HCG: a hormone with immunological and angiogenic properties
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Abstracts / Journal of Reproductive Immunology 81 (2009) 113–175 123 lying the formation of developmental toxicant-induced birth defects. doi:10.1016/j.jri.2009.06.147 L22 HCG: a hormone with immunological and angiogenic properties M. Tsampalas a , V. Gridelet a,b , S. Berndt b , C. Munaut b , J.M. Foidart b,c , V. Geenen a , S. Perrier d’Hauterive a,c a University of Liege, Centre of immunology, CHU Sart Tilman, B-4000 Liege, Belgium b University of Liege, Center for Experimental Cancer Research, CHU Sart Tilman, B-4000 Liege, Belgium c University of Liege, Department of Gynaecology and Obstetrics, Centre of AMP, CHR Citadelle, B-4000 Liege, Belgium The success of implantation depends on a receptive endometrium, a normal blastocyst and a synchronized crosstalk at the maternal-fetal interface. Pregnancy is closely related to immunological tolerance favouring survival of the conceptus. A cascade of cytokines inter- venes in this dialogue which is a crucial step at the crossroad between immunology and endocrinology. The first known human embryo specific signal is chori- onic gonadotropin (hCG). Data from literature show that through hCG, embryo profoundly intervenes in its own implantation and favors immunological tolerance and active angiogenesis that are crucial for successful implantation. High hCG levels were found to coincide with the development of peritrophoblastic immune tol- erance. HCG in human endometrium intervenes in the development of this local immune tolerance through the cellular system of programmed death Fas/Fas-Ligand. HCG also modulates the Th1/Th2 balance as injection of hCG to nonobese diabetic mice before the begin- ning of the symptoms inhibits the development of Th1 autoimmune diabetes. HCG also promotes innate func- tions of resident macrophages that play an essential role to prevent exposure by apoptotic cells of the pater- nal antigens to the maternal immune system in the decidua. In baboon, hCG acts on complement C3 and C4A/B factors suggesting a role in the modulation of the decidual immune environment. The transient toler- ance during gestation is though to be achieved, at least partially, via the presence of regulatory T cells which are attracted by hCG at the fetal–maternal interface during early human pregnancy. Finally, hCG treatment of activated dendritic cells results in up-regulation of MHC class II expression, of IL-10 and IDO expres- sion, leading to the decreased ability to stimulate T cell proliferation. Successful implantation requires an extensive endometrial angiogenesis in the implanta- tion site. Recent data have demonstrated an angiogenic effect of hCG directly or through VEGF production in several in vivo and in vitro experiments, through the interaction with endometrial and endothelial LH/hCG receptors. doi:10.1016/j.jri.2009.06.148 L23 Immunoregulation of bovine embryo development and implantation A. Al Naib, N. Mansouri-Attia, G.M. O’Gorman, S. Mammo, E. Reddy, T. Fair ∗ School of Agriculture, Food Science and Veterinary Medicine, University College Dublin, Ireland Poor fertility in commercial dairy cattle is generally reflected in relatively high rates of embryonic and foetal mortality, largely in the first 16 days post fertiliza- tion. Cattle are monovular, non-seasonal breeders with a similar gestation period to humans, thus are a use- ful comparative model for human embryo development. Our current research is concerned with characterizing the expression and regulatory effect of a number of immune factors in the developing bovine embryo and in the mater- nal endometrium. Cumulus oocyte complexes (COCs) were recovered from ovarian follicles and matured, fer- tilized in vitro and cultured in medium supplemented with a range of cytokines (IL1-, IL-3, IL-4, P4, IL- 10, LIF, IFN-, GM-CSF and G-CSF). Cleavage rate and blastocyst number were recorded. Day 7 blastocysts were snap frozen and stored at –80 o C. Messenger RNA was extracted from replicate pools of embryos and pro- cessed for qRT-PCR to compare transcript abundance of non-classical (NC) MHC-I genes (BOLA-NC1, NC2, NC3 and NC4). In addition, the mRNA expression pro- file of a number of these factors was characterized in bovine endometrial tissue samples on days 5, 7, 13 and 16 of the oestrus cycle or pregnancy. Although the addi- tion of these factors to in vitro embryo culture did not affect embryo development rates, there was an effect on the mRNA expression of NC MHC-I genes in the result- ing blastocysts in a cytokine and gene specific manner. Furthermore, the presence of a conceptus in the bovine endometrium appears to cause a downregulation of a
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Transcript of HCG: a hormone with immunological and angiogenic properties
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Abstracts / Journal of Reprodu
ying the formation of developmental toxicant-inducedirth defects.
oi:10.1016/j.jri.2009.06.147
22CG: a hormone with immunological and angiogenicroperties
. Tsampalas a, V. Gridelet a,b, S. Berndt b,. Munaut b, J.M. Foidart b,c, V. Geenen a,. Perrier d’Hauterive a,c
University of Liege, Centre of immunology, CHU Sartilman, B-4000 Liege, BelgiumUniversity of Liege, Center for Experimental Canceresearch, CHU Sart Tilman, B-4000 Liege, BelgiumUniversity of Liege, Department of Gynaecology andbstetrics, Centre of AMP, CHR Citadelle, B-4000iege, Belgium
he success of implantation depends on a receptivendometrium, a normal blastocyst and a synchronizedrosstalk at the maternal-fetal interface. Pregnancy islosely related to immunological tolerance favouringurvival of the conceptus. A cascade of cytokines inter-enes in this dialogue which is a crucial step at therossroad between immunology and endocrinology. Therst known human embryo specific signal is chori-nic gonadotropin (hCG). Data from literature showhat through hCG, embryo profoundly intervenes in itswn implantation and favors immunological tolerancend active angiogenesis that are crucial for successfulmplantation. High hCG levels were found to coincideith the development of peritrophoblastic immune tol-
rance. HCG in human endometrium intervenes in theevelopment of this local immune tolerance through theellular system of programmed death Fas/Fas-Ligand.CG also modulates the Th1/Th2 balance as injectionf hCG to nonobese diabetic mice before the begin-ing of the symptoms inhibits the development of Th1utoimmune diabetes. HCG also promotes innate func-ions of resident macrophages that play an essentialole to prevent exposure by apoptotic cells of the pater-al antigens to the maternal immune system in theecidua. In baboon, hCG acts on complement C3 and4A/B factors suggesting a role in the modulation of
he decidual immune environment. The transient toler-
nce during gestation is though to be achieved, at leastartially, via the presence of regulatory T cells whichre attracted by hCG at the fetal–maternal interfaceuring early human pregnancy. Finally, hCG treatmentmunology 81 (2009) 113–175 123
of activated dendritic cells results in up-regulation ofMHC class II expression, of IL-10 and IDO expres-sion, leading to the decreased ability to stimulate Tcell proliferation. Successful implantation requires anextensive endometrial angiogenesis in the implanta-tion site. Recent data have demonstrated an angiogeniceffect of hCG directly or through VEGF production inseveral in vivo and in vitro experiments, through theinteraction with endometrial and endothelial LH/hCGreceptors.
doi:10.1016/j.jri.2009.06.148
L23Immunoregulation of bovine embryo developmentand implantation
A. Al Naib, N. Mansouri-Attia, G.M. O’Gorman, S.Mammo, E. Reddy, T. Fair ∗
School of Agriculture, Food Science and VeterinaryMedicine, University College Dublin, Ireland
Poor fertility in commercial dairy cattle is generallyreflected in relatively high rates of embryonic and foetalmortality, largely in the first 16 days post fertiliza-tion. Cattle are monovular, non-seasonal breeders witha similar gestation period to humans, thus are a use-ful comparative model for human embryo development.Our current research is concerned with characterizing theexpression and regulatory effect of a number of immunefactors in the developing bovine embryo and in the mater-nal endometrium. Cumulus oocyte complexes (COCs)were recovered from ovarian follicles and matured, fer-tilized in vitro and cultured in medium supplementedwith a range of cytokines (IL1-�, IL-3, IL-4, P4, IL-10, LIF, IFN-�, GM-CSF and G-CSF). Cleavage rateand blastocyst number were recorded. Day 7 blastocystswere snap frozen and stored at –80oC. Messenger RNAwas extracted from replicate pools of embryos and pro-cessed for qRT-PCR to compare transcript abundanceof non-classical (NC) MHC-I genes (BOLA-NC1, NC2,NC3 and NC4). In addition, the mRNA expression pro-file of a number of these factors was characterized inbovine endometrial tissue samples on days 5, 7, 13 and16 of the oestrus cycle or pregnancy. Although the addi-tion of these factors to in vitro embryo culture did notaffect embryo development rates, there was an effect on
the mRNA expression of NC MHC-I genes in the result-ing blastocysts in a cytokine and gene specific manner.Furthermore, the presence of a conceptus in the bovineendometrium appears to cause a downregulation of a
