCM2-7interact with each other to form a stable heterohexamer, controlling replication origin firing to ensure that the DNA replicate only once per cell cycle and function as DNA helicases that melt the DNA double helix at the initiation step of DNA synthesis. Expression of MCM2is closely related to cell proliferation, highly expressed in proliferating cells, but not in resting cells. MCM2impairs the cell proliferation and genomic instability (GIN), leading to DNA damage and cell apoptosis.Considering the important role MCM2played in cell proliferation, we firstly investigated the role of MCM2during uterine decidualization in mouse. We performed in situ hybridization experiment and found that Mcm2was spatiotemporally expressed in the uterus during early pregnancy, highly expressed in actively proliferating stromal cells. The silencing of Mcm2gene by RNAi technology resulted in inhibition of the proliferation in uterine stromal cells and abnormity of decidualization. In addition, silencing of MCM2impaired cell cycles and downregulated CyclinD3and CDK4, which regulate cell cycles, and Wnt4, which promotes uterine decidualization. These above data suggest that MCM2regulates cell cycles during decidulization in the uterus. Our study demonstrates the important role of MCM2in regulating the proliferation of stromal cells during uterine decidualization for the first time, giving a contribution to the future research about the mechanisms of regulated proliferation and differentiation during uterine decidualization.