Home About us Contact
|
Home About us Contact | ||
|
|
||
Trophoblast
Kinds of Trophoblast Terms modified by Trophoblast Selected AbstractsToll-like receptors and pregnancy: Trophoblast as modulators of the immune responseJOURNAL OF OBSTETRICS AND GYNAECOLOGY RESEARCH (ELECTRONIC), Issue 2 2009Kaori Koga Abstract During normal pregnancy, the decidua is populated by a variety of leucocytes; however, cells of the innate immune system seem to dominate this tissue. Their presence suggests that the innate immune system is not indifferent to the fetus and has been associated with a response of the maternal immune system to the ,semi-allograft' fetus. New evidences, however, indicate that these immune cells are critical for decidual and trophoblast development rather than induction of tolerance. We hypothesized that during implantation, an inflammatory environment is necessary for the attachment and invasion of the blastocyst. The existence of an ,inflammatory-mediated embryo implantation' condition is dependent on the proper ,education' of the innate immune system which we propose is mediated by the trophoblast. Here we postulate that trophoblast cells successfully orchestrate their inflammatory environment and regulate immune cells differentiation and activation through Toll-like receptors (TLR). We will describe potential functions of TLR in trophoblast cells, their recognition and response to microorganisms, and their involvement in innate immunity. [source] Molecular Reproduction & Development: Volume 76, Issue 12MOLECULAR REPRODUCTION & DEVELOPMENT, Issue 12 2009Article first published online: 15 OCT 200 Heparin-binding EGF-like growth factor (HBEGF) at the fetal-maternal interface in the human placenta. Extravillous trophoblast cells, marked by cytokeratin 7 (red), invade interstitially into the uterine decidua. Trophoblast and some resident uterine cells produce HBEGF (green), which stimulates trophoblast differentiation to an invasive phenotype and limits cell death during gestation. Nuclei are counterstained with DAPI (blue). See the accompanying article by Jessmon et al. in this issue. [source] REVIEW ARTICLE: Maternal Immune Responses to Trophoblast: The Contribution of the Horse to Pregnancy ImmunologyAMERICAN JOURNAL OF REPRODUCTIVE IMMUNOLOGY, Issue 4 2010Leela E. Noronha Citation Noronha LE, Antczak DF. Maternal immune responses to trophoblast: the contribution of the horse to pregnancy immunology. Am J Reprod Immunol 2010 The horse has proven to be a distinctively informative species in the study of pregnancy immunology for several reasons. First, unique aspects of the anatomy and physiology of the equine conceptus facilitate approaches that are not possible in other model organisms, such as non-surgical recovery of early stage embryos and conceptuses and isolation of pure trophoblast cell populations. Second, pregnant mares make strong cytotoxic antibody responses to paternal major histocompatibility complex class I antigens expressed by the chorionic girdle cells, permitting detailed evaluation of the antigenicity of these invasive trophoblasts and how they affect the maternal immune system. Third, there is abundant evidence for local maternal cellular immune responses to the invading trophoblasts in the pregnant mare. The survival of the equine fetus in the face of strong maternal immune responses highlights the complex immunoregulatory mechanisms that result in materno,fetal tolerance. Finally, the parallels between human and horse trophoblast cell types, their gene expression, and function make the study of equine pregnancy highly relevant to human health. Here, we review the most pertinent aspects of equine reproductive immunology and how studies of the pregnant mare have contributed to our understanding of maternal acceptance of the allogeneic fetus. [source] REVIEW ARTICLE: Governing the Invasive Trophoblast: Current Aspects on Intra- and Extracellular RegulationAMERICAN JOURNAL OF REPRODUCTIVE IMMUNOLOGY, Issue 6 2010Justine S. Fitzgerald Citation Fitzgerald JS, Germeyer A, Huppertz B, Jeschke U, Knöfler M, Moser G, Scholz C, Sonderegger S, Toth B, Markert UR. Governing the invasive trophoblast: current aspects on intra- and extracellular regulation. Am J Reprod Immunol 2010 This review summarizes several aspects especially of regulating factors governing trophoblast invasion. Those include the composition of the extracellular matrix containing a variety of matrix metalloproeinases and their inhibitors, but also intracellular signals. Furthermore, a newly described trophoblast subtype, the endoglandular trophoblast, is presented. Its presence may provide a possible mechanism for opening and connecting uterine glands into the intervillous space. Amongst others, two intracellular signalling pathways are crucial for regulation of trophoblast functions and development: Wnt- and signal transducer and activator of transcription (STAT)3 signalling. Wnt signalling promotes implantation, placentation and trophoblast differentiation. Several Wnt-dependent cascades and regulatory mechanisms display different functions in trophoblast cells. The STAT3 signalling system is fundamental for induction and regulation of invasiveness in physiological trophoblastic cells, but also in tumours. The role of galectins (Gal) in trophoblast regulation and placenta development comes increasingly into focus. The Gal- 1,4, 7,10 and 12,14 have been detected in humans. Detailed information is only available for Gal-1, -2, -3, -4, -9 and -12 in endometrium and decidua. Gal-1, -3 and -13 (-14) have been detected and studied in trophoblast cells. [source] ORIGINAL ARTICLE: Activation of TLR3 in the Trophoblast is Associated with Preterm DeliveryAMERICAN JOURNAL OF REPRODUCTIVE IMMUNOLOGY, Issue 3 2009Kaori Koga Problem, Toll-like receptors (TLRs) recognize conserved sequences on the surface of pathogens and trigger effector cell functions. Previously, we described the expression of TLR3 by human trophoblast and their ability to respond to (Poly[I:C]). Here we evaluate the effect of Poly[I:C] on mouse pregnancy and characterize the local and systemic response. Method of study, C57B/6 wild type (wt) and TLR3 knockout (TLR3KO) mice were treated with Poly[I:C] at 16.5 dpc and pregnancy outcome recorded. Morphologic changes, cytokines and chemokines levels in blood and utero-placental tissue were determined. NF-,B pathway was evaluated in vivo and in vitro. Results, Poly[I:C] in C57B/6 wt mice caused preterm delivery within 24 hr (4.5 mg/kg). No effect was observed in TLR3KO mice. In addition, we observed local (placenta) and systemic (serum) response characterized by increased production of proinflammatory cytokines and chemokines. The NF-,B pathway was activated by Poly[I:C] in human and mice trophoblast cells. Conclusion, We report that Poly[I:C] induces preterm delivery via TLR3-dependent manner. Furthermore, we demonstrate that the trophoblast is able to recognize Poly[I:C] through TLR3 and respond to viral infection, modulating the immune system at the feto-maternal interface. [source] A Novel Three-Dimensional In Vitro System to Study Trophoblast,Endothelium Cell InteractionsAMERICAN JOURNAL OF REPRODUCTIVE IMMUNOLOGY, Issue 2 2007Paulomi B. Aldo Introduction Pregnancy complications have been linked to improper trophoblast migration and failure of spiral artery transformation. Endothelial cells play an essential role in directing trophoblast migration and transformation, although by an unknown mechanism. We describe a novel in vitro model to evaluate endothelial,trophoblast interaction and signaling in a three-dimensional system. Method of study Immortalized human endometrial endothelial cell line and first trimester trophoblast cells were co-cultured. Endothelial transformation into vessel-like structures occurred in MatrigelTM OpenLab Image Analysis software was used to monitor labeled trophoblast migration and endothelium transformation. Cytokine/chemokine production was determined using Multiplex. Results Trophoblast migrates toward endothelial cells in Matrigel, aligns on top of the endothelium within 4,8 hr and achieves complete replacement of the endothelium by 72,96 hr. Lipopolysaccharide treatment damages the endothelium and disrupts endothelium,trophoblast interaction. Conclusion We report a novel three-dimensional in vitro and in vivo system of trophoblast,endothelium cell interaction. Significant changes in endothelial cells' phenotype are observed upon differentiation in Matrigel. These changes may be necessary for endothelium to direct trophoblast migration and transformation. [source] Placental Trophoblast from Successful Human Pregnancies Expresses the Tolerance Signaling Molecule, CD200 (OX-2),AMERICAN JOURNAL OF REPRODUCTIVE IMMUNOLOGY, Issue 3 2003David A. Clark Problem: Th1 cytokine-dependent abortions in the CBA × DBA/2 mouse model have been linked to down-regulation of expression of the CD200 (OX-2) ,tolerance' signal on trophoblast and in decidua prior to onset of the abortion process. Abortions could be prevented by administration of a soluble CD200. Is CD200 expressed on trophoblast in successful human pregnancy? Method of study: As one cannot easily obtain trophoblasts in large quantities from successful human pregnancies in the first trimester prior to the onset of the abortion process at 6 weeks gestation, we examined as a first step, trophoblast isolated from term placentae (i.e. successful pregnancies). CD9, trophoblasts were isolated by affinity column and stained for intracellular cytokeratin, and surface CD200 using PE-anti-human CD200 monoclonal antibody. mRNA was extracted from CD9+ and CD9, cells and tested by reverse transcription,polymerase chain reaction for CD200 mRNA. CD9, placental cells were separated by velocity sedimentation and test for CD200-dependent suppression of an allogeneic human mixed lymphocyte culture where cytotoxic T cell (CTL) generation, and Th1 , Th2 cytokine production shift were measured. Results: CD9, but not CD9+ placental cell populations contained cells with mRNA for CD200, both a normal length transcript and a truncated transcript. Flow cytometry showed a CD200+ cytokeratin+ moderate-to-large-sized cell population compatible with trophoblasts and a smaller subset of cytokeratin, cells that expressed CD200 at normal and at high levels. The moderate-sized population proved most potent at inhibiting CTL generation and caused a Th1,Th2 cytokine shift. These effects were blocked by monoclonal anti-CD200. Conclusions: A subpopulation of cytokeratin+ placental trophoblasts express bioactive CD200 able to alter maternal immune responses in a favorable (Th2 > Th1) direction. Two populations of CD200+ small- and medium-small-sized cytokeratin, placental cells remain to be identified. Studies of karyotyped first trimester elective termination and spontaneous miscarriage tissues are needed. [source] Allometric studies on growth and development of the human placenta: growth of tissue compartments and diffusive conductances in relation to placental volume and fetal massJOURNAL OF ANATOMY, Issue 6 2006Terry M. Mayhew Abstract Correlations between placental size and fetal mass during gestation fail to account for changes in composition that accompany placental growth and maturation. This study uses stereological data on the sizes of different tissue compartments in human placentas from 10 weeks of gestation to term and relates them to placental volume and to fetal mass by means of allometric analysis. In addition, tissue dimensions are used to calculate a physiological transport measure (diffusive conductance) for the villous membrane. Histological sections randomly sampled from placentas and analysed stereologically provided estimates of structural quantities (volumes, exchange surface areas, lengths, numbers of nuclei, diffusion distances). These data were combined with a physicochemical quantity (Krogh's diffusion coefficient) in order to estimate oxygen diffusive conductances for the villous membrane and its two components (trophoblast and stroma). Allometric relationships between these quantities and placental volume or fetal mass were obtained by linear regression analyses after log-transformation. Placental tissues had different growth trajectories: most grew more rapidly than placental volume and all grew more slowly than fetal mass. Diffusion distances were inversely related to placental and fetal size. Differential growth impacted on diffusive conductances, which, again, did not improve commensurately with placental volume but did match exactly growth of the fetus. Findings show that successful integration between supply and demand can be achieved by differential tissue growth. Allometric analysis of results from recent studies on the murine placenta suggest further that diffusive conductances may also be matched to fetal mass during gestation and to fetal mass at term across species. [source] Villous trophoblast growth in pregnancy at high altitudeJOURNAL OF ANATOMY, Issue 5 2002T. M. Mayhew The trophoblastic epithelium of placental villi exhibits continuous turnover. Phases of proliferation, recruitment, maturation, terminal differentiation (apoptosis) and extrusion exist in steady state and occur in distinctive spatial compartments, viz. cytotrophoblast cells (CT), syncytiotrophoblast (ST), syncytial knots (SK), denudation sites (DEN) and syncytial fragments. Hypoxia in vitro stimulates CT proliferation but inhibits recruitment into ST. Pregnancy at high altitude (HA) is associated with reduced birthweight and provides a convenient model of preplacental (hypobaric) hypoxia. HA placentas show impoverished villous growth and changes in the incidences of CT cells and SK regions. Here we examine placentas from Amerindian and nonindigenous women who completed full-term pregnancies at low altitude (LA; 400 m; n = 25) and high altitude (HA; 3600 m; n = 45) in Bolivia. We test the hypothesis that HA pregnancy disturbs the epithelial steady state as reflected in the relative volumes and surfaces of trophoblast compartments. Masson trichrome stained tissue sections and microscopical fields were generated by uniform random sampling. Point and intersection counts were used to estimate the volumes and surface areas of nonsyncytial knots (nonSK), SK regions, syncytial bridges (SB) and denudation sites (DEN). Absolute values were compared by 2-way analyses of variance to resolve altitudinal from ethnic effects. At LA, trophoblast comprised about 85% nonSK, 8% SK, 5% SB and 3% CT by volume. Its maternal surface area comprised about 91% nonSK, 5% SK, 2% SB, and 3% DEN. Apart from CT (the fractional volume of which increased to 4%, P < 0.05), relative volumes of trophoblast compartments did not alter significantly at HA. However, there was a roughly 30% reduction in absolute volume of trophoblast at HA (P < 0.001) which could be explained mainly by a decrease in volume of nonSK regions (P < 0.001). The volume of CT was unaltered. Absolute surface areas of villi also declined at HA (by 20%, P < 0.01) and, again, this was attributed mainly to nonSK. The findings confirm that poor villous growth is partly due to failure of trophoblast to attain the growth seen at LA. The reduced trophoblastic growth occurs despite an increase in relative volume of CT cells (consistent with previously reported increases in proliferative activity) and, probably, by a combination of compromised syncytial fusion and continuing extrusion of syncytial fragments. [source] The amounts and deposition patterns of fibrin-type fibrinoid at the villous surface are altered in pregnancy at high altitudeJOURNAL OF ANATOMY, Issue 5 2002T. M. Mayhew In pregnancy at high altitude, there is preplacental (hypobaric) hypoxia and intrauterine fetal growth is restricted. Previous studies on placentas from Amerindian and nonindigenous women completing term pregnancies at low (LA; 400 m) and high (HA; 3600 m) altitudes in Bolivia showed that HA placentas had smaller surface areas of villi and smaller volumes of fibrin type fibrinoid (FTF). Recently we devised a stereological method for testing whether perivillous FTF (pFTF) is randomly distributed at the surface of villous trophoblast. Here the method is applied to test 2 experimental hypotheses: [1] deposition of pFTF is nonrandom regardless of altitude and [2] deposition patterns differ between altitudes. Uniform random samples of microscopical fields were drawn from Masson trichrome stained sections and intersection counts used to estimate the surface areas of, and patterns of pFTF on, 4 regions of trophoblast: nonsyncytial knots (nonSK), syncytial knots (SK), syncytial bridges (SB) and denudation sites (DEN). Absolute areas were compared by 2-way analyses of variance. Expected and observed distributions were compared by (2 and contingency table analyses. At LA the mean (SEM) volume of FTF was 8.4 (1.54) cm3 and villous surface area was 7.0 (0.43) m2. At HA FTF volume was reduced by about 50% (P < 0.01) and villous surface by 20% (P < 0.01). The surface composition of trophoblast in LA placentas was nonSK (91%), SK (5%) and SB and DEN (both less than 3%). Relative surfaces were not significantly altered in HA placentas but, due to the impoverished growth of villi at HA, the changes represented a real decline in absolute surface of nonSK. At HA, the total surface of pFTF on trophoblast decreased by about 40%, from 4430 (564) cm2,2570 (406) cm2 (P < 0.01). At both altitudes pFTF deposition was preferentially found at DEN (12-fold greater than expected for a random distribution). Pattern differences were detected between altitudes. In HA placentas the amount of pFTF deposited on nonSK regions was about 45% less (P < 0.05); apparent changes on SK and SB regions were not significant. These histometric findings suggest that the coagulation-fibrinolysis steady state is altered at HA and favours greater fibrinolysis. At least some of the fibrinolytic or anticoagulant activity seems to reside in or on thinner regions of villous trophoblast and the placenta may be a relatively privileged site in terms of fibrinolysis. Also, reduced deposition of pFTF is probably linked to changes in the steady state of trophoblast turnover which seems to be perturbed in HA pregnancies. [source] The Origination of a Human Being: A Reply to OderbergJOURNAL OF APPLIED PHILOSOPHY, Issue 4 2009INGMAR PERSSON abstract Recently David S. Oderberg has tried to refute three arguments that have been advanced in favour of the view that a human being does not begin to exist at fertilization. These arguments turn on the absence of differentiation between the embryoblast and trophoblast, the possibility of monozygotic twinning, and the totipotency of the cells during the first days after fertilization. It is here contended that Oderberg fails to rebut these arguments, though it is conceded that the first two arguments are not conclusive. They do, however, make it at least as reasonable to deny this early origination as to affirm it. It should be noticed that this is all that is needed by those who have used these arguments to dispute that something with a special moral status exists right from fertilization. Nonetheless, it will be seen that the third argument could be developed to the point of giving a conclusive reason to believe that a human being does not begin to exist at fertilization. [source] Metals in human placenta: focus on the effects of cadmium on steroid hormones and leptin,JOURNAL OF APPLIED TOXICOLOGY, Issue 3 2010Sandra Stasenko Abstract Cadmium and other metallic ions can act as metalloestrogens and endocrine disruptors of reproductive tissues and fetal development in mammals, including humans. The detrimental effects occur with respect to the synthesis of both steroid and polypeptide hormones in the placenta. Leptin is produced by the trophoblast and may regulate fetal organogenesis and development. In human term placentas, concentrations of toxic metals and their effects on steroidogenesis were assessed in healthy parturients (109 non-smokers and 99 smokers) in relation to tobacco smoking. Trace elements (cadmium, lead, iron, zinc and copper) were analyzed in placentas using atomic absorption spectroscopy, and steroid hormones (progesterone and estradiol) were assayed in placental samples by an enzyme-immunometric method. Cadmium concentrations were doubled in placentas of smokers as compared with non-smokers, and placental lead and zinc concentrations increased significantly. Placental concentrations of iron, copper, progesterone and estradiol did not differ. In addition, human trophoblast cells were co-cultured with 0, 5, 10 or 20,,µm CdCl2 for 96,,h and leptin mRNA assessed by quantitative polymerase chain reaction. Leptin mRNA declined dose-responsively as a result of CdCl2 exposure. Collectively, the results confirm that human placental tissue offers a unique opportunity to biomonitor cadmium exposure in both the maternal and the internal fetal environments. In addition, the results strongly suggest that cadmium may cause a decline in placental leptin synthesis, as we have previously shown for placental progesterone production. This may constitute further evidence of the endocrine-disrupting effects of cadmium, as a constituent of tobacco smoke, on reproduction in women. Copyright © 2009 John Wiley & Sons, Ltd. [source] Oxytocin and Oxytocin Receptors in Cancer Cells and ProliferationJOURNAL OF NEUROENDOCRINOLOGY, Issue 4 2004P. Cassoni Abstract The hypothalamic nonapeptide oxytocin plays a crucial role in many reproductive and behavioural functions. However, in recent years, an additional new role for oxytocin has been identified in neoplastic pathology. In tumours, oxytocin acts as a growth regulator, through the activation of a specific G-coupled transmembrane receptor, the oxytocin receptor. In vitro, oxytocin inhibits proliferation of neoplastic cells of either epithelial (mammary and endometrial), nervous or bone origin, all expressing oxytocin receptor. Furthermore, an oxytocin growth-inhibiting effect was also tested and confirmed in vivo in mouse and rat mammary carcinomas. In neoplastic cells derived from two additional oxytocin target tissues, trophoblast and endothelium, oxytocin was found to promote cell proliferation, an effect opposite to that previously described in all other neoplastic oxytocin-responsive cells. The signal transduction pathways coupled to the biological effects of oxytocin are different in oxytocin growth-inhibited or growth-stimulated cells, and may depend on the membrane localization of the oxytocin receptor itself. The inhibitory effect of oxytocin is apparently mediated by activation of the cAMP-protein kinase A pathway, a nonconventional oxytocin signalling pathway, whereas the mitogenic effect is coupled to the increase of intracellular [Ca2+] and tyrosine phosphorylation, ,classical' oxytocin transducers. Moreover, the oxytocin receptor localization in lipid rafts enriched in caveolin-1 turns the inhibition of cell growth into a proliferative response, eliciting different epidermal growth factor receptor/mitogen-activated protein kinase activation patterns. This unexpected role of oxytocin (and oxytocin analogues) in regulating cell proliferation, as well as the widespread expression of oxytocin receptors in neoplastic tissues of different origin, opens up new perspectives on the biological role of the oxytocin,oxytocin receptor system in cancer. [source] Toll-like receptors and pregnancy: Trophoblast as modulators of the immune responseJOURNAL OF OBSTETRICS AND GYNAECOLOGY RESEARCH (ELECTRONIC), Issue 2 2009Kaori Koga Abstract During normal pregnancy, the decidua is populated by a variety of leucocytes; however, cells of the innate immune system seem to dominate this tissue. Their presence suggests that the innate immune system is not indifferent to the fetus and has been associated with a response of the maternal immune system to the ,semi-allograft' fetus. New evidences, however, indicate that these immune cells are critical for decidual and trophoblast development rather than induction of tolerance. We hypothesized that during implantation, an inflammatory environment is necessary for the attachment and invasion of the blastocyst. The existence of an ,inflammatory-mediated embryo implantation' condition is dependent on the proper ,education' of the innate immune system which we propose is mediated by the trophoblast. Here we postulate that trophoblast cells successfully orchestrate their inflammatory environment and regulate immune cells differentiation and activation through Toll-like receptors (TLR). We will describe potential functions of TLR in trophoblast cells, their recognition and response to microorganisms, and their involvement in innate immunity. [source] In vivo expression of interferon tau mRNA by the embryonic trophoblast and uterine concentrations of interferon tau protein during early pregnancy in the cowMOLECULAR REPRODUCTION & DEVELOPMENT, Issue 4 2006R.S. Robinson Abstract In this study, we have measured uterine concentrations of interferon tau and intensity of embryonic interferon tau mRNA expression between day 14 and 18 in cows. While interferon tau concentrations rose dramatically (P,<,0.001) from day 14 to 18, there was no significant increase in the intensity of expression of interferon tau mRNA by the trophoblast. When results were analyzed on the basis of embryo size, well elongated embryos (>10 cm) produced significantly (P,<,0.001) more interferon tau than smaller embryos but showed similar levels of interferon tau mRNA expression. These results demonstrate that the increase in interferon tau concentrations responsible for the maternal recognition of pregnancy results from the increase in embryo size during elongation and not from any upregulation of mRNA expression. Mol. Reprod. Dev. © 2006 Wiley-Liss, Inc. [source] PLAC1 (Placenta-specific 1): a novel, X-linked gene with roles in reproductive and cancer biologyPRENATAL DIAGNOSIS, Issue 6 2010Michael Fant Abstract Placenta-specific 1 (PLAC1) is a recently described X-linked gene with expression restricted primarily to cells derived from trophoblast lineage during embryonic development. PLAC1 localizes to a region of the X chromosome thought to be important in placental development although its role in this process has not been defined. This review summarizes our current understanding of its expression, regulation, and function. PLAC1 is expressed throughout human pregnancy by the differentiated trophoblast and localizes to membranous structures in the syncytiotrophoblast, including the microvillous plasma membrane surface. Recent studies have demonstrated that PLAC1 is also expressed by a wide variety of human cancers. Studies of the PLAC1 promoter regions indicate that its expression in both normal placenta and cancer cells is driven by specific interactions involving a combination of transcription factors. Although functional insight into PLAC1 in the normal trophoblast is lacking, preliminary studies suggest that cancer-derived PLAC1 has the potential to promote tumor growth and function. In addition, it also appears to elicit a specific immunologic response that may influence survival in some cancer patients, suggesting that it may provide a therapeutic target for the treatment of some cancers. We also discuss a potential role for PLAC1 as a biomarker predictive of specific pregnancy complications, such as preeclampsia. Copyright © 2010 John Wiley & Sons, Ltd. [source] Glucose-regulated protein 78: A new partner of p53 in trophoblastPROTEINS: STRUCTURE, FUNCTION AND BIOINFORMATICS, Issue 23 2009Serge Arnaudeau Abstract Although wild-type p53 protein is overexpressed in first trimester trophoblast, it is inactive towards its target genes Metalloproteinase 2 and 9. This seems to be due to a complex mechanism of inactivation and stabilization of p53 relying on the formation of protein complexes involving the N-terminus of p53. To detect the proteins associated with this sequence, we incubated biotinylated p53 N-terminal peptide in cytotrophoblastic cell medium 24,h before lysis of cells. We purified the proteins retained on biotinylated peptide using a neutravidin affinity column. Proteins were then identified by peptide mass finger printing followed or not by peptide fragmentation sequencing. Among these proteins, we identified glucose-regulated protein 78 (GRP78) and verified its interaction with p53 in trophoblastic cells by immunoprecipitation and Western blot analysis. Moreover, the decreased expression of GRP78 induced by GRP78siRNA or versipelostatin decreased the formation of high molecular weight p53 complexes and p53 monomer and increased trophoblastic invasion. These results suggest that GRP78 is involved in inactivation and stabilization of p53 and in the regulation of trophoblastic invasion. [source] Reproductive ecology and the endometrium: Physiology, variation, and new directionsAMERICAN JOURNAL OF PHYSICAL ANTHROPOLOGY, Issue S49 2009Kathryn B.H. Clancy Abstract Endometrial function is often overlooked in the study of fertility in reproductive ecology, but it is crucial to implantation and the support of a successful pregnancy. Human female reproductive physiology can handle substantial energy demands that include the production of fecund cycles, ovulation, fertilization, placentation, a 9-month gestation, and often several years of lactation. The particular morphology of the human endometrium as well as our relative copiousness of menstruation and large neonatal size suggests that endometrial function has more resources allocated to it than many other primates. The human endometrium has a particularly invasive kind of hemochorial placentation and trophoblast that maximizes surface area and maternal,fetal contact, yet these processes are actually less efficient than the placentation of some of our primate relatives. The human endometrium and its associated processes appear to prioritize maximizing the transmission of oxygen and glucose to the fetus over efficiency and protection of maternal resources. Ovarian function controls many aspects of endometrial function and thus variation in the endometrium is often a reflection of ecological factors that impact the ovaries. However, preliminary evidence and literature from populations of different reproductive states, ages and pathologies also suggests that ecological stress plays a role in endometrial variation, different from or even independent of ovarian function. Immune stress and psychosocial stress appear to play some role in the endometrium's ability to carry a fetus through the mechanism of inflammation. Thus, within reproductive ecology we should move towards a model of women's fecundity and fertility that includes many components of ecological stress and their effects not only on the ovaries, but on processes related to endometrial function. Greater attention on the endometrium may aid in unraveling several issues in hominoid and specifically human evolutionary biology: a low implantation rate, high rates of early pregnancy loss, prenatal investment in singletons but postnatal support of several dependent offspring at once, and higher rate of reproductive and pregnancy-related pathology compared to other primates, ranging from endometriosis to preeclampsia. The study of the endometrium may also complicate some of these issues, as it raises the question of why humans have a maximally invasive placentation method and yet slow fetal growth rates. In this review, I will describe endometrial physiology, methods of measurement, variation, and some of the ecological variables that likely produce variation and pregnancy losses to demonstrate the necessity of further study. I propose several basic avenues of study that leave room for testable hypotheses in the field of reproductive ecology. And finally, I describe the potential of this work not just in reproductive ecology, but in the resolution of broader women's health issues. Yrbk Phys Anthropol 52:137,154, 2009. © 2009 Wiley-Liss, Inc. [source] Immunohistochemical Localization of Oestrogen Receptors , and ,, Progesterone Receptor and Aromatase in the Equine PlacentaREPRODUCTION IN DOMESTIC ANIMALS, Issue 2 2009MMM Abd-Elnaeim Contents The functions of placental oestrogens during equine pregnancy are still unclear. Yet, they may act predominantly as local regulators of growth and differentiation in the microplacentomes. Thus, expression patterns of oestrogen receptors (ERs) , and , were investigated in the microcotyledonary placenta from pregnant mares at 110, 121, 179, 199 and 309 days of gestation by immunohistochemistry. In microplacentomes, both the ER isoforms were detected in trophoblast (T) cells, chorionic villous stroma (FS), microcaruncular epithelium (ME) and microcaruncular stroma (MS). Proportions of positive cells were 38,91% (T), 11,41% (FS), 55,89% (ME), 17,51% (MS) for ER, and 66,76% (T), 21,37% (FS), 41,68% (ME) and 24,55% (MS) for ER,. Between days 110 and 199, proportions of cells positive for progesterone receptor (PR) varied between 19% and 62% (T), 3% and 50% (CS), 15% and 46% (ME), and 4% and 33% (MS). At day 309, PR was virtually absent in T, CS and ME (percentages < 0.1), whereas in MS 14.3% of cells were still positive. The expression of ERs and PR in equine microplacentomes gives evidence for a role of placental steroids as regulators of placental growth, differentiation and function. The detection of ER,, ER, and PR in foetal and maternal vascular tissue suggests that placental steroids are also involved in the control of placental angiogenesis and,/or vascular functions. The co-localization of ERs with aromatase in T suggests auto- or intracrine functions of oestrogens in this cell type. [source] REVIEW ARTICLE: Maternal Immune Responses to Trophoblast: The Contribution of the Horse to Pregnancy ImmunologyAMERICAN JOURNAL OF REPRODUCTIVE IMMUNOLOGY, Issue 4 2010Leela E. Noronha Citation Noronha LE, Antczak DF. Maternal immune responses to trophoblast: the contribution of the horse to pregnancy immunology. Am J Reprod Immunol 2010 The horse has proven to be a distinctively informative species in the study of pregnancy immunology for several reasons. First, unique aspects of the anatomy and physiology of the equine conceptus facilitate approaches that are not possible in other model organisms, such as non-surgical recovery of early stage embryos and conceptuses and isolation of pure trophoblast cell populations. Second, pregnant mares make strong cytotoxic antibody responses to paternal major histocompatibility complex class I antigens expressed by the chorionic girdle cells, permitting detailed evaluation of the antigenicity of these invasive trophoblasts and how they affect the maternal immune system. Third, there is abundant evidence for local maternal cellular immune responses to the invading trophoblasts in the pregnant mare. The survival of the equine fetus in the face of strong maternal immune responses highlights the complex immunoregulatory mechanisms that result in materno,fetal tolerance. Finally, the parallels between human and horse trophoblast cell types, their gene expression, and function make the study of equine pregnancy highly relevant to human health. Here, we review the most pertinent aspects of equine reproductive immunology and how studies of the pregnant mare have contributed to our understanding of maternal acceptance of the allogeneic fetus. [source] REVIEW ARTICLE: Immunological Paradigms and the Pathogenesis of Ovine Chlamydial AbortionAMERICAN JOURNAL OF REPRODUCTIVE IMMUNOLOGY, Issue 4 2010Gary Entrican Citation Entrican G, Wattegedera S, Wheelhouse N, Allan A, Rocchi M. Immunological paradigms and the pathogenesis of ovine chlamydial abortion. Am J Reprod Immunol 2010 Successful mammalian pregnancy involves complex immunological interactions between the mother and foetus that are not yet fully understood. A number of immunological paradigms have been established to explain the failure of the maternal immune system to reject the semi-allogeneic foetus, mainly based on studies in mice and humans. However, as placental structure, gestation periods and number of concepti per pregnancy can vary greatly between mammals, it is not always clear how applicable these immunological paradigms are to reproduction in other species. Here, we discuss the predictions of three important immunological paradigms in relation to the pathogenesis of ovine enzootic abortion (OEA), a common cause of infectious abortion in sheep and other ruminants. OEA is caused by the intracellular Gram-negative bacterium Chlamydophila abortus that exhibits a tropism for placental trophoblast. The paradigms of particular relevance to the pathogenesis of OEA are as follows: (i) intracellular bacterial infections are controlled by TH1-type CD4+ve T cells; (ii) indoleamine 2,3-dioxygenase is expressed in the placenta to prevent immunological rejection of the semi-allogeneic foetus; and (iii) pregnancy is a maternal TH2-type phenomenon. We discuss the relevance and validity of these paradigms for chlamydial abortion and reproductive immunology in sheep. [source] REVIEW ARTICLE: Placental Apoptosis in Health and DiseaseAMERICAN JOURNAL OF REPRODUCTIVE IMMUNOLOGY, Issue 3 2010Andrew N. Sharp Citation Sharp AN, Heazell AEP, Crocker IP, Mor G. Placental apoptosis in health and disease. Am J Reprod Immunol 2010; 64: 159,169 Apoptosis, programmed cell death, is an essential feature of normal placental development but is exaggerated in association with placental disease. Placental development relies upon effective implantation and invasion of the maternal decidua by the placental trophoblast. In normal pregnancy, trophoblast apoptosis increases with placental growth and advancing gestation. However, apoptosis is notably exaggerated in the pregnancy complications, hydatidiform mole, pre-eclampsia, and intrauterine growth restriction (IUGR). Placental apoptosis may be initiated by a variety of stimuli, including hypoxia and oxidative stress. In common with other cell-types, trophoblast apoptosis follows the extrinsic or intrinsic pathways culminating in the activation of caspases. In contrast, the formation of apoptotic bodies is less clearly identified, but postulated by some to involve the clustering of apoptotic nuclei and liberation of this material into the maternal circulation. In addition to promoting a favorable maternal immune response, the release of this placental-derived material is thought to provoke the endothelial dysfunction of pre-eclampsia. Widespread apoptosis of the syncytiotrophoblast may also impair trophoblast function leading to the reduction in nutrient transport seen in IUGR. A clearer understanding of placental apoptosis and its regulation may provide new insights into placental pathologies, potentially suggesting therapeutic targets. [source] Viral ssRNA Induces First Trimester Trophoblast Apoptosis through an Inflammatory MechanismAMERICAN JOURNAL OF REPRODUCTIVE IMMUNOLOGY, Issue 1 2010Paulomi B. Aldo Citation Aldo PB, Mulla MJ, Romero R, Mor G, Abrahams VM. Viral ssRNA induces first-trimester trophoblast apoptosis through an inflammatory mechanism. Am J Reprod Immunol 2010; 64: 27,37 Problem, Infection during pregnancy represents a significant cause of mobility and mortality. While viruses pose a major threat, little is known about their effect on early pregnancy, or the mechanisms involved. The objective of this study was to characterize the trophoblast response following exposure to viral ssRNA. Method of study, First trimester trophoblast cells were treated with or without viral ssRNA. Cytokine production was measured using multiplex analysis and ELISA. Apoptosis was determined using Hoechst staining, cell viability, and caspase activity assays. Results, Treatment of trophoblasts with viral ssRNA increased their secretion of IL-8, IL-6, and IFN,. However, the ssRNA also induced trophoblast apoptosis. To test whether the viral ssRNA-induced inflammatory response was responsible for this induction of apoptosis, conditioned media (CM) from trophoblasts were added to a fresh culture of cells. The CM from viral ssRNA-treated induced higher levels of trophoblast apoptosis than the control CM. Moreover, recombinant IFN, induced trophoblast apoptosis. Conclusion, We demonstrate that viral ssRNA induces a pro-inflammatory and type I interferon response in the trophoblast and this inflammatory process may indirectly induce trophoblast apoptosis. These results provide a novel mechanism by which certain viral infections might compromise placental integrity and function, and therefore, pregnancy outcome. [source] REVIEW ARTICLE: Research on Blastocyst Implantation Essential Factors (BIEFs)AMERICAN JOURNAL OF REPRODUCTIVE IMMUNOLOGY, Issue 6 2010Koji Yoshinaga Citation Yoshinaga K. Research on Blastocyst Implantation Essential Factors (BIEFs). Am J Reprod Immunol 2010 Blastocyst implantation is a process of interaction between embryo and the uterus. To understand this process, this review tries to summarize what blastocyst implantation essential factors (BIEFs) play what roles, as well as where in the uterus and at what stage of implantation process. Addition of more new data to this kind of compilation of information will help the development of diagnosis and treatment of infertility caused by implantation failure. The major, important cells of the endometrial cells that interact with invading blastocyst (trophoblast) are luminal epithelial cells, stromal cells (decidual cells) and resident immune cells. BIEFs regulate these cells to successfully maintain pregnancy. [source] REVIEW ARTICLE: Governing the Invasive Trophoblast: Current Aspects on Intra- and Extracellular RegulationAMERICAN JOURNAL OF REPRODUCTIVE IMMUNOLOGY, Issue 6 2010Justine S. Fitzgerald Citation Fitzgerald JS, Germeyer A, Huppertz B, Jeschke U, Knöfler M, Moser G, Scholz C, Sonderegger S, Toth B, Markert UR. Governing the invasive trophoblast: current aspects on intra- and extracellular regulation. Am J Reprod Immunol 2010 This review summarizes several aspects especially of regulating factors governing trophoblast invasion. Those include the composition of the extracellular matrix containing a variety of matrix metalloproeinases and their inhibitors, but also intracellular signals. Furthermore, a newly described trophoblast subtype, the endoglandular trophoblast, is presented. Its presence may provide a possible mechanism for opening and connecting uterine glands into the intervillous space. Amongst others, two intracellular signalling pathways are crucial for regulation of trophoblast functions and development: Wnt- and signal transducer and activator of transcription (STAT)3 signalling. Wnt signalling promotes implantation, placentation and trophoblast differentiation. Several Wnt-dependent cascades and regulatory mechanisms display different functions in trophoblast cells. The STAT3 signalling system is fundamental for induction and regulation of invasiveness in physiological trophoblastic cells, but also in tumours. The role of galectins (Gal) in trophoblast regulation and placenta development comes increasingly into focus. The Gal- 1,4, 7,10 and 12,14 have been detected in humans. Detailed information is only available for Gal-1, -2, -3, -4, -9 and -12 in endometrium and decidua. Gal-1, -3 and -13 (-14) have been detected and studied in trophoblast cells. [source] Enhanced monocyte binding to human cytomegalovirus-infected syncytiotrophoblast results in increased apoptosis via the release of tumour necrosis factor alphaTHE JOURNAL OF PATHOLOGY, Issue 4 2005Gary Chan Abstract We have shown that monocytes bound to intercellular adhesion molecules (ICAM-1) on syncytialized placental trophoblasts (ST) induce trophoblast apoptosis, and that ST infection by human cytomegalovirus (HCMV) up-regulates ICAM-1. We hypothesize that the focal loss of trophoblast seen in HCMV-infected placenta is mediated by increased adherence of monocytes at sites of infection. We find that ST cultures (differentiated from primary cytotrophoblasts) increase monocyte binding when infected with HCMV. Monocyte adhesion was inhibited by antibodies to ICAM-1 and its ligand leukocyte function-associated molecule (LFA-1) on monocytes. When co-cultured with adhering monocytes, infected ST cultures had higher levels of apoptosis than infected cultures alone. Although trophoblast apoptosis clustered around adhering monocytes, it occurred only in non-infected cells. Blocking monocyte binding with ICAM-1 and LFA-1 antibodies reduced the rate of apoptosis to that of the infected culture. Co-cultures incubated with TNF, antibody and EGF inhibited both monocyte- and HCMV-induced apoptosis but did not block binding. We conclude that HCMV stimulates ST culture expression of ICAM-1, which binds to LFA-1 on monocytes that release TNF,, thereby inducing apoptosis of neighbouring uninfected trophoblasts. The above data indicates that trophoblast loss associated with HCMV infection can be caused by increased monocyte adhesion to ST. Copyright © 2005 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd. [source] REVIEW ARTICLE: Immunology of Pre-EclampsiaAMERICAN JOURNAL OF REPRODUCTIVE IMMUNOLOGY, Issue 6 2010Christopher W. G. Redman Citation Redman CWG, Sargent IL. Immunology of Pre-eclampsia. Am J Reprod Immunol 2010 Pre-eclampsia develops in stages, only the last being the clinical illness. This is generated by a non-specific, systemic (vascular), inflammatory response, secondary to placental oxidative stress and not by reactivity to fetal alloantigens. However, maternal adaptation to fetal (paternal alloantigens) is crucial in the earlier stages. A pre-conceptual phase involves maternal tolerization to paternal antigens by seminal plasma. After conception, regulatory T cells, interacting with indoleamine 2,3-dioxygenase, together with decidual NK cell recognition of fetal HLA-C on extravillous trophoblast may facilitate placental growth by immunoregulation. Complete failure of this mechanism would cause miscarriage, while partial failure would cause poor placentation and dysfunctional uteroplacental perfusion. The first pregnancy preponderance and partner specificity of pre-eclampsia can be explained by this model. For the first time, the pathogenesis of pre-eclampsia can be related to defined immune mechanisms that are appropriate to the fetomaternal frontier. Now, the challenge is to prove the detail. [source] ORIGINAL ARTICLE: Antiphospholipid Antibodies Limit Trophoblast Migration by Reducing IL-6 Production and STAT3 ActivityAMERICAN JOURNAL OF REPRODUCTIVE IMMUNOLOGY, Issue 5 2010Melissa J. Mulla Citation Mulla MJ, Myrtolli K, Brosens JJ, Chamley LW, Kwak-Kim JY, Paidas MJ, Abrahams VM. Antiphospholipid antibodies limit trophoblast migration by reducing IL-6 production and STAT3 activity. Am J Reprod Immunol 2010 Problem Women with antiphospholipid antibodies (aPL) are at risk of recurrent miscarriage and pre-eclampsia. aPL target the placenta by binding to ,2 -glycoprotein I (,2 GPI) expressed by the trophoblast. The objective of this study was to evaluate if and how aPL affect first trimester trophoblast migration. Method of study First trimester trophoblast cells were treated with anti-,2 GPI monoclonal antibodies. Migration was determined using a two-chamber assay. Interleukin (IL)-6 production was evaluated by RT-PCR and enzyme-linked immunosorbent assay, and signal transducer and activator of transcription 3 (STAT3) activation was assessed by western blot. Results Trophoblast cells constitutively secreted IL-6 in a time-dependent manner and this directly correlated with STAT3 phosphorylation. In the presence of anti-,2 GPI Abs, trophoblast IL-6 mRNA levels and secretion was downregulated in a Toll-like receptor 4/MyD88-independent manner and this correlated with a reduction in phosphorylated STAT3 levels. In addition, the anti-,2 GPI Abs reduced the migratory potential of trophoblast. Heparin was able to reverse aPL-dependent inhibition of trophoblast IL-6 secretion and migration. Conclusion This study demonstrates that aPL limit trophoblast cell migration by downregulating trophoblast IL-6 secretion and STAT3 activity. As heparin was unable to prevent these effects, our findings may explain why women with antiphospholipid syndrome, treated with heparin, remain at risk of developing obstetrical syndromes, associated with impaired deep placentation, such as pre-eclampsia. [source] REVIEW ARTICLE: Tolerance Mechanisms in Pregnancy: A Reappraisal of the Role of Class I Paternal MHC Antigens,AMERICAN JOURNAL OF REPRODUCTIVE IMMUNOLOGY, Issue 2 2010David A. Clark Citation Clark DA, Chaouat G, Wong K, Gorczynski RM, Kinsky R. Tolerance mechanisms in pregnancy: a reappraisal of the role of class I paternal MHC antigens. Am J Reprod Immunol 2010; 63: 93,103 Problem, Allogeneic pregnancies have a survival advantage over syngeneic pregnancies, and paternal Class I MHC antigens have been implicated. In humans, HLA-C and HLA-G and E are expressed by subpopulations of fetal trophoblast. In mice, Qa-2, a Class Ib antigen, and classical H-2K antigens have been described. However, the mechanism of prevention of embryo demise in utero has not been critically assessed, and a number of conflicting ideas have not been addressed. The ,, T-cell receptor recognizes peptide bound to the groove in Class I MHC, and peptides have profound effects on the interaction of KIR receptors on T and NK cells with Class I MHC. Methods, Data on prevention of pregnancy loss (abortion) in poly IC-treated mice were reviewed along with information about prevention of losses in the abortion-prone CBA × DBA/2 model. This information was combined with data on paternal antigen expression at different times in pregnancy when key events determining outcome are thought to transpire, and role of tolerance signaling molecules such as CD200. Current data on models supporting a role for ,true' uterine NK cells (TuNKs) versus blood NK cells in the uterus (BuNKs) and role of MHC,KIR interaction were reviewed along with incompatible data in the literature. Results, Whilst paternal Class I MHC appears important, there is an important role for paternal non-MHC minor antigens (small peptides) that bind to the antigen-presenting groove of Class I MHC. BuNKs along with CD8+ T cells and Treg cells appear more important than TuNKs where the role of the latter appears primarily to promote angiogenesis. When during pregnancy the maternal immune system cells are first exposed to paternal Class I + peptide is uncertain, but at the time of implantation, if not earlier, seems likely. Conclusion, Suppression of pregnancy loss by paternal/embryo Class I MHC depends on the presence of paternal peptides. This greatly complicates existing models of Class I,KIR interactions in feto-maternal tolerance or rejection. It is important to consider all the data when devising explanatory models. [source] ORIGINAL ARTICLE: Antiphospholipid Antibodies Induce a Pro-Inflammatory Response in First Trimester Trophoblast Via the TLR4/MyD88 PathwayAMERICAN JOURNAL OF REPRODUCTIVE IMMUNOLOGY, Issue 2 2009Melissa J. Mulla Problem, Women with antiphospholipid antibodies (aPL) are at risk for recurrent miscarriage, pre-eclampsia, and pre-term labor. aPL target the placenta directly by binding to beta2 -glycoprotein I (,2GPI) expressed on the surface of trophoblast cells. The objective of this study was to determine the effects of aPL on trophoblast function and the mechanisms involved. Method of study, First trimester trophoblast cells were treated with anti-,2GPI monoclonal antibodies and patient-derived aPL, after which cell survival and function was evaluated. Results, We report that anti-,2GPI antibodies trigger an inflammatory response in trophoblast, characterized by increased secretion of interleukin (IL)-8, MCP-1, GRO-,, and IL-1,, and that this occurs in a TLR-4/MyD88-dependent manner. At high concentrations, these antibodies also induce caspase-mediated cell death. This was attenuated upon disabling of the MyD88 pathway, suggesting that anti-,2GPI-induced inflammatory mediators compromise trophoblast survival by acting in an autocrine/paracrine manner. Enhanced IL-8, GRO-,, and IL-1, secretion also occurred when trophoblast cells were incubated with antibodies from patients with antiphospholipid syndrome. Heparin, which acts as a pro-survival factor in human trophoblast, attenuated the anti-,2GPI antibody-mediated cell death, and also the pro-inflammatory response, but only at high concentrations. Conclusion, These findings demonstrate that aPL triggers a placental inflammatory response via the TLR-4/MyD88 pathway, which in turn compromises trophoblast survival. Thus, the TLR-4/MyD88 pathway may provide a new therapeutic target to improve pregnancy outcome in antiphospholipid syndrome patients. [source] | ||||||||||||||||||||||||||||||||||