Immunoregulation Of Cytokines And Apoptosis During The Embryonic Implantation

The embryonic implantation is the complicated immune tolerance of matrix-fetus. T helper2 (Th2) plays a dominant situation, and a shift towards Thl-type immunity is inclined to the implanting failure. Apoptosis occurs in fetal and maternal tissues during early pregnancy and plays an important role during implantation, decidualition, and in fetal development. In the regulation of apoptosis, Bcl-2 is one of the central proteins, and acts by inhibiting apoptosis. To the contrary, other members of the bcl-2 family such as Bax and Bcl-xl appear to be proapoptosis. Progesterone and some herbs can inhibite the role of mifepristone. We want to explore the immunological mechanism of the immune tolerance during implantation and provide theoretical foundation for effective precaution and treation. During the study, mifepristone, progestrone, and herbal medicine priscriptions were given at 7:00 a.m. in day4 of gestation, and the forage containing 25% herbal medicine priscriptions were feeded continually until the mice were killed. Salin was given as contrast in group 1. Mifepristone was given for the abortive model in group 2. Progesterone and mifepristone were injected in group 3. The 1st, 2nd, and 3rd Chinese herbal medicine prescription were administered i.g, while mifepristone being injected, respectively in group 4, 5, and 6. Mice were killed in 12h, or in 24h, or in 36h every group. Their right-handed uteri were grinded evenly for analyzing Thl-type (IL-2, IFN- ) and Th2-type (IL-4, IL-10) cytokines by Enzyme Linked Immunosorbent Assay (ELISA). The left-handed uteri were fixed for detecting the Bcl-2/Bax proteins by immunohistochemistry and the apoptotic cells by TUNEL (TdT-mediated dUTP-biotin nick end labeling) method. In the uterus tissue of normal implantation, the density of Interleukin-4 is 11.60pg/mg, lnterleukin-10 as 50.03 pg/mg, IL-2 as 21.33pg/mj, IFN- y as 564.67pg/mg. Apoptotic cells were mainly observed in trophoblast and decidua tissues rounding the sites of implantations on the basis of apoptotic signs in the samplesmorphologically. Bcl-2 and Bax had been observed properly, too. After injecting mifepristone, Thl-type cytokines were high remarkably comparing with the control experiment while the Th2-type cytokines changing little. In this group, the numbers of apoptotic cells in trophoblast and decidua tissues had also raised markedly. Progesterone maintains the desity of T helper for inhibiting mifepristone. After administering the Chinese herbal medicine prescriptions, secretion of thl-type cytokines decline transiently, th2-type rise persistly. The immunological microenvironment of uterus from normally embryonic implantation is dominant with Th2 type response, and enhancing Thl-type response and apoptosis all can mediate earlier embryo lose. Progesterone is indispensable to implantation by inhibiting Thl type respone. Mifepristone cause shift towards of the Thl-type immunol response and apoptosis by combining with the progesterone recepters in the decidua. The Chinese herbal medicine prescriptions not only decline the expression of thl-type cytokines, but also raise those of th2-type cytokines. But they had not affected markedly the cellular apoptosis. This may be the immunological mechanism of these Chinese herbal medicine precriptions.