Effect Of Progesterone And 17β-Estradiol On The Expression Of Baffr And BCL-2/Bax In Human Decidual Stromal Cells

Partâ… Effect of progesterone and 17β-estradiol on the expression of BAFFR in human decidual stromal cellsBackground:Maternal-fetal interface is composed of maternal decidua and fetal trophoblast.Decidual stromal cells(DSC),main part of decidua,is involved in immune relationship of mother to fetus.A lot of studies had found that the members of TNF super family taken part in the process of immune privilege,and played an important role in the proliferation and differentiation of placenta.BAFF was the new number of the TNF super family,and BAFF receptor(BAFFR,BR3) is one of three receptors for BAFF,appearing to be highly specific for BAFF and to be the principal receptor for BAFF-mediated mature B cell survival.Phillips TA et al.found that BAFF expressed on the Maternal-fetal interface,and which was in favor for the homeostasis,growth and remodeling of the normal pregnant placenta.We have recently found that BAFF and BAFFR were expressed in the human DSC.However,the roles of BAFFR in maternal-fetal interface remain to be elucidated.In this study,we investigated whether the mRNA and protein level of BAFFR would be influenced by the female sex steroids estradiol(E₂) and progesterone(P) in human DSC.Objective:we investigated the regulation of BAFFR by 17β-estradiol(E₂) and progesterone(P₄) in cultured human decidual stromal cells(DSC) to explore its role in the embryo implantation and the balance of materno-fetal immune,which will provide new basic experimental data for the diagnosis and treatment of pathological pregnancy.Methods:DSC isolated from the human deciduas of early pregnancy were purified and cultured in medium supplemented with 10%dextran-coated charcoal-treated fetal bovine serum.Then the cells were cultured in the same medium in absence or presence of E₂,P₄,and E₂ plus P₄ for 96 h.The cell proliferation of DSC was verified by MTT. The transcription and translation levels of BAFFR gene were analysed by real-time PCR and Flow cytometry respectively.Results:There were no significant differences in cell proliferation among the 4 groups, and the expression levels of BAFFR mRNA exhibiteed the same result as cell growth. However,the intracellular BAFFR protein levels were up-regulated significantly by P plus E(P＜0.05).Conclusion:These results suggest that up-regulation of intracellular BAFFR protein levels in human DSC by E₂ plus P₄ may participate in the process of embryo implantation and inhibit benefit for the immune function at the maternal-fetal interface, which may have an important role in the prevention and treatment of pathological pregnancy such as missed abortion,gestational trophoblastic disease,hypertensive disorder complicating pregnancy and so on.Partâ…¡Progesterone and estradiol contribute to human decidual stromal cells apoptosis by enhancement BaxBackground:Apoptosis have an important role in maintenance of the organism normal morphous and function,which also present in the placenta issue.After conception,the uterine endometrial stromal cells(ESC) differentiate to decidual stromal cells(DSC). Decidual tissue,the maternal component at maternal-fetal interface,is composed predominantly of DSC.Differentiation and apoptosis of ESC during the decidualization of the receptive endometrium are suggested to be crucial for the immune tolerance to the pregnancy and for the limited invasion of trophoblasts.Therefore,apoptosis of the DSC is an important determinant in the regulation of placental homeostasis,growth and remodelling.In fact,although DSC's apoptosis is a normal event in pregnancy,its mechanism is not fully understood.Apoptosis is regulated by various gene products including cytokines,interleukins and steroid hormones.Many promoters and inhibitors of apoptosis have been described. Maternal hormones are likely to have a role in the regulation of apoptotic signaling molecules.The apoptosis-related protein Bax have been shown to promote apoptosis, whereas the presence of Bcl-2 appears to inhibit this process.Bcl-2/Bax system is shown to be important in the development of local immunotolerance during and after implantation.However,few attempts have been made in the past to investigate the precise role of steroid hormones in human decidual apoptosis by hormone supplement in vitro.Objective:we investigated the effect of P₄ and E₂ on apoptosis and Bax/Bcl-2 protein expression in human DSC in vitro to explore the regulated role in the endometrial receptivity in the first trimester,which will provide new basic experimental data for the diagnosis and treatment of pathological pregnancy.Methods and Results:The DSC isolated from the human decidua in early pregnancy were purified and cultured in the medium treated with E₂,P₄,both or neither for 96 h respectively.MTT assay revealed that there was no significant difference in cell biological activity among 4 groups.Flow cytometry analyses found a significant increase in apoptosis and Bax protein levels in DSC treated with P₄ plus E₂ compared with the vehicle,whereas E₂ or P₄ alone was ineffective.On the other hand,the Bcl-2 protein in those cells was not detected in all groups.Conclusion:This study suggests that P₄ in combination with E₂ could induce apoptosis by up-regulating Bax expression in DSC,which may be benefit to the endometrial receptivity in the first trimester.This study will provide new idea and clue for the prevention and treatment of pathological pregnancy and the improvement of the implantation rate of the in vitro fertilization and embryo transfer(IVF-ET).