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Interactions between the embryo and maternal immune system during the preimplantation period in domestic animals
Abstracts / Journal of Reproductive Immunology 94 (2012) 5–130
the 9th week of gestation) and in 10 physiological pregnancies, were collected at 7/8 week of gestation. Leukocytes extracted from peripheral blood samples were stained for Flow cytometric analysis using FACScalibur (BectonDickinson) All antibodies used were purchased from eBioscences. Treg cells were the CD4 + CD25 + Foxp3+. Statistical analysis was performed using unpaired t test. RESULTS: Treg levels in peripheral blood of women treated with G-CSF during pregnancy were statistically significant higher than in women with RM treated with placebo and in women with physiological pregnancy (P < 0.001and P < 0.01 respectivelly). The other populations of lymphocytes did not show statisticaly significant differences. CONCLUSIONS: G-CSF administration in women with Recurrent Miscarriage increases the number of Treg cells in the peripheral blood. This may be one of the mechanism of action in the positive effect of G-CSF on the pregnancy outcome in these women. doi:10.1016/j.jri.2012.03.259 Session 4 Presidential Symposium IS 09 Interactions between the embryo and maternal immune system during the preimplantation period in domestic animals
13
sion of activated lymphocytes into the uterus can enhance embryonic survival into recipient females in cattle and embryonic development can be enhanced by cytokines such as interleukin-1 and colony stimulating factor 2. Proembryonic cytokines could be derived from leukocytes in the reproductive tract or by epithelial or stromal cells of the reproductive tract. The immunological milieu of the reproductive tract changes drastically in the days preceding and coincident with placentation. There is large-scale activation of immune response genes in the endometrium (documented in cow and sheep) and recruitment of leukocytes to the endometrium adjacent to implantation sites (documented in horse). Activation of immunologicallyactive cells and gene networks in the endometrium is a result of signals derived from the developing trophoblast. These signals comprise interferon genes in ruminants and pigs and MHC class I genes in invasive trophoblast of the horse. The importance of large-scale changes in immune-response related genes in the endometrium for the biology of pregnancy is not understood. The immune changes directed by anti-luteolytic trophoblast interferons, for example, could be central to the placentation process or, rather, could be an epiphenomen that occurs because an interferon was chosen during evolution to regulate endometrial prostaglandin synthesis. The fact that activation of immune response genes near the initiation of placentation is not phylogenetically restricted would suggest an important functional role for this process.
P.J. Hansen
doi:10.1016/j.jri.2012.03.260
Department of Animal Sciences and D.H. Barron Reproductive and Perinatal Biology Research Program, University of Florida, Gainesville, USA
IS 10
Most of what is known about pregnancy immunology comes from the study of pregnancy after the definitive placenta has formed. The immunological situation in early pregnancy, when the embryo exists unattached to the maternal endometrium, is different in important respects than later in pregnancy. The situation has been best described for domestic animals. Unlike later in pregnancy, when the fetus expresses paternal major histocompatibility antigens (MHC), the preimplantation embryo appears immunologically inert because of low expression of MHC genes. Moreover, until zona hatching, the embryo is surrounded by an acellular coat (the zona pellucida) that may restrict maternal access to embryonic cells. While the embryo may not be immunogenic, the reproductive tract itself contains an array of maternal leukocytes. Indeed, the process of semen deposition that precedes formation of the embryo leads to a massive inflammatory response in the reproductive tract characterized by upregulation of cytokine genes and influx of neutrophils into the lumen of the uterus. It is controversial as to whether semen-induced inflammation can enhance subsequent embryonic development. Some evidence for this idea exists but the weight of the experimental evidence is interpreted to indicate that embryonic development is not dependent upon prior semen-associated events in the reproductive tract. Nonetheless, there is a report that infu-
J. Roberts
Preeclampsia 2012 and beyond
Investigator, Magee-Womens Research Institute, Graduate School of Public Health and Clinical and Translational Sciences, Clinical and Translational Science Institute (TSI), University of Pittsburgh During the last 30 years our knowledge of preeclampsia has expanded enormously. Preeclampsia is now recognized as a multisystemic disorder that is far more than pregnancy induced hypertension. Studies guided by this concept have focused increasing attention to aberrations of maternal physiology with resulting evidence for the role of inflammation, endoplasmic and oxidative stress, all possibly converging at the level of maternal vascular endothelium. The root cause of preeclampsia is the placenta and part or all of the pathophysiology is related to failed implantation with failed remodeling of the maternal vessels supplying the placenta. However, the genetics of preeclampsia indicate that the major genetic contribution is maternal supporting the concept that preeclampsia is more than a fetal disease. Further not all abnormal placentation results in preeclampsia, which is clearly influenced by what the mother “brings in to” pregnancy. Interestingly, many such maternal constitutional factors are precursors of later life cardiovascular disease an observation supported by the increased cardiovascular risk in later life of
the 9th week of gestation) and in 10 physiological pregnancies, were collected at 7/8 week of gestation. Leukocytes extracted from peripheral blood samples were stained for Flow cytometric analysis using FACScalibur (BectonDickinson) All antibodies used were purchased from eBioscences. Treg cells were the CD4 + CD25 + Foxp3+. Statistical analysis was performed using unpaired t test. RESULTS: Treg levels in peripheral blood of women treated with G-CSF during pregnancy were statistically significant higher than in women with RM treated with placebo and in women with physiological pregnancy (P < 0.001and P < 0.01 respectivelly). The other populations of lymphocytes did not show statisticaly significant differences. CONCLUSIONS: G-CSF administration in women with Recurrent Miscarriage increases the number of Treg cells in the peripheral blood. This may be one of the mechanism of action in the positive effect of G-CSF on the pregnancy outcome in these women. doi:10.1016/j.jri.2012.03.259 Session 4 Presidential Symposium IS 09 Interactions between the embryo and maternal immune system during the preimplantation period in domestic animals
13
sion of activated lymphocytes into the uterus can enhance embryonic survival into recipient females in cattle and embryonic development can be enhanced by cytokines such as interleukin-1 and colony stimulating factor 2. Proembryonic cytokines could be derived from leukocytes in the reproductive tract or by epithelial or stromal cells of the reproductive tract. The immunological milieu of the reproductive tract changes drastically in the days preceding and coincident with placentation. There is large-scale activation of immune response genes in the endometrium (documented in cow and sheep) and recruitment of leukocytes to the endometrium adjacent to implantation sites (documented in horse). Activation of immunologicallyactive cells and gene networks in the endometrium is a result of signals derived from the developing trophoblast. These signals comprise interferon genes in ruminants and pigs and MHC class I genes in invasive trophoblast of the horse. The importance of large-scale changes in immune-response related genes in the endometrium for the biology of pregnancy is not understood. The immune changes directed by anti-luteolytic trophoblast interferons, for example, could be central to the placentation process or, rather, could be an epiphenomen that occurs because an interferon was chosen during evolution to regulate endometrial prostaglandin synthesis. The fact that activation of immune response genes near the initiation of placentation is not phylogenetically restricted would suggest an important functional role for this process.
P.J. Hansen
doi:10.1016/j.jri.2012.03.260
Department of Animal Sciences and D.H. Barron Reproductive and Perinatal Biology Research Program, University of Florida, Gainesville, USA
IS 10
Most of what is known about pregnancy immunology comes from the study of pregnancy after the definitive placenta has formed. The immunological situation in early pregnancy, when the embryo exists unattached to the maternal endometrium, is different in important respects than later in pregnancy. The situation has been best described for domestic animals. Unlike later in pregnancy, when the fetus expresses paternal major histocompatibility antigens (MHC), the preimplantation embryo appears immunologically inert because of low expression of MHC genes. Moreover, until zona hatching, the embryo is surrounded by an acellular coat (the zona pellucida) that may restrict maternal access to embryonic cells. While the embryo may not be immunogenic, the reproductive tract itself contains an array of maternal leukocytes. Indeed, the process of semen deposition that precedes formation of the embryo leads to a massive inflammatory response in the reproductive tract characterized by upregulation of cytokine genes and influx of neutrophils into the lumen of the uterus. It is controversial as to whether semen-induced inflammation can enhance subsequent embryonic development. Some evidence for this idea exists but the weight of the experimental evidence is interpreted to indicate that embryonic development is not dependent upon prior semen-associated events in the reproductive tract. Nonetheless, there is a report that infu-
J. Roberts
Preeclampsia 2012 and beyond
Investigator, Magee-Womens Research Institute, Graduate School of Public Health and Clinical and Translational Sciences, Clinical and Translational Science Institute (TSI), University of Pittsburgh During the last 30 years our knowledge of preeclampsia has expanded enormously. Preeclampsia is now recognized as a multisystemic disorder that is far more than pregnancy induced hypertension. Studies guided by this concept have focused increasing attention to aberrations of maternal physiology with resulting evidence for the role of inflammation, endoplasmic and oxidative stress, all possibly converging at the level of maternal vascular endothelium. The root cause of preeclampsia is the placenta and part or all of the pathophysiology is related to failed implantation with failed remodeling of the maternal vessels supplying the placenta. However, the genetics of preeclampsia indicate that the major genetic contribution is maternal supporting the concept that preeclampsia is more than a fetal disease. Further not all abnormal placentation results in preeclampsia, which is clearly influenced by what the mother “brings in to” pregnancy. Interestingly, many such maternal constitutional factors are precursors of later life cardiovascular disease an observation supported by the increased cardiovascular risk in later life of