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Mice Model CBA/J×DBA/2 Mating Combination-Based Study On The Mechanism Of Pregnancy Tolerance

Posted on:2003-03-17Degree:DoctorType:Dissertation
Country:ChinaCandidate:Y LinFull Text:PDF
GTID:1104360065957104Subject:Obstetrics and gynecology
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The mechanism of pregnancy tolerance is a hot point of life science and medicine. It will be helpful, as for the clarification of this mechanism, not only to the diagnosis and treatment of infertility, abortion and pre-eclampsia, but also to the research on tissue or organ transplantation.To some extent, fetus is a kind of special allogeneic or semi-allogeneic transplantation. Nevertheless, it is tolerated by maternal immune system. The mechanism responsible for this phenomenon is poorly understood.CBA/J and DBA/2 are among the most commonly used inbred mice. DBA/2 male mated CBA/J female (CBA/J X DBA/2 mating combination) is characterized by abortion-prone. Therefore, it is capable of serving as an animal model of recurrent spontaneous abortion. Undoubtedly, studiesbased on this model will be necessary to clarify the mechanism ofpregnancy tolerance step by step.Numerous studies have been undertaken to address the mechanisms of pregnancy tolerance. Elevated expression of CD69 was found on peripheral blood NK cells in women with recurrent spontaneous abortions and infertility of implantation failures after 3 or more in vitro fertilization and embryo transfer (IVF-ET) cycles, as compared to normal fertile controls. CD69 is an activation marker and it triggers NK cytotoxicity. What's the pattern of CD69 expression on NK cells at the fetomaternal interface in CBA/J X DBA/2 mice? And whether it is associated with the outcomes of murine fetuses and pups? It remains unanswered so far as we know.CD 16 is a kind of receptor for Fc portion of IgG (FcR Y III). The great majority of human peripheral blood NK cells are CD16+, while only a smaller percentage of human decidual NK cells express CD 16. Moreover, an increased proportion of CD 16+ NK cells were found on endometrial NK cells from recurrent aborters. Thus, reporters proposed that over-expressed CD 16 may be harmful to pregnancy. However, it remains unclear as for the pattern of CD 16 expression on NK cells at the fetomaternal interface in CBA/J X DBA/2 mice.Furthermore, in the cases of tissue or organ transplantation, researchers have shown that expression of either CD80 or CD86 alone is sufficient to support vigorous allograft rejection, whereas blocking both13molecules, even transiently, greatly prolongs allograft survival and in some models can induce transplantation tolerance. However, whether these costimulator molecules, i.e. CD80 and CD86, involve in the mechanisms by which maternal immune responses reject the embryos in CBA/JX DBA/2 mice model? It remains to be answered so far as we know.It is commonly accepted that Thl type cytokines such as IFN- Y and TNF- a are harmful to pregnancy, whereas Th2 type cytokines such as IL-10 and IL-6 are helpful. Researchers have shown that, on one hand, systemically administration of Thl type cytokines induces fetal death or increases fetal resorption. On the other hand, the deficiency of Th2 type cytokines results in the increase of resorption rate in CBA/JX DBA/2 model. In contrast, some reporters suggest that in humans and other mammals, Thl type cytokines are naturally produced by the trophoblast and the pregnant uterus, and these cytokines have been speculated to be important to normal pregnancy. In mice, some embryo-derived Thl type cytokines may be involved in implantation by binding to its receptor expressed on endometrium. Therefore, a balance may be critical during pregnancy between Thl type and Th2 type responses.Some researchers found that, in humans and other mammals, sperm, oocytes and gametes are tolerant to local lipopolysacchride (LPS) callenge, including LPS-induced Thl type cytokines and, to some extent, this mechanism protects gametes and conceptuses from maternal response to14mating-introduced bacteria and their potential endotoxins.Now that some stuyies suggested that the administration of IFN- Y and TNF-a can result in resorptions in CBA/JX DBA/2 model, while other studies shown that a variety of T cell subpopulations seems to be involved in the mechanisms...
Keywords/Search Tags:mouse, recurrent spontaneous abortion, lymphocyte subpopulation, anti-sperm antibody, fetomaternal interface, animal model, intrauterine pregnancy, cell surface marker
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