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Human Placenta (human + placenta)
Selected AbstractsFGF Ligand Family mRNA Expression Profile for Mouse Preimplantation Embryos, Early Gestation Human Placenta, and Mouse Trophoblast Stem CellsMOLECULAR REPRODUCTION & DEVELOPMENT, Issue 5 2006W. Zhong Abstract Signaling by fibroblast growth factor (FGF) is essential is for trophoblast stem (TS) cells and preimplantation embryos. FGF4 provides essential signaling, but the expression of the complete set of 23 FGF family members has not been analyzed. Here, semi-quantitative RT-PCR and microarray analyses were used to define expression of all FGF ligand mRNA. RT-PCR was done for developmentally important FGF subfamilies, FGF10/FGF22 and FGF8/FGF17/FGF18 as well as FGF11. FGF4 and FGF18 are detected at highest levels by RT-PCR and microarrays. FGF10 was detected at low levels in both assays. FGF11 was detected at moderate levels by microarray, but not by RT-PCR. FGF17 was detected at low levels by array and moderate levels by RT-PCR. FGF8 and FGF22 were detected by RT-PCR, but not by microarrays during late cleavage divisions. FGF8, FGF5, and FGF9 were detected in the oocyte by microarray. FGF2, FGF3, and FGF7 were not detected by RT-PCR or microarrays and FGF13, FGF14, and FGF23 were not detected by microarray. Since a major role of FGF is to maintain TS cells, we tested human and mouse placental cell lines and early gestation human placenta for expression of FGF ligands. Expression in mouse TS cells was compared with preimplantation embryos, and human placental cell line expression was compared with human placenta, to infer which ligands are expressed in placental lineage vs. other cell lineages. The data suggest that human and mouse placenta share FGF18 and its high expression suggests preimplantation and early placental function. Mol. Reprod. Dev. © 2006 Wiley-Liss, Inc. [source] ORIGINAL ARTICLE: Expression of Autotaxin, an Ectoenzyme that Produces Lysophosphatidic Acid, in Human PlacentaAMERICAN JOURNAL OF REPRODUCTIVE IMMUNOLOGY, Issue 2 2009Yuki Iwasawa Problem, Lysophosphatidic acid (LPA) is a bioactive lipid mediator and thought to play an important role in pregnancy. Plasma LPA is produced by autotaxin (ATX), and ATX activity in plasma increases during pregnancy paralleled with gestational weeks and decreases to near the non-pregnant level soon after delivery. However, the source of increased ATX during pregnancy is still uncertain. We hypothesized that the source of increased ATX might be placenta. Method of study, We investigated the protein and mRNA expression of ATX in human placenta using immunohistochemistry and RT-PCR, respectively. Results, At all 3 gestational trimesters, immunohistochemical staining for placenta tissues revealed the most marked positive staining of ATX protein in trophoblasts. Real-time PCR revealed that mRNA amounts of ATX in placenta tissues paralleled with gestational weeks, i.e. ATX level in plasma. Conclusion, These findings suggest that trophoblasts might produce ATX and its bioactive resultant substance, LPA, paralleled with gestational weeks. [source] Apoptosis and Bcl-2 Protein Expression in Human Placenta over the Course of Normal PregnancyANATOMIA, HISTOLOGIA, EMBRYOLOGIA, Issue 5 2010S. Soni With 2 figures and 2 tables Summary Apoptosis plays a central role in organ development, homeostasis and immune defence in multicellular organisms and is strictly controlled in part by members of Bcl-2 family. The Bcl-2 is a pro-survival molecule identified through its involvement in B-cell lymphomas. The aim of the study was to evaluate the incidence of apoptosis in the human placenta at different stages of pregnancy and to correlate it further with Bcl-2 expression. A total of 96 placental samples from first trimester, mid-trimester and uncomplicated term pregnancies were collected (n = 32 + 32 + 32). M30 cyto death monoclonal antibody was used to identify apoptotic cells. The apoptosis index of first trimester placentae was 2.33 ± 1.70, mid- trimester was 1.77 ± 1.36 and term placenta was 1.15 ± 0.21. Bcl-2 protein was found immunolocalized in the cytoplasm of syncytiotrophoblast. Apoptosis index was significantly reduced in term cases as compared with first trimester (P < 0.002) and mid-trimester placentae (P = 0.01). On the contrary, Bcl-2 expression was significantly higher at term cases than in first trimester (P < 0.0001) and mid-trimester cases (P < 0.001). The present study divulges the importance of apoptosis in permitting normal physiological turnover of villous trophoblast and also exhibits the contribution of bcl-2 in maintaining syncytial integrity throughout normal pregnancy. [source] Pathology of the Human Placenta (fourth edition).AUSTRALIAN AND NEW ZEALAND JOURNAL OF OBSTETRICS AND GYNAECOLOGY, Issue 3 2002James Scurry No abstract is available for this article. [source] Dlk1 expression marks developing endothelium and sites of branching morphogenesis in the mouse embryo and placentaDEVELOPMENTAL DYNAMICS, Issue 4 2006Aleksey Yevtodiyenko Abstract The protein product of the Delta-like 1 (Dlk1) gene belongs to the Delta-Notch family of signaling molecules, proteins involved in cell fate determination in many tissues during development. The DLK1 protein is believed to function as a growth factor, maintaining the proliferative state of undifferentiated cells, and is usually down-regulated as immature cells differentiate. The expression pattern of the DLK1 protein has been described in certain human tissues; however, Dlk1 expression is not well understood in the mouse, the most tractable mammalian genetic model system. To better understand the role of Dlk1 in embryonic development, the tissue-specific expression pattern of Dlk1 mRNA during mouse embryogenesis was analyzed by in situ hybridization. In embryonic day 12.5 (e12.5) embryos, high levels of Dlk1 were found in the developing pituitary, pancreas, lung, adrenal, and many mesodermally derived tissues. Strikingly, Dlk1 expression also marks the growing branches of organs that develop through the process of branching morphogenesis. At e16.5, Dlk1 expression is down-regulated in most tissues but remains in the pituitary, the adrenal gland, and in skeletal muscle. In the placenta, expression of Dlk1 is detected in endothelial cells lining the fetal blood vessels of the labyrinth. This pattern is distinct from that seen in the human placenta and suggests a role for Dlk1 in regulating maternal,fetal interactions. Developmental Dynamics 235:1115,1123, 2006. © 2006 Wiley-Liss, Inc. [source] Reciprocal chemokine receptor and ligand expression in the human placenta: Implications for cytotrophoblast differentiationDEVELOPMENTAL DYNAMICS, Issue 4 2004Penelope M. Drake Abstract At the onset of pregnancy, the human placenta, which forms the interface between the embryo/fetus and the mother, must rapidly develop into a life-sustaining organ. The many unusual processes entailed in placental development include the poorly understood phenomenon of maternal tolerance of the hemiallogeneic cells of the conceptus, including, most remarkably, placental trophoblasts that invade the uterine wall. To investigate whether this fetal organ exerts control over the maternal immune system at the level of leukocyte trafficking, we examined placental expression of chemokines, well-known cytokine regulators of leukocyte movements. In situ hybridization revealed abundant expression of 13 chemokines in the stromal but not the trophoblast compartment of chorionic villi. Potential roles for these molecules include recruitment of the resident macrophage (Hofbauer cell) population to the villi. In parallel, cytotrophoblast production of a panel of nine chemokine receptors was assessed by using RNase protection assays. The numerous receptors detected suggested the novel possibility that the paracrine actions of chemokine ligands derived from either the villous stroma or the decidua could mediate general aspects of placental development, with specific contributions to cytotrophoblast differentiation along the pathway that leads to uterine invasion. Developmental Dynamics 229:877,885, 2004. © 2004 Wiley-Liss, Inc. [source] Effect of cytofectins on the immune response of murine macrophages to mammalian DNAIMMUNOLOGY, Issue 2 2003Fu-Gang Zhu Summary DNA, depending on base sequence, can induce a wide range of immune responses. While bacterial DNA is stimulatory, mammalian DNA is inactive alone and can, moreover, inhibit the response to bacterial DNA. To determine whether the mode of cell entry affects the immune properties of mammalian DNA, we have investigated the effects of the cytofectin agents Fugene 6 (Roche Diagnostics Corp., Indianapolis, IN), Lipofectin and Lipofectamine (Life Technologies, Grand Island, NY) on the responses of murine macrophages to DNA from calf thymus and human placenta. Whereas calf thymus and human placenta DNA alone failed to stimulate J774 or RAW264·7 cell lines or bone marrow-derived macrophages, these DNAs in complexes with cytofectin agents stimulated macrophages to produce nitric oxide but not interleukin 12. Both single-stranded and double-stranded DNAs were active in the presence of cytofectins. Macrophage activation by the DNA,cytofectin complexes was reduced by chloroquine, suggesting a role of endosomal acidification in activation. As shown by flow cytometry and confocal microscopy, the cytofectins caused an increase in the uptake of DNA into cells. Our findings indicate that macrophages vary in their response to DNA depending on uptake pathway, suggesting that activation by DNA reflects not only sequence but also context or intracellular location. [source] Expression and regulation of the pattern recognition receptors Toll-like receptor-2 and Toll-like receptor-4 in the human placentaIMMUNOLOGY, Issue 1 2002Ulrika Holmlund Summary The placenta constitutes a physical and immunological barrier against invading infectious agents and has been suggested to be a pregnancy-specific component of the innate immune system. The aim of this study was to investigate the presence and regulation of Toll-like receptors-2 and -4 (TLR2 and TLR4) in the human placenta, because these receptors are believed to be important for immune responses against pathogens. Twenty-eight placentas from normal term pregnancies were analysed with immunohistochemistry, which showed a strong immunoreactivity for TLR2 and TLR4 in the villous and the intermediate trophoblasts. The regulation of TLR2 and TLR4 by microbial stimulus was assessed by incubating explants of term chorionic villi with zymosan or lipopolysaccharide (LPS) and analysed with real-time reverse transcriptase,polymerase chain reaction. Stimulation with zymosan and LPS readily induced interleukin (IL)-6 and IL-8 cytokine production in the placenta cultures, whereas TLR2 and TLR4 mRNA and protein expression remained at the same high level as in unstimulated explants. These data suggests a novel mechanism for the fetoplacental unit to interact with micro-organisms. [source] First identification of an ancient Egyptian mummified human placentaINTERNATIONAL JOURNAL OF OSTEOARCHAEOLOGY, Issue 1 2005A.-M. Mekota Abstract In the course of excavations at Thebes-West, Upper Egypt, a human organ was recovered from the poorly preserved torso of a female mummy, which was archaeologically dated to the New Kingdom. In the field, the organ was tentatively identified as a liver, but without much certainty. After rehydration and fixation, histological observations led to a rejection of this diagnosis and resulted in the hypothesis that this organ could be a placenta. Comparative histology, performed on an experimentally mummified modern human placenta, revealed a close similarity of microstructural features, which strongly supports the diagnosis of the organ as a placenta. In this paper, we can therefore present the first report of an ancient Egyptian mummified human placenta and provide new insight into Egyptian funeral practices in general, and the fate of the excavated female in particular. Copyright © 2004 John Wiley & Sons, Ltd. [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] Stereological comparison of 3D spatial relationships involving villi and intervillous pores in human placentas from control and diabetic pregnanciesJOURNAL OF ANATOMY, Issue 2 2000TERRY M. MAYHEW In human placenta, 3D spatial relationships between villi and the maternal vascular bed determine intervillous porosity and this, in turn, influences haemodynamics and transport. Recently-developed stereological methods were applied in order to examine and quantify these relationships. Placentas were collected after 37 wk from control pregnancies and those associated with maternal diabetes mellitus classified according to duration and severity (White classification scheme). Two principal questions were addressed: (1) are normal spatial arrangements maintained in well-controlled diabetes mellitus? and (2) do arrangements vary between diabetic groups? To answer these questions, tissue sections cut at random positions and orientations were generated by systematic sampling procedures. Volume densities of villi (terminal+intermediate), intervillous spaces and perivillous fibrin-type fibrinoid deposits were estimated by test point counting and converted to global volumes after multiplying by placental volumes. Design-based estimates of the sizes (volume- and surface-weighted volumes) of intervillous ,pores' were obtained by measuring the lengths of point- and intersection-sampled intercepts. From these, theoretical numbers of pores were calculated. Model-based estimates (cylinder model) of the hydraulic diameters and lengths of pores were also made. Second-order stereology was used to examine spatial relationships within and between villi and pores and to test whether pair correlation functions deviated from the value expected for ,random' arrangements. Estimated quantities did not differ significantly between diabetic groups but did display some departures from control values in non-insulin-dependent (type 2) diabetic placentas. These findings support earlier studies which indicate that essentially normal microscopical morphology is preserved in placentas from diabetic subjects with good glycaemic control. Therefore, it is likely that fetal hypoxia associated with maternal diabetes mellitus is due to metabolic disturbances rather than abnormalities in the quantities or arrangements of maternal vascular spaces. [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] Complete replication of human cytomegalovirus in explants of first trimester human placentaJOURNAL OF MEDICAL VIROLOGY, Issue 4 2001Liliana Gabrielli Abstract Tissue integrity and viability of first trimester placenta explants were obtained in culture for 3 weeks. Explants were infected with human cytomegalovirus (HCMV), several cycles of HCMV replication were obtained and the progression of the infection was observed within a tissue that maintains its normal cellular organization. In agreement with recent clinical data, 3 weeks were necessary for the virus to colonize the placenta fully. Complete HCMV replication was observed in trophoblasts, followed by subsequent transmission of the infection to the stromal fibroblasts and fetal endothelial capillary cells. Viral DNA replication was monitored and the production of infectious viral progeny documented. J. Med. Virol. 64:499,504, 2001. © 2001 Wiley-Liss, Inc. [source] The Mechanisms and Regulation of Placental Amino Acid Transport to the Human FoetusJOURNAL OF NEUROENDOCRINOLOGY, Issue 4 2008J. K. Cleal The mechanisms by which amino acids are transferred across the human placenta are fundamental to our understanding of foetal nutrition. Amino acid transfer across the human placenta is dependent on transport across both the microvillous and basal plasma membranes of the placental syncytiotrophoblast, and on metabolism within the syncytiotrophoblast. Although the principles underlying uptake of amino acids across the microvillous plasma membrane are well understood, the extent to which amino acids are metabolised within human placenta and the mechanisms by which amino acids are transported out of the placenta across the basal plasma membrane are not well understood. Understanding the mechanisms and regulation of amino acid transport is necessary to understand the causes of intrauterine growth restriction in human pregnancy. [source] Bifidobacterium and Lactobacillus DNA in the human placentaLETTERS IN APPLIED MICROBIOLOGY, Issue 1 2009R. Satokari Abstract Aims:, Bifidobacteria and lactobacilli are part of the human normal intestinal microbiota and may possibly be transferred to the placenta. It was hypothesized that intestinal bacteria or their components are present in the placenta and that the foetus may be exposed to them. We investigated the presence of bifidobacteria and lactobacilli and their DNA in the human placenta. Methods and Results:, We studied 34 human placentae (25 vaginal and nine caesarean deliveries) for the presence Bifidobacterium spp. and Lactobacillus rhamnosus. Cultivation was used for the detection of viable cells and genus and species-specific PCR for the detection of DNA. No bifidobacteria or lactobacilli were found by cultivation. Bifidobacterial DNA was detected in 33 and L. rhamnosus DNA in 31 placenta samples. Conclusions:, DNA from intestinal bacteria was found in most placenta samples. The results suggest that horizontal transfer of bacterial DNA from mother to foetus may occur via placenta. Significance and Impact of the Study:, Bacterial DNA contains unmethylated CpG oligodeoxynucleotide motifs which induce immune effects. Specific CpG motifs activate Toll-like receptor 9 and subsequently trigger Th-1-type immune responses. Although the newborn infant is considered immunologically immature, exposure by bacterial DNA may programme the infant's immune development during foetal life earlier than previously considered. [source] IgE in the human placenta: why there?ALLERGY, Issue 5 2010E. Rindsjö To cite this article: Rindsjö E, Joerink M, Papadogiannakis N, Scheynius A. IgE in the human placenta: why there? Allergy 2010; 65: 554,560. Abstract Immunoglobulin E (IgE) antibodies are key effector molecules in the allergic inflammatory response and are also involved in the protection against extracellular parasites. Allergic symptoms often develop early in life, and the intrauterine environment has been proposed to play an important role in affecting the risk of later allergy development. The placenta constitutes a selective barrier between the maternal and foetal circulation. Recently, we reported that maternal IgE antibodies are present on foetal macrophages in the villous tissue of the human placenta irrespective of maternal allergy status. This review discusses the presence of IgE antibodies in the human placenta and its possible roles in normal and pathologic pregnancy. It also deals with the relationship between placental IgE and development of allergy during childhood. A better understanding of the role of IgE in placenta could give us clues on how to prevent allergy development in the future generations. [source] Evidence for allergen-specific IgE of maternal origin in human placentaALLERGY, Issue 6 2009M. Joerink Background:, Immunoglobulin E (IgE) has been identified on macrophage-like cells in the villi of human placenta, irrespective of the serum IgE levels or allergy status of the mother. The origin of placental IgE is debated and it is not known if it is spontaneously produced, so-called ,natural IgE', or if it has any specificity for certain allergens. The aim of this study was to investigate if placental IgE originates from mother or child and to analyse its specificity. Methods:, Immunoglobulin E was eluted from placenta by lowering the pH. Total and allergen-specific IgEs were measured in placenta eluate, maternal and cord blood plasma by means of ImmunoCAP (Phadia AB). The levels of natural antibodies were determined with an anti-phosphorylcholine (PC) enzyme-linked immunosorbent assay, as natural IgE has been shown in one previous publication with this assay. Results:, Detectable amounts of IgE were eluted from 11/12 full-term placentas. Natural (anti-PC) IgE antibodies were detected in low amounts in maternal plasma but not in the placental eluate or in cord blood plasma. There was a significant correlation between the amount of total IgE eluted from placenta and the levels of total IgE in maternal plasma; however, not between maternal and cord blood plasma. Allergen-specific IgE was only found in placental eluates from mothers with specific IgE towards these allergens. Furthermore, there was a significant correlation between the amount of allergen-specific IgE eluted from placenta and the levels of allergen-specific IgE in maternal plasma. Allergen-specific IgE could not be detected in cord blood. Conclusion:, These results suggest a maternal origin of placental IgE, which can be allergen-specific. [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] FGF Ligand Family mRNA Expression Profile for Mouse Preimplantation Embryos, Early Gestation Human Placenta, and Mouse Trophoblast Stem CellsMOLECULAR REPRODUCTION & DEVELOPMENT, Issue 5 2006W. Zhong Abstract Signaling by fibroblast growth factor (FGF) is essential is for trophoblast stem (TS) cells and preimplantation embryos. FGF4 provides essential signaling, but the expression of the complete set of 23 FGF family members has not been analyzed. Here, semi-quantitative RT-PCR and microarray analyses were used to define expression of all FGF ligand mRNA. RT-PCR was done for developmentally important FGF subfamilies, FGF10/FGF22 and FGF8/FGF17/FGF18 as well as FGF11. FGF4 and FGF18 are detected at highest levels by RT-PCR and microarrays. FGF10 was detected at low levels in both assays. FGF11 was detected at moderate levels by microarray, but not by RT-PCR. FGF17 was detected at low levels by array and moderate levels by RT-PCR. FGF8 and FGF22 were detected by RT-PCR, but not by microarrays during late cleavage divisions. FGF8, FGF5, and FGF9 were detected in the oocyte by microarray. FGF2, FGF3, and FGF7 were not detected by RT-PCR or microarrays and FGF13, FGF14, and FGF23 were not detected by microarray. Since a major role of FGF is to maintain TS cells, we tested human and mouse placental cell lines and early gestation human placenta for expression of FGF ligands. Expression in mouse TS cells was compared with preimplantation embryos, and human placental cell line expression was compared with human placenta, to infer which ligands are expressed in placental lineage vs. other cell lineages. The data suggest that human and mouse placenta share FGF18 and its high expression suggests preimplantation and early placental function. Mol. Reprod. Dev. © 2006 Wiley-Liss, Inc. [source] A microarray-based approach for the identification of epigenetic biomarkers for the noninvasive diagnosis of fetal diseasePRENATAL DIAGNOSIS, Issue 11 2009Tianjiao Chu Abstract Objectives We describe a novel microarray-based approach for the high-throughput discovery of epigenetic biomarkers for use in the noninvasive detection of fetal genetic disease. Methods We combined a 215 060-probe custom oligonucleotide microarray with a comprehensive library preparation method and novel statistical tools to compare DNA methylation patterns in chorionic villus samples (CVS) with gestational age-matched maternal blood cell (MBC) samples. Our custom microarray was designed to provide high-resolution coverage across human chromosomes 13, 18 and 21. Results We identified 6311 MspI/HpaII sites across all three chromosomes that displayed tissue-specific differential CpG methylation patterns. To maximize the probability of identifying biomarkers that have clinical utility we filtered our data to identify MspI/HpaII sites that are within 150 bp of a highly polymorphic single nucleotide polymorphism (SNP) so that its allelic ratio may be determined for the detection of fetal aneuploidy. Our microarray design and the computational tools used for data analysis are available for download as is the entire data set. Conclusions This high-resolution analysis of DNA methylation patterns in the human placenta during the first trimester of pregnancy identifies numerous potential biomarkers for the diagnosis of fetal aneuploidy on chromosomes 13, 18 and 21. Copyright © 2009 John Wiley & Sons, Ltd. [source] ORIGINAL ARTICLE: Expression of Autotaxin, an Ectoenzyme that Produces Lysophosphatidic Acid, in Human PlacentaAMERICAN JOURNAL OF REPRODUCTIVE IMMUNOLOGY, Issue 2 2009Yuki Iwasawa Problem, Lysophosphatidic acid (LPA) is a bioactive lipid mediator and thought to play an important role in pregnancy. Plasma LPA is produced by autotaxin (ATX), and ATX activity in plasma increases during pregnancy paralleled with gestational weeks and decreases to near the non-pregnant level soon after delivery. However, the source of increased ATX during pregnancy is still uncertain. We hypothesized that the source of increased ATX might be placenta. Method of study, We investigated the protein and mRNA expression of ATX in human placenta using immunohistochemistry and RT-PCR, respectively. Results, At all 3 gestational trimesters, immunohistochemical staining for placenta tissues revealed the most marked positive staining of ATX protein in trophoblasts. Real-time PCR revealed that mRNA amounts of ATX in placenta tissues paralleled with gestational weeks, i.e. ATX level in plasma. Conclusion, These findings suggest that trophoblasts might produce ATX and its bioactive resultant substance, LPA, paralleled with gestational weeks. [source] ORIGINAL ARTICLE: Suppression of Mamu-AG by RNA InterferenceAMERICAN JOURNAL OF REPRODUCTIVE IMMUNOLOGY, Issue 6 2009Jessica G. Drenzek Problem, The role of placental major histocompatibility complex (MHC) class I molecules in pregnancy is not well understood. Mamu-AG, the rhesus monkey homology of human leukocyte antigen (HLA)-G expressed in the human placenta, was targeted for degradation by RNA interference (RNAi), a powerful tool to aid in determining gene function, to determine the effect that this knockdown has on NK cell function. Method of study, A series of potential target short hairpin RNA (shRNA) sequences to suppress Mamu-AG expression was screened, which identified an optimal sequence to use in transfection experiments. Knockdown in two different Mamu-AG-expressing cell lines was measured by flow cytometry. Cytotoxicity assays were performed to correlate Mamu-AG expression with NK cell cytotoxicity. Results, Decreased expression of Mamu-AG by short interfering RNA (siRNA) (70,80%) in cell types tested was associated with increased lysis of Mamu-AG target cells. Conclusion, Target sequences have been identified that knocked down Mamu-AG expression by RNAi and increased lysis by NK cells. This supports the concept that NK cell receptors recognize this placental non-classical MHC class I molecule. [source] P-96 Fetal endothelial cells in full-term placenta, but not in first trimester placenta, express Fc,RIIb2 mRNAAMERICAN JOURNAL OF REPRODUCTIVE IMMUNOLOGY, Issue 5 2004Mishima Takuya In the human placenta, IgG-transport from maternal to fetal blood starts in the second trimester and continues through the third trimester. There are two cellular barriers for IgG-transport: the first and second barriers are syncytiotrophoblast and fetal endothelial cells (ECs), respectively. Sorting via FcRn is considered the IgG-transporter in the first barrier. The mechanism of IgG-transport in the second barrier is not fully understood. Recently, we reported a novel Fc,RIIb-containing compartment that may serve as an IgG-transporter in the second barrier (Mol Biol Cell 13 (suppl) 548a, 2002). To further investigate the feasibility of the Fc,RIIb-vesicle involvement in IgG-transport in placental ECs, we have studied FcR-expression in the developing human placenta by RT-PCR and direct sequencing analysis. First trimester and full-term placentas were used. We proved that the Fc,RII expressed in villus ECs in full-term placenta was the b2 isoform. Fc,RIIb2 mRNA expression could not be detected in first trimester placenta, while it was expressed in full-term placenta. In contrast, FcRn mRNA expression was detectable in first trimester placenta as well as in full-term placenta. These results seem consistent with our hypothesis that in first trimester placenta IgG is transcytosed via FcRn across the first barrier but IgG cannot be transported in the second barrier that does not express Fc,RIIb2 and that the Fc,RIIb2-positive compartment is critical for IgG-transport in the human placenta. [source] Mammalian Expression Cloning of Two Human Trophoblast Suppressors of Major Histocompatibility Complex GenesAMERICAN JOURNAL OF REPRODUCTIVE IMMUNOLOGY, Issue 6 2001J. A. PEYMAN PROBLEM: Human trophoblasts suppress interferon-, (IFN-,)-simulated expression of major histocompatibility complex (MHC) class II genes and thereby protect the conceptus from maternal immune attack. The mechanism of this suppression is poorly understood. METHOD OF STUDY: IFN-,-responsive HeLa cells were stably transfected with trophoblast cDNA expression libraries and screened by negative immunoselection with an antibody to HLA-DR. RESULTS: Two suppressor cDNAs were isolated. One encoded the untranslated RNA trophoblast STAT utron (TSU), which blocked STAT1 nuclear translocation and can theoretically form triplex RNA,DNA at the class II transactivator gene promoters. The other encoded the N-terminal 28 residues of chorionic somatomammotropin (hCS). TSU-related genes were detected in human and macaque, but not in mouse, genomic DNA. CONCLUSIONS: The genetics of two human trophoblast MHC suppressors suggest that these functions have been gained in human placenta in recent evolutionary history. TSU and hCS play critical roles in suppression of MHC genes, which may lead to silencing by DNA methylation. [source] Apoptosis and Bcl-2 Protein Expression in Human Placenta over the Course of Normal PregnancyANATOMIA, HISTOLOGIA, EMBRYOLOGIA, Issue 5 2010S. Soni With 2 figures and 2 tables Summary Apoptosis plays a central role in organ development, homeostasis and immune defence in multicellular organisms and is strictly controlled in part by members of Bcl-2 family. The Bcl-2 is a pro-survival molecule identified through its involvement in B-cell lymphomas. The aim of the study was to evaluate the incidence of apoptosis in the human placenta at different stages of pregnancy and to correlate it further with Bcl-2 expression. A total of 96 placental samples from first trimester, mid-trimester and uncomplicated term pregnancies were collected (n = 32 + 32 + 32). M30 cyto death monoclonal antibody was used to identify apoptotic cells. The apoptosis index of first trimester placentae was 2.33 ± 1.70, mid- trimester was 1.77 ± 1.36 and term placenta was 1.15 ± 0.21. Bcl-2 protein was found immunolocalized in the cytoplasm of syncytiotrophoblast. Apoptosis index was significantly reduced in term cases as compared with first trimester (P < 0.002) and mid-trimester placentae (P = 0.01). On the contrary, Bcl-2 expression was significantly higher at term cases than in first trimester (P < 0.0001) and mid-trimester cases (P < 0.001). The present study divulges the importance of apoptosis in permitting normal physiological turnover of villous trophoblast and also exhibits the contribution of bcl-2 in maintaining syncytial integrity throughout normal pregnancy. [source] Transplacental transfer of citalopram, fluoxetine and their primary demethylated metabolites in isolated perfused human placentaBJOG : AN INTERNATIONAL JOURNAL OF OBSTETRICS & GYNAECOLOGY, Issue 9 2002Tuija Heikkinen Objective To investigate the transplacental transfer and the effects of protein binding on the transfer of citalopram, desmethylcitalopram, fluoxetine and desmethylfluoxetine in the isolated perfused human placenta model. Design Prospective observational study. Methods Fifteen term human placentas were obtained immediately after delivery with maternal consent and a 2-hour non-recirculating perfusion cycle of a single placental cotyledon was set up. Citalopram (1230 nmol/L) and desmethylcitalopram (600 nmol/L) or fluoxetine (1455 nmol/L) and desmethylfluoxetine (1525 nmol/L) were added to the maternal reservoir and their appearance to the fetal circulation was followed by repeated measurements. To investigate the effect of protein binding on the transfer of citalopram and fluoxetine, nine additional perfusions were performed without albumin in the perfusion medium. Citalopram and desmethylcitalopram concentrations were measured by reversed-phase high performance liquid chromatography. Fluoxetine and desmethylfluoxetine concentrations was measured by gas chromatography and antipyrine (used as a reference compound) concentrations spectrophotometrically. Results The mean (SD) steady-state transplacental transfer (TPTSS%) for citalopram, desmethylcitalopram, fluoxetine and desmethylfluoxetine was 9.1%, 5.6% (P= 0.017 compared with citalopram), 8.7% and 9.1%, respectively, calculated as the ratio between the steady-state concentrations in fetal venous and maternal arterial sides. The TPTSS%s of citalopram, desmethylcitalopram, fluoxetine and desmethylfluoxetine were 86%, 50%, 88% and 91% of that of freely diffusable antipyrine. The absence of albumin significantly reduced the transfer of citalopram and fluoxetine (TPTSS% 1.1% and 4.8%, respectively) but not the transfer of antipyrine. Conclusion Citalopram, fluoxetine and desmethylfluoxetine all cross the human placenta, and may, therefore, affect the perinatal outcome of infants exposed to these drugs during pregnancy. The transfer of desmethylcitalopram was significantly lower, which in the clinical setting may suggest lower fetal exposure of serotonin re-uptake inhibition by citalopram compared with fluoxetine. The presence of albumin was necessary for the transplacental transfer of both citalopram and fluoxetine. [source] Bifidobacterium and Lactobacillus DNA in the human placentaLETTERS IN APPLIED MICROBIOLOGY, Issue 1 2009R. Satokari Abstract Aims:, Bifidobacteria and lactobacilli are part of the human normal intestinal microbiota and may possibly be transferred to the placenta. It was hypothesized that intestinal bacteria or their components are present in the placenta and that the foetus may be exposed to them. We investigated the presence of bifidobacteria and lactobacilli and their DNA in the human placenta. Methods and Results:, We studied 34 human placentae (25 vaginal and nine caesarean deliveries) for the presence Bifidobacterium spp. and Lactobacillus rhamnosus. Cultivation was used for the detection of viable cells and genus and species-specific PCR for the detection of DNA. No bifidobacteria or lactobacilli were found by cultivation. Bifidobacterial DNA was detected in 33 and L. rhamnosus DNA in 31 placenta samples. Conclusions:, DNA from intestinal bacteria was found in most placenta samples. The results suggest that horizontal transfer of bacterial DNA from mother to foetus may occur via placenta. Significance and Impact of the Study:, Bacterial DNA contains unmethylated CpG oligodeoxynucleotide motifs which induce immune effects. Specific CpG motifs activate Toll-like receptor 9 and subsequently trigger Th-1-type immune responses. Although the newborn infant is considered immunologically immature, exposure by bacterial DNA may programme the infant's immune development during foetal life earlier than previously considered. [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] Stereological comparison of 3D spatial relationships involving villi and intervillous pores in human placentas from control and diabetic pregnanciesJOURNAL OF ANATOMY, Issue 2 2000TERRY M. MAYHEW In human placenta, 3D spatial relationships between villi and the maternal vascular bed determine intervillous porosity and this, in turn, influences haemodynamics and transport. Recently-developed stereological methods were applied in order to examine and quantify these relationships. Placentas were collected after 37 wk from control pregnancies and those associated with maternal diabetes mellitus classified according to duration and severity (White classification scheme). Two principal questions were addressed: (1) are normal spatial arrangements maintained in well-controlled diabetes mellitus? and (2) do arrangements vary between diabetic groups? To answer these questions, tissue sections cut at random positions and orientations were generated by systematic sampling procedures. Volume densities of villi (terminal+intermediate), intervillous spaces and perivillous fibrin-type fibrinoid deposits were estimated by test point counting and converted to global volumes after multiplying by placental volumes. Design-based estimates of the sizes (volume- and surface-weighted volumes) of intervillous ,pores' were obtained by measuring the lengths of point- and intersection-sampled intercepts. From these, theoretical numbers of pores were calculated. Model-based estimates (cylinder model) of the hydraulic diameters and lengths of pores were also made. Second-order stereology was used to examine spatial relationships within and between villi and pores and to test whether pair correlation functions deviated from the value expected for ,random' arrangements. Estimated quantities did not differ significantly between diabetic groups but did display some departures from control values in non-insulin-dependent (type 2) diabetic placentas. These findings support earlier studies which indicate that essentially normal microscopical morphology is preserved in placentas from diabetic subjects with good glycaemic control. Therefore, it is likely that fetal hypoxia associated with maternal diabetes mellitus is due to metabolic disturbances rather than abnormalities in the quantities or arrangements of maternal vascular spaces. [source] A hierarchical analysis of transcriptome alterations in intrauterine growth restriction (IUGR) reveals common pathophysiological pathways in mammals,THE JOURNAL OF PATHOLOGY, Issue 3 2007C Buffat Abstract Intra-uterine growth restriction (IUGR) is a frequent disease, affecting up to 10% of human pregnancies and responsible for increased perinatal morbidity and mortality. Moreover, low birth weight is an important cause of the metabolic syndrome in the adult. Protein depletion during the gestation of rat females has been widely used as a model for human IUGR. By transcriptome analysis of control and protein-deprived rat placentas, we were able to identify 2543 transcripts modified more than 2.5 fold (1347 induced and 1196 repressed). Automatic functional classification enabled us to identify clusters of induced genes affecting chromosome structure, transcription, intracellular transport, protein modifications and apoptosis. In particular, we suggest the existence of a complex balance regulating apoptosis. Among repressed genes, we noted several groups of genes involved in immunity, signalling and degradation of noxious chemicals. These observations suggest that IUGR placentas have a decreased resistance to external aggression. The promoters of the most induced and most repressed genes were contrasted for their composition in putative transcription factor binding sites. There was an over-representation of Znfinger (ZNF) proteins and Pdx1 (pancreatic and duodenal homeobox protein 1) putative binding sites. Consistently, Pdx1 and a high proportion of ZNF genes were induced at the transcriptional level. A similar analysis of ZNF promoters showed an increased presence of putative binding sites for the Tata box binding protein (Tbp). Consistently again, we showed that the Tbp and TBP-associated factors (Tafs) were up-regulated in IUGR placentas. Also, samples of human IUGR and control placentas showed that human orthologous ZNFs and PDX1 were transcriptionnally induced, especially in non-vascular IUGR. Immunohistochemistry revealed increased expression of PDX1 in IUGR human placentas. In conclusion, our approach permitted the proposition of hypotheses on a hierarchy of gene inductions/repressions leading to massive transcriptional alterations in the IUGR placenta, in humans and in rodents. Copyright © 2007 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd. [source] | ||||||||||||||||||||||||||||