| Background:The receptivity of Endometrium is an major factor for embryo implantation.The destruction of the uterine receptive is the main cause of infertility caused by endometriosis(EMT).Arginine methylation modification is mediated by histone arginine methyltransferases(PRMTs)and is widely exist during embryonic development,reproductive tumorigenesis,and reproductive endocrine regulation.Objective:Whether PRMTs participate in the establishment of endometrial acceptance;The expression of m RNA and protein of PRMTs members in endometrium and decidualization;The signaling pathways of PRMTs members in the establishment of uterine acceptance;The specific mechanism of the role of estrogen and progesterone-mediated PRMTs in the uterus.Methods:The expression of PRMTs in endometrial tissue of normal group and EMT patients were detected by real-time PCR and immunochemistry.Endometrial stromal cells in normal and EMT groups were cultured in vitro.The signal pathways and molecular mechanisms of PRMTs were detected by immunocytochemistry and Real-time PCR in blank group,estrogen treated group,progesterone treated group,c AMP treated group,decidualization treatment group and decidualization + EPZ015866 inhibitor-treated groups.Results: Real-time PCR results show the m RNA expression of PRMT4 in the PP,ESP,MSP and LSP of the menstrual cycle have no significant changes in normal group.The m RNA expression of PRMT5,PRMT6 and WDR77 in the MSP were significantly lower than that in the PP(P <0.05),and the m RNA expression of PRMT5,WDR77 in the LSP was significantly higher than that in the MSP(P <0.05),both of them have the same m RNA expression;In EMT patients,the m RNA level of PRMT4,PRMT5 and PRMT6 in MSP have no significant changes compared with the control group,and the m RNA expression of WDR77 was significantly higher than that of the control group(P <0.05).During the decidualization of stromal cells in the control and EMT groups,the m RNA expression of PRMT5 was significantly higher than that in the blank group(P<0.05),and the m RNA expression of PRMT6 and WDR77 were significantly lower than that in the blank group(P <0.05),of which the m RNA expression of PRMT4 was significantly increased in the control group(P <0.05)and decreased significantly in the EMT group(P <0.05).After the simultaneous application of the PRMT5-specific inhibitor EPZ015866 during decidualization,in the control group,the m RNA expression of PRMT5 was not significantly changed,and the m RNA expression of WDR77 was significantly increased(P <0.05).In the EMT group,the m RNA expression of PRMT5 was significantly increased.The m RNA expression of WDR77 has no significant change(P <0.05).In the control group,estrogen,progesterone,and c AMP have no effect on the m RNA expression of PRMT4 and PRMT5.Both estrogen,progesterone,and c AMP could down-regulate the m RNA expression of PRMT6(P <0.05).CAMP could down-regulate the m RNA expression of WDR77(P<0.05)and Progesterone had no effect on it;in the EMT group,estrogen,progesterone and c AMP have no effect on the m RNA expression of PRMT5,but all of them could down-regulate the m RNA expression of WDR77(P<0.05).Both progesterone and c AMP can down-regulate the m RNA expression of PRMT4 and PRMT6(P<0.05),while estrogen has no effect on both of them.Immunochemistry results showed that in the endometrium of the control group,PRMT4 protein was expressed in epithelium,stromal cells and decidual cells,and was well expressed during the proliferative phase and early secretory phase,and weakly expressed during the middle and late secretory phase.PRMT5 protein is expressed in epithelial stromal cells and decidual cells.Epithelial cells are strongly expressed at various stages,but weakly expressed in stromal cells and decidual cells.PRMT6 protein is expressed in epithelial,stromal,and decidual cell nuclei,and is strongly expressed during the proliferative phase,early secretory phase and intermediate secretory phase,and weakly expressed during late secretory phase.WDR77 protein is expressed in epithelium,stromal cells,and decidual cells.It is not significantly expressed during the proliferative phase,and is weakly expressed in the early,middle,and late secretory stages.In the EMT group,PRMT4 protein was weakly expressed in epithelial and stromal cells,PRMT5 and PRMT6 proteins were well expressed in epithelial and stromal cells,WDR77 protein was weakly expressed in epithelium,and no significant expression was observed in stromal cells.In the decidualized cells of the control group,the signals of PRMT4,PRMT5,and WDR77 were stronger than those of the blank group,and the signals of PRMT6 protein were weaker than those of the blank group.The signal of WDR77 protein was weaker than that of the blank group.After the simultaneous application of the PRMT5 specific inhibitor EPZ015866 during decidualization,PRMT5 and WDR77 proteins in the control group were stronger than those in decidualized cells,while PRMT5 and WDR77 proteins in the EMT group were weaker than those in decidualized cells.Conclusion: PRMTs are involved in the establishment of endometrial acceptance,and PRMTs may be closely related to low endometrial acceptance in patients with endometriosis.Among them,PRMT5 and WDR77 may participate in this process in the form of complexes and are regulated by estrogen and progesterone. |
