| Objective:The mifepristone is a synthesized steroid,its'structure is similar to the anorethisterone,and it has the characteristics of the resistance to the progesterone and the glucocorticoid as well as lightly antiandrogen.Early research showed that the mechanism of the mifepristone's resistance of early pregnancy is that the high concentrated progesterone can make the deciduas to perform the apoptosis and the necrosis, and induce the chorionic nutrient cells to perform the apomorphosis and the embryonic death,and lead to termination of pregnancy.with the further investigation,we found that the mifepristone can directly effect on the chorionic nutrient cells, which make us more confused at the mechanism of the resistance of early pregnancy induced by the mifepristone. Although the misoprostol is not in the direct relationship with the embryonic death,it can induce the contraction of uterus's smooth muscles so that the necrotic embryonic tissue could be eliminated.Mifepristone,an antagon of the progesterone's receptor,is able to influence the biological effect of the progesterone and has more activities on the gestation as well as the metabolism and morphosis of which's products.The mechanism of mifepristone is still in the exploration.The osteopontin(OPN)is an important cell factor of the extracellular matrix,and its'Arg-Gly-Asp(RGD)sequence is able to interact with the cell surface receptor,such as the avβ3 intergrin and their interactions are in the relationship with the aggregation, the adhesion,the generation, the migration,the removal and the immune function of the cells.Many kinds of cells in the body could secrete it.A recent study showed that the thirtieth day after the swine's being in pregnancy the OPN is expressed in the whole uterus-placenta surface.In addition,the OPN could be found in the immune-type cells of the compact layer of the endometria during the gestational stage.Therefore,we could have a conclusion that the OPN is expressed in the epithelium and the immunocyte of the endometrium.OPN is able to interact with the receptors (avβ3),then effect on the fetation-cyst and the uterus,and promote the growth of the fetation-cyst,and it could perform an important function during the adhesion of the blastocyst and the placentation.In addition,both the OPN and the avβ3 are expressed in the trophocyte,and the placental villus.The trophocyte could secrete the OPN,which could promote the cell adhesion, and induce the cell tendency,the migration of the trophoblast so that the location, adhesion and implantation of the spermovium are regulated.Both of low and over expression of the OPN could induce the diseases, for instance,the unexplained infertility, the abortion, the premature labor,the endometriosis, and the trophobiastic disease and so on.Choriogonadotrophin-β(β-HCG),which is produced and secreted by the syneytial cells and the trophocyte cells of the placenta,and composed of theɑandβchains,and the antigenic specificity ofβ-HCG is more powerful,which could more precisely reflect the HCG's concentration in the blood and the urine. The measurements ofβ-HCG in the blood can reflect the potentiality of the embryonic development.as a specific marker of the pregnancyβ-HCG's function is to maintain the growth of the early corpus luteum of the pregnancy till its'function is completely replaced by the placenta.The production ofβ-HCG in the blood could reflect the number and the development of the nutrient cells,Bischof et al reported that Mifepristone can strikingly suppress the production ofβ-HCG and PAPP-A,which is in the relation with the pregnancy, from the embryo nutritive layer in vitro culture.Such depressive effect could be eliminated by the progesterone (for PAPP-A andβ-HCG) and the corticosteroid (forβ-HCG).P53 protein was initially discovered in 1979,its'molecular mass is about 53kD,which is the reason why this protein is named P53.P53 is an important proto-oncogene involved in the regulation of cell cycle and the beginning of apoptosis.The expression of P53 is very important for the regulating the dynamic equilibrium of the embryonic trophoblast.Maybe the up-regulation of P53 induced by mifepristone has an important effect on the apoptosis of the mother-fetus interface.Inducing the apoptosis is another important function of P53.P53 directly participates in the apoptosis process by decreasing the expression of Bcl-2 and increasing the expression of Bax.Recently a study showed that the expression of Bcl-2 decreases and the expression of Bax increases in the mother-fetus limiting surface during the termination of pregnancy induced by the mifepristone.By now,no report about the research of the expression of OPN in the chorion and the decidua from early pregnancy by the mifepristone has been found.In the present study,we used the immunohistochemistry and transmission electron microscope to detect the expression of OPN,β-HCG and P53 induced by the mifepristone during the early pregnant stage.We further approached the mechanism of the resisting the early pregnancy induced by the mifepristone and established the rationale of OPN in the reproductive medicine field.Method1 MaterialsThe chorion and the decidua were derived from the patients with the 20 days'pregnancy,who were at the first administered the mifepristone 50mg,after they continued administered mifepristone 25mg,Bid,total 150mg,on the third morning at eight,they were administered the misoprostol 600μg and observed in the hospital, After fetation discharged,at once,the chorion and the decidua were collected.they were as the experiment group.The other group,the chorion and decidua were derived from the patients with the 20 days'pregnancy,who were performed the operation of the surgical aspiration for inducing the abortion,they were as the control group . 2 Light microscopeAll the samples were performed the routine Hestaining.The expressions of OPN,β-HCG,and P53 were determined by the immunohistochemistry.Furthermore,the relationship between OPN,β-HCGand P53 as well as the correlation with the clinic opathological parametes were analysed.3 Electron microscopeThe chorion was collected from the Mifepristone group and the artificial abortion by the operation of the surgical aspiration group,which's morphosis were observed by the usage of the transmission electron microscope.Results1 The results of HE stainingNormal histomorphology of the early pregnant chorial and decidual cells were found in the artificial abortion by the operation of the surgical aspiration group.The cytotrophoblast cell is cubic monolayer, and the cell membrane is integrated.The syncytiotrophoblast is thicker and the cytoplasm is fusional. There's no limit among the cells.The decidual cell body is hypertrophic,There are a lot of glucogen and lipid droplets in it.In the mifepristone group we found the interstitial edema in some chorion,a lot of fibrinoid materials adhered to the surface of the chorion and the vasodilatation. Some inflammatory cells infiltrate into the mesenchyme of the chorion.The structure of the trophoblast is very distinguished.Furthermore we found the patchy degeneration,the necrosis and the inflammatory cells infiltration in the decidua.We found the karyopyknosis,the quassation,the uneven cytoplasm,the vacuolar degeneration in a few cells,and the apoptotic cells could be found.2 The results of the immunohistochemistry2.1 From the results of the immunohistochemistry we found that theβ-HCG is located in the cytoplasm and/or on the cell membrane.In the induced abortion with the surgical aspiration group,theβ-HCG is stongly expressed in the cytoplasm of the syneytiotrophoblast of the chorion during the early pregnant stage, and still found in the cytoplasm,the ground substance,the glandular epithelium of the decidua.But in the mifepristone groupβ-HCG is weakly expressed in the homologus position of the decidua.The intensity change of the immune response is most obvious in the chorion syncytiotrophoblast,the decidual ground substance and the glandular epithelium.2.2 From the results of the immunohistochemistry we found that the OPN is located in the cytoplasm.In the induced abortion with the surgical aspiration group,OPN is strongly expressed in the Syncytiotrophoblast cell and cytotrophoblast cell of the chorion during the early pregnant stage.at the same time OPN is also strongly expressed in the decidua cavity epithelium,the glandular epithelium basilemma,the decidual cell.In the mifepristone group OPN is weakly expressed in the homologus position.2.3 From the results of the immunohistochemistry we found that the P53 protein is located in the nucleus.In the induced abortion with the surgical aspiration group,the P53 protein is expressed in a few cells of the chorion and decidua during the early pregnant stage,the P53 protein is mainly expressed in the cells of the cytotrophoblast.But in the mifepristone group,the P53 protein is expressed in the more cells of the cytotrophoblast the chorion,and the P53 protein is also expressed in the more cells of the decidua.3 The results of the electron microscopeAfter being administered mifepristone,a little of chorion could be found in the surface of the syncytiotrophoblast by the transmission electron microscope.Some chorion is degenerated, and some is inflatable,the lipid droplets increase in the cytoplasm,and the endoplasmic reticulum distend,the karyopykno- sis and the degeneration could be found in the cells of the syneytiotrophoblast and the cytotrophoblast.Conclusions1 From the results of the immunohistochemistry we found that the OPN is located in the cytoplasm.The OPN is expressed in the decidua and the camisia foetus during the early pregnant stage.In the mifepristone group the expression of the OPN is much less than in the induced abortion with the surgical aspiration group.There's a significant difference between two groups.The results suggest that the mifepristone is able to inhibit the synthesis of the OPN during the early pregnant stage as well as the capability of the adhesion, the proliferation and the migration of the trophocyte and the decidual cells.So both the imbedding of the blastocyst and the placental formation are affected,then the abortion occurs. 2 From the results of the immunohistochemistry we found that theβ-HCG is located in the cytoplasm and/or on the cell membrane.Theβ-HCG is expressed in the decidua and the camisia foetus during the early pregnant stage.In the mifepristone group the expression of theβ-HCG is much less than in the induced abortion with the surgical aspiration group. There's a significant difference between two groups.The results suggest that the mifepristone is able to inhibit the synthesis of theβ-HCG during the early pregnant stage.So the function of the corepus luteum is decreased,it's hard for the patients to have a fetation,then the abortion occurs.3 From the results of the immunohistochemistry we found that the P53 protein is located in the nucleus.The P53 protein is expressed in the decidua and chorion during the early pregnant stage.In the mifepristone group the expression of the P53 protein is more than in the induced abortion with the surgical aspiration group.The results suggest that the mifepristone is able to up-regulate the expression of P53 protein during the early pregnant stage,and promote the apoptosis of the trophocyte and the decidual cells.Finally the fetus could not continue to develop, and the pregnancy is ended.
|
PDF Full Text Request