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Sample records for placental thrombomodulin expression

  1. Placental thrombomodulin expression in recurrent miscarriage

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    Turi Angelo

    2010-01-01

    Full Text Available Abstract Background Early pregnancy loss can be associated with trophoblast insufficiency and coagulation defects. Thrombomodulin is an endothelial-associated anticoagulant protein involved in the control of hemostasis and inflammation at the vascular beds and it's also a cofactor of the protein C anticoagulant pathway. Discussion We evaluate the Thrombomodulin expression in placental tissue from spontaneous recurrent miscarriage and voluntary abortion as controls. Thrombomodulin mRNA was determined using real-time quantitative polymerase chain reaction. Reduced expression levels of thrombomodulin were found in recurrent miscarriage group compared to controls (1.82-fold of reduction, that corresponds to a reduction of 45% (from control group Delta CT of thrombomodulin expression in spontaneous miscarriage group respect the control groups. Summary We cannot state at present the exact meaning of a reduced expression of Thrombomodulin in placental tissue. Further studies are needed to elucidate the biological pathway of this important factor in the physiopathology of the trophoblast and in reproductive biology.

  2. Loss of Thrombomodulin in Placental Dysfunction in Preeclampsia.

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    Turner, Rosanne J; Bloemenkamp, Kitty W M; Bruijn, Jan A; Baelde, Hans J

    2016-04-01

    Preeclampsia is a pregnancy-specific syndrome characterized by placental dysfunction and an angiogenic imbalance. Systemically, levels of thrombomodulin, an endothelium- and syncytiotrophoblast-bound protein that regulates coagulation, inflammation, apoptosis, and tissue remodeling, are increased. We aimed to investigate placental thrombomodulin dysregulation and consequent downstream effects in the pathogenesis of preeclampsia. Placentas from 28 preeclampsia pregnancies, 30 uncomplicated pregnancies, and 21 pregnancies complicated by growth restriction as extra controls were included. Immunohistochemical staining of thrombomodulin, caspase-3, and fibrin was performed. Placental mRNA expression of thrombomodulin, inflammatory markers, matrix metalloproteinases 2 and 9, and soluble Flt-1 were measured with quantitative polymerase chain reaction. Thrombomodulin mRNA expression was determined in vascular endothelial growth factor-transfected trophoblast cell lines. Thrombomodulin protein and mRNA expression were decreased in preeclampsia as compared with both control groups (P=0.001). Thrombomodulin mRNA expression correlated with maternal body mass index (Ppreeclampsia. An increase in placental apoptotic cells was associated with preeclampsia (Ppreeclampsia, but not with fibrin deposits or inflammatory markers. Placental soluble Flt-1 expression correlated with decreased thrombomodulin expression. Vascular endothelial growth factor induced upregulation of thrombomodulin expression in trophoblast cells. Decreased thrombomodulin expression in preeclampsia may play a role in placental dysfunction in preeclampsia and is possibly caused by an angiogenic imbalance. Hypertension and obesity are associated with thrombomodulin downregulation. These results set the stage for further basic and clinical research on thrombomodulin in the pathogenesis of preeclampsia and other syndromes characterized by endothelial dysfunction. © 2016 American Heart Association, Inc.

  3. Loss of Thrombomodulin in Placental Dysfunction in Preeclampsia

    NARCIS (Netherlands)

    Turner, Rosanne J; Bloemenkamp, Kitty W M; Bruijn, Jan A; Baelde, Hans J

    OBJECTIVE: Preeclampsia is a pregnancy-specific syndrome characterized by placental dysfunction and an angiogenic imbalance. Systemically, levels of thrombomodulin, an endothelium- and syncytiotrophoblast-bound protein that regulates coagulation, inflammation, apoptosis, and tissue remodeling, are

  4. Loss of Thrombomodulin in Placental Dysfunction in Preeclampsia

    NARCIS (Netherlands)

    Turner, Rosanne J; Bloemenkamp, Kitty W M; Bruijn, Jan A; Baelde, Hans J

    2016-01-01

    OBJECTIVE: Preeclampsia is a pregnancy-specific syndrome characterized by placental dysfunction and an angiogenic imbalance. Systemically, levels of thrombomodulin, an endothelium- and syncytiotrophoblast-bound protein that regulates coagulation, inflammation, apoptosis, and tissue remodeling, are i

  5. Thrombomodulin gene polymorphism and thrombomodulin expression in essential hypertension

    Institute of Scientific and Technical Information of China (English)

    WANG Yun-ying; BAO Zhen-min; ZHANG Qi-yi; DONG Hai; YU Xin-juan

    2006-01-01

    @@ Patients with hypertension have the characteristics of abnormalities of vessel wall,blood constituents and blood flow. These abnormalities may confer a prothrombotic or hypercoagulable state and are related to the damage of target organs and long-term prognosis. Soluble thrombomodulin (sTM) as abnormalities of levels of specific plasma markers of endothelial damage or dysfunction may relate with the complications of hypertension and the determination of blood pressure itself. TM plays a critical role as a co-factor in the protein C pathway, 1 which is important in regulating coagulation as well as inflammation. Thus we hypothesized that the -33G>A polymorphism alter thrombomodulin expression and/or impair anticoagulant function, which can predispose to the damage of the target organs during the progress of hypertension. Then, we investigated a possible association of sTM, TM on monocytes and the -33G>A polymorphism with essential hypertension and cardiovascular disease (CVD) in the Chinese Han ethnic population.

  6. Differential Gene Expression in Thrombomodulin (TM; CD141)+ and TM− Dendritic Cell Subsets

    OpenAIRE

    Masaaki Toda; Zhifei Shao; Yamaguchi, Ken D.; Takehiro Takagi; Corina N D'Alessandro-Gabazza; Osamu Taguchi; Hugh Salamon; Leung, Lawrence L. K.; Gabazza, Esteban C.; John Morser

    2013-01-01

    Previously we have shown in a mouse model of bronchial asthma that thrombomodulin can convert immunogenic conventional dendritic cells into tolerogenic dendritic cells while inducing its own expression on their cell surface. Thrombomodulin(+) dendritic cells are tolerogenic while thrombomodulin(-) dendritic cells are pro-inflammatory and immunogenic. Here we hypothesized that thrombomodulin treatment of dendritic cells would modulate inflammatory gene expression. Murine bone marrow-derived de...

  7. EFFECTS OF RADIX SALVIAE MILTIORRHIZAE AND ITS COMPONENT "DANSHENSU" ON THE PRODUCTION OF PA, PAI, PGI2 AND EXPRESSION OF THROMBOMODULIN BY BOVINE ENDOTHELIAL CELLS IN CULTURE

    Institute of Scientific and Technical Information of China (English)

    顾扬洪; 张彩英; 黄桂秋; 王振义

    1992-01-01

    The effects of Radix Salviae Miltiorrhizae and its component "DANSHENSU" on the production of PA, PAI, PGI2 and expression of thrombomodulin by cultured bovine endothelial cells were studied. 6-Keto-PGF1α was measured with RIA. PA, PAI and thrombomodulin were measured with chromosenic substrate S2390 and S2238 respectively. The results showed that Radix Salviae Miltiorrhizae could promote PA activity and PGI2 production by bovine endothelial cell (BEC). It could inhibt activity of PAI secreted by BEC. Its component "DANSHENSU" had the same effects. In addition, Radix Salviae Miltiorrhizae could also increase thrombomodulin activity on the surface of BEC, but "DANSHENSU" did not.

  8. The placental RCAS1 expression during stillbirth

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    Tetlak Tomasz

    2005-06-01

    Full Text Available Abstract Background Independently of the fetal death cause the beginning and course of stillbirth is closely related with the growing cytotoxic activity at the maternal-fetal interface. RCAS1 participates in the inhibition of maternal immune response during pregnancy. The alterations of RCAS1 protein expression in placental cells seem to determine the beginning of the labor and participate in the placental abruption. The aim of the present study was to investigate RCAS1 expression in placentas obtained following stillbirths or normal term births. Methods: RCAS1 expression was evaluated by Western blot method with the use of monoclonal anti-RCAS1 antibody in 67 placental tissue samples. Pregnant women were divided into four groups according to the mode of labor onset – spontaneous or induced, and the type of labor, stillbirth or labor at term. Placental beta-Actin expression was chosen as a control protein. Relative amounts of placental RCAS1 were compared with the use of Student's t-test, whereas beta-Actin control data were compared with the use of Mann-Whitney U test. Results: The average relative amount of RCAS1 was significantly lower in women with induced stillbirths than in women with induced labor at term. Similarly, significantly lower RCAS1 placental levels were observed in patients with spontaneous stillbirths than in women with spontaneous labor at term. Significant differences in RCAS1 expression were also observed with the respect to the beginning of the stillbirth: spontaneous and induced. Lowest RCAS1 placental levels were observed in women with spontaneous stillbirth. Conclusions: These preliminary results indicate that the alterations of RCAS1 expression in the human placenta may be involved in the changes of maternal immune system that take place during stillbirth.

  9. Recombinant expression of placental growth factor in baculovirus expression system

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    Narges Arbabi

    2016-12-01

    Full Text Available Background: Angiogenesis or formation of new blood vessels is the most important factor in physiological and pathological conditions. Human Placental growth factor (hPLGF protein in is one of the most important proteins which stimulate angiogenesis. Baculovirus expression system has been used successfully to over express eukaryotic proteins in insect cells. This system uses a very strong viral promoter, AcNPV polyhedrin, for high level of protein expression. Methods: hPLGF gene cloned in pFastBac-HT vector and transformed in DH10Bac.The recombinant bacmid was extracted and used in SF9 insect cells and transfected by cellfectin method. Target protein expression was confirmed with Western blot. Results: Transferring of the recombinant vector into Bacmid was successful and the PLGF gene sequence was confirmed. PLGF and recombinant protein expression by Western blotting was confirmed. Conclusion: Baculovirus protein expression system expresses PLGF strongly and recombinant protein can be used in different tests.

  10. Activity of Ginkgo biloba Extract and Quercetin on Thrombomodulin Expression and Tissue-type Plasminogen Activator Secretion by Human Umbilical Vein Endothelial Cells

    Institute of Scientific and Technical Information of China (English)

    WEN-JUN LAN; XIAO-XIANG ZHENG

    2006-01-01

    In order to investigate the pharmacological properties of Ginkgo biloba extract (GBE) on improving blood circulation, the regulating action of GBE and quercetin (a main flavonoid ingredient in GBE) on thrombomodulin (TM)expression and tissue-type plasminogen activator (t-PA) secretion was studied. Methods Using flow cytometer and gel image system respectively, we evaluated the TM expression and the t-PA secretion by human umbilical vein endothelial cells (HUVECs) in vitro. Results The increase of TM expression on HUVECs surface was induced by GBE rather than quercetin in a dose- and time-dependent manner. Both GBE and quercetin increased the t-PA release significantly.Conclusion The effect of GBE on improving blood circulation may be partly attributed to its promoting TM expression and t-PA secretion by endothelial cells, and quercetin participated in the effect of GBE on t-PA secretion. However, the action of GBE on increasing TM expression needs further study.

  11. Alteration of placental haemostatic mechanisms in idiopathic intrauterine growth restriction

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    Jaime Eduardo Bernal Villegas

    2012-08-01

    Full Text Available Intrauterine growth restriction is a complication of pregnancy with a high probability of perinatal morbidity and mortality. It appears tobe caused by abnormal development of placental vasculature. Haemostatic processes are important for the development of the placenta,and an imbalance between procoagulant and anticoagulant factors has been associated with risk of intrauterine growth restriction.Objective. To evaluate coagulation abnormalities in placenta of pregnancies complicated with idiopathic intrauterine growth restriction.Materials and methods. Five placentas from pregnancies with idiopathic intrauterine growth restriction were compared to 19 controls.We performed gross and histological examination of the placenta. Analysis was made of both mRNA expression by real-time PCRand protein by ELISA of tissue factor and thrombomodulin in placental tissue. Results. Results based on histological evaluation wereconsistent with an increased prothrombotic state in placentas from pregnancies with idiopathic intrauterine growth restriction, andthrombosis of chorionic vessels was the most important finding. The study showed an increased expression of tissue factor protein(p=0.0411 and an increase in the ratio of tissue factor/thrombomodulin mRNA (p=0.0411 and protein (p=0.0215 in placentas frompregnancies with idiopathic intrauterine growth restriction. There were no statistically significant differences neither between cases andcontrols in the mRNA levels of tissue factor or thrombomodulin nor at the protein level of thrombomodulin. Conclusion. Evidence ofalteration of local haemostatic mechanisms at the level of the placenta, including abnormal expression of tissue factor and tissue factor/thrombomodulin ratio, in pregnancies that occur with idiopathic intrauterine growth restriction is presented.

  12. Cutting edge: JAM-C controls homeostatic chemokine secretion in lymph node fibroblastic reticular cells expressing thrombomodulin.

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    Frontera, Vincent; Arcangeli, Marie-Laure; Zimmerli, Claudia; Bardin, Florence; Obrados, Elodie; Audebert, Stéphane; Bajenoff, Marc; Borg, Jean-Paul; Aurrand-Lions, Michel

    2011-07-15

    The development and maintenance of secondary lymphoid organs, such as lymph nodes, occur in a highly coordinated manner involving lymphoid chemokine production by stromal cells. Although developmental pathways inducing lymphoid chemokine production during organogenesis are known, signals maintaining cytokine production in adults are still elusive. In this study, we show that thrombomodulin and platelet-derived growth factor receptor α identify a population of fibroblastic reticular cells in which chemokine secretion is controlled by JAM-C. We demonstrate that Jam-C-deficient mice and mice treated with Ab against JAM-C present significant decreases in stromal cell-derived factor 1α (CXCL12), CCL21, and CCL19 intranodal content. This effect is correlated with reduced naive T cell egress from lymph nodes of anti-JAM-C-treated mice.

  13. Glucocorticoids enhance CD163 expression in placental Hofbauer cells.

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    Tang, Zhonghua; Niven-Fairchild, Tracy; Tadesse, Serkalem; Norwitz, Errol R; Buhimschi, Catalin S; Buhimschi, Irina A; Guller, Seth

    2013-01-01

    Periplacental levels of glucocorticoid (GC) peak at parturition, and synthetic GC is administered to women at risk for preterm delivery. However, little is known concerning cell-type-specific effects of GC in placenta. Hofbauer cells (HBCs) are fetal macrophages that are located adjacent to fetal capillaries in placenta. The goal of the current study was to determine whether GC treatment altered HBC gene expression and function. Western blotting and flow cytometry revealed CD163 and folate receptor-β (FR-β), markers of antiinflammatory M2 macrophages, were specifically expressed by primary cultures of HBCs immunopurified from human term placentas. GC receptor mRNA and protein levels were higher in HBCs compared with placental fibroblasts. Treatment of HBCs with cortisol or dexamethasone (DEX) markedly and specifically enhanced CD163 protein and mRNA levels, whereas expression of FR-β and CD68 were largely unresponsive to GC treatment. DEX treatment also increased hemoglobin uptake by HBCs, evidence of enhanced HBC function. The level of CD163 mRNA, but not FR-β or CD68 mRNA, was stimulated in placental explant cultures by DEX treatment, and increased CD163/FR-β and CD163/CD68 mRNA ratios sensitively reflected the response to GC. Maternal GC administration was associated with increased CD163/FR-β and CD163/CD68 mRNA ratios in placentas from women with spontaneous preterm birth. In conclusion, in vitro studies indicated that GC treatment specifically up-regulated CD163 expression in HBCs and enhanced HBC function. In addition, the observed alterations in patterns of expression of macrophage marker genes associated with maternal GC administration suggest that HBCs are in vivo targets of GC action.

  14. Human placental trophoblasts express the immunosuppressive cytokine IL-35.

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    Mao, Haiting; Gao, Wenjuan; Ma, Chao; Sun, Jintang; Liu, Jia; Shao, Qianqian; Song, Bingfeng; Qu, Xun

    2013-07-01

    Studies of maternal-fetal tolerance focus on defining mechanisms for establishment of immunological privilege within the uterus during pregnancy. Fetal trophoblasts play a key role in maternal tolerance, in part through cytokines production. As a novel inhibitory cytokine, IL-35 is produced by Foxp3(+) regulatory T cells (Tregs) and mediates maximal suppression of Tregs. The purpose of the study is to analyze the expression of IL-35 in first-trimester human placental trophoblasts. IL-35 expression was detected at both protein and mRNA levels by immunohistochemical staining and quantitative real-time PCR method, respectively and secretion of IL-35 was measured by ELISA assay. Our results demonstrated that human trophoblasts constitutively expressed IL-35. Ebi3 and p35 (two subunits of IL-35) mRNA was shown to be co-expressed in trophoblast cells. Moreover, large amounts of secreted IL-35 were detected in the supernatants of trophoblast cells. But we did not detect the constitutive expression of IL-35 in decidual stromal cells. Our findings confirmed for the first time that first-trimester human trophoblast cells expressed and secreted IL-35, which might contribute to their suppressive capacity to maternal immune cells. Therefore, IL-35 may be an important factor of the cytokine network regulating local immune responses during human pregnancy.

  15. Differential expression of Nogo-B in preeclampsia placental tissue and normal placental tissue and its correlation with illness-related molecule expression

    Institute of Scientific and Technical Information of China (English)

    Fu-Rong Xu; Hai-Yan Wang

    2016-01-01

    Objective:To study the differential expression of Nogo-B in preeclampsia placental tissue and normal placental tissue and its correlation with illness-related molecule expression.Methods:Placental tissue of preeclampsia puerperas and normal pregnancy puerperas was collected, PCR method was used to detect mRNA contents of Nogo-B and apoptosis genes (Fas, Caspase-3 and Caspase-9) and Elisa was used to detect protein contents of inflammatory factors (TNF-α, IL-1β, IL-6, IL-8, CD40L and VCAM-1) and endothelial injury molecules (LOX-1, ox-LDL, PTX3 and ADM).Results:mRNA content of Nogo-B in preeclampsia placental tissue was significantly higher than that in normal placental tissue and the more severe the disease, the higher the mRNA content of Nogo-B; mRNA contents of Fas, Caspase-3 and Caspase-9 as well as protein contents of TNF-α, IL-1β, IL-6, IL-8, CD40L, VCAM-1, LOX-1, ox-LDL, PTX3 and ADM in preeclampsia placental tissue were significantly higher than those in normal placental tissue; mRNA content of Nogo-B was positively correlated with mRNA contents of Fas, Caspase-3 and Caspase-9 as well as protein contents of TNF-α, IL-1β, IL-6, IL-8, CD40L, VCAM-1, LOX-1, ox-LDL, PTX3 and ADM.Conclusions:Nogo-B expression in preeclampsia placental tissue significantly increases, and the molecule can regulate the generation of apoptosis genes, inflammatory factors and endothelial injury molecules to be involved in the occurrence of preeclampsia.

  16. Paternal uniparental disomy 14 and related disorders: placental gene expression analyses and histological examinations.

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    Kagami, Masayo; Matsuoka, Kentaro; Nagai, Toshiro; Yamanaka, Michiko; Kurosawa, Kenji; Suzumori, Nobuhiro; Sekita, Yoichi; Miyado, Mami; Matsubara, Keiko; Fuke, Tomoko; Kato, Fumiko; Fukami, Maki; Ogata, Tsutomu

    2012-10-01

    Although recent studies in patients with paternal uniparental disomy 14 [upd(14)pat] and other conditions affecting the chromosome 14q32.2 imprinted region have successfully identified underlying epigenetic factors involved in the development of upd(14)pat phenotype, several matters, including regulatory mechanism(s) for RTL1 expression, imprinting status of DIO3 and placental histological characteristics, remain to be elucidated. We therefore performed molecular studies using fresh placental samples from two patients with upd(14)pat. We observed that RTL1 expression level was about five times higher in the placental samples of the two patients than in control placental samples, whereas DIO3 expression level was similar between the placental samples of the two patients and the control placental samples. We next performed histological studies using the above fresh placental samples and formalin-fixed and paraffin-embedded placental samples obtained from a patient with a maternally derived microdeletion involving DLK1, the-IG-DMR, the MEG3-DMR and MEG3. Terminal villi were associated with swollen vascular endothelial cells and hypertrophic pericytes, together with narrowed capillary lumens. DLK1, RTL1 and DIO3 proteins were specifically identified in vascular endothelial cells and pericytes, and the degree of protein staining was well correlated with the expression dosage of corresponding genes. These results suggest that RTL1as-encoded microRNA functions as a repressor of RTL1 expression, and argue against DIO3 being a paternally expressed gene. Furthermore, it is inferred that DLK1, DIO3 and, specially, RTL1 proteins, play a pivotal role in the development of vascular endothelial cells and pericytes.

  17. Overlap Chronic Placental Inflammation Is Associated with a Unique Gene Expression Pattern.

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    Raman, Kripa; Wang, Huaqing; Troncone, Michael J; Khan, Waliul I; Pare, Guillaume; Terry, Jefferson

    2015-01-01

    Breakdown of the balance between maternal pro- and anti-inflammatory pathways is thought to allow an anti-fetal maternal immune response that underlies development of chronic placental inflammation. Chronic placental inflammation is manifested by the influx of maternal inflammatory cells, including lymphocytes, histiocytes, and plasma cells, into the placental membranes, villi, and decidua. These infiltrates are recognized pathologically as chronic chorioamnionitis, chronic villitis of unknown etiology, and chronic deciduitis. Each of these histological entities is associated with adverse fetal outcomes including intrauterine growth restriction and preterm birth. Studying the gene expression patterns in chronically inflamed placenta, particularly when overlapping histologies are present, may lead to a better understanding of the underlying mechanism(s). Therefore, this study compared tissue with and without chronic placental inflammation, manifested as overlapping chronic chorioamnionitis, chronic villitis of unknown etiology, and chronic deciduitis. RNA expression profiling was conducted on formalin fixed, paraffin embedded placental tissue using Illumina microarrays. IGJ was the most significant differentially expressed gene identified and had increased expression in the inflamed tissue. In addition, IGLL1, CXCL13, CD27, CXCL9, ICOS, and KLRC1 had increased expression in the inflamed placental samples. These differentially expressed genes are associated with T follicular helper cells, natural killer cells, and B cells. Furthermore, these genes differ from those typically associated with the individual components of chronic placental inflammation, such as chronic villitis, suggesting that the inflammatory infiltrate associated with overlapping chronic chorioamnionitis, chronic villitis of unknown etiology, and chronic deciduitis differs is unique. To further explore and validate gene expression findings, we conducted immunohistochemical assessment of protein level

  18. Metallothionein expression in placental tissue in Menkes' disease

    DEFF Research Database (Denmark)

    Hærslev, T.; Krag Jacobsen, G.; Horn, N.

    1995-01-01

    Menkes' disease is a recessive X-linked disturbance of copper metabolism, resulting in accumulation of copper in several extra-hepatic tissues including the placenta. Metallothionein (MT) is a low-molecular weight protein with a high affinity for group II metal ions, such as copper. Its synthesis....... The avidin-biotin-complex (ABC)-technique was used. The copper content was measured by neutron activation analysis (NAA). In all placental tissue sections positive MT immunostaining appeared only in the trophoblast and only in proliferating cells. In placental tissue sections obtained from foetuses...

  19. Prothrombotic Effect of Anti-beta-2 Glycoprotein-1 Antibodies on the Expression of Tissue Factor, Thrombomodulin, and Plasminogen Activator Inhibitor-1 in Endothelial Cells

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    Rikarni Rikarni

    2015-03-01

    Full Text Available Aim: to analyse the effects of immunoglobulin (IgG and IgM anti-beta-2 glycoprotein-1 (anti-β2GP1 on the expression of tissue factor (TF, thrombomodulin (TM, and plasminogen activator inhibitor-1(PAI-1 of endothelial cells in the messenger RNA level. Methods: laboratory experimental study in human umbilical vein endothelial cells (HUVEC was done at Cipto Mangunkusumo Hospital/Faculty of Medicine, Universitas Indonesia. Samples are purified IgG anti-β2GP1 from six  antiphospholipid syndrome (APS patients serum and IgM anti-β2GP1 from six APS patients serum. For controls, purified IgG from six normal human serum (IgM-NHS and purified IgM from six normal human serum (IgM-NHS were used. HUVEC were treated with purified IgG anti-β2GP1, IgM anti-β2GP1, IgG-NHS, IgM-NHS for four hours of incubation. We measured TF, TM, and PAI-1 of HUVEC in mRNA relative expression levels (before and after treatment by real time reverse transcription polymerase chain reaction. Results: the mean value of TF, TM, and PAI-1 mRNA levels in HUVEC after treated with IgG anti-β2GP1 compared to Ig-NHS were 3.14 (0.93-, 0.31 (0.13-, 5.33 (2.75-fold respectively. In other hand, after treated with IgM anti-β2GP1 compared to IgM-NHS, mRNA levels of TF, TM, and PAI-1 were 4.33 (1.98-, 0.33 (0.22-, 5.47 (2.64-fold respectively. Before and after treatment with IgG anti-β2GP1 showed significant differences of TF mRNA levels {1.09 (0.76 versus 3.14 (0.93, p=0.003}, TM mRNA levels {0.91 (0.11 versus 0.31(0.13, p=0.001}, and PAI-1 mRNA levels 0.93 (0.13 versus 5.33 (2.75, p=0.013}. Before and after treatment with IgM anti-β2GP1 showed significant differences of TF mRNA levels {1.03 (0.11 versus 4.33 (1.98, p=0.008}, TM mRNA levels {0.93 (0.08 versus 0.33 (0.22, p=0.003}, and PAI-1 mRNA levels {1.02 (0.10 versus 5.47 (2.64, p=0.01}. Conclusion: IgG anti-β2GP1 and IgM anti-β2GP1 increased TF and PAI-1 mRNA levels. However, IgG anti-β2GP1 and IgM anti-β2GP1 decreased TM m

  20. Human placental expression of SLIT/ROBO signaling cues: effects of preeclampsia and hypoxia.

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    Liao, Wu-Xiang; Laurent, Louise C; Agent, Sally; Hodges, Jennifer; Chen, Dong-Bao

    2012-04-01

    Preeclampsia is characterized by dysfunctional endothelium and impaired angiogenesis. Recent studies suggest that the neuronal guidance SLIT/ROBO system regulates tumor angiogenesis. This study investigated if SLIT and ROBO are differentially expressed in healthy term and preeclamptic placentas and if hypoxia regulates SLIT and ROBO expression in placental trophoblast and endothelial cells. Total RNA and protein were extracted from placental tissues of healthy term (n = 5) and preeclamptic (n = 6) pregnancies and used for SLIT/ROBO expression analyses with reverse transcription-polymerase chain reaction (RT-PCR), real-time quantitative-PCR, and immunoblotting. Paraffin-embedded tissues were processed to localize SLIT/ROBO proteins in placental villi by immunohistochemistry. BeWo choriocarcinoma cells and human umbilical vein endothelial cells (HUVEC) were treated with 2% or 10% oxygen or the hypoxia mimetic deferoxamine mesylate (100 μM) to test if hypoxia regulates SLIT/ROBO expression. SLIT2, SLIT3, ROBO1, and ROBO4 mRNA and proteins were detected in the placenta. SLIT2 and ROBO1 proteins localized in the syncytiotrophoblast, and SLIT3, ROBO1, and ROBO4 in capillary endothelium of the placental villi. Levels of ROBO1 and ROBO4 as well as sFLT1 (soluble fms-like tyrosine kinase-1) proteins were significantly greater in preeclamptic placentas compared to normal controls. Hypoxia significantly increased both mRNA and protein levels of SLIT2 in BeWo cells and of SLIT3, ROBO1, and ROBB4 in HUVEC. Thus, trophoblast and endothelial coexpression of SLIT/ROBO suggests an autocrine/paracrine regulatory system for regulating placental function. Differential expression of SLITs and ROBOs in healthy term and preeclamptic placentas and hypoxia regulation of their expressions in placental cells implicate a potential pathophysiological role for this system in preeclampsia.

  1. Altered placental expression of PAPPA2 does not affect birth weight in mice

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    Christians Julian K

    2010-07-01

    Full Text Available Abstract Background Pregnancy-associated plasma protein A2 (PAPPA2 is an insulin-like growth factor binding protein (IGFBP protease expressed in the placenta and upregulated in pregnancies complicated by pre-eclampsia. The mechanism linking PAPPA2 expression and pre-eclampsia and the consequences of altered PAPPA2 expression remain unknown. We previously identified PAPPA2 as a candidate gene for a quantitative trait locus (QTL affecting growth in mice and in the present study examined whether this QTL affects placental PAPPA2 expression and, in turn, placental or embryonic growth. Methods Using a line of mice that are genetically homogenous apart from a 1 megabase QTL region containing the PAPPA2 gene, we bred mice homozygous for alternate QTL genotypes and collected and weighed placentae and embryos at E12.5. We used quantitative RT-PCR to measure the mRNA levels of PAPPA2, as well as mRNA levels of IGFBP-5 (PAPPA2's substrate, and PAPPA (a closely related IGFBP protease to examine potential feedback and compensation effects. Western blotting was used to quantify PAPPA2 protein. Birth weight was measured in pregnancies allowed to proceed to parturition. Results PAPPA2 mRNA and protein expression levels in the placenta differed by a factor of 2.5 between genotypes, but we did not find a significant difference between genotypes in embryonic PAPPA2 mRNA levels. Placental IGFBP-5 and PAPPA mRNA expression levels were not altered in response to PAPPA2 levels, and we could not detect IGFBP-5 protein in the placenta by Western blotting. The observed difference in placental PAPPA2 expression had no significant effect on placental or embryonic mass at mid-gestation, birth weight or litter size. Conclusions Despite a significant difference between genotypes in placental PAPPA2 expression similar in magnitude to the difference between pre-eclamptic and normal placentae previously reported, we observed no difference in embryonic, placental or birth weight

  2. Targeted expression of Cre recombinase provokes placental-specific DNA recombination in transgenic mice.

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    Cissy Chenyi Zhou

    Full Text Available BACKGROUND: Inadequate placental development is associated with a high incidence of early embryonic lethality and serious pregnancy disorders in both humans and mice. However, the lack of well-defined trophoblast-specific gene regulatory elements has hampered investigations regarding the role of specific genes in placental development and fetal growth. PRINCIPAL FINDINGS: By random assembly of placental enhancers from two previously characterized genes, trophoblast specific protein α (Tpbpa and adenosine deaminase (Ada, we identified a chimeric Tpbpa/Ada enhancer that when combined with the basal Ada promoter provided the highest luciferase activity in cultured human trophoblast cells, in comparison with non-trophoblast cell lines. We used this chimeric enhancer arrangement to drive the expression of a Cre recombinase transgene in the placentas of transgenic mice. Cre transgene expression occurred throughout the placenta but not in maternal organs examined or in the fetus. SIGNIFICANCE: In conclusion, we have provided both in vitro and in vivo evidence for a novel genetic system to achieve placental transgene expression by the use of a chimeric Tpbpa/Ada enhancer driven transgene. The availability of this expression vector provides transgenic opportunities to direct the production of desired proteins to the placenta.

  3. Hypertension produced by placental ischemia in pregnant rats is associated with increased soluble endoglin expression.

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    Gilbert, Jeffrey S; Gilbert, Sara A B; Arany, Marietta; Granger, Joey P

    2009-02-01

    Recent clinical studies indicate that an excess of angiostatic factors, such as soluble endoglin (sEng), is related to the occurrence of preeclampsia. Although recent clinical studies report that sEng is increased in preeclamptic women, the mechanisms underlying its overexpression remain unclear. Evidence suggests that hypoxia and induction of heme oxygenase-1 have opposing effects on sEng expression, the former stimulatory and the latter inhibitory. Hence, we hypothesized that placental ischemia because of reduced uterine perfusion pressure (RUPP) in the pregnant rat would increase sEng expression and decrease heme oxygenase-1. Mean arterial pressure was obtained via arterial catheter, and serum and placental proteins were measured by Western blot. Mean arterial pressure was increased (132+/-3 mm Hg versus 102+/-2 mm Hg; Papu] versus 0.05+/-0.01 apu; Papu versus 1.45+/-0.42 apu; Papu versus 0.68+/-0.09 apu; Papu versus 2.5+/-0.1 apu; P<0.05) expression decreased in the RUPP compared with normal pregnant dams. The present findings support our hypothesis that placental ischemia because of RUPP increases the expression of sEng and shifts the balance of angiogenic factors in the maternal circulation toward an angiostatic state. The present study provides further evidence that placental ischemia is a strong in vivo stimulus of angiostatic factors during pregnancy.

  4. Increased maternal and fetal cholesterol efflux capacity and placental CYP27A1 expression in preeclampsia.

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    Mistry, Hiten D; Kurlak, Lesia O; Mansour, Yosef T; Zurkinden, Line; Mohaupt, Markus G; Escher, Geneviève

    2017-06-01

    Preeclampsia is a pregnancy-specific condition that leads to increased cardiovascular risk in later life. A decrease in cholesterol efflux capacity is linked to CVD. We hypothesized that in preeclampsia there would be a disruption of maternal/fetal plasma to efflux cholesterol, as well as differences in the concentrations of both placental sterol 27-hydroxylase (CYP27A1) and apoA1 binding protein (AIBP). Total, HDL-, and ABCA1-mediated cholesterol effluxes were performed with maternal and fetal plasma from women with preeclampsia and normotensive controls (both n = 17). apoA1 and apoE were quantified by chemiluminescence, and 27-hydroxycholesterol (27-OHC) by GC-MS. Immunohistochemistry was used to determine placental expression/localization of CYP27A1, AIBP, apoA1, apoE, and SRB1. Maternal and fetal total and HDL-mediated cholesterol efflux capacities were increased in preeclampsia (by 10-20%), but ABCA1-mediated efflux was decreased (by 20-35%; P < 0.05). Maternal and fetal apoE concentrations were higher in preeclampsia. Fetal plasma 27-OHC levels were decreased in preeclamptic samples (P < 0.05). Placental protein expression of both CYP27A1 and AIBP were localized around fetal vessels and significantly increased in preeclampsia (P = 0.04). Placental 27-OHC concentrations were also raised in preeclampsia (P < 0.05). Increased HDL-mediated cholesterol efflux capacity and placental CYP27A1/27-OHC could be a rescue mechanism in preeclampsia, to remove cholesterol from cells to limit lipid peroxidation and increase placental angiogenesis. Copyright © 2017 by the American Society for Biochemistry and Molecular Biology, Inc.

  5. Microarray analysis of differentially expressed genes in preeclamptic and normal placental tissues.

    Science.gov (United States)

    Ma, K; Lian, Y; Zhou, S; Hu, R; Xiong, Y; Ting, P; Xiong, Y; Li, X; Wang, X

    2014-01-01

    To detect the candidate genes for preeclampsia (PE). The gene expression profiles in preeclamptic and normal placental tissues were analyzed using cDNA microarray approach and the altered expression of important genes were further confirmed by real-time RT-PCR (reverse transcription polymerase chain reaction) technique. Total RNA was extracted from placental tissues of three cases with severe PE and from three cases with normal pregnancy. After scanning, differentially expressed genes were detected by software. In two experiments (the fluorescent labels were exchanged), a total of 111 differentially expressed genes were detected. In placental tissue ofpreeclamptic pregnancy, 68 differentially expressed genes were up-regulated, and 44 differentially expressed genes were down-regulated. Of these genes, 16 highly differentially expressed genes were confirmed by real-time fluorescent quantitative RT-PCR, and the result showed that the ratio of gene expression differences was comparable to that detected by cDNA microarray. The results of bioinformatic analysis showed that encoding products of differentially expressed genes were correlated to infiltration of placenta trophoblastic cells, immunomodulatory factors, pregnancy-associated plasma protein, signal transduction pathway, and cell adhesion. Further studies on the biological function and regulating mechanism of these genes will provide new clues for better understanding of etiology and pathogenesis of PE.

  6. Quantitative Immunohistochemical Analyses of the Expression of E-Cadherin, Thrombomodulin, CD44H and CD44v6 in Primary Tumours of pharynx/larynx Squamous Cell Carcinoma and their Lymph Node Metastases

    Directory of Open Access Journals (Sweden)

    Rocío Hernández Gaspar

    1999-01-01

    Full Text Available The quantitative expression of E‐cadherin, thrombomodulin, CD44H and CD44v6 in 32 specimens of primary tumours of pharynx/larynx squamous cell carcinoma and their lymph node metastases was studied by immunohistochemistry. With the aim of obtaining comparative and objective data, image acquisition conditions were kept unaltered for all the measurements and the immunostaining intensity was quantified by applying an image processing system. On the one hand, correlations were only observed between CD44H and CD44v6, both in primary tumours and metastases, and between E‐cadherin and TM in metastases. On the other hand, statistical analyses of paired data did not show significant differences in the expression of these markers between the two tumour sites. In agreement with previous reports, E‐cadherin expression was rather low or negative in primary tumours and metastases of the three poorly differentiated specimens we studied, as well as that of TM, but otherwise some of these samples showed intermediate immunostaining levels of CD44H/CD44v6. It may be concluded from the present study that the quantitative expression of these adhesion molecules in well established lymph node metastases of pharynx/larynx squamous cell carcinoma is essentially unaltered in relation to their primary sites.

  7. Expression and trafficking of placental microRNAs at the feto-maternal interface.

    Science.gov (United States)

    Chang, Guojing; Mouillet, Jean-François; Mishima, Takuya; Chu, Tianjiao; Sadovsky, Elena; Coyne, Carolyn B; Parks, W Tony; Surti, Urvashi; Sadovsky, Yoel

    2017-07-01

    During pregnancy, placental trophoblasts at the feto-maternal interface produce a broad repertoire of microRNA (miRNA) species. These species include miRNA from the primate-specific chromosome 19 miRNA cluster (C19MC), which is expressed nearly exclusively in the placenta. Trafficking of these miRNAs among the maternal, placental, and fetal compartments is unknown. To determine miRNA expression and trafficking patterns during pregnancy, we sequenced miRNAs in triads of human placenta and of maternal and fetal blood and found large subject-to-subject variability, with C19MC exhibiting compartment-specific expression. We therefore created humanized mice that transgenically express the entire 160-kb human C19MC locus or lentivirally express C19MC miRNA members selectively in the placenta. C19MC transgenic mice expressed a low level of C19MC miRNAs in diverse organs. When pregnant, female C19MC mice exhibited a strikingly elevated (>40-fold) expression of C19MC miRNA in the placenta, compared with other organs, that resembled C19MC miRNAs patterns in humans. Our mouse models showed that placental miRNA traffic primarily to the maternal circulation and that maternal miRNA can traffic to the placenta and even into the fetal compartment. These findings define an extraordinary means of nonhormonal, miRNA-based communication between the placenta and feto-maternal compartments.-Chang, G., Mouillet, J.-F., Mishima, T., Chu, T., Sadovsky, E., Coyne, C. B., Parks, W. T., Surti, U., Sadovsky, Y. Expression and trafficking of placental microRNAs at the feto-maternal interface. © FASEB.

  8. Placental Vitamin D-Binding Protein Expression in Human Idiopathic Fetal Growth Restriction

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    Alice F. Wookey

    2017-01-01

    Full Text Available Vitamin D-binding protein is a multifunctional serum protein with multiple actions related to normal health. Vitamin D-binding protein transports vitamin D and influences the metabolism of this key hormone but it also has additional immunomodulatory and actin-clearing properties. We investigated whether vitamin D-binding protein expression is altered in fetal growth restriction-associated placental dysfunction. Protein was extracted from 35 placentae derived from 17 healthy control subjects and 18 gestation-matched subjects with fetal growth restriction (FGR. FGR subjects were further subdivided as idiopathic (n=9 and nonidiopathic (n=9. Vitamin D-binding protein and 25(OH vitamin D were measured by ELISA and normalized to protein concentration. The results showed significantly reduced levels of placental vitamin D-binding protein (control versus FGR, p<0.05, Student’s t-test that were strongly associated with idiopathic fetal growth restriction (p<0.01, Kruskal-Wallis, whereas levels of vitamin D-binding protein were not associated with placental 25(OH vitamin D stores (p=0.295, Pearson’s correlation. As such, vitamin D-binding protein may be a factor in unexplained placental dysfunction associated with idiopathic fetal growth restriction and may potentially serve as a biomarker of this disease.

  9. Differential mouse-strain specific expression of Junctional Adhesion Molecule (JAM)-B in placental structures.

    Science.gov (United States)

    Stelzer, Ina Annelies; Mori, Mayumi; DeMayo, Francesco; Lydon, John; Arck, Petra Clara; Solano, Maria Emilia

    2016-03-03

    The junctional adhesion molecule (JAM)-B, a member of the immunoglobulin superfamily, is involved in stabilization of interendothelial cell-cell contacts, formation of vascular tubes, homeostasis of stem cell niches and promotion of leukocyte adhesion and transmigration. In the human placenta, JAM-B protein is abundant and mRNA transcripts are enriched in first-trimester extravillous trophoblast in comparison to the villous trophoblast. We here aimed to elucidate the yet unexplored spatio-temporal expression of JAM-B in the mouse placenta. We investigated and semi-quantified JAM-B protein expression by immunohistochemistry in early post-implantation si tes and in mid- to late gestation placentae of various murine mating combinations. Surprisingly, the endothelium of the placental labyrinth was devoid of JAM-B expression. JAM-B was mainly present in spongiotrophoblast cells of the junctional zone, as well as in the fetal vessels of the chorionic plate, the umbilical cord and in maternal myometrial smooth muscle. We observed a strain-specific placental increase of JAM-B protein expression from mid- to late gestation in Balb/c-mated C57BL/6 females, which was absent in DBA/2J-mated Balb/c females. Due to the essential role of progesterone during gestation, we further assessed a possible modulation of JAM-B in mid-gestational placentae deficient in the progesterone receptor (Pgr(-/-)) and observed an increased expression of JAM-B in Pgr(-/-) placentae, compared to Pgr(+/+) tissue samples. We propose that JAM-B is an as yet underappreciated trophoblast lineage-specific protein, which is modulated via the progesterone receptor and shows unique strain-specific kinetics. Future work is needed to elucidate its possible contribution to placental processes necessary to ensuring its integrity, ultimately facilitating placental development and fetal growth.

  10. Regulation of leptin expression by 17beta-estradiol in human placental cells involves membrane associated estrogen receptor alpha.

    Science.gov (United States)

    Gambino, Yésica P; Pérez Pérez, Antonio; Dueñas, José L; Calvo, Juan Carlos; Sánchez-Margalet, Víctor; Varone, Cecilia L

    2012-04-01

    The placenta produces a wide number of molecules that play essential roles in the establishment and maintenance of pregnancy. In this context, leptin has emerged as an important player in reproduction. The synthesis of leptin in normal trophoblastic cells is regulated by different endogenous biochemical agents, but the regulation of placental leptin expression is still poorly understood. We have previously reported that 17β-estradiol (E(2)) up-regulates placental leptin expression. To improve the understanding of estrogen receptor mechanisms in regulating leptin gene expression, in the current study we examined the effect of membrane-constrained E(2) conjugate, E-BSA, on leptin expression in human placental cells. We have found that leptin expression was induced by E-BSA both in BeWo cells and human placental explants, suggesting that E(2) also exerts its effects through membrane receptors. Moreover E-BSA rapidly activated different MAPKs and AKT pathways, and these pathways were involved in E(2) induced placental leptin expression. On the other hand we demonstrated the presence of ERα associated to the plasma membrane of BeWo cells. We showed that E(2) genomic and nongenomic actions could be mediated by ERα. Supporting this idea, the downregulation of ERα level through a specific siRNA, decreased E-BSA effects on leptin expression. Taken together, these results provide new evidence of the mechanisms whereby E(2) regulates leptin expression in placenta and support the importance of leptin in placental physiology.

  11. Immunohistochemical Expression of Myeloperoxidase in Placental Samples of Systematic Lupus Erythematosus Pregnancies

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    Zahra Heidari

    2016-08-01

    Full Text Available Objective: Reports of increased level of Myeloperoxidase (MPO in plasma and placental extracts of Systematic Lupus Erythematosus (SLE has been proposed that MPO may have an important role in this pregnancy complication. In present study immunohistochemical MPO expression was investigated in placental samples of SLE women compared with normal controls.Materials and methods: Ten patients with SLE were recruited as case group. Control group was selected from mothers with normal uncomplicated pregnancies. A monoclonal antibody specific for MPO was used for immunohistochemical staining and then the staining was quantified and differences between groups were compared using Mann-Whitney U test.Results: There were significant differences in the expression levels of MPO in the syncytiotrophoblast cells and the extravillous trophoblast cells between the control and SLE groups (p < 0.05. There were no significant differences in the expression level of MPO in the vascular endothelium and the relative number of the MPO-positive leukocytes in placental tissue between SLE and control groups (p > 0.05.Conclusion: The present study showed that MPO expression is increased in syncytiotrophoblast cells and the extravillous trophoblast cells of SLE placentas compared to healthy subjects. It seems that these changes are able to impress structure and function of placenta and survival of the fetus.

  12. Unusual interleukin-1 and -6 expression in fetal cartilage is associated with placental abnormalities.

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    Robert Klepacz

    2010-06-01

    Full Text Available Unusual expression of interleukin-1alpha, -1beta and -6 was previously found in the epiphyseal cartilage of rat fetuses prenatally exposed to various non-steroidal anti-inflammatory drugs (NSAID, i.e., ibuprofen, piroxicam, tolmetin and selective cyclooxygenase-2 inhibitor (DFU. The aim of the present study was to evaluate the role of placenta in such phenomenon. Morphology of the organ, thickness of basal and labyrinth layer, immunoexpression of COX isoenzymes were examined, and confronted with maternal biochemical data and fetal developmental parameters. Higher maternal urea level, as well as lower placental weight and labyrinth thickness were found in the group of fetuses who revealed expression of genes coded the selected interleukins, when compared with the xenobiotic-exposed pups without the selected genes expression and untreated control. A significant correlation between placental weight and maternal total protein or urea level was revealed. Histological changes like inflammatory infiltration and calcification were observed sporadically. Location and intensity of COX-1 staining was similar in all cases. However, more intense COX-2 staining for majority of cells of the basal zone and in dispersed giant cells of the labyrinth was found in inflamed organs. It could be concluded that abnormal expression of the selected interleukins is associated with low placental weight and decrease of its thickness, especially labyrinth zone, as well as with high maternal urea level.

  13. Placental triglyceride accumulation in maternal type 1 diabetes is associated with increased lipase gene expression

    DEFF Research Database (Denmark)

    Lindegaard, Marie Louise Skakkebæk; Damm, Peter; Mathiesen, Elisabeth R

    2006-01-01

    RNA expression of lipoprotein lipase and lysosomal lipase were similar in women with diabetes and the control group. Immunohistochemistry showed EL protein in syncytiotrophoblasts facing the maternal blood and endothelial cells facing the fetal blood in placentas from both normal women and women with diabetes......Maternal diabetes can cause fetal macrosomia and increased risk of obesity, diabetes, and cardiovascular disease in adulthood of the offspring. Although increased transplacental lipid transport could be involved, the impact of maternal type 1 diabetes on molecular mechanisms for lipid transport...... in placenta is largely unknown. To examine whether maternal type 1 diabetes affects placental lipid metabolism, we measured lipids and mRNA expression of lipase-encoding genes in placentas from women with type 1 diabetes (n = 27) and a control group (n = 21). The placental triglyceride (TG) concentration...

  14. Both pituitary and placental growth hormone transcripts are expressed in human peripheral blood mononuclear cells (PBMC)

    NARCIS (Netherlands)

    Melen, L; Hennen, G; Dullaart, RPF; Igout, A

    1997-01-01

    The hGH-V gene codes for a variant of human pituitary growth hormone (hGH-N) named placental growth hormone (hPGH). hPGH shares 93% amino acid identity with hGH-N. Until now the hGH-V gene was considered to be exclusively expressed in human placenta, where it replaces maternal circulating hGH-N at t

  15. Placental Lactogen Is Expressed but Is Not Translated into Protein in Breast Cancer

    OpenAIRE

    2014-01-01

    Introduction Several studies reported that the pregnancy-specific hormone placental lactogen (hPL) is expressed at both mRNA and protein levels in breast cancer. The overall objective was to establish hPL, the product of the CSH1 and CSH2 genes, as a biomarker for breast cancer. Methods CSH expression was determined at the mRNA level in breast cancer cell lines (BCC) and primary carcinomas by real-time and conventional PCR and the products verified as CSH1 by sequencing. Expression of hPL pro...

  16. IL-10 inhibits while calcitriol reestablishes placental antimicrobial peptides gene expression.

    Science.gov (United States)

    Olmos-Ortiz, Andrea; Noyola-Martínez, Nancy; Barrera, David; Zaga-Clavellina, Verónica; Avila, Euclides; Halhali, Ali; Biruete, Benjamín; Larrea, Fernando; Díaz, Lorenza

    2015-04-01

    IL-10 and calcitriol help to achieve a successful pregnancy by suppressing active maternal immunity; however, these factors exert opposite effects upon microbial infections. In the skin and immune cells, IL-10 downregulates β-defensins while calcitriol induces cathelicidin gene expression in various tissues including placenta. Though, the regulation of human placental β-defensins by IL-10 and calcitriol has not been studied. Therefore, we explored the regulation of these antimicrobial peptides expression in cultured placental cells by calcitriol and IL-10 alone and combined. Real time PCR showed that calcitriol stimulated, while IL-10 inhibited, β-defensins and cathelicidin gene expression (Pantimicrobial peptides gene expression above control values, overriding IL-10 inhibitory effects. Calcitriol downregulated endogenous IL-10 secretion. Interestingly, calcitriol and TNF-α cooperatively enhanced β-defensins, while TNF-α reduced basal and calcitriol-stimulated cathelicidin gene expression. In summary, calcitriol and IL-10 exerted opposite effects on antimicrobial peptides expression in the human placenta, suggesting that unbalanced production of IL-10 and calcitriol could be deleterious to innate immune responses during gestation. Our results suggest that calcitriol enhancement of placental defenses involves two mechanisms: (1) downregulation of IL-10 secretion and (2) direct upregulation of β-defensins and cathelicidin gene expression. Considering that IL-10 and calcitriol differentially regulate the innate immune response in the placenta, in the case of an infection, calcitriol might restrict IL-10 permissive actions towards microbial invasion while restrains inflammation, allowing for pregnancy to continue in quiescence. These results strongly advice maternal vitamin D sufficiency during pregnancy.

  17. Embryonic IGF2 expression is not associated with offspring size among populations of a placental fish.

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    Matthew Schrader

    Full Text Available In organisms that provision young between fertilization and birth, mothers and their developing embryos are expected to be in conflict over embryonic growth. In mammalian embryos, the expression of Insulin-like growth factor II (IGF2 plays a key role in maternal-fetal interactions and is thought to be a focus of maternal-fetal conflict. Recent studies have suggested that IGF2 is also a focus of maternal-fetal conflict in placental fish in the family Poeciliidae. However, whether the expression of IGF2 influences offspring size, the trait over which mothers and embryos are likely to be in conflict, has not been assessed in a poeciliid. We tested whether embryonic IGF2 expression varied among four populations of a placental poeciliid that display large and consistent differences in offspring size at birth. We found that IGF2 expression varied significantly among embryonic stages with expression being 50% higher in early stage embryos than late stage embryos. There were no significant differences among populations in IGF2 expression; small differences in expression between population pairs with different offspring sizes were comparable in magnitude to those between population pairs with the same offspring sizes. Our results indicate that variation in IGF2 transcript abundance does not contribute to differences in offspring size among H. formosa populations.

  18. Maternal Factors Are Associated with the Expression of Placental Genes Involved in Amino Acid Metabolism and Transport.

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    Pricilla E Day

    Full Text Available Maternal environment and lifestyle factors may modify placental function to match the mother's capacity to support the demands of fetal growth. Much remains to be understood about maternal influences on placental metabolic and amino acid transporter gene expression. We investigated the influences of maternal lifestyle and body composition (e.g. fat and muscle content on a selection of metabolic and amino acid transporter genes and their associations with fetal growth.RNA was extracted from 102 term Southampton Women's Survey placental samples. Expression of nine metabolic, seven exchange, eight accumulative and three facilitated transporter genes was analyzed using quantitative real-time PCR.Increased placental LAT2 (p = 0.01, y+LAT2 (p = 0.03, aspartate aminotransferase 2 (p = 0.02 and decreased aspartate aminotransferase 1 (p = 0.04 mRNA expression associated with pre-pregnancy maternal smoking. Placental mRNA expression of TAT1 (p = 0.01, ASCT1 (p = 0.03, mitochondrial branched chain aminotransferase (p = 0.02 and glutamine synthetase (p = 0.05 was positively associated with maternal strenuous exercise. Increased glutamine synthetase mRNA expression (r = 0.20, p = 0.05 associated with higher maternal diet quality (prudent dietary pattern pre-pregnancy. Lower LAT4 (r = -0.25, p = 0.05 and aspartate aminotransferase 2 mRNA expression (r = -0.28, p = 0.01 associated with higher early pregnancy diet quality. Lower placental ASCT1 mRNA expression associated with measures of increased maternal fat mass, including pre-pregnancy BMI (r = -0.26, p = 0.01. Lower placental mRNA expression of alanine aminotransferase 2 associated with greater neonatal adiposity, for example neonatal subscapular skinfold thickness (r = -0.33, p = 0.001.A number of maternal influences have been linked with outcomes in childhood, independently of neonatal size; our finding of associations between placental expression of transporter and metabolic genes and maternal smoking

  19. Maternal Factors Are Associated with the Expression of Placental Genes Involved in Amino Acid Metabolism and Transport.

    Science.gov (United States)

    Day, Pricilla E; Ntani, Georgia; Crozier, Sarah R; Mahon, Pam A; Inskip, Hazel M; Cooper, Cyrus; Harvey, Nicholas C; Godfrey, Keith M; Hanson, Mark A; Lewis, Rohan M; Cleal, Jane K

    2015-01-01

    Maternal environment and lifestyle factors may modify placental function to match the mother's capacity to support the demands of fetal growth. Much remains to be understood about maternal influences on placental metabolic and amino acid transporter gene expression. We investigated the influences of maternal lifestyle and body composition (e.g. fat and muscle content) on a selection of metabolic and amino acid transporter genes and their associations with fetal growth. RNA was extracted from 102 term Southampton Women's Survey placental samples. Expression of nine metabolic, seven exchange, eight accumulative and three facilitated transporter genes was analyzed using quantitative real-time PCR. Increased placental LAT2 (p = 0.01), y+LAT2 (p = 0.03), aspartate aminotransferase 2 (p = 0.02) and decreased aspartate aminotransferase 1 (p = 0.04) mRNA expression associated with pre-pregnancy maternal smoking. Placental mRNA expression of TAT1 (p = 0.01), ASCT1 (p = 0.03), mitochondrial branched chain aminotransferase (p = 0.02) and glutamine synthetase (p = 0.05) was positively associated with maternal strenuous exercise. Increased glutamine synthetase mRNA expression (r = 0.20, p = 0.05) associated with higher maternal diet quality (prudent dietary pattern) pre-pregnancy. Lower LAT4 (r = -0.25, p = 0.05) and aspartate aminotransferase 2 mRNA expression (r = -0.28, p = 0.01) associated with higher early pregnancy diet quality. Lower placental ASCT1 mRNA expression associated with measures of increased maternal fat mass, including pre-pregnancy BMI (r = -0.26, p = 0.01). Lower placental mRNA expression of alanine aminotransferase 2 associated with greater neonatal adiposity, for example neonatal subscapular skinfold thickness (r = -0.33, p = 0.001). A number of maternal influences have been linked with outcomes in childhood, independently of neonatal size; our finding of associations between placental expression of transporter and metabolic genes and maternal smoking

  20. Expression of glucocorticoid receptor and glucose transporter-1 during placental development in the diabetic rat

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    Ramazan Demir

    2011-07-01

    Full Text Available In various tissues, glucocorticoids (GCs are known to downregulate glucose transport systems; however, their effects on glucose transporters (GLUTs in the placenta of a diabetic rat are unknown. Glucocorticoid hormone action within the cell is regulated by the glucocorticoid receptor (GR. Thus, this study was designed to investigate the relationship between GR and glucose transporter expression in the placenta of the diabetic rat. Our immunohistochemical results indicated that GR and glucose transporter protein 1 (GLUT 1 are expressed ubiquitously in the trophoblast and endothelial cells of the labyrinthine zone, where maternal fetal transport takes place in the rat placenta. Expression of GR in the junctional zone of the rat placenta was detected in giant cells, and in some spongiotrophoblast cells, but not in the glycogen cells. GLUT 1 was present, especially in glycogen cells during early pregnancy, and in the spongiotrophoblast cells of the junctional zone during late pregnancy. Amounts of GR and GLUT 1 protein were increased towards the end of gestation both in the control and the diabetic placenta. However, at days 17 and 19 of gestation, only the placental GR protein was significantly increased in the streptozotocin-induced diabetic rats compared to control rats. Diabetes led to a significant decrease in placental weight at gestation day 15. In contrast, at gestational days 17 and 21, the weights of the diabetic placenta were significantly increased as compared with the controls. Moreover, diabetes induced fetus intrauterine growth retardation at gestational days 13, 17 and 21. In conclusion, the localization pattern of GR and GLUT 1 proteins in the same cell types led us to believe that there might be a relationship between GR and GLUT 1 expressions at the cellular level. GLUT 1 does not play a pivotal role in diabetic pregnancies. However, placental growth abnormalities during diabetic pregnancy may be related to the amount of GR

  1. First Trimester Pregnancy Loss and the Expression of alternatively spliced NKp30 isoforms in Maternal Blood and Placental Tissue

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    Avishai eShemesh

    2015-06-01

    Full Text Available In this study, we aimed to investigate whether first trimester pregnancy loss is associated with differences in expression of NKp30 splice variants (isoforms in maternal peripheral blood or placental tissue. We conducted a prospective case-control study; a total of 33 women undergoing dilation and curettage due to first trimester pregnancy loss were further subdivided into groups with sporadic or recurrent pregnancy loss. The control group was comprised of women undergoing elective termination of pregnancy. The qPCR approach was employed to assess the relative expression of NKp30 isoforms as well as the total expression of NKp30 and NKp46 receptors between the selected groups. Results show that in both PBMC and placental tissue, NKp46 and NKp30 expression was mildly elevated in the pregnancy loss groups compared with the elective group. In particular, NKp46 elevation was significant. Moreover, expression analysis of NKp30 isoforms manifested a different profile between PBMC and the placenta. NKp30-a and NKp30-b isoforms in the placental tissue, but not in PBMC, showed a significant increase in the pregnancy loss groups compared with the elective group. Placental expression of NKp30 activating isoforms -a and -b in the pregnancy loss groups was negatively correlated with PLGF expression. In contrast, placental expression of these isoforms in the elective group was positively correlated with TNFα, IL-10 and VEGF-A expression. The altered expression of NKp30 activating isoforms in placental tissue from patients with pregnancy loss compared to the elective group and the different correlations with cytokine expression point to the involvement of NKp30-mediated function in pregnancy loss.

  2. Triamcinolone up-regulates GLUT 1 and GLUT 3 expression in cultured human placental endothelial cells.

    Science.gov (United States)

    Kipmen-Korgun, Dijle; Ozmen, Asli; Unek, Gozde; Simsek, Mehmet; Demir, Ramazan; Korgun, Emin Turkay

    2012-01-01

    The placenta is a glucocorticoid target organ, and glucocorticoids (GCs) are essential for the development and maturation of fetal organs. They are widely used for treatment of a variety of diseases during pregnancy. In various tissues, GCs have regulated by glucose transport systems; however, their effects on glucose transporters in the human placental endothelial cells (HPECs) are unknown. In the present study, HPECs were cultured 24 h in the presence or absence of 0.5, 5 and 50 µmol · l(-1) of synthetic GC triamcinolone (TA). The glucose carrier proteins GLUT 1, GLUT 3 and GC receptor (GR) were detected in the HPECs. We showed increased expression of GLUT 1 and GLUT 3 proteins and messenger RNA (mRNA) levels (p GLUT 1 and GLUT 3 expression through GR. Excessive exposure to GCs causes maternal and fetal hypoglycemia and diminished fetal growth. We speculate that to compensate for fetal hypoglycemia and diminished fetal growth, the expression of placental endothelial glucose transporters might be increased.

  3. Expression of Organic Anion Transporting Polypeptide 1c1 and Monocarboxylate Transporter 8 in the Rat Placental Barrier and the Compensatory Response to Thyroid Dysfunction

    OpenAIRE

    Yi-na Sun; Yuan-jun Liu; Lu Zhang; Yan Ye; Lai-xiang Lin; Yong-mei Li; Yu-qin Yan; Zu-pei Chen

    2014-01-01

    Thyroid hormones (THs) must pass from mother to fetus for normal fetal development and require the expression of placental TH transporters. We investigate the compensatory effect of placental organic anion transporting polypeptide 1c1 (Oatp1c1) and monocarboxylate transporter 8 (Mct8) on maternal thyroid dysfunction. We describe the expressions of these two transporters in placental barriers and trophoblastic cell populations in euthyroidism and thyroid dysfunction resulting from differential...

  4. Altered expression of mitochondrial related genes in the native Tibetan placents by mitochondrial cDNA array analysis

    Institute of Scientific and Technical Information of China (English)

    Luo Yongjun; Gao Wenxiang; Zhao Xiuxin; Suo Lang; Chen Li; Liu Fuyu; Song Tonglin; Chen Jian; Gao Yuqi

    2009-01-01

    Objective: To explore the mechanism of native Tibetan fetuses adaptation to hypoxia, we tried to find the different expression genes about mitochondrial function in the native Tibetan placents. Methods: In this study, the placents of native Tibetan and the high-altitude Han (ha-Han) were collected. After the total RNA extraction, the finally synthesized cDNAs were hybridized to mitochondrial array to find the altered expression genes between them. Then, the cytochrome c oxidase 17 (Coxl7), dynactin 2 (DCTN2, also known as p50), and vascular endothelial growth factor receptor (VEGFR, also known as KDR) were chosen from the altered expression genes to further verify the array results using the SYBR Green real-time PCR. Because the altered expression genes (such as Cybb and Coxl 7) in the array results related to the activities of COXI and COXIV, the placental mitochondria activities of COXI and COXIV were measured to find their changes in the hypoxia. Results: By a standard of >1.5 or <0.67, there were 24 different expressed genes between the native Tibetan and the ha-Han placents, including 3 up-regulated genes and 21 down-regulated genes. These genes were related to energy metabolism, signal transduction, cell proliferation, electron transport, cell adhesion, nucleotide-excision repair. The array results of Coxl7, DCTN2 and KDR were further verified by the real-time RT-PCR. Through the mitochondria respiration measurements, the activity of COXI in the native Tibetan placents were higher than that of ha-Han, there was no difference in COXIV activity between them. Conclusion: The altered mitochondrial related genes in the native Tibetan placents may have a role in the high altitude adaptation for fetuses through changing the activity of mitochondrial COX.

  5. Expression of Leptin In Early Placental Development- Its Association With Maternal Nutritional Status

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    Babu JJ Geddam

    2012-07-01

    Full Text Available Background: Placenta is a transient embryonic organ of communication between mother and fetus during pregnancy and is the only channel for transfer of nutrition as well as other factors from mother to fetus. Placental tissues from humans contain leptin and its receptors. As already known leptin is an endocrine hormone and growth factor that is important for the regulation of body fat, feeding and energy homeostasis and also plays a crucial role. Objectives: To assess and compare the expression of leptin in the products of consumption during early gestation (5 to 12 weeks from mothers of low and high socioeconomic status groups (LSEG and HSEG and to relate to their nutritional status. Material: Products of conception obtained at 5 to 12 weeks of gestation, from healthy women undergoing medical termination of pregnancy constituted the study material. Methodology: A total about 18 placental samples from low and 11 from high socio economic group (HSEG were examined. Products of conception obtained from the scrapings of basal plate after vacuum extraction following termination of pregnancy were stored in formalin. Sections from basal plate were selected and stained for leptin. Imuuno histochemical stained sections were studied for percentage of villi, percentage of cytotrophoblast and percentage of stained positive blood vessels as well as intensity of staining pattern were carried out by using kits (Santa Cruz, Biotechnology, California. Nutritional status of the subjects were measured by recording weight, height, hemoglobin, serum retinol, serum folic acid and serum zinc levels. Results: Percentage of villi staining positively for leptin was significantly higher 80.7% (P<0.05 in the undernourished group when compared to well nourished 70.8% but expression of leptin in Cytotrophoblast (CTB was significantly 59.7% (P<0.05 higher in well-nourished group. Conclusion: Expression of leptin in villi was significantly higher in the undernourished groups as

  6. Influence of cloning by chromatin transfer on placental gene expression at Day 45 of pregnancy in cattle.

    Science.gov (United States)

    Mesquita, Fernando S; Machado, Sergio A; Drnevich, Jenny; Borowicz, Pawel; Wang, Zhongde; Nowak, Romana A

    2013-01-30

    Poor success rates in somatic cell cloning are often attributed to abnormal early embryonic development as well as late abnormal fetal growth and placental development. Although promising results have been reported following chromatin transfer (CT), a novel cloning method that includes the remodeling of the donor nuclei in vitro prior to their transfer into enucleated oocytes, animals cloned by CT show placental abnormalities similar to those observed following conventional nuclear transfer. We hypothesized that the placental gene expression pattern from cloned fetuses was ontologically related to the frequently observed placental phenotype. The aim of the present study was to compare global gene expression by microarray analysis of Day 44-47 cattle placentas derived from CT cloned fetuses with those derived from in vitro fertilization (i.e. control), and confirm the altered mRNA and protein expression of selected molecules by qRT-PCR and immunohistochemistry, respectively. The differentially expressed genes identified in the present study are known to be involved in a range of activities associated with cell adhesion, cell cycle control, intracellular transport and proteolysis. Specifically, an imprinted gene, involved with cell proliferation and placentomegaly in humans (CDKN1C) and a peptidase that serves as a marker for non-invasive trophoblast cells in human placentas (DPP4), had mRNA and protein altered in CT placentas. It was concluded that the altered pattern of gene expression observed in CT samples may contribute to the abnormal placental development phenotypes commonly identified in cloned offspring, and that expression of imprinted as well as trophoblast invasiveness-related genes is altered in cattle cloned by CT.

  7. Placental Nkx2-5 and target gene expression in early-onset and severe preeclampsia.

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    Rivers, Elena R; Horton, Anthony J; Hawk, Angela F; Favre, Elizabeth G; Senf, Katherine M; Nietert, Paul J; Chang, Eugene Y; Foley, Ann C; Robinson, Christopher J; Lee, Kyu-Ho

    2014-11-01

    Preeclampsia (PE) affects 2-8% of pregnancies worldwide and is a significant source of maternal and neonatal morbidity and mortality. However, the mechanisms underlying PE are poorly understood and major questions regarding etiology and risk factors remain to be addressed. Our objective was to examine whether abnormal expression of the cardiovascular developmental transcription factor, Nkx2-5, was associated with early onset and severe preeclampsia (EOSPE). Using qPCR and immunohistochemical assay, we examined expression of Nkx2-5 and target gene expression in EOSPE and control placental tissue. We tested resulting mechanistic hypotheses in cultured cells using shRNA knockdown, qPCR, and western blot. Nkx2-5 is highly expressed in racially disparate fashion (Caucasians > African Americans) in a subset of early EOSPE placentae. Nkx2-5 mRNA expression is highly correlated (Caucasians > African Americans) to mRNA expression of the preeclampsia marker sFlt-1, and of the Nkx2-5 target and RNA splicing factor, Sam68. Knockdown of Sam68 expression in cultured cells significantly impacts sFlt-1 mRNA isoform generation in vitro, supporting a mechanistic hypothesis that Nkx2-5 impacts EOSPE severity in a subset of patients via upregulation of Sam68 to increase sFlt-1 expression. Expression of additional Nkx2-5 targets potentially regulating metabolic stress response is also elevated in a racially disparate fashion in EOSPE. Expression of Nkx2-5 and its target genes may directly influence the genesis and racially disparate severity, and define a mechanistically distinct subclass of EOSPE.

  8. The effects of antenatal depression and antidepressant treatment on placental gene expression

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    Jocelien DA Olivier

    2015-01-01

    Full Text Available The effects of antenatal depression and antidepressant treatment during pregnancy on both mother and child are vigorously studied, but the underlying biology for these effects is largely unknown. The placenta plays a crucial role in the growth and development of the fetus. We performed a gene expression study on the fetal side of the placenta to investigate gene expression patterns in mothers with antenatal depression and in mothers using antidepressant treatment during pregnancy.Placental samples from mothers with normal pregnancies, from mothers with antenatal depression, and from mothers using antidepressants were collected. We performed a pilot microarray study to investigate alterations in the gene expression and selected several genes from the microarray for biological validation with qPCR in a larger sample.In mothers with antenatal depression 108 genes were differentially expressed, whereas 109 genes were differentially expressed in those using antidepressants. Validation of the microarray revealed more robust gene expression differences in the seven genes picked for confirmation in antidepressant-treated women than in depressed women. Among the genes that were validated ROCK2 and C12orf39 were differentially expressed in both depressed and antidepressant-treated women, whereas ROCK1, GCC2, KTN1, and DNM1L were only differentially expressed in the antidepressant-treated women. In conclusion, antenatal depression and antidepressant exposure during pregnancy are associated with altered gene expression in the placenta. Findings on those genes picked for validation were more robust among antidepressant-treated women than in depressed women, possibly due to the fact that depression is a multifactorial condition with varying degrees of endocrine disruption. It remains to be established whether the alterations found in the gene expression of the placenta are found in the fetus as well.

  9. The role of thrombomodulin lectin-like domain in inflammation

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    Li Yi-Heng

    2012-03-01

    Full Text Available Abstract Thrombomodulin (TM is a cell surface glycoprotein which is widely expressed in a variety of cell types. It is a cofactor for thrombin binding that mediates protein C activation and inhibits thrombin activity. In addition to its anticoagulant activity, recent evidence has revealed that TM, especially its lectin-like domain, has potent anti-inflammatory function through a variety of molecular mechanisms. The lectin-like domain of TM plays an important role in suppressing inflammation independent of the TM anticoagulant activity. This article makes an extensive review of the role of TM in inflammation. The molecular targets of TM lectin-like domain have also been elucidated. Recombinant TM protein, especially the TM lectin-like domain may play a promising role in the management of sepsis, glomerulonephritis and arthritis. These data demonstrated the potential therapeutic role of TM in the treatment of inflammatory diseases.

  10. Thrombomodulin: A Bifunctional Modulator of Inflammation and Coagulation in Sepsis

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    Takayuki Okamoto

    2012-01-01

    Full Text Available Deregulated interplay between inflammation and coagulation plays a pivotal role in the pathogenesis of sepsis. Therapeutic approaches that simultaneously target both inflammation and coagulation hold great promise for the treatment of sepsis. Thrombomodulin is an endogenous anticoagulant protein that, in cooperation with protein C and thrombin-activatable fibrinolysis inhibitor, serves to maintain the endothelial microenvironment in an anti-inflammatory and anticoagulant state. A recombinant soluble form of thrombomodulin has been approved to treat patients suffering from disseminated intravascular coagulation (DIC and has thus far shown greater therapeutic potential than heparin. A phase II clinical trial is currently underway in the USA to study the efficacy of thrombomodulin for the treatment of sepsis with DIC complications. This paper focuses on the critical roles that thrombomodulin plays at the intersection of inflammation and coagulation and proposes the possible existence of interactions with integrins via protein C. Finally, we provide a rationale for the clinical application of thrombomodulin for alleviating sepsis.

  11. HCG concentration and receptor gene expression in placental tissue from trisomy 18 and 21.

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    Jauniaux, E; Bao, S; Eblen, A; Li, X; Lei, Z M; Meuris, S; Rao, C V

    2000-01-01

    Trisomy 21 is associated with high maternal serum concentrations of intact human chorionic gonadotrophin alpha(HCG) and free beta-HCG whereas these concentrations are markedly decreased in trisomy 18. In this study, we investigated the effect of trisomy 21 and 18 on endogenous HCG concentrations and luteinizing hormone (LH)/HCG receptor expression in placental villous tissue in eight trisomy 21, six trisomy 18 and 42 chromosomally normal samples, collected at 12-16 weeks gestation. The tissue concentrations of intact HCG, free alpha-HCG and free beta-HCG subunits were measured using solid-phase two-site immunoradiometric assay. LH/HCG receptor expression was evaluated with immunohistochemistry and in-situ hybridization. Villous tissue in trisomy 21 contained higher beta-HCG concentrations than the controls (P trisomy 18 cases, the beta-HCG concentration was lower than in the control group (P trisomy 21 and 18, compared with controls with the strongest signal in cases of trisomy 18 (P trisomy 21 the high tissue HCG concentration and expression of LH/HCG receptor in the trophoblast may reflect the relative immaturity of the trophoblastic tissue whereas in trisomy 18, the very low concentration of endogenous HCG, associated with an over-expression of LH/HCG receptor in the trophoblast, is probably secondary to the poor differentiation of the cytotrophoblast.

  12. Altered expression of adipose differentiation-related protein gene in placental tissue of pre-eclampsia

    Institute of Scientific and Technical Information of China (English)

    ZHANG Chun-li; YAO Yuan-qing; LI Dong-hong; ZHANG Wei

    2006-01-01

    Objective: To investigate the altered expression of lipid metabolism-related gene adipose differentiation-related protein (ADRP) in pre-eclampsia. Methods: Semi-quantitative RT-PCR and Western blotting were used to validate the altered expression of ADRP gene between pre-eclamptic placentas (preeclampsia group) and normotensive placentas (control group) respectively. In situ hybridization (ISH)was used to localize ADRP mRNA in pre-eclamptic placentas. Results: There was a significant difference in the levels of placental ADRP mRNA between pre-eclampsia group and control group (1.98± 0. 50 vs 1. 09±0. 20, P<0.01). Western blotting showed that placentas both in pre-eclampsia group and control group expressed the special ADRP band at 48. 1 kD. The relative levels of ADRP protein in pre-eclampsia group were significantly higher than those of control group (0. 40 ±0. 19 vs 0. 19 ±0. 09, P< 0. 01).ADRP mRNA was diffusely distributed in pre-eclamptic placentas. Their positive staining existed in cytoplasm of trophoblast. Conclusion: Abnormal expression of ADRP gene in pre-eclamptic placenta may be associated with the pathogenesis of pre-eclampsia.

  13. Placental lactogen is expressed but is not translated into protein in breast cancer.

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    Traci R Tuttle

    Full Text Available Several studies reported that the pregnancy-specific hormone placental lactogen (hPL is expressed at both mRNA and protein levels in breast cancer. The overall objective was to establish hPL, the product of the CSH1 and CSH2 genes, as a biomarker for breast cancer.CSH expression was determined at the mRNA level in breast cancer cell lines (BCC and primary carcinomas by real-time and conventional PCR and the products verified as CSH1 by sequencing. Expression of hPL protein was examined by western blots and immuno-histochemistry, using commercial and custom-made polyclonal and monoclonal antibodies.Variable levels of CSH mRNA were detected in several BCC, and in some primary tumors. We detected a protein, slightly larger than recombinant hPL by western blotting using several antibodies, leading us to postulate that it represents an hPL variant ('hPL'. Furthermore, some monoclonal antibodies detected 'hPL' by immunohistochemistry in breast carcinomas but not in normal breast. However, further examination revealed that these antibodies were non-specific, as efficient suppression of CSH mRNA by shRNA did not abolish the 'hPL' band. Custom-made monoclonal antibodies against recombinant hPL detected hPL of the correct size in placental lysate and hPL-overexpressing BCC, but not in unmodified cells or primary carcinomas. hPL protein was detected only when mRNA was increased several thousand fold.We call into question previous reports of hPL expression in breast cancer which relied on mRNA levels as surrogates for protein and/or used improperly validated antibodies to measure hPL protein levels. Our data suggests that an inhibitory mechanism(s prevents translation of CSH mRNA in breast cancer when not highly expressed. The mechanism by which translation of CSH mRNA is inhibited is intriguing and should be further investigated.

  14. Placental Lactogen Is Expressed but Is Not Translated into Protein in Breast Cancer

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    Tuttle, Traci R.; Hugo, Eric R.; Tong, Wilson S.; Ben-Jonathan, Nira

    2014-01-01

    Introduction Several studies reported that the pregnancy-specific hormone placental lactogen (hPL) is expressed at both mRNA and protein levels in breast cancer. The overall objective was to establish hPL, the product of the CSH1 and CSH2 genes, as a biomarker for breast cancer. Methods CSH expression was determined at the mRNA level in breast cancer cell lines (BCC) and primary carcinomas by real-time and conventional PCR and the products verified as CSH1 by sequencing. Expression of hPL protein was examined by western blots and immuno-histochemistry, using commercial and custom-made polyclonal and monoclonal antibodies. Results Variable levels of CSH mRNA were detected in several BCC, and in some primary tumors. We detected a protein, slightly larger than recombinant hPL by western blotting using several antibodies, leading us to postulate that it represents an hPL variant (‘hPL’). Furthermore, some monoclonal antibodies detected ‘hPL’ by immunohistochemistry in breast carcinomas but not in normal breast. However, further examination revealed that these antibodies were non-specific, as efficient suppression of CSH mRNA by shRNA did not abolish the ‘hPL’ band. Custom-made monoclonal antibodies against recombinant hPL detected hPL of the correct size in placental lysate and hPL-overexpressing BCC, but not in unmodified cells or primary carcinomas. hPL protein was detected only when mRNA was increased several thousand fold. Conclusions We call into question previous reports of hPL expression in breast cancer which relied on mRNA levels as surrogates for protein and/or used improperly validated antibodies to measure hPL protein levels. Our data suggests that an inhibitory mechanism(s) prevents translation of CSH mRNA in breast cancer when not highly expressed. The mechanism by which translation of CSH mRNA is inhibited is intriguing and should be further investigated. PMID:24475273

  15. Soluble Thrombomodulin and Major Orthopedic Surgery

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    Irina P. Antropova

    2016-09-01

    Full Text Available Background: A high level of soluble thrombomodulin (sTM is associated with a lower risk of thrombosis but can cause severe bleeding after operations. Deep vein thrombosis (DVT and blood loss are serious threats after orthopedic surgery. The aim of our pilot study was to evaluate the effect of the preoperative level of sTM on coagulation and inflammation as well as the blood loss and the development of symptomatic DVT after total large joint replacement. Methods and Results: In all patients (n=50 who underwent total hip or knee replacement, sTM, PrC, D-dimer, vWF, CRP, and platelets were determined before and after the operation. According to the preoperative sTM level, patients were divided into 2 groups: the thrombomodulin low (TML group (n=25 and thrombomodulin high (TMH group (n=25. The concentration of sTM was 4.4 [3.4, 4.7] ng/ml in the TML-group and 8.7[7.3, 10.6] ng/ml in the TMH-group. After surgery, D-dimer, vWF, platelet count and CRP were higher and total blood loss was lower in the TML group. In the TML-group, a symptomatic DVT was detected in 3(12% patients; in the TMH-group, a symptomatic DVT was identified only in 1(4% case. Conclusion: These findings support the important role of sTM in coagulation, inflammation, bleeding, and presumably in venous thrombosis after major orthopedic surgery.

  16. Expression and its clinical significance of HLA-G in HCMV-infected placental villi at early pregnant stage

    Institute of Scientific and Technical Information of China (English)

    ZHANG Xin-wen; LI Fen; SHENG Qiu; YU Xue-wen; REN Yong-hui; LI Xue-cheng

    2007-01-01

    Objective: To study the expression and its clinical significance of HLA-G in HCMV intrauterine infected placental villi at early pregnant stage. Methods: PCR (polymerase chain reaction) was used to screen the peripheral blood for HCMV-DNA in 462 women who had willingly undergone induced abortion.Then immunohistochemistry was also used to detect expressions of mouse anti-HCMV early antigen (HCMV-EA) and mouse anti-HLA-G in HCMV-DNA positive cases' placental villi. The difference of HLA-G expressions between the intrauterine infection group(HCMV EA positives), the intrauterine infection-free group (HCMV-EA negatives) and the normal control group (50 cases of healthy early placental villi) was compared. Results: Of the 78 cases,which were detected HCMV DNA positive, 11 (14.10%)were HCMV-EA positive. Compared with the other two groups, HLA-G expressions in the intrauterine infection group were both obviously decreased(both P<0.001). HLA-G expression positions in all three groups were mainly located in the cytotrophoblast. Conclusion: Intrauterine HCMV infection at early pregnant stage is closely related to HLA-G expression at the maternal-fetal interface. The virogenetic products may affect the expression of HLA-G at the maternal-fetal interface and that of its immunological function,thus leading to different clinical outcomes.

  17. INFLUENCE OF SOLUBLE PLACENTAL TISSUE-DERIVED MOLECULES UPON EXPRESSION OF ADHESION MOLECULES BY EA.HY926 ENDOTHELIAL CELLS

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    O. I. Stepanova

    2011-01-01

    Full Text Available Abstract.  Leukocyte  recruitment  to  placental  tissue  is  an  important  factor  of  its  development.  In  this respect, adhesion molecules at the endothelial cell surface represent a key determining factor of leukocyte adhesion and their trans-endothelial migration. The goal of investigation was to evaluate changed expression of adhesion molecules on the endothelial cells induced by supernates of placental tissue cultures. Placental tissue supernatants produced by the first- and third-trimester placental tissue from normal pregnancy, as well as from women with gestosis, induced higher expression of CD31, CD9, CD62E, CD62P, CD34, CD54, CD51/61, CD49d  and  integrin  β7  expression  by  endothelial  cells,  as  compared  with  their  baseline  levels.  However, the  supernates  from  pre-eclamptic  placental  tissue (3rd  trimester  caused  an  increased  CD9  expression by  endothelial  cells,  as  compared  with  effects  of placental  supernates  from  eclampsia-free  cases.  Our data  contribute  to  understanding  a  possible  role  of endothelial cell adhesion molecules in recruitment of leukocytes to placental tissue and possible participation of adhesion molecules in pathogenesis of pre-eclampsia. The work was supported by a grant from Russian Ministry of Education and Science ГК №02.740.11.0711 and Presidential grant № НШ-3594.2010.7 and МД-150.2011.7. (Med. Immunol., 2011, vol. 13, N 6, pp 589-596

  18. Placental expression of myostatin and follistatin-like-3 protein in a model of developmental programming.

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    Peiris, Hassendrini N; Ponnampalam, Anna P; Osepchook, Claire C; Mitchell, Murray D; Green, Mark P

    2010-04-01

    Maternal undernutrition during gestation is known to be detrimental to fetal development, leading to a propensity for metabolic disorders later in the adult lives of the offspring. Identifying possible mediators and physiological processes involved in modulating nutrient transport within the placenta is essential to prevent and/or develop treatments for the effects of aberrant nutrition, nutrient transfer, and detrimental changes to fetal development. A potential role for myostatin as a mediator of nutrient uptake and transport from the mother to the fetus was shown through the recent finding that myostatin acts within the human placenta to modulate glucose uptake and therefore homeostasis. The mRNA and protein expression of myostatin and its inhibitor, follistatin-like-3 (FSTL3), was studied in the placenta and skeletal muscle of a transgenerational Wistar rat model of gestational maternal undernutrition in which the F2 offspring postweaning consumed a high-fat (HF) diet. Alterations in placental characteristics and offspring phenotype, specifically glucose homeostasis, were evident in the transgenerationally undernourished (UNAD) group. Myostatin and FSTL3 protein expression were also higher (P UNAD compared with the control group. At maturity, UNAD HF-fed animals had higher (P < 0.05) skeletal muscle expression of FSTL3 than control animals. In summary, maternal undernutrition during gestation results in the aberrant regulation of myostatin and FSTL3 in the placenta and skeletal muscle of subsequent generations. Myostatin, through the disruption of maternal nutrient supply to the fetus, may thus be a potential mediator of offspring phenotype.

  19. Expressed sequence tags as a tool for phylogenetic analysis of placental mammal evolution.

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    Morgan Kullberg

    Full Text Available BACKGROUND: We investigate the usefulness of expressed sequence tags, ESTs, for establishing divergences within the tree of placental mammals. This is done on the example of the established relationships among primates (human, lagomorphs (rabbit, rodents (rat and mouse, artiodactyls (cow, carnivorans (dog and proboscideans (elephant. METHODOLOGY/PRINCIPAL FINDINGS: We have produced 2000 ESTs (1.2 mega bases from a marsupial mouse and characterized the data for their use in phylogenetic analysis. The sequences were used to identify putative orthologous sequences from whole genome projects. Although most ESTs stem from single sequence reads, the frequency of potential sequencing errors was found to be lower than allelic variation. Most of the sequences represented slowly evolving housekeeping-type genes, with an average amino acid distance of 6.6% between human and mouse. Positive Darwinian selection was identified at only a few single sites. Phylogenetic analyses of the EST data yielded trees that were consistent with those established from whole genome projects. CONCLUSIONS: The general quality of EST sequences and the general absence of positive selection in these sequences make ESTs an attractive tool for phylogenetic analysis. The EST approach allows, at reasonable costs, a fast extension of data sampling from species outside the genome projects.

  20. Endoglin Expression and The Level of TGF- β are Increased in The Placental Tissue and Correlated with Low Fetal Weight in Malaria Infected Mice

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    Sujarot Dwi Sasmito

    2015-01-01

    Full Text Available Malaria infection during pregnancy can cause accumulation of infected red blood cells in placental intervillous space and induces placental tissue inflammation and hypoxia. This condition triggers endoglin expressionand release of soluble endoglin that can interfere TGF-β binding with the receptor. The aim of this study was to investigate the correlation between placental endoglin expression and TGF-β level with low fetal weight (LFW in malaria-infected mice. Nine pregnant mice infected with Plasmodium berghei on the day ninth post mating (malaria-infected group and eight normal pregnant mice (non-infected group were used in this study. The mice were sacrificed on the day 18th post mating, and all fetal body weights were measured by analytical scale. Enzyme Link Immunosorbent Assay (ELISA was done to determine the level of placental TGF-β while immunohistochemical staining was performed to examine endoglin expression in placental tissue. The mean of fetal body weights of malaria-infected group was significantly lower than non-infected group (p= 0,002, while the expression of placental endoglin in malaria- infected group was substantially higher than non-infected group (p= 0.003. The level of placental TGF-β in malaria-infected group was also considerably higher than non-infected group, but the difference was not significant (p= 0.064. Pearson correlation test showed that there were significant negative correlations between fetal body weights with the level of placental TGF-β (p= 0.017, r= -0.568 and the expression of placental endoglin (p= 0.002, r= -0.694. Malaria infection in pregnant mice will increase both TGF-β and endoglin in placenta tissue and correlate with low fetal weight.

  1. Analysis of IgG with specificity for variant surface antigens expressed by placental Plasmodium falciparum isolates

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    Kremsner Peter G

    2004-07-01

    Full Text Available Abstract Background Pregnancy-associated malaria (PAM is caused by Plasmodium falciparum-infected erythrocytes that can sequester in placental intervillous space by expressing particular variant surface antigens (VSA that can mediate adhesion to chondroitin sulfate A (CSA in vitro. IgG antibodies with specificity for the VSA expressed by these parasites (VSAPAM are associated with protection from maternal anaemia, prematurity and low birth weight, which is the greatest risk factor for death in the first month of life. Methods In this study, the development of anti-VSAPAM antibodies in a group of 151 women who presented to the maternity ward of Albert Schweitzer Hospital in Lambaréné, Gabon for delivery was analysed using flow cytometry assays. Plasma samples from placenta infected primiparous women were also investigated for their capacity to inhibit parasite binding to CSA in vitro. Results In the study cohort, primiparous as well as secundiparous women had the greatest risk of infection at delivery as well as during pregnancy. Primiparous women with infected placentas at delivery showed higher levels of VSAPAM-specific IgG compared to women who had no malaria infections at delivery. Placental isolates of Gabonese and Senegalese origin tested on plasma samples from Gabon showed parity dependency and gender specificity patterns. There was a significant correlation of plasma reactivity as measured by flow cytometry between different placental isolates. In the plasma of infected primiparous women, VSAPAM-specific IgG measured by flow cytometry could be correlated with anti-adhesion antibodies measured by the inhibition of CSA binding. Conclusion Recognition of placental parasites shows a parity- and sex- dependent pattern, like that previously observed in laboratory strains selected to bind to CSA. Placental infections at delivery in primiparous women appear to be sufficient to induce functional antibodies which can both recognize the surface of

  2. Expression patterns of microRNAs in porcine endometrium and their potential roles in embryo implantation and placentation.

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    Su, Lijie; Liu, Ruize; Cheng, Wei; Zhu, Mengjin; Li, Xiaoping; Zhao, Shuhong; Yu, Mei

    2014-01-01

    Implantation and placentation are critical steps for successful pregnancy. The pig has a non-invasive placenta and the uterine luminal epithelium is intact throughout pregnancy. To better understand the regulation mechanisms in functions of endometrium at three certain gestational stages that are critical for embryo/fetal loss in pigs, we characterized microRNA (miRNA) expression profiles in the endometrium on days 15 (implantation period), 26 (placentation period) and 50 (mid-gestation period) of gestation. The differentially expressed miRNAs across gestational days were detected and of which, 65 miRNAs were grouped into 4 distinct categories according to the similarities in their temporal expression patterns: (1) categories A and B contain majority of miRNAs (51 miRNAs, such as the miR-181 family) that were down- or up-regulated between gestational days 15 and 26, respectively; (2) categories C and D (14 miRNAs) consist miRNAs that were down- or up-regulated between gestational days 26 and 50, respectively. The expression patterns represented by eleven miRNAs were validated by qPCR. The majority of miRNAs were in categories A and B, suggesting that these miRNAs were involved in regulation of embryo implantation and placentation. The pathway analysis revealed that the predicted targets were involved in several pathways, such as focal adhesion, cell proliferation and tissue remolding. Furthermore, we identified that genes well-known to affect embryo implantation in pigs, namely SPP1, ITGB3 and ESR1, contain the miR-181a or miR-181c binding sites using the luciferase reporter system. The present study revealed distinctive miRNA expression patterns in the porcine endometrium during the implantation, placentation or mid-gestation periods. Additionally, our results suggested that miR-181a and miR-181c likely play important roles in the regulation of genes and pathways that are known to be involved in embryo implantation and placentation in pigs.

  3. Expression patterns of microRNAs in porcine endometrium and their potential roles in embryo implantation and placentation.

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    Lijie Su

    Full Text Available Implantation and placentation are critical steps for successful pregnancy. The pig has a non-invasive placenta and the uterine luminal epithelium is intact throughout pregnancy. To better understand the regulation mechanisms in functions of endometrium at three certain gestational stages that are critical for embryo/fetal loss in pigs, we characterized microRNA (miRNA expression profiles in the endometrium on days 15 (implantation period, 26 (placentation period and 50 (mid-gestation period of gestation. The differentially expressed miRNAs across gestational days were detected and of which, 65 miRNAs were grouped into 4 distinct categories according to the similarities in their temporal expression patterns: (1 categories A and B contain majority of miRNAs (51 miRNAs, such as the miR-181 family that were down- or up-regulated between gestational days 15 and 26, respectively; (2 categories C and D (14 miRNAs consist miRNAs that were down- or up-regulated between gestational days 26 and 50, respectively. The expression patterns represented by eleven miRNAs were validated by qPCR. The majority of miRNAs were in categories A and B, suggesting that these miRNAs were involved in regulation of embryo implantation and placentation. The pathway analysis revealed that the predicted targets were involved in several pathways, such as focal adhesion, cell proliferation and tissue remolding. Furthermore, we identified that genes well-known to affect embryo implantation in pigs, namely SPP1, ITGB3 and ESR1, contain the miR-181a or miR-181c binding sites using the luciferase reporter system. The present study revealed distinctive miRNA expression patterns in the porcine endometrium during the implantation, placentation or mid-gestation periods. Additionally, our results suggested that miR-181a and miR-181c likely play important roles in the regulation of genes and pathways that are known to be involved in embryo implantation and placentation in pigs.

  4. Nuclear transfer alters placental gene expression and associated histone modifications of the placental-specific imprinted gene pleckstrin homology-like domain, family A, member 2 (PHLDA2) in cattle.

    Science.gov (United States)

    Arnold, Daniel R; Gaspar, Roberta C; da Rocha, Carlos V; Sangalli, Juliano R; de Bem, Tiago H C; Corrêa, Carolina A P; Penteado, João C T; Meirelles, Flavio V; Lopes, Flavia L

    2017-03-01

    Abnormal placental development is frequent in nuclear transfer (NT) pregnancies and is likely to be associated with altered epigenetic reprogramming. In the present study, fetal and placental measurements were taken on Day 60 of gestation in cows with pregnancies produced by AI, IVF and NT. Placentas were collected and subjected to histological evaluation, the expression of genes important in trophoblast differentiation and expression of the placental imprinted gene pleckstrin homology-like domain, family A, member 2 (PHLDA2), as well as chromatin immunoprecipitation (ChIP) for histone marks within the promoter of PHLDA2. Fewer binucleated cells were observed in NT cotyledons, followed by IVF and AI cotyledons (P<0.05). Expression of heart and neural crest derivatives expressed 1 (HAND1), placental lactogen (PL), pregnancy-associated glycoprotein 9 (PAG-9) and PHLDA2 was elevated in NT cotyledons compared with AI cotyledons. Expression of PHLDA2 was higher in IVF than AI samples (P<0.05). ChIP revealed an increase in the permissive mark dimethylation of lysine 4 on histone H3 (H3K4me2), surprisingly associated with the silent allele of PHLDA2, and a decrease in the inhibitory mark H3K9me2 in NT samples. Thus, genes critical for placental development were altered in NT placentas, including an imprinted gene. Allele-specific changes in the permissive histone mark in the PHLDA2 promoter indicate misregulation of imprinting in clones. Abnormal trophoblast differentiation could have resulted in lower numbers of binucleated cells following NT. These results suggest that the altered expression of imprinted genes associated with NT are also caused by changes in histone modifications.

  5. Decreased miR-143 and increased miR-21 placental expression levels are associated with macrosomia.

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    Zhang, Ji-Tai; Cai, Qian-Ying; Ji, Si-Si; Zhang, Heng-Xin; Wang, Yu-Huan; Yan, Hong-Tao; Yang, Xin-Jun

    2016-04-01

    Macrosomia, a birth weight ≥ 4,000 g, is associated with maternal and infant health problems. The dysregulation of microRNAs (miRNAs) in the placenta is associated with adverse birth outcomes, yet whether aberrantly expressed placental miRNAs are associated with macrosomia remains unknown. The aim of the current study was to characterize the expression of three placental miRNAs (miR‑6, ‑21 and ‑143) and evaluate their association with macrosomia. The miRNA expression in placental tissues from 67 macrosomic pregnancies and 64 normal pregnancies were analyzed using reverse transcription‑quantitative polymerase chain reaction. The expression of miR‑21 was observed to be elevated in macrosomic placenta compared with control samples, while miR‑143 expression was significantly lower than in control placenta (Pmacrosomia increased with miR‑21 expression quartile: Q2, odds ratio (OR)=6.67 [95% confidence interval (CI), 1.39‑32.05]; Q3, OR=4.10 (95% CI, 0.88‑19.11); Q4, OR=16.19 (95% CI, 2.46‑106.68). Conversely, higher levels of miR‑143 expression were protective against macrosomia: Q2, OR=0.22 (95% CI, 0.049‑0.98); Q3, OR=0.11 (95% CI, 0.024‑0.55), and Q4, OR=0.16 (95% CI, 0.032‑0.79). Thus, statistical analysis demonstrated that high levels of miR‑21 expression and low levels of miR‑143 expression predict the risk for macrosomia, indicating an interaction between the two miRNAs. Bioinformatic analysis suggested that they are likely to function in the mitogen‑activated protein kinases signaling pathway to influence the risk of macrosomia. The results of the present study provide evidence that placental miR-21 and -143 are important in the formation of macrosomia.

  6. Placental apoptosis in recurrent miscarriage

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    Tarek A. Atia

    2017-09-01

    Full Text Available Apoptosis is an interactive and dynamic biological process involved in all phases of embryogenesis. We aimed to study the effect of placental apoptosis on recurrent miscarriage (RM. Placental tissue samples were collected from 40 women with RM (study group and 30 women with sporadic spontaneous abortion (control group. Samples were prepared and stained immunohistochemically with markers for both the apoptotic protein (p53 and anti-apoptotic Bcl-2 antibodies. Our results showed that expression of the apoptotic (p53 protein was significantly increased in the placental tissues of the RM group (p = 0.003. By contrast, the expression of anti-apoptotic (Bcl-2 antibodies was significantly increased in the placental tissues of the control group (p = 0.025. We concluded that placental apoptosis plays a crucial role in pregnancy continuation. However, increased p53 expression in placental tissue in early pregnancy could negatively affect pregnancy continuation.

  7. Maternal immune stimulation reduces both placental morphologic damage and down-regulated placental growth-factor and cell cycle gene expression caused by urethane: are these events related to reduced teratogenesis?

    Science.gov (United States)

    Sharova, L V; Sharov, A A; Sura, P; Gogal, R M; Smith, B J; Holladay, S D

    2003-07-01

    Activation of the maternal immune system in mice decreased cleft palate caused by the chemical teratogen, urethane. Direct and indirect mechanisms for this phenomenon have been suggested, including maternal macrophages that cross the placenta to find and eliminate pre-teratogenic cells, or maternal immune proteins (cytokines) that cross placenta to alleviate or partially alleviate toxicant-mediated effects in the developing fetus. A third mechanism to explain improved fetal developmental outcome in teratogen-challenged pregnant mice might involve beneficial effects of immune stimulation on the placenta. In the present experiments, urethane treatment altered placental morphology and impaired placental function, the latter indicated by down-regulated activity of cell cycle genes and of genes encoding cytokines and growth factors. Maternal immune stimulation with either Freund's complete adjuvant (FCA) or interferon-gamma (IFNgamma) reduced morphologic damage to the placenta caused by urethane and normalized expression of several genes that were down-regulated by urethane. Urethane treatment also shifted placental cytokine gene expression toward a T cell helper 1 (Th1) profile, while immunostimulation tended to restore a Th2 profile that may be more beneficial to pregnancy and fetal development. These data suggest that the beneficial effects of maternal immune stimulation on fetal development in teratogen-exposed mice may, in part, result from improved placental structure and function.

  8. Placental gene therapy

    OpenAIRE

    David, A. L.; Ashcroft, R

    2009-01-01

    Gene therapy uses genetic material as a drug delivery vehicle to express therapeutic proteins. Placental gene therapy may be useful for correction of two important obstetric conditions, foetal growth restriction and pre-eclampsia in which there is a failure of the physiological trophoblast remodelling of the uterine spiral arteries in early pregnancy. The patient in this scenario is the foetus. Placental gene therapy might be justifiable when: there is reasonable certainty that the foetus wil...

  9. A differentially expressed proteomic analysis in placental tissues in relation to pungency during the pepper fruit development.

    Science.gov (United States)

    Lee, Je Min; Kim, Seyoon; Lee, Ji Young; Yoo, Eun Young; Cho, Myeong Cheoul; Cho, Min Rae; Kim, Byung-Dong; Bahk, Young Yil

    2006-10-01

    Using proteomic analysis including 2-DE, image analysis, and protein identification with LC-MS/MS, an investigation aimed at a better understanding of the differentially expressed proteins and/or gene products was carried out with total cell extracts from placental tissues in nonpungent (Capsicum annuum cv. Saeng-Ryeog #213) and pungent peppers (C. annuum cv. Saeng-Ryeog #211). Mobilization of the most abundant proteins, which were on the gels of pH ranges of 4-7, 4.5-5.5, 5.5-6.7, and 6-9, and showed very similar profiles in the two tissues, revealing approximately 2600 protein spots consisting of 1200 on pH 4-7, 600 on 4.5-5.5, 550 on 5.5-6.7, 250 on 6-9. Of these, 37 protein spots, which appeared in only pungent tissues but not in nonpungent tissues or markedly increased in their staining intensities on the gels from pungent tissue, were selected, excised, in-gel trypsin digested, and analyzed by LC-ESI-MS/MS. Peptide MS/MS data were searched against publicly available protein and EST databases, and 22 proteins were identified. Based on this result, we tested and compared the differential expression during fruit development on the 2-DE gels with total cell extracts from placental tissues of pungent and nonpungent peppers at an interval of 10 days from 10 to 40 days after flowering. In addition, this differential protein expression was further confirmed for some subsets of candidates by Northern-blot analysis with RNA samples from placental tissues harvested from each pepper fruit at the same sampling intervals. In this study, the physiological implications, revealed from the experimental data in the levels of proteome and transcripts, are discussed in the context of a complex biosynthesis network of capsaicinoids in pepper cells responsive to pungency.

  10. Expression of heparanase is associated with breed-specific morphological characters of placental folded bilayer between Yorkshire and Meishan pigs.

    Science.gov (United States)

    Hong, Linjun; Hou, Chunyan; Li, Xiaoping; Li, Changchun; Zhao, Shuhong; Yu, Mei

    2014-03-01

    The pig has a noninvasive epitheliochorial placenta, and trophoblast-endometrial epithelial bilayer development could impact on placental function. This work compared the morphological structures, the cell proliferation status as assessed by Ki67 staining, as well as the location and gene and protein expression of heparanase (HPSE) at the maternal-fetal interface between Yorkshire and Meishan pigs on Days 26, 50, and 95 of gestation. Histomorphometry showed that the widths of placental folds, endometrial stroma, and placental stroma in Meishan pigs were smaller than those in Yorkshire pigs during late gestation, while the complexity and the cell proliferation ability of the folded bilayer were greater in Meishan pigs in this period. The location and expression levels of HPSE mRNA and protein at the maternal-fetal interface were similar between the two breeds during early and midgestation. However, during late gestation, the mRNA and protein levels were higher in Meishan placentae. In addition, the HPSE mRNA was expressed by all the trophoblast cells, and the protein was located both at trophoblast and luminal epithelium cells in Meishan pigs during late gestation, while in Yorkshire pigs, the HPSE mRNA and protein were only identified in trophoblast cells located at the bottom and side of folds. The findings suggest that Meishan pigs may rely more upon the increase in the complexity of the folded bilayer within a reduced placenta to expand the exchange surface area and the HPSE may contribute to the development of the folded bilayer in pigs.

  11. A Retroviral Promoter and a Cellular Enhancer Define a Bipartite Element Which Controls env ERVWE1 Placental Expression

    Science.gov (United States)

    Prudhomme, Sarah; Oriol, Guy; Mallet, François

    2004-01-01

    The HERV-W family contains hundreds of loci diversely expressed in several physiological and pathological contexts. A unique locus termed ERVWE1 encodes an envelope glycoprotein (syncytin) involved in hominoid placental physiology. Here we show that syncytin expression is regulated by a bipartite element consisting of a cyclic AMP (cAMP)-inducible long terminal repeat (LTR) retroviral promoter adjacent to a cellular enhancer conferring a high level of expression and placental tropism. Deletion mutant analysis showed that the ERVWE1 5′ LTR contains binding sites essential for basal placental activity in the region from positions +1 to +125. The region from positions +125 to +310 represents a cAMP-responsive core HERV-W promoter active in all cell types. Site-directed mutagenesis analysis highlighted the complexity of U3 regulation. ERVWE1 placenta-specific positive (e.g., T240) and negative (e.g., G71) regulatory sites were identified, as were essential sites required for basic activity (e.g., A247). The flanking sequences of the ERVWE1 provirus contain several putative regulatory elements. The upstream HERV-H and HERV-P LTRs were found to be inactive. Conversely, the 436-bp region located between the HERV-P LTR and ERVWE1 was shown to be an upstream regulatory element (URE) which is significantly active in placenta cells. This URE acts as a tissue-specific enhancer. Genetic and functional analyses of hominoid UREs revealed large differences between UREs of members of the Hominidae and the Hylobatidae. These data allowed the identification of a positive regulatory region from positions −436 to −128, a mammalian apparent LTR retrotransposon negative regulatory region from positions −128 to −67, and a trophoblast-specific enhancer (TSE) from positions −67 to −35. Putative AP-2, Sp-1, and GCMa binding sites are essential constituents of the 33-bp TSE. PMID:15507602

  12. Growth factor concentrations and their placental mRNA expression are modulated in gestational diabetes mellitus: possible interactions with macrosomia

    Directory of Open Access Journals (Sweden)

    Khairi Hédi

    2010-02-01

    Full Text Available Abstract Background Gestational diabetes mellitus (GDM is a form of diabetes that occurs during pregnancy. GDM is a well known risk factor for foetal overgrowth, termed macrosomia which is influenced by maternal hypergycemia and endocrine status through placental circulation. The study was undertaken to investigate the implication of growth factors and their receptors in GDM and macrosomia, and to discuss the role of the materno-foeto-placental axis in the in-utero regulation of foetal growth. Methods 30 women with GDM and their 30 macrosomic babies (4.75 ± 0.15 kg, and 30 healthy age-matched pregnant women and their 30 newborns (3.50 ± 0.10 kg were recruited in the present study. Serum concentrations of GH and growth factors, i.e., IGF-I, IGF-BP3, FGF-2, EGF and PDGF-B were determined by ELISA. The expression of mRNA encoding for GH, IGF-I, IGF-BP3, FGF-2, PDGF-B and EGF, and their receptors, i.e., GHR, IGF-IR, FGF-2R, EGFR and PDGFR-β were quantified by using RT-qPCR. Results The serum concentrations of IGF-I, IGF-BP3, EGF, FGF-2 and PDGF-B were higher in GDM women and their macrosomic babies as compared to their respective controls. The placental mRNA expression of the growth factors was either upregulated (FGF-2 or PDGF-B or remained unaltered (IGF-I and EGF in the placenta of GDM women. The mRNA expression of three growth factor receptors, i.e., IGF-IR, EGFR and PDGFR-β, was upregulated in the placenta of GDM women. Interestingly, serum concentrations of GH were downregulated in the GDM women and their macrosomic offspring. Besides, the expression of mRNAs encoding for GHR was higher, but that encoding for GH was lower, in the placenta of GDM women than control women. Conclusions Our results demonstrate that growth factors might be implicated in GDM and, in part, in the pathology of macrosomia via materno-foeto-placental axis.

  13. Hypoxia-independent upregulation of placental hypoxia inducible factor-1α gene expression contributes to the pathogenesis of preeclampsia.

    Science.gov (United States)

    Iriyama, Takayuki; Wang, Wei; Parchim, Nicholas F; Song, Anren; Blackwell, Sean C; Sibai, Baha M; Kellems, Rodney E; Xia, Yang

    2015-06-01

    Accumulation of hypoxia inducible factor-1α (HIF-1α) is commonly an acute and beneficial response to hypoxia, whereas chronically elevated HIF-1α is associated with multiple disease conditions, including preeclampsia, a serious hypertensive disease of pregnancy. However, the molecular basis underlying the persistent elevation of placental HIF-1α in preeclampsia and its role in the pathogenesis of preeclampsia are poorly understood. Here we report that Hif-1α mRNA and HIF-1α protein were elevated in the placentas of pregnant mice infused with angiotensin II type I receptor agonistic autoantibody, a pathogenic factor in preeclampsia. Knockdown of placental Hif-1α mRNA by specific siRNA significantly attenuated hallmark features of preeclampsia induced by angiotensin II type I receptor agonistic autoantibody in pregnant mice, including hypertension, proteinuria, kidney damage, impaired placental vasculature, and elevated maternal circulating soluble fms-like tyrosine kinase-1 levels. Next, we discovered that Hif-1α mRNA levels and HIF-1α protein levels were induced in an independent preeclampsia model with infusion of the inflammatory cytokine tumor necrosis factor superfamily member 14 (LIGHT). SiRNA knockdown experiments also demonstrated that elevated HIF-1α contributed to LIGHT-induced preeclampsia features. Translational studies with human placentas showed that angiotensin II type I receptor agonistic autoantibody or LIGHT is capable of inducing HIF-1α in a hypoxia-independent manner. Moreover, increased HIF-1α was found to be responsible for angiotensin II type I receptor agonistic autoantibody or LIGHT-induced elevation of Flt-1 gene expression and production of soluble fms-like tyrosine kinase-1 in human villous explants. Overall, we demonstrated that hypoxia-independent stimulation of HIF-1α gene expression in the placenta is a common pathogenic mechanism promoting disease progression. Our findings reveal new insight to preeclampsia and highlight

  14. Analysis of differentially expressed genes in placental tissues of preeclampsia patients using microarray combined with the Connectivity Map database.

    Science.gov (United States)

    Song, Y; Liu, J; Huang, S; Zhang, L

    2013-12-01

    Preeclampsia (PE), which affects 2-7% of human pregnancies, causes significant maternal and neonatal morbidity and mortality. To better understand the pathophysiology of PE, the gene expression profiles of placental tissue from 5 controls and 5 PE patients were assessed using microarray. A total of 224 transcripts were significantly differentially expressed (>2-fold change and q value <0.05, SAM software). Gene Ontology (GO) enrichment analysis indicated that genes involved in hypoxia and oxidative and reductive processes were significantly changed. Three differentially expressed genes (DEGs) involved in these biological processes were further verified by quantitative real-time PCR. Finally, the potential therapeutic agents for PE were explored via the Connectivity Map database. In conclusion, the data obtained in this study might provide clues to better understand the pathophysiology of PE and to identify potential therapeutic agents for PE patients. Copyright © 2013 Elsevier Ltd. All rights reserved.

  15. Maternal Prenatal Mental Health and Placental 11β-HSD2 Gene Expression: Initial Findings from the Mercy Pregnancy and Emotional Wellbeing Study

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    Sunaina Seth

    2015-11-01

    Full Text Available High intrauterine cortisol exposure can inhibit fetal growth and have programming effects for the child’s subsequent stress reactivity. Placental 11beta-hydroxysteroid dehydrogenase (11β-HSD2 limits the amount of maternal cortisol transferred to the fetus. However, the relationship between maternal psychopathology and 11β-HSD2 remains poorly defined. This study examined the effect of maternal depressive disorder, antidepressant use and symptoms of depression and anxiety in pregnancy on placental 11β-HSD2 gene (HSD11B2 expression. Drawing on data from the Mercy Pregnancy and Emotional Wellbeing Study, placental HSD11B2 expression was compared among 33 pregnant women, who were selected based on membership of three groups; depressed (untreated, taking antidepressants and controls. Furthermore, associations between placental HSD11B2 and scores on the State-Trait Anxiety Inventory (STAI and Edinburgh Postnatal Depression Scale (EPDS during 12–18 and 28–34 weeks gestation were examined. Findings revealed negative correlations between HSD11B2 and both the EPDS and STAI (r = −0.11 to −0.28, with associations being particularly prominent during late gestation. Depressed and antidepressant exposed groups also displayed markedly lower placental HSD11B2 expression levels than controls. These findings suggest that maternal depression and anxiety may impact on fetal programming by down-regulating HSD11B2, and antidepressant treatment alone is unlikely to protect against this effect.

  16. Expression of organic anion transporting polypeptide 1c1 and monocarboxylate transporter 8 in the rat placental barrier and the compensatory response to thyroid dysfunction.

    Directory of Open Access Journals (Sweden)

    Yi-na Sun

    Full Text Available Thyroid hormones (THs must pass from mother to fetus for normal fetal development and require the expression of placental TH transporters. We investigate the compensatory effect of placental organic anion transporting polypeptide 1c1 (Oatp1c1 and monocarboxylate transporter 8 (Mct8 on maternal thyroid dysfunction. We describe the expressions of these two transporters in placental barriers and trophoblastic cell populations in euthyroidism and thyroid dysfunction resulting from differential iodine nutrition at gestation day (GD 16 and 20, that is, before and after the onset of fetal thyroid function. Immunohistochemistry revealed that in the blood-placenta barrier, these two TH transporters were strongly expressed in the villous interstitial substance and were weakly expressed in trophoblast cells. Levels of Oatp1c1 protein obviously increased in the placental fetal portion during maternal thyroid deficiency at GD16. Under maternal thyroid deficiency after the production of endogenous fetal TH, quantitative PCR analysis revealed down-regulation of Oatp1c1 occurred along with up-regulation of Mct8 in trophoblast cell populations isolated by laser capture microdissection (LCM; this was consistent with the protein levels in the fetal portion of the placenta. In addition, decreased D3 mRNA at GD16 and increased D2 mRNA on two gestational days were observed in trophoblast cells with thyroid dysfunction. However, levels of Oatp1c1 mRNA at GD16 and D3 mRNA at GD20 were too low to be detectable in trophoblast cells. In conclusion, placental Oatp1c1 plays an essential compensatory role when the transplacental passage of maternal THs is insufficient at the stage before the fetal TH production. In addition, the coordinated effects of Oatp1c1, Mct8, D2 and D3 in the placental barrier may regulate both transplacental TH passage and the development of trophoblast cells during thyroid dysfunction throughout the pregnancy.

  17. Expression of organic anion transporting polypeptide 1c1 and monocarboxylate transporter 8 in the rat placental barrier and the compensatory response to thyroid dysfunction.

    Science.gov (United States)

    Sun, Yi-na; Liu, Yuan-jun; Zhang, Lu; Ye, Yan; Lin, Lai-xiang; Li, Yong-mei; Yan, Yu-qin; Chen, Zu-pei

    2014-01-01

    Thyroid hormones (THs) must pass from mother to fetus for normal fetal development and require the expression of placental TH transporters. We investigate the compensatory effect of placental organic anion transporting polypeptide 1c1 (Oatp1c1) and monocarboxylate transporter 8 (Mct8) on maternal thyroid dysfunction. We describe the expressions of these two transporters in placental barriers and trophoblastic cell populations in euthyroidism and thyroid dysfunction resulting from differential iodine nutrition at gestation day (GD) 16 and 20, that is, before and after the onset of fetal thyroid function. Immunohistochemistry revealed that in the blood-placenta barrier, these two TH transporters were strongly expressed in the villous interstitial substance and were weakly expressed in trophoblast cells. Levels of Oatp1c1 protein obviously increased in the placental fetal portion during maternal thyroid deficiency at GD16. Under maternal thyroid deficiency after the production of endogenous fetal TH, quantitative PCR analysis revealed down-regulation of Oatp1c1 occurred along with up-regulation of Mct8 in trophoblast cell populations isolated by laser capture microdissection (LCM); this was consistent with the protein levels in the fetal portion of the placenta. In addition, decreased D3 mRNA at GD16 and increased D2 mRNA on two gestational days were observed in trophoblast cells with thyroid dysfunction. However, levels of Oatp1c1 mRNA at GD16 and D3 mRNA at GD20 were too low to be detectable in trophoblast cells. In conclusion, placental Oatp1c1 plays an essential compensatory role when the transplacental passage of maternal THs is insufficient at the stage before the fetal TH production. In addition, the coordinated effects of Oatp1c1, Mct8, D2 and D3 in the placental barrier may regulate both transplacental TH passage and the development of trophoblast cells during thyroid dysfunction throughout the pregnancy.

  18. Human Wharton’s jelly-derived mesenchymal stem cells express oocyte developmental genes during co-culture with placental cells

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    Hamid Reza Asgari

    2015-01-01

    Conclusion: Placental cell supplementsTransforming growth factor (TGF α, β and basic fibroblast growth factor (bFGF in a co-culture model can provide proper environment for induction of HUMSCs into PGCs and expression of oocyte-like markers.

  19. Moderate Hypoxia Down-Regulates Interleukin-6 Secretion and TLR4 Expression in Human Sw.71 Placental Cells

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    Koumei Shirasuna

    2015-07-01

    Full Text Available Background/Aims: The placenta is a vital organ for pregnancy. Many in vitro placental experiments are conducted under 21% O2; however, O2 tension could influence cellular functions, including cytokine secretion. We investigated the effects of oxygen tension between moderate hypoxia (5% O2 and normoxia (21% O2 by testing the hypothesis that moderate hypoxia regulates cellular phenotypes differently from normoxia in human trophoblast cells. Methods and Results: Sw.71 trophoblast cells were incubated under normoxic or moderately hypoxic conditions. Cells were also treated with lipopolysaccharide (LPS as a Toll-like receptor 4 (TLR4 ligand inducing inflammation. Interleukin-6 (IL-6 as an inflammatory cytokine was determined, and TLR4, hypoxia-induced factor-1α (HIF1α, and reactive oxygen species (ROS production were detected. Moderate hypoxia increased HIF1α expression and cell proliferation and acted by two different mechanisms to decrease IL-6 secretion compared with normoxia: it limits the TLR4 expression and ROS production. Treatment with cobalt chloride as an HIF1 activator inhibited IL-6 secretion and TLR4 expression; this effect was reversed on treatment with PX-12 as an HIF1 suppressor. Conclusion: IL-6 secretion, TLR4 expression, and ROS production, classical markers of inflammation, are down-regulated by moderate hypoxia, and HIF1α and ROS have a potential to regulate these responses in human trophoblast cells.

  20. The effect of acetaminophen on the expression of BCRP in trophoblast cells impairs the placental barrier to bile acids during maternal cholestasis

    Energy Technology Data Exchange (ETDEWEB)

    Blazquez, Alba G., E-mail: albamgb@usal.es [Laboratory of Experimental Hepatology and Drug Targeting (HEVEFARM), IBSAL, University of Salamanca, Salamanca (Spain); CIBERehd, Instituto de Salud Carlos III, Madrid (Spain); Briz, Oscar, E-mail: obriz@usal.es [Laboratory of Experimental Hepatology and Drug Targeting (HEVEFARM), IBSAL, University of Salamanca, Salamanca (Spain); CIBERehd, Instituto de Salud Carlos III, Madrid (Spain); Gonzalez-Sanchez, Ester, E-mail: u60343@usal.es [Laboratory of Experimental Hepatology and Drug Targeting (HEVEFARM), IBSAL, University of Salamanca, Salamanca (Spain); Perez, Maria J., E-mail: mjperez@usal.es [Laboratory of Experimental Hepatology and Drug Targeting (HEVEFARM), IBSAL, University of Salamanca, Salamanca (Spain); University Hospital of Salamanca, IECSCYL-IBSAL, Salamanca (Spain); CIBERehd, Instituto de Salud Carlos III, Madrid (Spain); Ghanem, Carolina I., E-mail: cghanem@ffyb.uba.ar [Instituto de Investigaciones Farmacologicas, Facultad de Farmacia y Bioquimica, CONICET, Universidad de Buenos Aires, Buenos Aires (Argentina); Marin, Jose J.G., E-mail: jjgmarin@usal.es [Laboratory of Experimental Hepatology and Drug Targeting (HEVEFARM), IBSAL, University of Salamanca, Salamanca (Spain); CIBERehd, Instituto de Salud Carlos III, Madrid (Spain)

    2014-05-15

    Acetaminophen is used as first-choice drug for pain relief during pregnancy. Here we have investigated the effect of acetaminophen at subtoxic doses on the expression of ABC export pumps in trophoblast cells and its functional repercussion on the placental barrier during maternal cholestasis. The incubation of human choriocarcinoma cells (JAr, JEG-3 and BeWo) with acetaminophen for 48 h resulted in no significant changes in the expression and/or activity of MDR1 and MRPs. In contrast, in JEG-3 cells, BCRP mRNA, protein, and transport activity were reduced. In rat placenta, collected at term, acetaminophen administration for the last three days of pregnancy resulted in enhanced mRNA, but not protein, levels of Mrp1 and Bcrp. In fact, a decrease in Bcrp protein was found. Using in situ perfused rat placenta, a reduction in the Bcrp-dependent fetal-to-maternal bile acid transport after treating the dams with acetaminophen was found. Complete biliary obstruction in pregnant rats induced a significant bile acid accumulation in fetal serum and tissues, which was further enhanced when the mothers were treated with acetaminophen. This drug induced increased ROS production in JEG-3 cells and decreased the total glutathione content in rat placenta. Moreover, the NRF2 pathway was activated in JEG-3 cells as shown by an increase in nuclear NRF2 levels and an up-regulation of NRF2 target genes, NQO1 and HMOX-1, which was not observed in rat placenta. In conclusion, acetaminophen induces in placenta oxidative stress and a down-regulation of BCRP/Bcrp, which may impair the placental barrier to bile acids during maternal cholestasis. - Highlights: • Acetaminophen induces changes in placental BCRP expression in vitro. • This drug reduces the ability of placental cells to export BCRP substrates. • Acetaminophen induces changes in Bcrp expression in rat placenta. • Placental barrier to bile acids is impaired in rats treated with this drug.

  1. Uterine and placental expression of TRPV6 gene is regulated via progesterone receptor- or estrogen receptor-mediated pathways during pregnancy in rodents

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    Choi Kyung-Chul

    2009-05-01

    Full Text Available Abstract Transient receptor potential cation channel, subfamily V, member 6 (TRPV6 is an epithelial Ca2+ channel protein expressed in calcium absorbing organs. In the present study, we investigated the expression and regulation of uterine and placental TRPV6 during gestation in rodents. Uterine TRPV6 peaked at pregnancy day (P 0.5, P5.5 and, P13.5 and was detected in uterine epithelium and glands of rats, while placental TRPV6 mRNA levels increased in mid-gestation. Uterine and placental TRPV6 mRNA levels in rats appear to cyclically change during pregnancy, suggesting that TRPV6 may participate in the implantation process. In addition, uterine TRPV6 mRNA is only expressed in placenta-unattached areas of the uterus, and uterine TRPV6 immunoreactivity was observed in luminal and glandular epithelial cells. In the placenta, TRPV6 was detected in the labyrinth and spongy zone. These results may indicate that TRPV6 has at least two functions: implantation of the embryo and maintenance of pregnancy. To investigate the pathway(s mediating TRPV6 expression in rodents, anti-steroid hormone antagonists were injected prior to maximal TRPV6 expression. In rats, TRPV6 expression was reduced by RU486 (an anti-progesterone through progesterone receptors, and ICI 182,780 (an anti-estrogen blocked TRPV6 expression via estrogen receptors in mice. The juxtaposition of uterine and placental TRPV6 expressed in these tissues supports the notion that TRPV6 participates in transferring calcium ions between the maternal and fetal compartments. Taken together, TRPV6 gene may function as a key element in controlling calcium transport in the uterus between the embryo and the placenta during pregnancy.

  2. Mammalian Placentation

    DEFF Research Database (Denmark)

    Carter, Anthony Michael; Mess, A. M.

    2014-01-01

    This guide to animal models of human placentation assesses the strengths and weaknesses of species in common use. We argue that structural differences from human placenta, though important in some contexts, are less of a drawback than differences in reproductive strategy. Many laboratory rodents...... to consider animal models with longer gestations and well-developed neonates. Placentation in different orders of mammal is surveyed and their proximity to humans described in an evolutionary context. Animal models are then compared with the human in terms of the functional anatomy, physiology, and immunology...... have brief gestations resulting in the birth of poorly developed young. They can provide useful insights on placental development and function relevant to early human pregnancy. However, to model the events of a 9-month gestation, which imposes added requirements on the placenta, it is necessary...

  3. Maternal protein restriction reduces expression of angiotensin I-converting enzyme 2 in rat placental labyrinth zone in late pregnancy.

    Science.gov (United States)

    Gao, Haijun; Yallampalli, Uma; Yallampalli, Chandra

    2012-02-01

    Both the systemic and the uteroplacental renin-angiotensin system (RAS) display dramatic changes during pregnancy. However, whether gestational protein insufficiency affects the expressions of RAS in the placenta remains unknown. In this study, we hypothesized that the expression of Ace2 in the placental labyrinth was reduced by maternal protein restriction. Pregnant Sprague-Dawley rats were fed a normal diet or a low-protein diet (LP) from Day 1 of pregnancy until they were killed at Day 14 or Day 18. The labyrinth zone (LZ) of the placenta was then dissected and snap frozen for expression analysis by quantitative real-time PCR of Ace, Ace2, Agtr1a, Agtr1b, and Agtr2. Formalin-fixed placentas were used for immunohistochemical analysis on ACE and ACE2 proteins. The findings include 1) the expression of Ace2 in rat LZ was reduced by maternal protein restriction in late pregnancy; 2) ACE protein was mainly present in syncytiotrophoblasts, whereas ACE2 protein was found predominantly in fetal mesenchymal tissue and fetal capillaries; 3) Agtr1a was predominant in the rat LZ, and its mRNA levels, but not protein levels, were reduced by LP; 4) expressions of Ace, Ace2, and Agtr1a in the rat LZ and their response to LP occurred in a gender-dependent manner. These results may indicate that a reduced expression of Ace2 and perhaps an associated reduction in angiotensin (1-7) production in the placenta by maternal protein restriction may be responsible for fetal growth restriction and associated programming of adulthood hypertension.

  4. Expression of placental protein 14 by the new endometrial cancer cell line MFE-280 in vitro and by endometrial carcinomas in vivo.

    Science.gov (United States)

    Hackenberg, R; Loos, S; Nia, A H; Kunzmann, R; Schulz, K D

    1998-01-01

    MFE-280 endometrial cancer cells express PP14 (placental protein 14) in vitro. PP14 is normally found in the secretory endometrium and in placental tissue. MFE-280 cells, which are tumorigenic in nude mice, were derived from a recurrent, poorly differentiated endometrial carcinoma. The cells were initially grown in suspension culture and later transferred to monolayer cultures. Karyotyping revealed near-diploidy with a complex heterogeneous aberration pattern. MFE-280 cells were positive for the cytokeratins 7, 8, 18 and 19 as well as for vimentin. The expression of PP14 in MFE-280 cells was demonstrated by immunochemistry and reverse transcriptase--polymerase chain reaction. PP14-mRNA was also detected in one out of five endometrial cancer specimen. In tumor tissue the expression of PP14 was not dependent on progestins.

  5. Placental Aromatase Is Deficient in Placental Ischemia and Preeclampsia.

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    Alejandra Perez-Sepulveda

    placental ischemia and hypoxia later in gestation.Placental aromatase expression and functionality are diminished in pregnancies complicated by preeclampsia in comparison with healthy pregnant controls.

  6. Hexachlorobenzene and pentachlorobenzene accumulation, metabolism and effect on steroid secretion and on CYP11A1 and CYP19 expression in cultured human placental tissue.

    Science.gov (United States)

    Gregoraszczuk, E L; Ptak, A; Karpeta, A; Fiedor, E; Wróbel, A; Milewicz, T; Falandysz, J

    2014-01-01

    Hexachlorobenzene and pentachlorobenzene accumulation and the effect on CYP1A1, SULT1A, COMT and steroid secretion in term placental tissue were determined. Explants of placental tissue were exposed to between 0.02 and 2 ng/ml HCBz or PeCBz for 6-72 h. Accumulation was measured by capillary gas chromatography and quadrupole mass spectrometry. CYP1A1, SULT1A, COMT activity and progesterone secretion were analysed by EIA. Protein expression was quantified by Western blot; 6% HCBz and 7% PeCBz were detected in the tissue. Fast induction of CYP1A1 activity and protein expression in the presence of HCBz were observed. HCBz increased, while PeCBz decreased COMT protein expression. The stimulatory effect of HCBz, and the inhibitory of PeCBz on progesterone secretion and CYP11A1 protein expression were noted. Later activation of CYP1A1, inhibition of COMT protein expression and progesterone secretion by PeCBz suggest greater exposure to PeCBz and pointing at PeCBz as the main factor responsible for the disruption of placental function.

  7. Angiotensin II upregulates the expression of placental growth factor in human vascular endothelial cells and smooth muscle cells

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    Guo Yingqiang

    2010-05-01

    Full Text Available Abstract Background Atherosclerosis is now recognized as a chronic inflammatory disease. Angiotensin II (Ang II is a critical factor in inflammatory responses, which promotes the pathogenesis of atherosclerosis. Placental growth factor (PlGF is a member of the vascular endothelial growth factor (VEGF family cytokines and is associated with inflammatory progress of atherosclerosis. However, the potential link between PlGF and Ang II has not been investigated. In the current study, whether Ang II could regulate PlGF expression, and the effect of PlGF on cell proliferation, was investigated in human vascular endothelial cells (VECs and smooth muscle cells (VSMCs. Results In growth-arrested human VECs and VSMCs, Ang II induced PlGF mRNA expression after 4 hour treatment, and peaked at 24 hours. 10-6 mol/L Ang II increased PlGF protein production after 8 hour treatment, and peaked at 24 hours. Stimulation with Ang II also induced mRNA expression of VEGF receptor-1 and -2(VEGFR-1 and -2 in these cells. The Ang II type I receptor (AT1R antagonist blocked Ang II-induced PlGF gene expression and protein production. Several intracellular signals elicited by Ang II were involved in PlGF synthesis, including activation of protein kinase C, extracellular signal-regulated kinase 1/2 (ERK1/2 and PI3-kinase. A neutralizing antibody against PlGF partially inhibited the Ang II-induced proliferation of VECs and VSMCs. However, this antibody showed little effect on the basal proliferation in these cells, whereas blocking antibody of VEGF could suppress both basal and Ang II-induced proliferation in VECs and VSMCs. Conclusion Our results showed for the first time that Ang II could induce the gene expression and protein production of PlGF in VECs and VSMCs, which might play an important role in the pathogenesis of vascular inflammation and atherosclerosis.

  8. Elevated expression of placental growth factor is associated with airway-wall vascular remodelling and thickening in smokers with asthma

    Science.gov (United States)

    Wu, Dong; Lai, Tianwen; Yuan, Yalian; Chen, Min; Xia, Jun; Li, Wen; Pan, Guihai; Yuan, Binfan; Lv, Quanchao; Li, Yanyu; Li, Dongmin; Wu, Bin

    2017-01-01

    The increased expression of placental growth factor (PlGF) in chronic obstructive pulmonary disease and allergy-related asthma suggests its role in the pathogenesis of these diseases. In asthmatic smokers, airway remodelling is accompanied by an accelerated decline in lung function. However, whether PlGF contributes to the persistent airflow obstruction and vascular remodelling typically seen in asthmatic smokers is unknown. In this study we measured lung function, airway-wall thickening, and PlGF levels in serum and induced sputum in 74 asthmatic and 42 healthy smokers and never-smokers. Using human lung microvascular endothelial cells (HLMECs), we evaluated the in vitro effects of PlGF on each step of vascular remodelling, including proliferation, migration, stress-fibre expression, and tubule formation. Our data showed significantly higher serum and sputum PlGF levels in asthma patients, especially asthmatic smokers, than in healthy controls. Serum and sputum PlGF levels correlated negatively with post-bronchodilator forced expiratory volume in 1 s (FEV1) and the FEV1/forced vital capacity, but positively with airway-wall thickening. Stimulation of HLMECs with rhPlGF promoted all of the steps of airway-microvascular remodelling. These findings provide insights into the influence of cigarette smoking on the structural changes in the airways of asthmatics and the important pathogenic role played by PlGF. PMID:28220848

  9. Impact of equine assisted reproductive technologies (standard embryo transfer or intracytoplasmic sperm injection (ICSI) with in vitro culture and embryo transfer) on placenta and foal morphometry and placental gene expression.

    Science.gov (United States)

    Valenzuela, Orlando A; Couturier-Tarrade, Anne; Choi, Young-Ho; Aubrière, Marie-Christine; Ritthaler, Justin; Chavatte-Palmer, Pascale; Hinrichs, Katrin

    2017-07-24

    Assisted reproductive technologies (ARTs) such as intracytoplasmic sperm injection (ICSI), in vitro embryo culture and embryo transfer (ET) may be associated with alterations in fetal and placental development. In horses, ET has been used for decades. More recently, in vitro embryo production by ICSI and in vitro culture, followed by embryo transfer (ICSI-C) has become an accepted method for clinical foal production. However, no information is available on the effects of ICSI-C or even of standard ET itself on placental and neonatal parameters in horses. We therefore evaluated placental and neonatal morphology and placental gene expression in reining- and cutting-type American Quarter Horse foals produced using different technologies. Thirty foals and placentas (naturally conceived (NC), ET and ICSI-C; 10 in each group) were examined morphometrically. The only parameter that differed significantly between groups was the length of the foal upper hindlimb, which was longer in ET and ICSI-C than in NC foals. Evaluation of placental mRNA expression for 17 genes related to growth and vascularisation showed no difference in gene expression between groups. These data indicate that within this population, use of ARTs was not associated with meaningful changes in foal or placental morphometry or in expression of the placental genes evaluated.

  10. Placental expression of proBNP/NT-proBNP and plasma levels of NT-proBNP in early- and late-onset preeclampsia.

    Science.gov (United States)

    Junus, Katja; Wikström, Anna-Karin; Larsson, Anders; Olovsson, Matts

    2014-09-01

    Levels of plasma N-terminal pro B-type natriuretic peptide (NT-proBNP) are elevated in preeclampsia. In this study, the possibility that the placenta produces and releases proBNP/NT-proBNP was explored. Plasma levels of NT-proBNP in early- and late-onset preeclampsia were also measured. Placental proBNP mRNA in early-onset preeclampsia (n = 7), late-onset preeclampsia (n = 8), and controls of similar gestational age (n = 10) was assessed by quantitative real-time polymerase chain reaction. ProBNP/NT-proBNP protein was studied in placental samples with immunohistochemistry (n = 8) and tissue culture (n = 2). Plasma levels of NT-proBNP were measured in early-onset preeclampsia (n = 18), late-onset preeclampsia (n = 20), and relevant controls (n = 36). Transcripts of proBNP mRNA were found in 20 out of 25 samples, there were no differences in expression between the groups. ProBNP/NT-proBNP protein was observed in maternal spiral arteries and in syncytiotrophoblasts in all placental samples. After placental tissue culture, there were measurable amounts of NT-proBNP in the culture media. Women with both early- (365 [14-9815] pg/ml) and late-onset preeclampsia (176 [33-2547] pg/ml) had higher levels of NT-proBNP than their controls (P preeclampsia than in women with late-onset preeclampsia (P = 0.057). The results indicate possible placental production and release of proBNP/NT-proBNP into the maternal circulation. © American Journal of Hypertension, Ltd 2014. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

  11. Increased placental fatty acid transporter 6 and binding protein 3 expression and fetal liver lipid accumulation in a mouse model of obesity in pregnancy.

    Science.gov (United States)

    Díaz, Paula; Harris, Jessica; Rosario, Fredrick J; Powell, Theresa L; Jansson, Thomas

    2015-12-15

    Obesity in pregnancy is associated with increased fetal growth and adiposity, which, in part, is determined by transplacental nutrient supply. Trophoblast uptake and intracellular trafficking of lipids are dependent on placental fatty acid transport proteins (FATP), translocase (FAT/CD36), and fatty acid binding proteins (FABP). We hypothesized that maternal obesity in mice leads to increased placental expression of FAT/CD36, FATPs, and FABPs, and lipid accumulation in the fetal liver. C57/BL6J female mice were fed either a control (C; n = 10) or an obesogenic (OB; n = 10) high-fat, high-sugar diet before mating and throughout pregnancy. At E18.5, placentas and fetal livers were collected. Trophoblast plasma membranes (TPM) were isolated from placental homogenates. Expression of FAT/CD36 and FATP (TPM) and FABP (homogenates) was determined by immunoblotting. Gene expression was assessed by RT-quantitative PCR. Sections of fetal livers were stained for Oil Red O, and lipid droplets were quantified. TPM protein expression of FAT/CD36, FATP 2, and FATP 4 was comparable between C and OB groups. Conversely, TPM FATP 6 expression was increased by 35% in OB compared with C placentas without changes in mRNA expression. FABPs 1, 3-5 and PPARγ were expressed in homogenates, and FABP 3 expression increased 27% in OB compared with C placentas; however, no changes were observed in mRNA expression. Lipid droplet accumulation was 10-fold higher in the livers of fetuses from OB compared with C group. We propose that increased lipid transport capacity in obese mice promotes transplacental fatty acid transport and contributes to excess lipid accumulation in the fetal liver.

  12. Placental economies

    DEFF Research Database (Denmark)

    Lee, Jieun

    2016-01-01

    and sustained through the relations and practices of care that animate the placenta in different forms. On the basis of an ethnographic fieldwork conducted in Korea, this article focuses on two different forms of care (lab workers’ care of cells, and pregnant women’s care of fetuses) that enable the (re......Thinking with the vital materiality of placentas as it is evinced in a placental stem cell research lab in Korea, this article explores the relations and practices of care that are essential to the circulation of biological matters as infrastructure of tissue economies. I attend to the flows...... of care that sustain tissue economies with the notion of ‘placental economies’. Shifting attention from donor subjects and tissue objects to practices and relations of care as an infrastructure for the circulation of tissues, I explore how the vitality of biological matters is an achievement made...

  13. Mammalian Placentation

    DEFF Research Database (Denmark)

    Carter, Anthony Michael; Mess, A. M.

    2014-01-01

    This guide to animal models of human placentation assesses the strengths and weaknesses of species in common use. We argue that structural differences from human placenta, though important in some contexts, are less of a drawback than differences in reproductive strategy. Many laboratory rodents...... to consider animal models with longer gestations and well-developed neonates. Placentation in different orders of mammal is surveyed and their proximity to humans described in an evolutionary context. Animal models are then compared with the human in terms of the functional anatomy, physiology, and immunology...... of the placenta. This information is collated both to assess common animal models such as mouse, sheep, and primates and to introduce some alternatives that we consider worthy of attention....

  14. In vivo behavior of detergent-solubilized purified rabbit thrombomodulin on intravenous injection into rabbits

    Energy Technology Data Exchange (ETDEWEB)

    Ehrlich, H.J.; Esmon, N.L.; Bang, N.U. (Eli Lilly and Company, Indianapolis, IN (USA))

    1990-02-01

    Thrombomodulin is a thrombin endothelial cell membrane receptor. The thrombomodulin-thrombin complex rapidly activates protein C resulting in anticoagulant activity. We investigated the anticoagulant effects and pharmacokinetic behavior of detergent-solubilized purified rabbit thrombomodulin labeled with iodine 125 when intravenously injected into rabbits. Thrombomodulin half-life (t1/2) was determined by tracking the 125I-radiolabeled protein and the biologic activity as determined by the prolongation of the activated partial thromboplastin time (APTT) and thrombin clotting time (TCT). When 200 micrograms/kg 125I-thrombomodulin was injected into rabbits, the APTT and TCT were immediately prolonged, whereas no effect on the prothrombin time was seen. In vitro calibration curves enabled us to convert the prolongations of the clotting times into micrograms per milliliter thrombomodulin equivalents. The best fit (r greater than 0.99) for the disappearance curves was provided by a two-compartment model with mean t1/2 alpha (distribution phase) of 18 minutes for 125I, 12 minutes for APTT, and 20 minutes for TCT, and mean t1/2 beta (elimination phase) of 385 minutes for 125I, 460 for APTT, and 179 for TCT. The administration of two doses of endotoxin (50 micrograms/kg) 24 hours apart did not accelerate the turnover rate of 125I-thrombomodulin as measured by the disappearance of 125I from the circulation. Thus, detergent-solubilized purified thrombomodulin administered intravenously circulates in a biologically active form for appreciable time periods.

  15. Placental expression of miR-517a/b and miR-517c contributes to trophoblast dysfunction and preeclampsia.

    Directory of Open Access Journals (Sweden)

    Lauren Anton

    Full Text Available Preeclampsia is a pregnancy specific hypertensive disease that confers significant maternal and fetal risks. While the exact pathophysiology of preeclampsia is unknown, it is widely accepted that placental dysfunction is mechanistically involved. Recent studies reported aberrant expression of placenta-specific microRNAs (miRNAs in preeclampsia including miR-517a/b and miR-517c. Using placental biopsies from a preeclampsia case-control study, we found increased expression of miR-517a/b in term and preterm preeclampsia vs controls, while, miR-517c was increased only in preterm preeclampsia vs controls. To determine if miR-517a/b and miR-517c are regulated by hypoxia, we treated first trimester primary extravillous trophoblast cells (EVTs with a hypoxia mimetic and found both were induced. To test for a mechanistic role in placental function, we overexpressed miR-517a/b or miR-517c in EVTs which resulted in decreased trophoblast invasion. Additionally, we found that miR-517a/b and miR-517c overexpression increased expression of the anti-angiogenic protein, sFLT1. The regulation of sFLT1 is mostly unknown, however, TNFSF15, a cytokine involved in FLT1 splicing, was also increased by miR-517a/b and miR-517c in EVTs. In summary, we demonstrate that miR-517a/b and miR-517c contribute to the development of preeclampsia and suggest that these miRNAs play a critical role in regulating trophoblast and placental function.

  16. Association of cord blood des-acyl ghrelin with birth weight, and placental GHS-R1 receptor expression in SGA, AGA, and LGA newborns.

    Science.gov (United States)

    González-Domínguez, Martha I; Lazo-de-la-Vega-Monroy, Maria-Luisa; Zaina, Silvio; Sabanero, Myrna; Daza-Benítez, Leonel; Malacara, Juan Manuel; Barbosa-Sabanero, Gloria

    2016-07-01

    Although ghrelin in cord blood has been associated to birth weight, its role in fetal and postnatal growth has not been elucidated. The aim of this study was to analyze total ghrelin, acyl ghrelin (AG), and des-acyl ghrelin (DAG) in cord blood of newborns with idiopathic birth weight alterations, and to evaluate protein expression of placental GHS-R1, in order to investigate their correlation with birth weight and placental weight. We performed a cross-sectional comparative study in umbilical cord blood and placentas from healthy mothers of SGA, AGA, and LGA (small, adequate and large for gestational age) term newborns (n = 20 per group). Cord blood total ghrelin, AG, and DAG were measured by ELISA, and placental GHS-R1 expression was evaluated by Western blot. Cord blood DAG was higher in SGA compared to AGA newborns (902.1 ± 109.1 and 597.4 ± 58.2 pg/ml, respectively, p = 0.01) while LGA and AGA showed similar values (627.2 ± 76.4 pg/ml for LGA, p = 0.80). DAG negatively correlated with birthweight (r = -0.31, p = 0.02) and placental weight (r = -0.33, p = 0.02). No differences in AG or total ghrelin were found. GHS-R1 protein in placenta was not differentially expressed among SGA, AGA, and LGA. Our results suggest a role of DAG in intrauterine growth. Further studies are needed in order to elucidate the mechanisms by which DAG participates in fetal growth.

  17. High doses of ursodeoxycholic acid up-regulate the expression of placental breast cancer resistance protein in patients affected by intrahepatic cholestasis of pregnancy.

    Directory of Open Access Journals (Sweden)

    Francesco Azzaroli

    Full Text Available BACKGROUND: Ursodeoxycholic acid (UDCA administration in intrahepatic cholestasis of pregnancy (ICP induces bile acids (BA efflux from the foetal compartment, but the molecular basis of this transplacental transport is only partially defined. AIM: To determine if placental breast cancer resistance protein (BCRP, able to transport BA, is regulated by UDCA in ICP. METHODS: 32 pregnant women with ICP (14 untreated, 34.9±5.17 years; 18 treated with UDCA--25 mg/Kg/day, 32.7±4.62 years, and 12 healthy controls (33.4±3.32 years agreed to participate in the study. Placentas were obtained at delivery and processed for membrane extraction. BCRP protein expression was evaluated by immunoblotting techniques and chemiluminescence quantified with a luminograph measuring emitted photons; mRNA expression with real time PCR. Statistical differences between groups were evaluated by ANOVA with Dunn's Multiple Comparison test. RESULTS: BCRP was expressed only on the apical membrane of the syncytiotrophoblast. A significant difference was observed among the three groups both for mRNA (ANOVA, p = 0.0074 and protein (ANOVA, p<0.0001 expression. BCRP expression was similar in controls and in the untreated ICP group. UDCA induced a significant increase in placental BCRP mRNA and protein expression compared to controls (350.7±106.3 vs 100±18.68% of controls, p<0.05 and 397.8±56.02 vs 100±11.44% of controls, p<0.001, respectively and untreated ICP (90.29±17.59% of controls, p<0.05 and 155.0±13.87%, p<0.01. CONCLUSION: Our results confirm that BCRP is expressed only on the apical membrane of the syncytiotrophoblast and show that ICP treatment with high dose UDCA significantly upregulates placental BCRP expression favouring BA efflux from the foetal compartment.

  18. 肝X受体激动剂上调人肾小球内皮细胞血栓调节蛋白表达的机制和作用%Mechanism and role of LXR agonist upregulating thrombo-modulin expression in human glomerular endothelial cells

    Institute of Scientific and Technical Information of China (English)

    丁涵露; 李怡; 冯韵霖; 陈瑾; 钟翔; 王楠; 汪伟; 张萍; 王莉

    2016-01-01

    目的:探讨肝X受体(LXR)激动剂T0901317上调人肾小球内皮细胞(HRGEC)血栓调节蛋白(TM)表达的机制和作用。方法 Western blot检测25 mmol高糖和2μmol T0901317刺激后的HRGEC上IκBα、磷酸化IκBα、核转录因子-κB(NF-κB)p65、磷酸化NF-κB p65表达;免疫共沉淀法检测LXR与P300之间有无结合;重组腺病毒AdTMshRNA转染HRGEC,观察其对高糖下HRGEC分泌炎症介质的影响。结果T0901317能显著降低高糖刺激后的IκBα和NF-κB p65磷酸化(0.05)。结论LXR可能通过与P300发生相互作用阻断了NF-κB与P300之间的竞争性结合而提高TM的表达并抑制炎症介质的分泌。%Objective To explore the effect of liver X receptor (LXR) agonist T0901317 on thrombomodulin (TM) expression in human glomerular endothelial cells (HUGECs) and its mechanism. Methods Western blot was used to detect the expressions of IκBα, p-IκBα, nuclear transcription factor-κB (NF-κβ) p65 and p-NF-κB p65 in HUGECs stimulated by 25 mmol high glucose and 2μmol T0901317. The interaction between LXR and the transcriptional coactivator p300 in HUGECs was detected using co-immunoprecipitation (Co-IP) assay. The concentrations of IL-1β and TNF-α in the supernatant of HUGECs transfected with or without AdTMshRNA were determined using commercially available ELISA kits. Results T0901317 (2 μmol) significantly reduced the phosphorylation of IκBα and NF-κB p65 in the HUGECs stimulated by high glucose ( 0.05). Conclusions LXR agonist increases TM expression and inhibits secretion of inflammatory mediators probably by competitively blocking the interaction between NF-κB and p300 through interaction with p300.

  19. Immunohistochemical features of progesterone receptors expression of placental barrier in women with multiple pregnancies resulting from assisted reproduction

    Directory of Open Access Journals (Sweden)

    T. D. Zadorozhna

    2016-01-01

    Full Text Available Hormonal disorders are one of the main known causes of miscarriage and preterm birth in multiple pregnancies resulting from assisted reproductive technology (ART. Progesterone and the number of its receptors play an important role in the preservation and prolongation of pregnancy and it is the pressing issue of our time. The study of placentas, as the main site of synthesis of progesterone, has high informative potential and it is the most important diagnostic object, and information received by its research is essential for the full conclusion on the causes, mechanisms, close and long-term effects of multiple pregnancy pathology. Aim. The aim of our study was to investigate immunohistochemical features of placentas from women with dichorionic diamniotic twin pregnancies in spontaneous fertilization and after use of assisted reproductive technology (ART. Methods and results. According to this goal we examined 94 women, 44 of whom had multiple pregnancies due to ART, 42 with separate multiple pregnancy and 38 women with a singleton pregnancy. We carried out clinical and statistical analysis of the course of pregnancy and childbirth in the studied groups. During the study it was found that multiple pregnancies due to assisted reproduction belong to the high risk of gestation, at which premature births occur much more frequently than in singleton pregnancies. We were the first to carry out the immunohistochemical study of placentas in which the highest expression of progesterone receptors in the nuclei of cells of decidua (45% related to the parent structure of the placenta from women with multiple pregnancies caused by ART is found. It is also found that with increasing gestational age, there has been a significant decrease in the expression of the activity of progesterone receptors (from 45 to 2.5%, regardless of the method of conception and the number of fetuses. Conclusions. The results of the study point to the definitive link of structures of

  20. Immunobiology and therapeutic applications of protein c/protein s/thrombomodulin in human and experimental allotransplantation and xenotransplantation.

    Science.gov (United States)

    Hancock, W W; Bach, F H

    1997-07-01

    Protein C (PC), protein S (PS), and thrombomodulin (TM) constitute a well-established, physiologically important anticoagulant pathway, but they also possess significant antiinflammatory and immunoregulatory properties through their ability to regulate macrophage activation. In vivo and in vitro data concerning these antiinflammatory actions are reviewed, with an emphasis on changes in the levels of these proteins during allograft and xenograft rejection, and potential therapeutic applications arising from their exogenous administration, or genetic engineering to maintain their expression, posttransplantation. (Trends Cardiovasc Med 1997;7:174-183). © 1997, Elsevier Science Inc.

  1. Definitive class I human leukocyte antigen expression in gestational placentation: HLA-F, HLA-E, HLA-C, and HLA-G in extravillous trophoblast invasion on placentation, pregnancy, and parturition.

    Science.gov (United States)

    Hackmon, Rinat; Pinnaduwage, Lakmini; Zhang, Jianhong; Lye, Stephen J; Geraghty, Daniel E; Dunk, Caroline E

    2017-06-01

    The extravillous trophoblasts (EVT) express HLA-C and HLA-G, but HLA-E and HLA-F are the subject of conflicting reports. In this study, we define the HLA expression profile during active EVT placental implantation, pregnancy development, and parturition. Immunohistochemistry, q-PCR, and Western blot were used to investigate HLA-C, HLA-E, and HLA-F placental expression across gestation from the early first trimester, late first trimester, second trimester (n=10 in each), preterm gestation (n=6) to elective term cesarean section and term vaginal deliveries (n=12, 38-41 weeks). EVT explants and Swan71 cells were used to assess HLA-C and HLA-F during active EVT migration. HLA-G, HLA-C, and HLA-F were expressed by 1st-trimester EVT and became intracellular and weaker as gestation progressed. HLA-E was only expressed in 1st-trimester placenta. HLA-F and HLA-C mRNA and protein expression levels showed a significant increase in the fetal villous mesenchyme across gestation. HLA-C levels increased with labor. We detected a 100-kDa HLA-F band in early pregnancy suggesting dimer formation on the EVT surface. These results were confirmed in EVT outgrowths and Swan71 trophoblast which showed that HLA-F and HLA-G are increased on the cell surface of migrating EVT, while HLA-C was internalized. Expression of HLA-F and HLA-G on the cell surface of actively migrating EVT supports their specific role in early EVT invasion and interactions with uterine natural killer cells. HLA-C's limited expression to the proliferative EVT suggests a protective role in the earliest events of implantation but not in active EVT invasion. We also show for the first time that HLA-C may be involved in parturition. © 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  2. Placental Estrogen Suppresses Cyclin D1 Expression in the Nonhuman Primate Fetal Adrenal Cortex*

    Science.gov (United States)

    Dumitrescu, Adina; Aberdeen, Graham W.; Pepe, Gerald J.

    2014-01-01

    We have previously shown that estrogen selectively suppresses growth of the fetal zone of the baboon fetal adrenal cortex, which produces the C19-steroid precursors, eg, dehydroepiandrosterone sulfate, which are aromatized to estrogen within the placenta. In the present study, we determined whether fetal adrenal expression of cell cycle regulators are altered by estrogen and thus provide a mechanism by which estrogen regulates fetal adrenocortical development. Cyclin D1 mRNA levels in the whole fetal adrenal were increased 50% (P < .05), and the number of cells in the fetal adrenal definitive zone expressing cyclin D1 protein was increased 2.5-fold (P < .05), whereas the total number of cells in the fetal zone and fetal serum dehydroepiandrosterone sulfate levels were elevated 2-fold (P < .05) near term in baboons in which fetal serum estradiol levels were decreased by 95% (P < .05) after maternal administration of the aromatase inhibitor letrozole and restored to normal by concomitant administration of letrozole plus estradiol throughout second half of gestation. However, fetal adrenocortical expression of cyclin D2, the cyclin-dependent kinase (Cdk)-2, Cdk4, and Cdk6, and Cdk regulatory proteins p27Kip1 and p57Kip2 were not changed by letrozole or letrozole plus estradiol administration. We suggest that estrogen controls the growth of the fetal zone of the fetal adrenal by down-regulating cyclin D1 expression and thus proliferation of progenitor cells within the definitive zone that migrate to the fetal zone. We propose that estrogen restrains growth and function of the fetal zone via cyclin D1 to maintain estrogen levels in a physiological range during primate pregnancy. PMID:25247468

  3. Placental estrogen suppresses cyclin D1 expression in the nonhuman primate fetal adrenal cortex.

    Science.gov (United States)

    Dumitrescu, Adina; Aberdeen, Graham W; Pepe, Gerald J; Albrecht, Eugene D

    2014-12-01

    We have previously shown that estrogen selectively suppresses growth of the fetal zone of the baboon fetal adrenal cortex, which produces the C19-steroid precursors, eg, dehydroepiandrosterone sulfate, which are aromatized to estrogen within the placenta. In the present study, we determined whether fetal adrenal expression of cell cycle regulators are altered by estrogen and thus provide a mechanism by which estrogen regulates fetal adrenocortical development. Cyclin D1 mRNA levels in the whole fetal adrenal were increased 50% (P < .05), and the number of cells in the fetal adrenal definitive zone expressing cyclin D1 protein was increased 2.5-fold (P < .05), whereas the total number of cells in the fetal zone and fetal serum dehydroepiandrosterone sulfate levels were elevated 2-fold (P < .05) near term in baboons in which fetal serum estradiol levels were decreased by 95% (P < .05) after maternal administration of the aromatase inhibitor letrozole and restored to normal by concomitant administration of letrozole plus estradiol throughout second half of gestation. However, fetal adrenocortical expression of cyclin D2, the cyclin-dependent kinase (Cdk)-2, Cdk4, and Cdk6, and Cdk regulatory proteins p27(Kip1) and p57(Kip2) were not changed by letrozole or letrozole plus estradiol administration. We suggest that estrogen controls the growth of the fetal zone of the fetal adrenal by down-regulating cyclin D1 expression and thus proliferation of progenitor cells within the definitive zone that migrate to the fetal zone. We propose that estrogen restrains growth and function of the fetal zone via cyclin D1 to maintain estrogen levels in a physiological range during primate pregnancy.

  4. A Positive Feedback Loop between Glial Cells Missing 1 and Human Chorionic Gonadotropin (hCG) Regulates Placental hCGβ Expression and Cell Differentiation

    Science.gov (United States)

    Cheong, Mei-Leng; Wang, Liang-Jie; Chuang, Pei-Yun; Chang, Ching-Wen; Lee, Yun-Shien; Lo, Hsiao-Fan; Tsai, Ming-Song

    2015-01-01

    Human chorionic gonadotropin (hCG) is composed of a common α subunit and a placenta-specific β subunit. Importantly, hCG is highly expressed in the differentiated and multinucleated syncytiotrophoblast, which is formed via trophoblast cell fusion and stimulated by cyclic AMP (cAMP). Although the ubiquitous activating protein 2 (AP2) transcription factors TFAP2A and TFAP2C may regulate hCGβ expression, it remains unclear how cAMP stimulates placenta-specific hCGβ gene expression and trophoblastic differentiation. Here we demonstrated that the placental transcription factor glial cells missing 1 (GCM1) binds to a highly conserved promoter region in all six hCGβ paralogues by chromatin immunoprecipitation-on-chip (ChIP-chip) analyses. We further showed that cAMP stimulates GCM1 and the CBP coactivator to activate the hCGβ promoter through a GCM1-binding site (GBS1), which also constitutes a previously identified AP2 site. Given that TFAP2C may compete with GCM1 for GBS1, cAMP enhances the association between the hCGβ promoter and GCM1 but not TFAP2C. Indeed, the hCG-cAMP-protein kinase A (PKA) signaling pathway also stimulates Ser269 and Ser275 phosphorylation of GCM1, which recruits CBP to mediate GCM1 acetylation and stabilization. Consequently, hCG stimulates the expression of GCM1 target genes, including the fusogenic protein syncytin-1, to promote placental cell fusion. Our study reveals a positive feedback loop between GCM1 and hCG regulating placental hCGβ expression and cell differentiation. PMID:26503785

  5. Altered fibrinolysis in autosomal dominant thrombomodulin-associated coagulopathy

    Science.gov (United States)

    Burley, Kate; Whyte, Claire S.; Westbury, Sarah K.; Walker, Mary; Stirrups, Kathleen E.; Turro, Ernest; Chapman, Oliver G.; Reilly-Stitt, Christopher; Mutch, Nicola J.

    2016-01-01

    Thrombomodulin-associated coagulopathy (TM-AC) is a newly recognized dominant bleeding disorder in which a p.Cys537Stop variant in the thrombomodulin (TM) gene THBD, results in high plasma TM levels and protein C-mediated suppression of thrombin generation. Thrombin in complex with TM also activates thrombin-activatable fibrinolysis inhibitor (TAFI). However, the effect of the high plasma TM on fibrinolysis in TM-AC is unknown. Plasma from TM-AC cases and high-TM model control samples spiked with recombinant soluble TM showed reduced tissue factor–induced thrombin generation. Lysis of plasma clots from TM-AC cases was significantly delayed compared with controls but was completely restored when TM/thrombin-mediated TAFI activation was inhibited. Clots formed in blood from TM-AC cases had the same viscoelastic strength as controls but also showed a TAFI-dependent delay in fibrinolysis. Delayed fibrinolysis was reproduced in high-TM model plasma and blood samples. Partial restoration of thrombin generation with recombinant activated factor VII or activated prothrombin complex concentrate did not alter the delayed fibrinolysis in high-TM model blood. Our finding of a previously unrecognized fibrinolytic phenotype indicates that bleeding in TM-AC has a complex pathogenesis and highlights the pivotal role of TM as a regulator of hemostasis. PMID:27436851

  6. Folic acid supplementation during pregnancy induces sex-specific changes in methylation and expression of placental 11β-hydroxysteroid dehydrogenase 2 in rats.

    Directory of Open Access Journals (Sweden)

    Reyna Penailillo

    Full Text Available In the placenta, 11β-hydroxysteroid dehydrogenase type 2 (11β-HSD2 limits fetal glucocorticoid exposure and its inhibition has been associated to low birth weight. Its expression, encoded by the HSD11B2 gene is regulated by DNA methylation. We hypothesized that maternal diets supplemented with folic acid (FA during pregnancy modify the expression of placental HSD11B2 through gene methylation. Wistar rats were fed with high (8 mg/kg or normal low (1mg/kg, control levels of FA during pregnancy. Concentrations of mRNA and protein in placentas were determined by qRT-PCR and Western blot respectively. Methylation in five CpG sites of the placental HSD11B2 promoter (-378 to -275 was analyzed by bacterial cloning and subsequent sequencing. In the FA-supplemented group, mRNA and protein levels of 11β-HSD2 decreased by 58% and increased by 89%, respectively, only in placentas attached to males. In controls, most CpG sites were not methylated except for the CpG2 site which was 80% methylated. CpG2 methylation level increased under the FA treatment; however, only in placentas attached to females was this increase significant (113%. This change was not related to HSD11B2 expression. Fetal weight of females from FA- supplemented mothers was 6% higher than females from control mothers. In conclusion, this is the first study reporting that FA over supplementation during pregnancy modifies the placental HSD11B2 gene expression and methylation in a sex-dependent manner, suggesting that maternal diets with high content of FA can induce early sex-specific responses, which may lead to long-term consequences for the offspring.

  7. Folic acid supplementation during pregnancy induces sex-specific changes in methylation and expression of placental 11β-hydroxysteroid dehydrogenase 2 in rats.

    Science.gov (United States)

    Penailillo, Reyna; Guajardo, Angelica; Llanos, Miguel; Hirsch, Sandra; Ronco, Ana Maria

    2015-01-01

    In the placenta, 11β-hydroxysteroid dehydrogenase type 2 (11β-HSD2) limits fetal glucocorticoid exposure and its inhibition has been associated to low birth weight. Its expression, encoded by the HSD11B2 gene is regulated by DNA methylation. We hypothesized that maternal diets supplemented with folic acid (FA) during pregnancy modify the expression of placental HSD11B2 through gene methylation. Wistar rats were fed with high (8 mg/kg) or normal low (1mg/kg, control) levels of FA during pregnancy. Concentrations of mRNA and protein in placentas were determined by qRT-PCR and Western blot respectively. Methylation in five CpG sites of the placental HSD11B2 promoter (-378 to -275) was analyzed by bacterial cloning and subsequent sequencing. In the FA-supplemented group, mRNA and protein levels of 11β-HSD2 decreased by 58% and increased by 89%, respectively, only in placentas attached to males. In controls, most CpG sites were not methylated except for the CpG2 site which was 80% methylated. CpG2 methylation level increased under the FA treatment; however, only in placentas attached to females was this increase significant (113%). This change was not related to HSD11B2 expression. Fetal weight of females from FA- supplemented mothers was 6% higher than females from control mothers. In conclusion, this is the first study reporting that FA over supplementation during pregnancy modifies the placental HSD11B2 gene expression and methylation in a sex-dependent manner, suggesting that maternal diets with high content of FA can induce early sex-specific responses, which may lead to long-term consequences for the offspring.

  8. DSCR9 gene simultaneous expression in placental, testicular and renal tissues from baboon (papio hamadryas

    Directory of Open Access Journals (Sweden)

    Rodriguez-Sanchez Irám

    2012-06-01

    Full Text Available Abstract Background In 2002 Takamatsu and co-workers described the human DSCR9 gene and observed that it was transcriptionally active in human testicular tissue, but no protein was identified as a product of this transcript. Similar results were obtained in chimpanzee tissue. This gene has not been detected in species other than primates, suggesting that DSCR9 is exclusively found in these mammals. Results We report evidence of DSCR9 expression in placenta, testis and kidney of baboon (Papio hamadryas. We used primers specific for DSCR9 to amplify transcripts through reverse transcription (RT coupled to polymerase chain reaction (PCR. Furthermore, PCR was used to amplify the complete DSCR9 gene from genomic DNA from three baboons. We amplified and sequenced five overlapping segments that were assembled into the 3284 bp baboon DSCR9 gene, including the putative promoter and the entire transcriptional unit (5'-UTR, CDS and 3'-UTR. Conclusions The baboon DSCR9 gene is highly similar to the human counterpart. The isolated transcripts from baboon tissues (placenta, testis and kidney of three different baboons correspond to the human orthologous gene.

  9. Human monoclonal IgG selection of Plasmodium falciparum for the expression of placental malaria-specific variant surface antigens

    DEFF Research Database (Denmark)

    Soerli, J; Barfod, L; Lavstsen, T;

    2009-01-01

    Pregnancy-associated Plasmodium falciparum malaria (PAM) is a major cause of morbidity and mortality in African women and their offspring. PAM is characterized by accumulation of infected erythrocytes (IEs) that adhere to chondroitin sulphate A (CSA) in the placental intervillous space. We show...

  10. Placental leptin mRNA expression and serum leptin levels in pre-eclampsia associated with HIV infection.

    Science.gov (United States)

    Haffejee, Firoza; Naicker, Thajasvarie; Singh, Moganavelli; Kharsany, Ayesha B M; Adhikari, Miriam; Singh, Ravesh; Maharaj, Niren; Moodley, Jagidesa

    2017-01-01

    Leptin, primarily produced by adipocytes, is implicated in the development of pre-eclampsia. This study examines placental leptin production and serum leptin levels in HIV infected and uninfected normotensive and pre-eclamptic pregnancies. Placental leptin production was analysed by RT-PCR and serum leptin levels by ELISA in normotensive (n = 90) and pre-eclamptic (n = 90) pregnancies which were further stratified by HIV status. Placental leptin production was higher in pre-eclampsia compared to normotensive pregnancies irrespective of HIV status (p = .04). Serum leptin was non-significantly raised in HIV uninfected (p = .42) but lower in HIV-infected (p = .03) pre-eclampsia. The latter had lower BMI (p = .007) and triceps skin-fold thickness (p leptin and triceps skin-fold thickness (p leptin. Thus, serum leptin levels are not indicative of increased placental production when pre-eclampsia is associated with HIV infection.

  11. Effect of curcumin on expressions of NF-κBp65, TNF-α and IL-8 in placental tissue of premature birth of infected mice.

    Science.gov (United States)

    Guo, Yan-Zi; He, Ping; Feng, Ai-Min

    2017-02-01

    To observe the effect of curcumin on expressions of nuclear transcription factor-kappa Bp65 (NF-κBp65), TNF-α and IL-8 in placental tissue of premature birth of infected mice induced by lipopolysaccharide (LPS). A total of 60 C57BL/6 mice pregnant with 15 d were collected and randomly divided into control group, model group, treatment group and preventative group. LPS was repeatedly injected in abdominal cavity to construct infected premature birth model, while mice of control group were given with 100 mg/kg of vitamin C through abdominal cavity injection and mice of treatment group and preventative group were given curcumin of 100 mg/kg through abdominal cavity injection after modeling operation and before 1 d of modeling operation, respectively. A total of 5 mice of four groups respectively were executed by cervical dislocation after 6 h, 12 h and 24 h after constructing model. Placental tissues were collected and the immunohistochemical method SABC of immunologic tissue was used to detect the expression of NF-κBp65, TNF-α and IL-8 and peripheral blood of executed mice after 24 h was collected to detect the concentrations of IL-8, malondialdehyde (MDA) and superoxide dismutase (SOD), meanwhile live birth rate of four groups was contrasted. Staining intensity of NF-κBp65, TNF-α and IL-8 in placental tissue of treatment group and preventative group was significantly higher than control group but lower than model group (P premature birth of infected mice, reduce the expression of TNF-α and IL-8 and relieve the damage of lipid peroxide of oxidative stress of LPS on mother-fetus and further to achieve the objective of preventing and curing premature birth induced with infection. Copyright © 2017 Hainan Medical University. Production and hosting by Elsevier B.V. All rights reserved.

  12. Unravelling the pluripotency paradox in fetal and placental mesenchymal stem cells: Oct-4 expression and the case of The Emperor's New Clothes.

    Science.gov (United States)

    Ryan, Jennifer M; Pettit, Allison R; Guillot, Pascale V; Chan, Jerry K Y; Fisk, Nicholas M

    2013-08-01

    Mesenchymal stem cells (MSC) from fetal-placental tissues have translational advantages over their adult counterparts, and have variably been reported to express pluripotency markers. OCT-4 expression in fetal-placental MSC has been documented in some studies, paradoxically without tumourogenicity in vivo. It is possible that OCT-4 expression is insufficient to induce true "stemness", but this issue is important for the translational safety of fetal-derived MSC. To clarify this, we undertook a systematic literature review on OCT-4 in fetal or adnexal MSC to show that most studies report OCT-4 message or protein expression, but no study provides definitive evidence of true OCT-4A expression. Discrepant findings were attributable not to different culture conditions, tissue sources, or gestational ages but instead to techniques used. In assessing OCT-4 as a pluripotency marker, we highlight the challenges in detecting the correct OCT-4 isoform (OCT-4A) associated with pluripotency. Although specific detection of OCT-4A mRNA is achievable, it appears unlikely that any antibody can reliably distinguish between OCT-4A and the pseudogene OCT-4B. Finally, using five robust techniques we demonstrate that fetal derived-MSC do not express OCT-4A (or by default OCT-4B). Reports suggesting OCT-4 expression in fetal-derived MSC warrant reassessment, paying attention to gene and protein isoforms, pseudogenes, and antibody choice as well as primer design. Critical examination of the OCT-4 literature leads us to suggest that OCT-4 expression in fetal MSC may be a case of "The Emperor's New Clothes" with early reports of (false) positive expression amplified in subsequent studies without critical attention to emerging refinements in knowledge and methodology.

  13. IFPA Meeting 2013 Workshop Report II: use of 'omics' in understanding placental development, bioinformatics tools for gene expression analysis, planning and coordination of a placenta research network, placental imaging, evolutionary approaches to understanding pre-eclampsia.

    Science.gov (United States)

    Ackerman, W E; Adamson, L; Carter, A M; Collins, S; Cox, B; Elliot, M G; Ermini, L; Gruslin, A; Hoodless, P A; Huang, J; Kniss, D A; McGowen, M R; Post, M; Rice, G; Robinson, W; Sadovsky, Y; Salafia, C; Salomon, C; Sled, J G; Todros, T; Wildman, D E; Zamudio, S; Lash, G E

    2014-02-01

    Workshops are an important part of the IFPA annual meeting as they allow for discussion of specialized topics. At the IFPA meeting 2013 twelve themed workshops were presented, five of which are summarized in this report. These workshops related to various aspects of placental biology but collectively covered areas of new technologies for placenta research: 1) use of 'omics' in understanding placental development and pathologies; 2) bioinformatics and use of omics technologies; 3) planning and coordination of a placenta research network; 4) clinical imaging and pathological outcomes; 5) placental evolution.

  14. Correlation of STAT4 and STAT6 expression levels in preeclampsia placenta with sFlt-1 and ADMA generation as well as placental hypoxia

    Institute of Scientific and Technical Information of China (English)

    Dong-Mei Su

    2016-01-01

    Objective:To study the correlation of STAT4 and STAT6 expression levels in preeclampsia placenta with soluble fms-like tyrosine kinase-1 (sFlt-1) and asymmetric dimethylarginine (ADMA) generation as well as placental hypoxia.Methods:A total of 40 pregnant women with preeclampsia were selected as preeclampsia group (PE group) of the study, 40 healthy pregnant women preparing for the delivery in our hospital during the same period were selected as the control group of the study, serum was collected to determine STAT4, STAT6, sFlt-1 and ADMA levels, the placenta was collected to determine STAT4, STAT6, HIF-1α and HSP70 expression, and ultrasonography was conducted to measure uterine spiral artery PI, RI and S/D.Results:STAT4 expression levels in placenta and serum of PE group were significantly higher than those of control group while STAT6 expression levels were significantly lower than those of control group; HSP70 and HIF-1α expression levels in placenta of PE group were significantly higher than those of control group, positively correlated with STAT4 and negatively correlated with STAT6, sFlt-1 and ADMA levels in serum were significantly higher than those of control group, positively correlated with STAT4 and negatively correlated with STAT6, and uterine spiral artery PI, RI and S/D were significantly higher than those of control group, positively related with STAT4 and negatively correlated with STAT6.Conclusions:High expression of STAT4 and low expression of STAT6 in preeclampsia placenta are closely related to placental hypoxia.

  15. Differential expression of angiotensin II type 1 and type 2 receptors at the maternal-fetal interface: potential roles in early placental development.

    Science.gov (United States)

    Tower, C L; Lui, S; Charlesworth, N R; Smith, S D; Aplin, J D; Jones, R L

    2010-12-01

    Angiotensin II (Ang II) is locally generated in the placenta and regulates syncytial transport, vascular contractility and trophoblast invasion. It acts through two receptor subtypes, AGTR1 and AGTR2 (AT1 and AT2), which typically mediate antagonising actions. The objectives of this study are to characterise the cellular distribution of AGTR1 and AGTR2 at the maternal-fetal interface and explore the effects on cytotrophoblast turnover. Low levels of AGTR2 mRNA were detected in first trimester placental homogenates using real-time PCR. Immunohistochemistry using polyclonal antibodies against AGTR1 and AGTR2 detected the receptors in first trimester placenta, decidua basalis and villous tip outgrowths in culture. Serial staining with cytokeratin-7 was used to identify extravillous trophoblasts (EVTs). AGTR1 was found in the syncytiotrophoblast microvillous membrane, in a subpopulation of villous cytotrophoblasts, and in Hofbauer cells. AGTR1 was strongly upregulated in cytotrophoblasts in cell columns and villous tip outgrowths, but was absent in interstitial and endovascular EVTs within the decidua. AGTR2 immunostaining was present in Hofbauer cells and villous cytotrophoblasts, but was absent from syncytiotrophoblast. Faint staining was detected in cell column cytotrophoblasts and villous outgrowths, but not in EVTs within the decidua. Both receptors were detected in placental homogenates by western blotting. Ang II significantly increased proliferation of cytotrophoblasts in both villous explants and villous tip outgrowths, but did not affect apoptosis. Blockade of AGTR1 and AGTR2 together abrogated this effect. This study shows specific expression patterns for AGTR1 and AGTR2 in distinct trophoblast populations at the maternal-fetal interface and suggests that Ang II plays a role in placental development and generation of EVTs.

  16. Expression and Functional Activity of the Human Bitter Taste Receptor TAS2R38 in Human Placental Tissues and JEG-3 Cells

    Directory of Open Access Journals (Sweden)

    Ute Wölfle

    2016-03-01

    Full Text Available Bitter taste receptors (TAS2Rs are expressed in mucous epithelial cells of the tongue but also outside the gustatory system in epithelial cells of the colon, stomach and bladder, in the upper respiratory tract, in the cornified squamous epithelium of the skin as well as in airway smooth muscle cells, in the testis and in the brain. In the present work we addressed the question if bitter taste receptors might also be expressed in other epithelial tissues as well. By staining a tissue microarray with 45 tissue spots from healthy human donors with an antibody directed against the best characterized bitter taste receptor TAS2R38, we observed an unexpected strong TAS2R38 expression in the amniotic epithelium, syncytiotrophoblast and decidua cells of the human placenta. To analyze the functionality we first determined the TAS2R38 expression in the placental cell line JEG-3. Stimulation of these cells with diphenidol, a clinically used antiemetic agent that binds TAS2Rs including TAS2R38, demonstrated the functionality of the TAS2Rs by inducing calcium influx. Restriction enzyme based detection of the TAS2R38 gene allele identified JEG-3 cells as PTC (phenylthiocarbamide-taster cell line. Calcium influx induced by PTC in JEG-3 cells could be inhibited with the recently described TAS2R38 inhibitor probenecid and proved the specificity of the TAS2R38 activation. The expression of TAS2R38 in human placental tissues points to further new functions and hitherto unknown endogenous ligands of TAS2Rs far beyond bitter tasting.

  17. Expression and Functional Activity of the Human Bitter Taste Receptor TAS2R38 in Human Placental Tissues and JEG-3 Cells.

    Science.gov (United States)

    Wölfle, Ute; Elsholz, Floriana A; Kersten, Astrid; Haarhaus, Birgit; Schumacher, Udo; Schempp, Christoph M

    2016-03-03

    Bitter taste receptors (TAS2Rs) are expressed in mucous epithelial cells of the tongue but also outside the gustatory system in epithelial cells of the colon, stomach and bladder, in the upper respiratory tract, in the cornified squamous epithelium of the skin as well as in airway smooth muscle cells, in the testis and in the brain. In the present work we addressed the question if bitter taste receptors might also be expressed in other epithelial tissues as well. By staining a tissue microarray with 45 tissue spots from healthy human donors with an antibody directed against the best characterized bitter taste receptor TAS2R38, we observed an unexpected strong TAS2R38 expression in the amniotic epithelium, syncytiotrophoblast and decidua cells of the human placenta. To analyze the functionality we first determined the TAS2R38 expression in the placental cell line JEG-3. Stimulation of these cells with diphenidol, a clinically used antiemetic agent that binds TAS2Rs including TAS2R38, demonstrated the functionality of the TAS2Rs by inducing calcium influx. Restriction enzyme based detection of the TAS2R38 gene allele identified JEG-3 cells as PTC (phenylthiocarbamide)-taster cell line. Calcium influx induced by PTC in JEG-3 cells could be inhibited with the recently described TAS2R38 inhibitor probenecid and proved the specificity of the TAS2R38 activation. The expression of TAS2R38 in human placental tissues points to further new functions and hitherto unknown endogenous ligands of TAS2Rs far beyond bitter tasting.

  18. Pregnancy Complications: Placental Abruption

    Science.gov (United States)

    ... wall of the uterus (womb) and supplies the baby with food and oxygen through the umbilical cord. Placental abruption ... wall of the uterus (womb) and supplies the baby with food and oxygen through the umbilical cord. Placental abruption ...

  19. Thrombomodulin Ala455Val Polymorphism and the risk of cerebral infarction in a biracial population: the Stroke Prevention in Young Women Study

    Directory of Open Access Journals (Sweden)

    Mitchell Braxton D

    2004-12-01

    associated with increased risk of early onset ischemic stroke. Removing strokes potentially related to cardioembolic phenomena increased this association. Further studies are needed to determine whether this polymorphism is functionally related to thrombomodulin expression or whether the association is due to population stratification or linkage to a nearby functional polymorphism.

  20. Acceleration of the thrombin inactivation of single chain urokinase-type plasminogen activator (pro-urokinase) by thrombomodulin

    NARCIS (Netherlands)

    Munk, G.A.W. de; Groeneveld, E.; Rijken, D.C.

    1991-01-01

    The in vitro effects of thrombomodulin on the inactivation of single chain urokinase-type plasminogen activator (scu-PA) by thrombin were investigated by incubating scu-PA with varying concentrations of human thrombin, in both the absence and presence of soluble rabbit thrombomodulin. 50%

  1. Spatio-temporal expression patterns of anandamide-binding receptors in rat implantation sites: evidence for a role of the endocannabinoid system during the period of placental development

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    Konje Justin C

    2009-10-01

    Full Text Available Abstract Background Although there is growing evidence that endocannabinoids play a critical role in early pregnancy, there are no studies describing the possible targets for this system after implantation. The endometrial stroma, which undergoes extensive proliferation and differentiation giving rise to the decidua and the trophoblast cells that invade after the initial stages of implantation, are potential targets. Since high anandamide (AEA levels, the main endocannabinoid, are detrimental to implantation and in order to gain insight into the role of the endocannabinoid system in the development of the fetoplacental unit, the spatio-temporal pattern of expression of the anandamide-binding receptors, CB1, CB2 and the vanilloid receptor (TRPV1, were investigated by quantitative RT-PCR, western blot and immunohistochemistry. Methods Rat uterine maternal tissues from different days of pregnancy were used to investigate the expression of CB1, CB2 and vanilloid receptors by quantitative RT-PCR, western blot and immunohistochemistry. Results The data indicate that all the three receptors were expressed in decidualized cells and placenta. Interestingly, CB1 and CB2 were also expressed in smooth muscle cells of maternal blood vessels and in endovascular trophoblast cells, whereas TRPV1 was mainly expressed in uterine natural killer (uNK cells and in the longitudinal muscle layer throughout pregnancy. In all tissues, CB2 protein was present at a lower level than CB1. Conclusion These observations support a role for the endocannabinoid system during the period of decidualization and placental development.

  2. The physiological expression of scavenger receptor SR-B1 in canine endometrial and placental epithelial cells and its potential involvement in pathogenesis of pyometra.

    Science.gov (United States)

    Gabriel, C; Becher-Deichsel, A; Hlavaty, J; Mair, G; Walter, I

    2016-06-01

    Pyometra, the purulent inflammation of the uterus, is a common uterine disease of bitches that has potentially life-threatening consequences. The opportunistic bacterial infection of the uterus often progresses into the serious systemic inflammatory response syndrome. In a previous study, we characterized epithelial foam cells in the canine endometrial surface occurring in metestrus, and we regularly observed pronounced epithelial foam-cell formations in pyometra-affected uteri. Therefore, it was assumed that the mechanism behind lipid droplet accumulation in surface epithelial cells might even increase bacterial binding capacity and promote pyometra development. Lipid droplet accumulation in epithelial cells is accomplished via specialized lipid receptors called scavenger receptors (SR). Scavenger receptor class B type 1 (SR-B1) is an important receptor for lipid accumulation in diverse cell types, but it is also a strong binding partner for bacteria, and thereby enhances bacterial adhesion and clinical signs of systemic inflammatory response syndrome. In the present study, after the isolation of metestrous surface epithelial cells from canine uteri by laser capture microdissection, SR-B1 was identified at the messenger RNA (mRNA) level by quantitative real time polymerase chain reaction and also at the protein level by means of immunohistochemistry. In pyometra-affected uteri, SR-B1 mRNA expression was higher than that in the healthy control samples, and SR-B1 protein was expressed in the surface and crypt epithelial cells. Furthermore, to understand the physiological role of SR-B1 expression in the metestrus surface epithelial cells, we investigated its expression in the epithelial cells of the glandular chambers of canine placenta in different stages of gestation because these cells are also characterized by lipid droplet accumulation. SR-B1 was present in the placental epithelial cells of the glandular chambers from 25 to 30 and 45 to 50 days of gestation

  3. 携人血栓调节蛋白基因慢病毒载体的构建及其在内皮祖细胞中的表达%Construction of lentiviral vector containing human thrombomodulin gene and its expression in endothelial progenitor cells of rabbits

    Institute of Scientific and Technical Information of China (English)

    赵国峰; 邓钢; 侯居攀; 吴志平; 许荣睿; 秦永林; 金晖

    2014-01-01

    Objective To construct the lentiviral vector containing human thrombomodulin (hTM) gene,and examine the expression of hTM in rabbit peripheral endothelial progenitor cells (EPCs)after transduction and its effect on the biological functions of EPCs.Methods The lentivirus plenti6.3-hTM-IRES-EGFP was reconstructed by polymerase chain reaction (PCR).EPCs were isolated from fresh blood obtained from the heart of a rabbit by density-gradient centrifugation and then were transduced with above lentiviral vector.To evaluate the transduction efficiency of plenti6.3-hTM-IRES-EGFP,quantitativepolymerase chain reaction (Q-PCR),Western blotting and facial action coding system(FACS) were performed.Acetylated low density lipoprotein (DiI-ac-LDL) and fluorescein isothiocyanate (FITC)-UEA-1 double fluorescent labeling was used for the identification of EPCs.Methyl thiazol tetrazolium (MTT) and transwell assays were carried out to examine the proliferation and migration of EPCs in the presence or absence of hTM.Results The recombinant plenti6.3-hTM-IRES-EGFP was confirmed by the evidence of DNA sequence analysis and Western blotting.The transduced EPCs were found overexpressing hTM by Q-PCR,Western blotting and FACS,suggesting the recombinant lentivirus system was successfully constructed.There were no changes in the biological functions of EPCs overexpressing hTM.Conclusion The plenti6.3-hTM-IRES-EGFP has been successfully constructed and hTM can be efficiently and highly expressed in EPCs.All of these provide us experimental evidence for gene-cell combined therapy and further study of TM on inhibiting thrombotic restenosis of arterial occlusive diseases after percutaneous transluminal angioplasty (PTA) treatment.%目的 构建携带人血栓调节蛋白(hTM)基因的慢病毒表达载体(plenti6.3-hTM-IRES-EGFP),体外转染兔外周血内皮祖细胞(EPCs),并观察其在EPCs中的表达及对其功能的影响.方法 采用DNA重组技术构建plenti6.3-hTM-IRES-EGFP慢病毒表

  4. In Vitro Infection of Trypanosoma cruzi Causes Decrease in Glucose Transporter Protein-1 (GLUT1 Expression in Explants of Human Placental Villi Cultured under Normal and High Glucose Concentrations

    Directory of Open Access Journals (Sweden)

    Luciana Mezzano

    2012-01-01

    Full Text Available Trypanosoma cruzi, the etiologic Chagas' disease agent, induces changes in protein pattern of the human placenta syncytiotrophoblast. The glucose transporter protein-1 (GLUT1 is the primary isoform involved in transplacental glucose transport. We carried out in vitro assays to determine if T. cruzi infection would induce changes in placental GLUT1 protein expression under normal and high concentration of glucose. Using Western blot and immunohistological techniques, GLUT1 expression was determined in normal placental villi cultured under normal or high concentrations of glucose, with or without in vitro T. cruzi infection, for 24 and 48 hours. High glucose media or T. cruzi infection alone reduced GLUT1 expression. A yet more accentuated reduction was observed when infection and high glucose condition took place together. We inform, for the first time, that T. cruzi infection may induce reduction of GLUT1 expression under normal and high glucose concentrations, and this effect is synergic to high glucose concentrations.

  5. Placental transfusion: a review

    Science.gov (United States)

    Katheria, A C; Lakshminrusimha, S; Rabe, H; McAdams, R; Mercer, J S

    2017-01-01

    Recently there have been a number of studies and presentations on the importance of providing a placental transfusion to the newborn. Early cord clamping is an avoidable, unphysiologic intervention that prevents the natural process of placental transfusion. However, placental transfusion, although simple in concept, is affected by multiple factors, is not always straightforward to implement, and can be performed using different methods, making this basic procedure important to discuss. Here, we review three placental transfusion techniques: delayed cord clamping, intact umbilical cord milking and cut-umbilical cord milking, and the evidence in term and preterm newborns supporting this practice. We will also review several factors that influence placental transfusion, and discuss perceived risks versus benefits of this procedure. Finally, we will provide key straightforward concepts and implementation strategies to ensure that placental-to-newborn transfusion can become routine practice at any institution. PMID:27654493

  6. Plasma thrombomodulin changes in acute cerebral infarction or hypertension patients An observation for verification

    Institute of Scientific and Technical Information of China (English)

    Pu Feng; Hui Zhang; Bingyi Yang; Yonggang Zheng; Jinhui Xie; Ying Wang; Jinchuan Li

    2008-01-01

    BACKGROUND: Thrombomodulin concentration greatly increases in plasma when vascular endothelial cells are injured, and it is one of the specific molecular markers for endothelial injury.OBJECTIVE: To analyze the plasma levels of thrombomodulin after cerebral infarction or hypertension, and to compare levels with those from healthy control subjects.DESIGN: A case-controlled observation. SETTING: Yuquan Hospital of Tsinghua University.PARTICIPANTS: Patients with hypertension (n = 37) and acute cerebral infarction (n = 26) were selected from the outpatient and inpatient Department of Neurology, Yuquan Hospital of Tsinghua University from February 2003 to February 2006. The cerebral infarction group consisted of 24 males and 2 females, 36–77 years of age, with a mean age of 62 years. All patients fulfilled the diagnosis criteria for cerebral infarction, according to the diagnostic standards revised by the Second National Academic Meeting for Cerebrovascular Disease, and were confirmed by CT or MRI. The hypertension group consisted of 27 males and 10 females, 36–77 years of age, with a mean age of 56 years. These patients fulfilled the diagnostic criteria for hypertension set by WHO. In addition, 43 healthy physical examinees were selected as the control group, consisting of 23 males and 20 females, 35–67 years of age.Informed consent was obtained from all participants.METHODS: In the cerebral infarction group, thrombomodulin plasma levels were determined by enzyme-linked immunoabsorbent assay at days 1, 3, 7, and 14 after attack. Thrombomodulin plasma levels were determined only once in the hypertension group and the control group. The results from the cerebral infarction group were compared with those from the hypertension group and the control group. MAIN OUTCOME MEASURES: Level of thrombomodulin in plasma.RESULTS: All 63 patients and 43 healthy volunteers were included in the final analysis of results. ① At 7 days after the attack, the plasma levels of

  7. Characterization of placental cholesterol transport

    DEFF Research Database (Denmark)

    Lindegaard, Marie L; Wassif, Christopher A; Vaisman, Boris

    2008-01-01

    Patients with Smith-Lemli-Opitz syndrome (SLOS) are born with multiple congenital abnormalities. Postnatal cholesterol supplementation is provided; however, it cannot correct developmental malformations due to in utero cholesterol deficit. Increased transport of cholesterol from maternal to fetal...... circulation might attenuate congenital malformations. The cholesterol transporters Abca1, Abcg1, and Sr-b1 are present in placenta; however, their potential role in placental transport remains undetermined. In mice, expression analyses showed that Abca1 and Abcg1 transcripts increased 2-3-fold between...... embryonic days 13.5 and 18.5 in placental tissue; whereas, Sr-b1 expression decreased. To examine the functional role of Abca1, Abcg1 and Sr-b1 we measured the maternal-fetal transfer of (14)C-cholesterol in corresponding mutant embryos. Disruption of either Abca1 or Sr-b1 decreased cholesterol transfer...

  8. Progesterone receptor (PR) isoforms PRA and PRB differentially regulate expression of the breast cancer resistance protein in human placental choriocarcinoma BeWo cells.

    Science.gov (United States)

    Wang, Honggang; Lee, Eun-Woo; Zhou, Lin; Leung, Peter C K; Ross, Douglas D; Unadkat, Jashvant D; Mao, Qingcheng

    2008-03-01

    Breast cancer resistance protein (BCRP) plays a significant role in drug disposition and in conferring multidrug resistance in cancer cells. Previous studies have shown that steroid hormones such as 17beta-estradiol and progesterone can affect BCRP expression in cancer cells. In this study, we investigated the molecular mechanism by which BCRP expression in human placental choriocarcinoma BeWo cells is regulated by progesterone. Transfection of the progesterone receptor (PR) isoforms PRA and PRB resulted in a similarly increased expression of PRA and PRB, respectively. However, progesterone significantly increased BCRP expression and activity only in PRB-transfected cells. This stimulatory effect of progesterone was abrogated by the PR antagonist mifepristone (RU-486). Consistently, transcriptional activity of the BCRP promoter was induced 2- to 6-fold by 10(-8) to 10(-5) M progesterone in PRB-transfected cells. Progesterone had little effect on BCRP expression and activity and transcriptional activity of the BCRP promoter in PRA-transfected cells; however, cotransfection of PRA and PRB significantly decreased the progesterone-response compared with that in cells transfected with only PRB. Mutations in a novel progesterone response element (PRE) identified between -243 to -115 bp of the BCRP promoter region significantly attenuated the progesterone-response in PRB-transfected cells, and deletion of the PRE nearly completely abrogated the progesterone effect. Specific binding of both PRA and PRB to the BCRP promoter through the identified PRE was confirmed using the electrophoretic mobility shift assay. Collectively, progesterone induces BCRP expression in BeWo cells via PRB but not PRA. PRA represses the PRB activity. Thus, PRA and PRB differentially regulate BCRP expression in BeWo cells.

  9. The distinct proteome of placental malaria parasites.

    Energy Technology Data Exchange (ETDEWEB)

    Fried, Michal; Hixson, Kim K.; Anderson, Lori; Ogata, Yuko; Mutabingwa, Theonest K.; Duffy, Patrick E.

    2007-09-01

    Malaria proteins expressed on the surface of Plasmodium falciparum infected erythrocytes (IE) mediate adhesion and are targeted by protective immune responses. During pregnancy, IE sequester in the placenta. Placental IE bind to the molecule chondroitin sulfate A (CSA) and preferentially transcribe the gene that encodes VAR2CSA, a member of the PfEMP1 variant surface antigen family. Over successive pregnancies women develop specific immunity to CSA-binding IE and antibodies to VAR2CSA. We used tandem mass spectrometry together with accurate mass and time tag technology to study IE membrane fractions of placental parasites. VAR2CSA peptides were detected in placental IE and in IE from children, but the MC variant of VAR2CSA was specifically associated with placental IE. We identified six conserved hypothetical proteins with putative TM or signal peptides that were exclusively expressed by the placental IE, and 11 such proteins that were significantly more abundant in placental IE. One of these hypothetical proteins, PFI1785w, is a 42kDa molecule detected by Western blot in parasites infecting pregnant women but not those infecting children.

  10. Liquid-Diet with Alcohol Alters Maternal, Fetal and Placental Weights and the Expression of Molecules Involved in Integrin Signaling in the Fetal Cerebral Cortex

    Directory of Open Access Journals (Sweden)

    Ujjwal K. Rout

    2010-11-01

    Full Text Available Maternal alcohol consumption during pregnancy causes wide range of behavioral and structural deficits in children, commonly known as Fetal Alcohol Syndrome (FAS. Children with FAS may suffer behavioral deficits in the absence of obvious malformations. In rodents, the exposure to alcohol during gestation changes brain structures and weights of offspring. The mechanism of FAS is not completely understood. In the present study, an established rat (Long-Evans model of FAS was used. The litter size and the weights of mothers, fetuses and placentas were examined on gestation days 18 or 20. On gestation day 18, the effects of chronic alcohol on the expression levels of integrin receptor subunits, phospholipase-Cγ and N-cadherin were examined in the fetal cerebral cortices. Presence of alcohol in the liquid-diet reduced the consumption and decreased weights of mothers and fetuses but increased the placental weights. Expression levels of β1 and α3 integrin subunits and phospholipase-Cγ2 were significantly altered in the fetal cerebral cortices of mothers on alcohol containing diet. Results show that alcohol consumption during pregnancy even with protein, mineral and vitamin enriched diet may affect maternal and fetal health, and alter integrin receptor signaling pathways in the fetal cerebral cortex disturbing the development of fetal brains.

  11. Recombinant thrombomodulin protects mice against histone-induced lethal thromboembolism.

    Directory of Open Access Journals (Sweden)

    Mayumi Nakahara

    Full Text Available INTRODUCTION: Recent studies have shown that histones, the chief protein component of chromatin, are released into the extracellular space during sepsis, trauma, and ischemia-reperfusion injury, and act as major mediators of the death of an organism. This study was designed to elucidate the cellular and molecular basis of histone-induced lethality and to assess the protective effects of recombinant thrombomodulin (rTM. rTM has been approved for the treatment of disseminated intravascular coagulation (DIC in Japan, and is currently undergoing a phase III clinical trial in the United States. METHODS: Histone H3 levels in plasma of healthy volunteers and patients with sepsis and DIC were measured using enzyme-linked immunosorbent assay. Male C57BL/6 mice were injected intravenously with purified histones, and pathological examinations were performed. The protective effects of rTM against histone toxicity were analyzed both in vitro and in mice. RESULTS: Histone H3 was not detectable in plasma of healthy volunteers, but significant levels were observed in patients with sepsis and DIC. These levels were higher in non-survivors than in survivors. Extracellular histones triggered platelet aggregation, leading to thrombotic occlusion of pulmonary capillaries and subsequent right-sided heart failure in mice. These mice displayed symptoms of DIC, including thrombocytopenia, prolonged prothrombin time, decreased fibrinogen, fibrin deposition in capillaries, and bleeding. Platelet depletion protected mice from histone-induced death in the first 30 minutes, suggesting that vessel occlusion by platelet-rich thrombi might be responsible for death during the early phase. Furthermore, rTM bound to extracellular histones, suppressed histone-induced platelet aggregation, thrombotic occlusion of pulmonary capillaries, and dilatation of the right ventricle, and rescued mice from lethal thromboembolism. CONCLUSIONS: Extracellular histones cause massive

  12. The Vitamin E Analog Gamma-Tocotrienol (GT3 and Statins Synergistically Up-Regulate Endothelial Thrombomodulin (TM

    Directory of Open Access Journals (Sweden)

    Rupak Pathak

    2016-11-01

    Full Text Available Statins; a class of routinely prescribed cholesterol-lowering drugs; inhibit 3-hydroxy-3-methylglutaryl-coenzymeA reductase (HMGCR and strongly induce endothelial thrombomodulin (TM; which is known to have anti-inflammatory; anti-coagulation; anti-oxidant; and radioprotective properties. However; high-dose toxicity limits the clinical use of statins. The vitamin E family member gamma-tocotrienol (GT3 also suppresses HMGCR activity and induces TM expression without causing significant adverse side effects; even at high concentrations. To investigate the synergistic effect of statins and GT3 on TM; a low dose of atorvastatin and GT3 was used to treat human primary endothelial cells. Protein-level TM expression was measured by flow cytometry. TM functional activity was determined by activated protein C (APC generation assay. Expression of Kruppel-like factor 2 (KLF2, one of the key transcription factors of TM, was measured by quantitative reverse transcription polymerase chain reaction (qRT-PCR. TM expression increased in a dose-dependent manner after both atorvastatin and GT3 treatment. A combined treatment of a low-dose of atorvastatin and GT3 synergistically up-regulated TM expression and functional activity. Finally; atorvastatin and GT3 synergistically increased KLF2 expression. These findings suggest that combined treatment of statins with GT3 may provide significant health benefits in treating a number of pathophysiological conditions; including inflammatory and cardiovascular diseases.

  13. Isolation and characterization of the glycosaminoglycan component of rabbit thrombomodulin proteoglycan

    Energy Technology Data Exchange (ETDEWEB)

    Bourin, M.C.; Lundgren-Akerlund, E.; Lindahl, U. (Swedish Univ. of Agricultural Sciences, Uppsala (Sweden))

    1990-09-15

    Previous studies on rabbit thrombomodulin (TM) revealed that certain anticoagulant activities expressed by TM depend on the presence of an acidic domain tentatively identified as a sulfated galactosaminoglycan. The glycan was released by alkaline beta-elimination, isolated by ion-exchange chromatography, and radiolabeled by partial N-deacetylation (hydrazinolysis) followed by re-N-(3H)acetylation. The labeled product behaved like standard chondroitin sulfate on ion-exchange chromatography, exhibited a Mr of 10-12 x 10(3) on gel chromatography, and was susceptible to degradation by chondroitinase and testicular hyaluronidase. The major labeled degradation products following digestion of the glycosaminoglycan with chondroitinase were identified, depending on the incubation conditions, either as 4/6-mono-O-sulfated, 4,5-unsaturated disaccharides (delta HexA-GalNAc)S and N-acetylgalactosamine 4,6-di-O-sulfate GalcNAc (diS), the latter component accounting for approximately 25% of the total label, or as a major fraction of labeled trisaccharide, with the predominant structure GalNAc(diS)-GlcA-GalNAc(diS). The terminal GalNAc(diS) unit (not substituted at C3) was shown to be more susceptible to N-deacetylation during hydrazinolysis than were the internal GalNAc units (substituted at C3), and thus was more extensively labeled, resulting in over-representation of this unit. It is concluded that rabbit TM is a chondroitin sulfate proteoglycan, which carries a single glycan side chain characterized by an unusual accumulation of sulfate groups at the nonreducing terminus. Metabolically 35S-labeled TM was isolated from cultured rabbit heart endothelial cells and characterized as a chondroitin sulfate proteoglycan which accounted for 1-2% of the total 35S-labeled cell-associated macromolecules.

  14. Adenosine A2A receptor regulates expression of vascular endothelial growth factor in feto-placental endothelium from normal and late-onset pre-eclamptic pregnancies.

    Science.gov (United States)

    Acurio, Jesenia; Herlitz, Kurt; Troncoso, Felipe; Aguayo, Claudio; Bertoglia, Patricio; Escudero, Carlos

    2017-03-01

    We aim to investigate whether A2A/nitric oxide-mediated regulation of vascular endothelial growth factor (VEGF) expression is impaired in feto-placental endothelial cells from late-onset pre-eclampsia. Cultures of human umbilical vein endothelial cells (HUVECs) and human placental microvascular endothelial cells (hPMECs) from normal and pre-eclamptic pregnancies were used. Assays by using small interference RNA (siRNA) for A2A were performed, and transfected cells were used for estimation of messenger RNA (mRNA) levels of VEGF, as well as for cell proliferation and angiogenesis in vitro. CGS-21680 (A2A agonist, 24 h) increases HUVEC and hPMEC proliferation in a dose response manner. Furthermore, similar to CGS-21680, the nitric oxide donor, S-nitroso-N-acetyl-penicillamine oxide (SNAP), increased cell proliferation in a dose response manner (logEC50 10(-9.2) M). In hPMEC, CGS-21680 increased VEGF protein levels in both normal (∼1.5-fold) and pre-eclamptic pregnancies (∼1.2-fold), an effect blocked by the A2A antagonist, ZM-241385 (10(-5) M) and the inhibitor of NO synthase, N ω-nitro-L-arginine methyl ester hydrochloride (L-NAME). Subsequently, SNAP partially recovered cell proliferation and in vitro angiogenesis capacity of cells from normal pregnancies exposed to siRNA for A2A. CGS-21680 also increased (∼1.5-fold) the level of VEGF mRNA in HUVEC from normal pregnancies, but not in pre-eclampsia. Additionally, transfection with siRNA for A2A decrease (∼30 %) the level of mRNA for VEGF in normal pregnancy compared to untransfected cells, an effect partially reversed by co-incubation with SNAP. The A2A-NO-VEGF pathway is present in endothelium from microcirculation and macrocirculation in both normal and pre-eclamptic pregnancies. However, NO signaling pathway seems to be impaired in HUVEC from pre-eclampsia.

  15. Microsomal enzyme activity, glutathione S-transferase-placental form expression, cell proliferation, and vitamin A stores in livers of rats consuming Great Lakes salmon.

    Science.gov (United States)

    Iverson, F; Mehta, R; Hierlihy, L; Gurofsky, S; Lok, E; Mueller, R; Bourbonnais, D H; Spear, P A

    1998-02-01

    Male and female Sprague-Dawley rats were fed diets incorporating lyophilized chinook salmon obtained from Lake Ontario and Lake Huron. After 70 days, females were bred and the progeny (F1) were reared on the same fish-based diets as the adults (F0). After 78-133 days on the diets, males and females of both generations were sacrificed and hepatic microsomal enzyme activities determined, along with glutathione S-transferase-placental form (GSTP) expression and hepatic cellular proliferation. Hepatic P450 enzyme activities (MROD, EROD, PROD, BROD, and aminopyrine) were increased significantly by fish diets from both sources. Increases in hepatic enzyme activity were greatest for fish caught from Lake Ontario and reflected the total levels of organochlorine contaminants in the fish. GSTP and cell proliferation rates did not show any diet-related or dose-related changes. Vitamin A stores were analyzed as the concentration of liver retinyl palmitate. In rats receiving the highest TEQ dose (i.e., 20% Lake Ontario fish diet), vitamin A stores were significantly lower in F0 adults, F1 weanlings, and F1 adult females.

  16. Placental gene-expression profiles of intrahepatic cholestasis of pregnancy reveal involvement of multiple molecular pathways in blood vessel formation and inflammation.

    Science.gov (United States)

    Du, QiaoLing; Pan, YouDong; Zhang, YouHua; Zhang, HaiLong; Zheng, YaJuan; Lu, Ling; Wang, JunLei; Duan, Tao; Chen, JianFeng

    2014-07-07

    Intrahepatic cholestasis of pregnancy (ICP) is a pregnancy-associated liver disease with potentially deleterious consequences for the fetus, particularly when maternal serum bile-acid concentration >40 μM. However, the etiology and pathogenesis of ICP remain elusive. To reveal the underlying molecular mechanisms for the association of maternal serum bile-acid level and fetal outcome in ICP patients, DNA microarray was applied to characterize the whole-genome expression profiles of placentas from healthy women and women diagnosed with ICP. Thirty pregnant women recruited in this study were categorized evenly into three groups: healthy group; mild ICP, with serum bile-acid concentration ranging from 10-40 μM; and severe ICP, with bile-acid concentration >40 μM. Gene Ontology analysis in combination with construction of gene-interaction and gene co-expression networks were applied to identify the core regulatory genes associated with ICP pathogenesis, which were further validated by quantitative real-time PCR and histological staining. The core regulatory genes were mainly involved in immune response, VEGF signaling pathway and G-protein-coupled receptor signaling, implying essential roles of immune response, vasculogenesis and angiogenesis in ICP pathogenesis. This implication was supported by the observed aggregated immune-cell infiltration and deficient blood vessel formation in ICP placentas. Our study provides a system-level insight into the placental gene-expression profiles of women with mild or severe ICP, and reveals multiple molecular pathways in immune response and blood vessel formation that might contribute to ICP pathogenesis.

  17. Indoleamine 2,3-dioxygenase (IDO) is expressed at feto-placental unit throughout mouse gestation: An immunohistochemical study

    Science.gov (United States)

    Hemmati, Shayda; Jeddi-Tehrani, Mahmood; Torkabadi, Ebrahim; Ghassemi, Jamileh; Kazemi sefat, Golnaz Ensieh; Danesh, Parivash; Barzegar Yarmohammadi, Leila; Akhondi, Mohammad Mehdi; Zarnani, Amir Hassan

    2009-01-01

    Introduction The cells expressing Indoleamine 2, 3-dioxygenase (IDO) in feto-maternal interface mediate tryptophan catabolism, hence protect allogeneic fetus from lethal rejection by maternal immune responses. In this study, we report immuno-localization of IDO+ cells in murine reproductive tract and placenta throughout mouse pregnancy by immunohistochemistry. Materials and Methods Syngeneic pregnant mice were examined for vaginal plug to discover about their state of pregnancy. A total of three pregnant mice were examined at each stage.The examination was further confirmed by the detection of sperm in vaginal smear. On the gestational days of 2nd, 12th and 18th, the uterus and oviduct were removed and expression of IDO was investigated in the endometrium, placenta and oviduct by immunohistochemistry. Results Our results showed that IDO is expressed consistently in feto-maternal interface throughout pregnancy. In endometrium, expression of IDO was predominantly confined to luminal and glandular epithelial cells. Cells at junctional and labyrinth zones of placenta showed strong IDO immunoreactivity as well. Conclusion Expression of IDO at the protein level in reproductive tract of pregnant mice during entire periods of gestation points to its potential protective role in maintenance of pregnancy. In our knowledge this is the first report of expression of IDO in feto-maternal phase during murine pregnancy. PMID:23926466

  18. Plasma levels of thrombomodulin, plasminogen activator inhibitor-1 and fibrinogen in elderly, diabetic patients with depressive symptoms

    OpenAIRE

    2015-01-01

    Background Diabetes, depression and aging have been associated with pro-inflammatory and prothrombotic state. Aim The aim of the study was to determine the plasma levels of thrombomodulin, plasminogen activator inhibitor-1 (PAI-1) and fibrinogen in elderly diabetic patients with and without depressive symptoms and to examine factors (including thrombomodulin, PAI-1, fibrinogen levels) associated with depressive symptoms in elderly patients with type 2 diabetes (T2DM). Methods A total of 276 T...

  19. Placental Expression Patterns of Galectin-1, Galectin-2, Galectin-3 and Galectin-13 in Cases of Intrauterine Growth Restriction (IUGR

    Directory of Open Access Journals (Sweden)

    Stefan Hutter

    2016-04-01

    Full Text Available Galectins (gal are members of the mammalian β-galactoside-binding proteins and recognize Galβ1-4GlcNAc and Galβ1-4GalNac (Thomsen-Friedenreich antigen (TF sequences of several cell surface oligosaccharides. In this study, gal-1, -2, -3 and -13 were investigated systematically in the trophoblast and decidua compartment of intrauterine growth restriction (IUGR placentas and normal third trimester control placentas and stratified by fetal gender and gestational age. Within this study, 29 third trimester placentas after delivery were analyzed. Fetal gender was equally divided within both groups, and immunohistochemical staining was analyzed according to fetal gender and gestational age. Double immune-fluorescence with trophoblast-specific markers was used to identify galectin-expressing cells at the feto-maternal interface in the decidua. Gal-3 was significantly downregulated only in the extravillous trophoblast of IUGR placentas. In contrast, expressions of gal-2 and gal-13 were downregulated in both villous and extravillous trophoblast cells of IUGR placentas. In addition, gal-2 and gal-13 showed a highly correlated expression scheme in the placenta. There are significant gender-specific expression patterns for single prototype galectins with downregulation of gal-2 and gal-13 of male gender placentas in cases of IUGR. Gal-3 as the chimera type galectin shows only little gender-specific differences in expression, which disappear in IUGR cases.

  20. The Influence of Sub-Unit Composition and Expression System on the Functional Antibody Response in the Development of a VAR2CSA Based Plasmodium falciparum Placental Malaria Vaccine

    DEFF Research Database (Denmark)

    Nielsen, Morten A; dos Santos Marques Resende, Mafalda; de Jongh, Willem A;

    2015-01-01

    of VAR2CSA, a parasite-derived antigen. Protection against PM is mediated by antibodies that inhibit binding of IE in the placental intervillous space. VAR2CSA is a large antigen incompatible with large scale recombinant protein expression. Vaccines based on sub-units encompassing the functionally......-functional antibodies, and furthermore influence the folding, stability and yield of expression. Candidate antigens from the pre-clinical development expressed in High-Five insect cells using the baculovirus expression vector system were transitioned into the Drosophila Schneider-2 cell (S2) expression-system compliant...... with clinical development. The functional capacity of antibodies against antigens expressed in High-Five cells or in S2 cells was equivalent. This enabled an extensive down-selection of S2 insect cell-expressed antigens primarily encompassing the minimal CSA-binding region of VAR2CSA. In general, we found...

  1. The relationship of placental expression of leptin and disease development in patients with pre-eclampsia%子痫前期患者胎盘组织瘦素的表达与病情的相关性研究

    Institute of Scientific and Technical Information of China (English)

    高咏梅; 仵妍

    2010-01-01

    目的 探讨子痫前期患者胎盘组织瘦素的表达水平与病情的关系.方法 选择妊娠期高血压疾病患者10例、子痫前期轻度患者10例、子痫前期重度患者10例,采用RT-PCR技术检测患者胎盘组织瘦素mRNA的表达水平,并与15例正常孕妇(对照者)进行比较.同时检测子痫前期患者24 h尿蛋白定量及平均动脉压.结果 胎盘组织瘦素mRNA表达水平子痫前期重度患者(0.507±0.036)及子痫前期轻度患者(0.476±0.023)均高于对照者(0.441±0.030)(P<0.01),子痫前期重度患者高于子痫前期轻度患者(P<0.05);妊娠期高血压疾病患者瘦素mRNA表达水平(0.463±0.024)与对照者比较,差异无统计学意义(P>0.05).子痫前期患者胎盘组织瘦素mRNA表达水平与24 h尿蛋白定量、平均动脉压呈正相关(P<0.05).结论 子痫前期患者胎盘组织瘦素表达水平明显升高,且表达水平与病情有关.%Objective To study the relationship of placental expression of leptin and disease development in patients with pre-eclampsia.Methods The placental expression of leptin gene was determined in gestational hypertension(10 cases),mild pre-eclampsia(10 cases),Severe pre-eclampsia(10cases)and normal pregnant women(15 cases,control group)by reverse txanscription/polymerase chain reaction(RT/PCR).Meanwhile,24 hour urine protein and mean arterial blood pressure(MAP)were detected in patients with pre-eclampsia.Results The expression of leptin mRNA in placenta were significantly higher in severe and mild pre-eclarnpsia than that in normal pregnant women(0.507 ±0.036,0.476±0.023vs 0.441 ±0.030)(P<0.01),meanwhile,in the severe pre-eclampsia was higher than that in the mild preeclampsia(P<0.05).The difference was not significant between the gestafional hypertension(0.463±0.024)and the normal pregnant women(P>0.05).There was a positive correlation between the placental leptin mRNA expression levels in pre-eclampsia and the 24 hour urine protein

  2. Expression and function of thyroid hormone transporters in the microvillous plasma membrane of human term placental syncytiotrophoblast.

    Science.gov (United States)

    Loubière, L S; Vasilopoulou, E; Glazier, J D; Taylor, P M; Franklyn, J A; Kilby, M D; Chan, Shiao Y

    2012-12-01

    The transplacental passage of thyroid hormones (THs) from mother to fetus in humans has been deduced from observational clinical studies and is important for normal fetoplacental development. To investigate the transporters that regulate TH uptake by syncytiotrophoblast (the primary barrier to maternal-fetal exchange, which lies in direct contact with maternal blood), we isolated the microvillous plasma membrane (MVM) of human term syncytiotrophoblasts. We have demonstrated that MVM vesicles express plasma membrane TH transporter proteins, including system-L (L-type amino acid transporter 1 and CD98), monocarboxylate transporters (MCTs) 8 and 10, organic anion-transporting polypeptides 1A2 and 4A1. We provide the first definitive evidence that the human syncytiotrophoblast MVM is capable of rapid, saturable T(4) and T(3) uptake at similar rates and in a Na(+)-independent manner. These two major forms of THs could not significantly inhibit each others' uptake, suggesting that each is mediated by largely different transporters. No single transporter was noted to play a dominant role in either T(4) or T(3) uptake. Using combinations of transporter inhibitors that had an additive effect on TH uptake, we provide evidence that 67% of saturable T(4) uptake is facilitated by system-L and MCT10 with a minor role played by organic anion-transporting polypeptides, whereas 87% of saturable T(3) uptake is mediated by MCT8 and MCT10. Our data demonstrate that syncytiotrophoblast may control the quantity and forms of THs taken up by the human placenta. Thus, syncytiotrophoblast could be critical in regulating transplacental TH supply from the mother to the fetus.

  3. Maternal low protein diet leads to placental angiogenic compensation via dysregulated M1/M2 macrophages and TNFa expression in Sprague-Dawley rats

    Science.gov (United States)

    A maternal low-protein (LP) diet results in low birth weight, increased offspring rapid adipose tissue catch-up growth, adult obesity, and insulin resistance in Sprague-Dawley rats. The placenta plays key roles in nutrient transport and fetal growth. Placental function is dependent on regulation of ...

  4. Adenovirus-mediated gene transfer of placental growth factor to perivascular tissue induces angiogenesis via upregulation of the expression of endogenous vascular endothelial growth factor-A

    NARCIS (Netherlands)

    Roy, H; Bhardwaj, S; Babu, M; Jauhiainen, S; Herzig, KH; Bellu, AR; Haisma, HJ; Carmeliet, P; Alitalo, K; Yla-Herttuala, S

    2005-01-01

    Placental growth factor (PIGF) is a member of the vascular endothelial growth factor (VEGF) family that binds specifically to VEGF receptor (VEGFR)-1. However, the mechanism of PIGF- and VEGFR-1-mediated angiogenesis has remained unclear and some in vitro studies suggest that VEGF-A/VEGFR-2

  5. Risk factors of placental abruption

    OpenAIRE

    2013-01-01

    Background: Placental abruption is one of the most common causes of bleeding during pregnancy. Multiple factors are known to be associated with increase of risk of placental abruption such as alcohol, cocaine use and cigarette smoking. The objective of this study was to identify risk factors for placental abruption in an Iranian women population. Materials and Methods: In a retrospective case - control study birth records included 78 cases with placental abruption and 780 randomly selected co...

  6. The Influence of Sub-Unit Composition and Expression System on the Functional Antibody Response in the Development of a VAR2CSA Based Plasmodium falciparum Placental Malaria Vaccine.

    Directory of Open Access Journals (Sweden)

    Morten A Nielsen

    Full Text Available The disease caused by Plasmodium falciparum (Pf involves different clinical manifestations that, cumulatively, kill hundreds of thousands every year. Placental malaria (PM is one such manifestation in which Pf infected erythrocytes (IE bind to chondroitin sulphate A (CSA through expression of VAR2CSA, a parasite-derived antigen. Protection against PM is mediated by antibodies that inhibit binding of IE in the placental intervillous space. VAR2CSA is a large antigen incompatible with large scale recombinant protein expression. Vaccines based on sub-units encompassing the functionally constrained receptor-binding domains may, theoretically, circumvent polymorphisms, reduce the risk of escape-mutants and induce cross-reactive antibodies. However, the sub-unit composition and small differences in the borders, may lead to exposure of novel immuno-dominant antibody epitopes that lead to non-functional antibodies, and furthermore influence the folding, stability and yield of expression. Candidate antigens from the pre-clinical development expressed in High-Five insect cells using the baculovirus expression vector system were transitioned into the Drosophila Schneider-2 cell (S2 expression-system compliant with clinical development. The functional capacity of antibodies against antigens expressed in High-Five cells or in S2 cells was equivalent. This enabled an extensive down-selection of S2 insect cell-expressed antigens primarily encompassing the minimal CSA-binding region of VAR2CSA. In general, we found differential potency of inhibitory antibodies against antigens with the same borders but of different var2csa sequences. Likewise, we found that subtle size differences in antigens of the same sequence gave varying levels of inhibitory antibodies. The study shows that induction of a functional response against recombinant subunits of the VAR2CSA antigen is unpredictable, demonstrating the need for large-scale screening in order to identify antigens

  7. Placental Protein 13 (PP13 – a placental immunoregulatory galectin protecting pregnancy

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    Nandor Gabor Than

    2014-08-01

    Full Text Available Galectins are glycan-binding proteins that regulate innate and adaptive immune responses, and some confer maternal-fetal immune tolerance in eutherian mammals. A chromosome 19 cluster of galectins has emerged in anthropoid primates, species with deep placentation and long gestation. Three of the five human cluster galectins are solely expressed in the placenta, where they may confer additional immunoregulatory functions to enable deep placentation. One of these is galectin-13, also known as Placental Protein 13 (PP13. It has a jelly-roll fold, carbohydrate-recognition domain and sugar-binding preference resembling to other mammalian galectins. PP13 is predominantly expressed by the syncytiotrophoblast and released from the placenta into the maternal circulation. Its ability to induce apoptosis of activated T cells in vitro, and to divert and kill T cells as well as macrophages in the maternal decidua in situ suggests important immune functions. Indeed, mutations in the promoter and an exon of LGALS13 presumably leading to altered or non-functional protein expression are associated with a higher frequency of preeclampsia and other obstetrical syndromes, which involve immune dysregulation. Moreover, decreased placental expression of PP13 and its low first trimester maternal serum concentrations are associated with elevated risk of preeclampsia. Indeed, PP13 turned to be a good early biomarker to assess maternal risk for the subsequent development of pregnancy complications caused by impaired placentation. Due to the ischemic placental stress in preterm preeclampsia, there is an increased trophoblastic shedding of PP13 immunopositive microvesicles starting in the second trimester, which leads to high maternal blood PP13 concentrations. Our meta-analysis suggests that this phenomenon may enable the potential use of PP13 in directing patient management near to or at the time of delivery. Recent findings on the beneficial effects of PP13 on decreasing

  8. Analysis of IgG with specificity for variant surface antigens expressed by placental Plasmodium falciparum isolates

    DEFF Research Database (Denmark)

    Khattab, Ayman; Reinhardt, Christina; Staalsoe, Trine

    2004-01-01

    women who presented to the maternity ward of Albert Schweitzer Hospital in Lambaréné, Gabon for delivery was analysed using flow cytometry assays. Plasma samples from placenta infected primiparous women were also investigated for their capacity to inhibit parasite binding to CSA in vitro. RESULTS......: In the study cohort, primiparous as well as secundiparous women had the greatest risk of infection at delivery as well as during pregnancy. Primiparous women with infected placentas at delivery showed higher levels of VSAPAM-specific IgG compared to women who had no malaria infections at delivery. Placental...... isolates of Gabonese and Senegalese origin tested on plasma samples from Gabon showed parity dependency and gender specificity patterns. There was a significant correlation of plasma reactivity as measured by flow cytometry between different placental isolates. In the plasma of infected primiparous women...

  9. Proinflammatory cytokines and thrombomodulin in patients with peptic ulcer disease and gastric cancer, infected with Helicobacter pylori

    Directory of Open Access Journals (Sweden)

    Mehrdad Haghazali

    2011-01-01

    Full Text Available Backgrounds: Helicobacter pylori infect more than half of the global population. It is suggested to be related with gastritis, peptic ulcer disease (PUD, and gastric cancer. Aims: The aim of this present study was to evaluate proinflammatory cytokines including interleukin 1, 6, 8, 10, and thrombomodulin in H. pylori-infected patients with PUD and gastric cancer. Patients: This cross-sectional study was conducted in Taleghani Hospital on 111 patients with H. pylori infection. Materials and Methods: Patients were divided into three groups of PUD, cancer, and control (normal on endoscopy, according to the results of endoscopy. The serum levels of interleukins 1, 6, 8, and 10 and thrombomodulin was determined using enzyme-linked immunosorbent assay (ELISA technique. H. pylori infection was diagnosed by histological examination of the endoscopic biopsy. Results: One hundred eleven patients were included in the study; 30 as PUD group, 30 as gastric cancer group, and 51 as controls. There was no significant difference between the means of IL-1 and IL-10 levels among the three groups (P = 0.744 and 0.383, respectively. IL-6, IL-8, and thrombomodulin levels were found to be statically different among the three groups (P < 0.05. The level of IL-6, IL-8, and thrombomodulin in cancer group was significantly higher than PUD and control groups (P < 0.05. Conclusion: There is a significant association between H. pylori infection and serum IL-6, IL-8, and thrombomodulin but such relation is not present between H. pylori and IL-1 and IL-10. Immunity response (IL-6, IL-8 and thrombomodulin is more severe in cancer patient than PUD.

  10. LFA-1 and Mac-1 integrins bind to the serine/threonine-rich domain of thrombomodulin

    Energy Technology Data Exchange (ETDEWEB)

    Kawamoto, Eiji [Department of Molecular Pathobiology and Cell Adhesion Biology, Mie University Graduate School of Medicine, 2-174 Edobashi, Tsu, Mie 514-8507 (Japan); Emergency and Critical Care Center, Mie University Hospital, 2-174 Edobashi, Tsu 514-8507 (Japan); Okamoto, Takayuki, E-mail: okamotot@doc.medic.mie-u.ac.jp [Department of Molecular Pathobiology and Cell Adhesion Biology, Mie University Graduate School of Medicine, 2-174 Edobashi, Tsu, Mie 514-8507 (Japan); Takagi, Yoshimi [Department of Molecular Pathobiology and Cell Adhesion Biology, Mie University Graduate School of Medicine, 2-174 Edobashi, Tsu, Mie 514-8507 (Japan); Honda, Goichi [Medical Affairs Department, Asahi Kasei Pharma Corporation, 1-105 Kanda Jinbo-cho, Chiyoda-ku, Tokyo 101-8101 (Japan); Suzuki, Koji [Faculty of Pharmaceutical Science, Suzuka University of Medical Science, 3500-3, Minamitamagaki-cho, Suzuka, Mie 513-8679 (Japan); Imai, Hiroshi [Emergency and Critical Care Center, Mie University Hospital, 2-174 Edobashi, Tsu 514-8507 (Japan); Shimaoka, Motomu, E-mail: shimaoka@doc.medic.mie-u.ac.jp [Department of Molecular Pathobiology and Cell Adhesion Biology, Mie University Graduate School of Medicine, 2-174 Edobashi, Tsu, Mie 514-8507 (Japan)

    2016-05-13

    LFA-1 (αLβ2) and Mac-1 (αMβ2) integrins regulate leukocyte trafficking in health and disease by binding primarily to IgSF ligand ICAM-1 and ICAM-2 on endothelial cells. Here we have shown that the anti-coagulant molecule thrombomodulin (TM), found on the surface of endothelial cells, functions as a potentially new ligand for leukocyte integrins. We generated a recombinant extracellular domain of human TM and Fc fusion protein (TM-domains 123-Fc), and showed that pheripheral blood mononuclear cells (PBMCs) bind to TM-domains 123-Fc dependent upon integrin activation. We then demonstrated that αL integrin-blocking mAb, αM integrin-blocking mAb, and β2 integrin-blocking mAb inhibited the binding of PBMCs to TM-domains 123-Fc. Furthermore, we show that the serine/threonine-rich domain (domain 3) of TM is required for the interaction with the LFA-1 (αLβ2) and Mac-1 (αMβ2) integrins to occur on PBMCs. These results demonstrate that the LFA-1 and Mac-1 integrins on leukocytes bind to TM, thereby establishing the molecular and structural basis underlying LFA-1 and Mac-1 integrin interaction with TM on endothelial cells. In fact, integrin-TM interactions might be involved in the dynamic regulation of leukocyte adhesion with endothelial cells. - Highlights: • LFA-1 and Mac-1 integrins bind to the anti-coagulant molecule thrombomodulin. • The serine/threonine-rich domain of thrombomodulin is essential to interact with the LFA-1 and Mac-1 integrins on PBMCs. • Integrin-TM interactions might be involved in the dynamic regulation of leukocyte adhesion with endothelial cells.

  11. Maternal-fetal iron status and the relationship between it and the expression of placental iron transporters%母-胎铁状态及与胎盘铁转运因子表达的关系

    Institute of Scientific and Technical Information of China (English)

    李燕琴; 贾志; 白斌; 颜虹; 张耀辉

    2012-01-01

    目的 对母-胎铁营养之间的关系及其与胎盘铁转运因子表达的关系进行分析,为进一步理解母-胎铁营养关系及其调节机制提供线索.方法 以健康足月的40名不同铁营养状态孕妇为研究对象,采集分娩时母亲静脉血及脐血、胎盘,进行血液学检测及Western Blot和实时定量PCR检测.结果 胎儿的各项血液学参数均高于母亲.母亲血红蛋白浓度与胎儿的红细胞计数有显著相关性(r=0.504,P<0.05);母亲血红蛋白浓度和胎盘组织铁蛋白的蛋白表达呈显著相关性(r=0.436,P<0.05).其余各指标之间均无明显的相关性.结论 母-胎铁状态之间及其与胎盘铁转运因子的表达之间仅部分具有一定的相关性.%Objective To analyze the correlation between-maternal and fetal iron status and the relationship between maternd-fetal iron status and the expression of placental iron transporters, so as to provide clue for further understanding of maternal-fetal iron nutrition and its regulatory mechanism. Methods Forty healthy full-term pregnant women with different iron nutrition status were chosen for the research. Maternal vein blood, umbilical cord blood and placental tissues were collected at the delivery. Routine blood test, Western Blot and realtime PCR test were conducted in this study. Results All hematological parameters of umbilical cord blood were higher than those of maternal blood. The maternal hemoglobin level was significantly correlated with fetal red blood count( r = 0. 504, P <0. 05 ). There were also significant correlations between maternal hemoglobin level and the protein expression of placental ferritin( r = 0. 436, P < 0. 05 ). The other indexes showed no significant correlation. Conclusion Only some of parameters of maternal-fetal iron status and placental iron transporters are correlated.

  12. Expression and significance of leukemia inhibitory factor in placental tissues of patients with preeclampsia%白血病抑制因子在子痫前期患者胎盘组织中的表达及意义

    Institute of Scientific and Technical Information of China (English)

    王海燕; 杨海澜; 马惠静; 冯敏; 索明莉

    2011-01-01

    目的:测定白血病抑制因子(LIF)在子痫前期患者胎盘组织中的表达变化,探讨其在子痫前期发病过程中的作用.方法:选取子痛前期(子痫前期轻度组和重度组)和正常妊娠孕妇作为研究组和对照组,采用免疫组化法测定其胎盘组织中LIF的表达,并通过BI2000医学图像分析系统对染色结果进行定量检测并作比较.结果:LIF在3组中均有表达,且主要表达于滋养细胞胞质中;子痛前期轻度组及重度组与正常妊娠组相比,胎盘组织中LIF的表达明显减弱,差异有统计学意义(P0.05).结论:LIF对正常妊娠的维持起到了一定的保护作用;LIF在胎盘组织中的低表达影响了滋养细胞的浸润能力,可能是子痛前期发病的病因之一.%Objective: To detect the changes of leukemia inhibitory factor (LIF) expression in placental tissues of patients with preeclampsia, explore its value in pathogenesis of preeclampsia. Methods: The women with preeclampsia and normal pregnant women were selected as study group ( mild preeclampsia group and severe preeclampsia group) and control group, respectively; immunohistochemical method was used to detect the expression levels of LIF in placental tissues of the two groups; BI2000 medical image analysis system was used for quantitative detection and comparison. Results: LIF expressed in the three groups, mostly locating in cytoplasma of trophoblast cells; compared with control group, the expression level of LIF in study group decreased significantly (P <0. 01 ); there was no significant difference in the expression level of LIF between mild precclampsia group and severe preeclampsia group ( P > 0. 05 ) . Conclusion: LIF may play a protective role in the maintenance of normal pregnancy; the low expression of LIF in placental tissues affects the invasive ability of trophoblast cells, which may be one of the pathogenesis of preeclampsia.

  13. Placental dysfunction and fetal programming: the importance of placental size, shape, histopathology, and molecular composition.

    Science.gov (United States)

    Longtine, Mark S; Nelson, D Michael

    2011-05-01

    Normal function of the placenta is pivotal for optimal fetal growth and development. Fetal programming commonly is associated with placental dysfunction that predisposes to obstetric complications and suboptimal fetal outcomes. We consider several clinical phenotypes for placental dysfunction that likely predispose to fetal programming. Some of these reflect abnormal development of the chorioallantoic placenta in size, shape, or histopathology. Others result when exogenous stressors in the maternal environment combine with maladaptation of the placental response to yield small placentas with limited reserve, as typical of early-onset intrauterine growth restriction and preeclampsia. Still others reflect epigenetic changes, including altered expression of imprinted genes, altered enzymatic activity, or altered efficiencies in nutrient transport. Although the human placenta is a transient organ that persists only 9 months, the effects of this organ on the offspring remain for a lifetime.

  14. Adenoviral-mediated placental gene transfer of IGF-1 corrects placental insufficiency via enhanced placental glucose transport mechanisms.

    Directory of Open Access Journals (Sweden)

    Helen N Jones

    Full Text Available Previous work in our laboratory demonstrated that over-expression of human insulin-like growth factor -1 (hIGF-1 in the placenta corrects fetal weight deficits in mouse, rat, and rabbit models of intrauterine growth restriction without changes in placental weight. The underlying mechanisms of this effect have not been elucidated. To investigate the effect of intra-placental IGF-1 over-expression on placental function we examined glucose transporter expression and localization in both a mouse model of IUGR and a model of human trophoblast, the BeWo Choriocarcinoma cell line.At gestational day 18, animals were divided into four groups; sham-operated controls, uterine artery branch ligation (UABL, UABL+Ad-hIGF-1 (10(8 PFU, UABL+Ad-LacZ (10(8 PFU. At gestational day 20, pups and placentas were harvested by C-section. For human studies, BeWo choriocarcinoma cells were grown in F12 complete medium +10%FBS. Cells were incubated in serum-free control media ± Ad-IGF-1 or Ad-LacZ for 48 hours. MOIs of 10∶1 and 100∶1 were utilized. The RNA, protein expression and localization of glucose transporters GLUT1, 3, 8, and 9 were analyzed by RT-PCR, Western blot and immunohistochemistry.In both the mouse placenta and BeWo, GLUT1 regulation was linked to altered protein localization. GLUT3, localized to the mouse fetal endothelial cells, was reduced in placental insufficiency but maintained with Ad-I GF-1 treatment. Interestingly, GLUT8 expression was reduced in the UABL placenta but up-regulated following Ad-IGF-1 in both mouse and human systems. GLUT9 expression in the mouse was increased by Ad-IGF-1 but this was not reflected in the BeWo, where Ad-IGF-1 caused moderate membrane relocalization.Enhanced GLUT isoform transporter expression and relocalization to the membrane may be an important mechanism in Ad-hIGF-1mediated correction of placental insufficiency.

  15. Highly sensitive turn-on fluorescence detection of thrombomodulin based on fluorescence resonance energy transfer

    Science.gov (United States)

    Kong, Liyan; Zhu, Jiaming; Wang, Wen; Jin, Lehe; Fu, Yanjiao; Duan, Bohui; Tan, Liang

    2017-02-01

    As an integral glycoprotein on the surface of endothelial cells, thrombomodulin (TM) has very high affinity for thrombin. TM has been regarded to be a marker of endothelial damage since it can be released during endothelial cell injury. In this work, a highly sensitive fluorescence method for the quantitative detection of TM was developed. TM antibody (Ab) and bovine serum albumin (BSA) were bound on gold nanoparticles (AuNPs) to construct BSA-AuNPs-Ab nanocomposites and they were characterized by transmission electron microscope and UV-vis spectrophotometry. The fluorescence of acridine orange (AO) was quenched by the prepared gold nanocomposites based on fluorescence resonance energy transfer (FRET). In the presence of TM, the fluorescence was turned on due to the effective separation of AO from the surface of gold nanocomposites. Under optimum conditions, the enhanced fluorescence intensity displayed a linear relationship with the logarithm of the TM concentration from 0.1 pg mL- 1 to 5 ng mL- 1 with a low detection limit of 12 fg mL- 1. The release of soluble thrombomodulin (sTM) by the injured HUVEC-C cells in the presence of H2O2 was investigated using the proposed method. The released sTM content in the growth medium was found to be increased with the enhancement of contact time of the cells with H2O2.

  16. Elevated Adenosine Induces Placental DNA Hypomethylation Independent of A2B Receptor Signaling in Preeclampsia.

    Science.gov (United States)

    Huang, Aji; Wu, Hongyu; Iriyama, Takayuki; Zhang, Yujin; Sun, Kaiqi; Song, Anren; Liu, Hong; Peng, Zhangzhe; Tang, Lili; Lee, Minjung; Huang, Yun; Ni, Xin; Kellems, Rodney E; Xia, Yang

    2017-07-01

    Preeclampsia is a prevalent pregnancy hypertensive disease with both maternal and fetal morbidity and mortality. Emerging evidence indicates that global placental DNA hypomethylation is observed in patients with preeclampsia and is linked to altered gene expression and disease development. However, the molecular basis underlying placental epigenetic changes in preeclampsia remains unclear. Using 2 independent experimental models of preeclampsia, adenosine deaminase-deficient mice and a pathogenic autoantibody-induced mouse model of preeclampsia, we demonstrate that elevated placental adenosine not only induces hallmark features of preeclampsia but also causes placental DNA hypomethylation. The use of genetic approaches to express an adenosine deaminase minigene specifically in placentas, or adenosine deaminase enzyme replacement therapy, restored placental adenosine to normal levels, attenuated preeclampsia features, and abolished placental DNA hypomethylation in adenosine deaminase-deficient mice. Genetic deletion of CD73 (an ectonucleotidase that converts AMP to adenosine) prevented the elevation of placental adenosine in the autoantibody-induced preeclampsia mouse model and ameliorated preeclampsia features and placental DNA hypomethylation. Immunohistochemical studies revealed that elevated placental adenosine-mediated DNA hypomethylation predominantly occurs in spongiotrophoblasts and labyrinthine trophoblasts and that this effect is independent of A2B adenosine receptor activation in both preeclampsia models. Extending our mouse findings to humans, we used cultured human trophoblasts to demonstrate that adenosine functions intracellularly and induces DNA hypomethylation without A2B adenosine receptor activation. Altogether, both mouse and human studies reveal novel mechanisms underlying placental DNA hypomethylation and potential therapeutic approaches for preeclampsia. © 2017 American Heart Association, Inc.

  17. Expression of heme oxygenase-1 protein in placental trophoblast cells of patients with pregnancy-induce hypertension%妊娠高血压综合征患者胎盘滋养层细胞中血红素氧合酶-1的表达

    Institute of Scientific and Technical Information of China (English)

    马天平; 黄引平; 周洁

    2011-01-01

    Objective To investigate the expression of hemo oxygenase- 1(HO- 1) protein in placental trophoblast cells of patients with pregnant- induced hypertension (PIH).Methods Placental villi folial was taken from the normal terminal pregnant women and patients women with PIH for cell culture, and HO- 1 protein in placental tissue was detected by Western- blot method.Placental villi folial taken from normal early pregnant women was cultured with serum of normal terminal pregnant women (NTP) and midrange and advanced PIH patients, respectively.The quantity of HO- 1 protein in different group was detected with Western- blot.Results The expression of HO- 1 protein in placental tissue of PIH patients was lower than that of NTP group (P<0.001).The HO- 1 protein expression in placental trophoblast cells cultured with serum from PIH patients was also lower than that cultured with the serum of NTP woman.Conclusion The HO- 1 protein expression decreases in placental villi tissue of PIH patients and the placental trophoblast cells induced by serum of PIH patient.%目的 观察正常晚孕妇女(NTP)及妊娠高血压综合征(PIH)患者胎盘滋养层细胞中血红素氧合酶-1(HO-1)的表达.方法 取15例NTP和PIH患者剖宫产术的胎盘绒毛小叶进行培养,应用免疫印迹法(Western Blot)检测胎盘组织中HO-1的蛋白含量.取正常早孕妇女胎盘绒毛小叶进行细胞培养,然后分别加入NTP血清(NTP组)及中重度PIH患者血清(PIH组),进行分组培养.应用Western Blot检测HO-1的蛋白含量.结果 PIH组胎盘组织中HO-1的蛋白含量与NTP组比较差异有统计学意义(P<0.01);PIH患者血清培养的滋养细胞中HO-1的蛋白含量低于正常组.结论 PIH患者胎盘滋养细胞中HO-1的蛋白表达明显减少.

  18. The lectin like domain of thrombomodulin is involved in the defence against pyelonephritis.

    Science.gov (United States)

    Lattenist, Lionel; Teske, Gwendoline; Claessen, Nike; Florquin, Sandrine; Conway, Edward M; Roelofs, Joris J T H

    2015-12-01

    Pyelonephritis, a common complication of urinary tract infections, is frequently associated with kidney scarring and may lead to end-stage renal disease. During bacterial infections inflammatory and coagulation pathways and their mutual interaction are playing pivotal roles in the host response. Given that thrombomodulin (TM) is crucially involved in the interplay between coagulation and inflammation, we aimed to investigate the roles of its EGF and lectin-like domains in inflammation during acute pyelonephritis. Indeed, the EGF-like and the lectin-like domains of TM, are especially known to orchestrate inflammation and coagulation in different ways. Acute pyelonephritis was induced by intravesical inoculation of 1 × 10(8) CFU of uropathogenic Escherichia coli in two strains of TM transgenic mice. TM(pro/pro) mice carry a mutation in the EGF-like domain making them unable to activate protein C, an anticoagulant and anti-inflammatory protein. TM(LeD/LeD) mice lack the lectin-like domain of TM, which is critical for its anti-inflammatory and cytoprotective properties. Mice were sacrificed 24 and 48 h after inoculation. Bacterial loads, the immune response and the activation of coagulation were evaluated in the kidney and the bladder. TM(LeD/LeD) mice showed elevated bacterial load in bladder and kidneys compared to WT mice, whereas TM(pro/pro) had similar bacterial load as WT mice. TM(LeD/LeD) mice displayed a reduced local production of pro-inflammatory cytokines and neutrophil renal infiltration. Activation of coagulation was comparable in TM(LeD/LeD) and WT mice. From these data, we conclude that the lectin-like domain of thrombomodulin is critically involved in host defence against E. coli induced acute pyelonephritis. Copyright © 2015 Elsevier Ltd. All rights reserved.

  19. Risk factors of placental abruption

    Directory of Open Access Journals (Sweden)

    Hooria Seyedhosseini Ghaheh

    2013-01-01

    Full Text Available Background: Placental abruption is one of the most common causes of bleeding during pregnancy. Multiple factors are known to be associated with increase of risk of placental abruption such as alcohol, cocaine use and cigarette smoking. The objective of this study was to identify risk factors for placental abruption in an Iranian women population. Materials and Methods: In a retrospective case - control study birth records included 78 cases with placental abruption and 780 randomly selected controls were investigated. Statistical analysis for comparing the studied risk factors between groups was performed using Pearson ′ s Chi-square test along with presenting relevant odds ratio (OR. Results: From 7301 deliveries included in the study, 78 (1% was complicated placental abruption. Women aged 35 or more likely for experiencing (OR = 3.650, 95% confidence interval [CL] = 1.57-6.83 and those who had a previous cesarean section (OR = 2.65, 95% CL = 3.91- 33.41 were in higher risk for placental abruption ([50 cases] 64% vs. [28 cases] 36% P < 0.01. Conclusion: The results indicate that among the placental abruption is one of the most common causes of bleeding during the pregnancy and one of the major obstetrical emergency.

  20. Risk factors of placental abruption

    Science.gov (United States)

    Ghaheh, Hooria Seyedhosseini; Feizi, Awat; Mousavi, Maryam; Sohrabi, Davood; Mesghari, Leila; Hosseini, Zahra

    2013-01-01

    Background: Placental abruption is one of the most common causes of bleeding during pregnancy. Multiple factors are known to be associated with increase of risk of placental abruption such as alcohol, cocaine use and cigarette smoking. The objective of this study was to identify risk factors for placental abruption in an Iranian women population. Materials and Methods: In a retrospective case – control study birth records included 78 cases with placental abruption and 780 randomly selected controls were investigated. Statistical analysis for comparing the studied risk factors between groups was performed using Pearson's Chi-square test along with presenting relevant odds ratio (OR). Results: From 7301 deliveries included in the study, 78 (1%) was complicated placental abruption. Women aged 35 or more likely for experiencing (OR = 3.650, 95% confidence interval [CL] = 1.57-6.83) and those who had a previous cesarean section (OR = 2.65, 95% CL = 3.91- 33.41) were in higher risk for placental abruption ([50 cases] 64% vs. [28 cases] 36% P < 0.01). Conclusion: The results indicate that among the placental abruption is one of the most common causes of bleeding during the pregnancy and one of the major obstetrical emergency. PMID:24174950

  1. Epithelial membrane protein 2 (EMP2) deficiency alters placental angiogenesis, mimicking features of human placental insufficiency.

    Science.gov (United States)

    Williams, Carmen J; Chu, Alison; Jefferson, Wendy N; Casero, David; Sudhakar, Deepthi; Khurana, Nevil; Hogue, Claire P; Aryasomayajula, Chinmayi; Patel, Priya; Sullivan, Peggy; Padilla-Banks, Elizabeth; Mohandessi, Shabnam; Janzen, Carla; Wadehra, Madhuri

    2017-03-14

    Epithelial membrane protein-2 (EMP2) is a tetraspan protein predicted to regulate placental development. Highly expressed in secretory endometrium and trophectoderm cells, previous studies suggest that it may regulate implantation by orchestrating the surface expression of integrins and other membrane proteins. In order to test the role of EMP2 in pregnancy, mice lacking EMP2 (Emp2(-/-) ) were generated. Emp2(-/-) females are fertile but have reduced litter sizes when carrying Emp2(-/-) but not Emp2(+/-) fetuses. Placentas of Emp2(-/-) fetuses exhibit dysregulation in pathways related to neoangiogenesis, coagulation, and oxidative stress, and have increased fibrin deposition and altered vasculature. Given that these findings often occur due to placental insufficiency resulting in an oxygen-poor environment, the expression of hypoxia-inducible factor-1 alpha (HIF-1α) was examined. Placentas from Emp2(-/-) fetuses had increased total HIF-1α expression in large part through an increase in uterine NK (uNK) cells, demonstrating a unique interplay between uNK cells and trophoblasts modulated through EMP2. To determine if these results translated to human pregnancy, placentas from normal, term deliveries or those complicated by placental insufficiency resulting in intrauterine growth restriction (IUGR) were stained for EMP2. EMP2 was significantly reduced in both villous and extravillous trophoblast populations in IUGR placentas. Experiments in vitro using human trophoblast cells lines indicate that EMP2 modulates angiogenesis by altering HIF-1α expression. Our results reveal a novel role for EMP2 in regulating trophoblast function and vascular development in mice and humans and suggest it may be a new biomarker for placental insufficiency.

  2. Intact feto-placental growth in microRNA-210 deficient mice.

    Science.gov (United States)

    Krawczynski, Kamil; Mishima, Takuya; Huang, Xin; Sadovsky, Yoel

    2016-11-01

    MicroRNA-210 (miR-210) has been implicated in homeostatic adaptation during hypoxia. We hypothesized that miR-210 deficiency impacts feto-placental growth. As expected, mir-210 knockout (ko) mice exhibited markedly reduced placental miR-210 expression, compared to wild-type (wt) mice. Mating of mir-210 heterozygotes resulted in near Mendelian progeny distribution, with insignificant differences between wt and ko animals with regard to embryo or placental weight and gross morphology. Intriguingly, exposure of mice to non-severe hypoxia (O2 = 12%) between E11.5-E17.5 reduced placental miR-210 expression, with slight expression changes of some miR-210 target mRNAs. Thus, miR-210 is likely dispensable for feto-placental growth in normoxia or non-severe hypoxia. Copyright © 2016 Elsevier Ltd. All rights reserved.

  3. Adhesion of Plasmodium falciparum infected erythrocytes in ex vivo perfused placental tissue

    DEFF Research Database (Denmark)

    Pehrson, Caroline; Mathiesen, Line; Heno, Kristine K;

    2016-01-01

    BACKGROUND: Placental malaria occurs when Plasmodium falciparum infected erythrocytes sequester in the placenta. Placental parasite isolates bind to chondroitin sulphate A (CSA) by expression of VAR2CSA on the surface of infected erythrocytes, but may sequester by other VAR2CSA mediated mechanisms...... placental tissue. RESULTS: The ex vivo placental perfusion model was modified to study adhesion of infected erythrocytes binding to CSA, endothelial protein C receptor (EPCR) or a transgenic parasite where P. falciparum erythrocyte membrane protein 1 expression had been shut down. Infected erythrocytes...... expressing VAR2CSA accumulated in perfused placental tissue whereas the EPCR binding and the transgenic parasite did not. Soluble CSA and antibodies specific against VAR2CSA inhibited binding of infected erythrocytes. CONCLUSION: The ex vivo model provides a novel way of studying receptor-ligand interactions...

  4. Placental perfusion - a human alternative

    DEFF Research Database (Denmark)

    Mose, Tina; Knudsen, Lisbeth E

    2006-01-01

    Foetal exposures to environmental and medicinal products have impact on the growth of the foetus (e.g. cigarette smoke) and development of organs (e.g. methylmercury and Thalidomide). Perfusion studies of the human term placenta enable investigation of placental transport of chemical substances...... between the mother and foetus. Dual perfusion of a single cotyledon in the human placenta can contribute to a better understanding of the placental barrier, transport rate and mechanisms of different substances and placental metabolism. The perfusion system has recently been established in Copenhagen...

  5. Potential effect of Olea europea leaves, Sonchus oleraceus leaves and Mangifera indica peel extracts on aromatase activity in human placental microsomes and CYP19A1 expression in MCF-7 cell line: Comparative study.

    Science.gov (United States)

    Shaban, N Z; Hegazy, W A; Abdel-Rahman, S M; Awed, O M; Khalil, S A

    2016-08-29

    Aromatase inhibitors (AIs) provide novel approaches to the adjuvant therapy for postmenopausal women with estrogen-receptor-positive (ER+) breast cancers. In this study, different plant extracts from Olea europaea leaves (OLE), Sonchus oleraceus L. (SOE) and Mangifera indica peels (MPE) were prepared to identify phytoconstituents and measure antioxidant capacities. The effects of these three extracts on aromatase activity in human placental microsomes were evaluated. Additionally, the effects of these extracts on tissue-specific promoter expression of CYP19A1 gene in cell culture model (MCF-7) were assessed using qRT-PCR. Results showed a concentration-dependent decrease in aromatase activity after treatment with OLE and MPE, whereas, SOE showed a biphasic effect. The differential effects of OLE, SOE and MPE on aromatase expression showed that OLE seems to be the most potent suppressor followed by SOE and then MPE. These findings indicate that OLE has effective inhibitory action on aromatase at both the enzymatic and expression levels, in addition to its cytotoxic effect against MCF-7 cells. Also, MPE may be has the potential to be used as a tissue-specific aromatase inhibitor (selective aromatase inhibitor) and it may be promising to develop a new therapeutic agent against ER+ breast cancer.

  6. Association of thrombomodulin Ala455Val dimorphism and inflammatory cytokines with carotid atherosclerosis in the Chinese Han population

    Directory of Open Access Journals (Sweden)

    Qian G

    2012-11-01

    Full Text Available Gaochao Qian,1 Zhixiang Ding,1 Binxia Zhang,2 Qihua Li,2 Wentao Jin,1 Qi Zhang21Clinical Laboratory Department, 2Department of Cardiology, Changzhou TCM Hospital Affiliated to Nanjing TCM University, Changzhou, ChinaBackground and methods: It has been reported that C/T dimorphism at position 1418 of the thrombomodulin gene causes a cytosine (C transition to thymidine (T, resulting in an alanine (A to valine (V substitution at amino acid position 455 (TM455. TM455 had been found not only in African American and American whites, but also in whites in The Netherlands and Sweden. Among these populations, the C/C genotype is predominant, although the distribution of this dimorphism is different. Thrombomodulin is an important anticoagulant protein that is downregulated in endothelial cells overlying atherosclerotic plaques and is also an anti-inflammatory molecule. TM455 is located in the last epidermal growth factor-like repeat of thrombomodulin, which is functionally important for protein C activation and thrombin binding. The distribution of thrombomodulin polymorphism and association between TM455, inflammatory cytokines, and carotid atherosclerosis in the Chinese Han population is unclear.Methods: This thrombomodulin dimorphism was analyzed by allele-specific amplification in 144 patients with carotid atherosclerosis and in 384 healthy controls. TM455 was found in the Chinese Han population, but the genotype frequency and distribution of each genotype in this population differed substantially from that in other ethnic subgroups. The C/T and T/T genotypes were predominant in the Chinese Han population, and the frequency of the T allele in this population (63.8% was much higher than that in whites in The Netherlands (18%, Sweden (26.1%, and the US (18.4%, and in blacks in the US (7.6%. The frequencies of these single nucleotide polymorphisms complied well with the Hardy-Weinberg equilibrium in healthy individuals. The C allele was significantly

  7. Placental Transmogrification of the lung

    Energy Technology Data Exchange (ETDEWEB)

    Kim, Jin Woo; Park, Il Hwan; Kwon, Woo Cheol; Eom, Min Seob; Kim, Young Ju; Hwan, Joong Hwan [Yonsei University Wonju College of Medicine, Wonju (Korea, Republic of)

    2013-12-15

    Placental transmogrification is a very rare lung disease, where the alveoli resemble the chorionic villi of placenta, and this change is a characteristic finding. A 31-year-old female patient presented with cough and dyspnea that had begun 2 weeks prior to admission. Along with giant bulla found in the left upper lung field, subsegmental consolidation was also identified in the lingular segment on plain chest radiograph and CT scan. Wedge resection was performed to remove the bulla. Pathologic examination of the resected bulla revealed destruction of the normal structures and characteristic villous and papillary changes. These changes led to a diagnosis of placental transmogrification. We made an encounter of an unusual placental transmogrification which had different image findings from other reported transmogrification cases. Thus, we report an atypical placental transmogrification case where both consolidation and giant bulla coexist.

  8. Placental abruption: a persisting killer

    Directory of Open Access Journals (Sweden)

    Shakuntala Amirchand Chhabra

    2014-06-01

    Full Text Available Background: Placental abruption, common disorder in obstetric practice, enigma too, is uniquely fraught with dangers to mother baby. Objectives of study were to study trends of placental abruption, risk factors, management strategies to learn more for reduction in morbidity-mortality of mother-baby, even with low resources, also get insight for future research. Methods: Records of cases of placental abruption managed over 27 years (between 1985 to 2011 were divided into three yearly blocks, A to I and analysed. Details including operative procedures like dilatation-curettage, Caesarean Section (CS or Ante-Partum Haemorrhage (APH in past, disorders like chronic hypertension, threatened abortion, pregnancy specific hypertension, diabetes, anaemia in index pregnancy, management done maternal-neonatal outcome were analysed using stata 6 software. Results: There were 66,459 births during analysis period with 667 cases of placental abruption, 1% births, increasing trends from, 0.73% between 1985-1987 to, 1.11% in 2009-2011. In these 667 cases of placental abruption, 211 (32.5% perinatal deaths occurred. Ratio of perinatal deaths due to placental abruption to overall perinatal deaths increased from 2.12% (8 cases between 1985-1987 (Block A to 5.12% (37 cases between 2009-2011 (Block I. Case fatality in cases of placental abruption has been fluctuating between 3 to 5% till 2004, contributing to around 12-15%, maternal mortality, with no fatality in last 7 years. Conclusions: Cases of placental abruption have been increasing with no obvious reason. In recent past maternal deaths could be prevented but perinatal deaths, have been persisting actually more in last decade. [Int J Reprod Contracept Obstet Gynecol 2014; 3(3.000: 604-609

  9. Regional changes of placental vascularization in preeclampsia: a review.

    Science.gov (United States)

    Sahay, Akriti S; Sundrani, Deepali P; Joshi, Sadhana R

    2015-08-01

    Preeclampsia is characterized by vascular dysfunction and results in maternal and fetal morbidity and mortality. The placenta plays a critical role in the growth and development of the fetus, and recent studies indicate that placental architecture, oxygen availability, and oxidative stress indices vary across different regions of the placenta. Our earlier studies have reported altered maternal angiogenesis and differential placental gene expression and methylation patterns of angiogenic factors in women with preeclampsia when compared with normotensive women. We have also demonstrated lower maternal and placental neurotrophin (NT) levels in women with preeclampsia. Studies suggest that oxidative stress is associated with proteases like matrix metalloproteinases (MMPs) and growth factors like NTs and angiogenic factors known to be involved in the process of angiogenesis. Recently, we have reported regionwise differential oxidative stress, antioxidant enzyme activity, and NT levels in placenta from normotensive control women and women with preeclampsia. The current review describes the regional changes in the placenta and highlights the role of placental oxidative stress in influencing regional differences in the expression of angiogenic factors, MMPs, and NTs. This review discusses the need for further research on various growth factors and proteins involved in the process of placental development across different regions of the placenta. This would help to understand whether regional differences in these factors affect the growth and development of the fetus.

  10. The effect of 7 days of letrozole pretreatment combined with misoprostol on the expression of progesterone receptor and apoptotic factors of placental and decidual tissues from first-trimester abortion: a randomized controlled trial.

    Science.gov (United States)

    Yung, Sofie Shuk Fei; Lee, Vivian Chi Yan; Chiu, Philip Chi Ngong; Li, Hang Wun Raymond; Ng, Ernest Hung Yu; Yeung, William Shu Biu; Ho, Pak Chung

    2016-04-01

    To evaluate if letrozole-induced suppression of estradiol reduces progesterone receptor expression and apoptosis in the first-trimester placenta. We performed a double-blinded, randomized, placebo-controlled trial. We randomized 20 women requesting first-trimester abortion with gestation up to 63 days to receive either letrozole 10 mg daily or placebo pretreatment for 7 days before administrating 400 mcg of vaginal misoprostol followed by suction abortion. We collected the placental and decidual tissues on which we performed immunohistochemical staining for progesterone receptor and apoptotic markers (active caspase 3, caspase 3, Bcl2, CD95, fas ligand) and determined H-scores of each based on the intensities of staining. We performed terminal deoxynucleotidyl transferase-mediated dUTP-digoxigenin nick end labeling (TUNEL) assay for apoptosis in the samples of four women to confirm the findings from apoptotic markers. We excluded one woman in the letrozole group from the analysis because she had passage of abortus after taking letrozole, leaving 19 women (9 in the letrozole group, 10 in the placebo group) for analysis. There was no significant difference in the H-scorings of progesterone receptor and apoptotic markers, as well as proportion of apoptotic cells on TUNEL assay between the two groups. The H-scores for the progesterone receptor were 8.17 ± 2.67 (mean ± SD) in the letrozole group and 9.01 ± 2.82 in the placebo group (p=0.36). We did not detect a difference in the expression of progesterone receptor and apoptotic markers in placental and decidual tissues after letrozole pretreatment for 7 days in first-trimester abortion. We did not confirm the hypothesis that letrozole reduces progesterone receptor expression and induces apoptosis in the first-trimester placenta. Further studies are required to allow better understanding of the mechanism by which estrogen suppression following the use of letrozole can lead to improved abortion rate in the first

  11. Protein Profiling of Preeclampsia Placental Tissues

    Science.gov (United States)

    Shu, Chang; Liu, Zitao; Cui, Lifeng; Wei, Chengguo; Wang, Shuwen; Tang, Jian Jenny; Cui, Miao; Lian, Guodong; Li, Wei; Liu, Xiufen; Xu, Hongmei; Jiang, Jing; Lee, Peng; Zhang, David Y.

    2014-01-01

    Preeclampsia is a multi-system disorder involved in pregnancy without an effective treatment except delivery. The precise pathogenesis of this complicated disorder is still not completely understood. The objective of this study is to evaluate the alterations of protein expression and phosphorylations that are important in regulating placental cell function in preterm and term preeclampsia. Using the Protein Pathway Array, 38 proteins in placental tissues were found to be differentially expressed between preterm preeclampsia and gestational age matched control, while 25 proteins were found to be expressed differentially between term preeclampsia and matched controls. Among these proteins, 16 proteins and their associated signaling pathways overlapped between preterm and term preeclampsia, suggesting the common pathogenesis of two subsets of disease. On the other hand, many proteins are uniquely altered in either preterm or term preeclampsia and correlated with severity of clinical symptoms and outcomes, therefore, providing molecular basis for these two subsets of preeclampsia. Furthermore, the expression levels of some of these proteins correlated with neonatal small for gestational age (PAI-1 and PAPP-A) and adverse outcomes (Flt-1) in women with preterm preeclampsia. These proteins could potentially be used as candidate biomarkers for predicting outcomes of preeclampsia. PMID:25392996

  12. Protein profiling of preeclampsia placental tissues.

    Science.gov (United States)

    Shu, Chang; Liu, Zitao; Cui, Lifeng; Wei, Chengguo; Wang, Shuwen; Tang, Jian Jenny; Cui, Miao; Lian, Guodong; Li, Wei; Liu, Xiufen; Xu, Hongmei; Jiang, Jing; Lee, Peng; Zhang, David Y; He, Jin; Ye, Fei

    2014-01-01

    Preeclampsia is a multi-system disorder involved in pregnancy without an effective treatment except delivery. The precise pathogenesis of this complicated disorder is still not completely understood. The objective of this study is to evaluate the alterations of protein expression and phosphorylations that are important in regulating placental cell function in preterm and term preeclampsia. Using the Protein Pathway Array, 38 proteins in placental tissues were found to be differentially expressed between preterm preeclampsia and gestational age matched control, while 25 proteins were found to be expressed differentially between term preeclampsia and matched controls. Among these proteins, 16 proteins and their associated signaling pathways overlapped between preterm and term preeclampsia, suggesting the common pathogenesis of two subsets of disease. On the other hand, many proteins are uniquely altered in either preterm or term preeclampsia and correlated with severity of clinical symptoms and outcomes, therefore, providing molecular basis for these two subsets of preeclampsia. Furthermore, the expression levels of some of these proteins correlated with neonatal small for gestational age (PAI-1 and PAPP-A) and adverse outcomes (Flt-1) in women with preterm preeclampsia. These proteins could potentially be used as candidate biomarkers for predicting outcomes of preeclampsia.

  13. Placental Growth Factor Administration Abolishes Placental Ischemia-Induced Hypertension.

    Science.gov (United States)

    Spradley, Frank T; Tan, Adelene Y; Joo, Woo S; Daniels, Garrett; Kussie, Paul; Karumanchi, S Ananth; Granger, Joey P

    2016-04-01

    Preeclampsia is a pregnancy-specific disorder of new-onset hypertension. Unfortunately, the most effective treatment is early delivery of the fetus and placenta. Placental ischemia appears central to the pathogenesis of preeclampsia because placental ischemia/hypoxia induced in animals by reduced uterine perfusion pressure (RUPP) or in humans stimulates release of hypertensive placental factors into the maternal circulation. The anti-angiogenic factor soluble fms-like tyrosine kinase-1 (sFlt-1), which antagonizes and reduces bioavailable vascular endothelial growth factor and placental growth factor (PlGF), is elevated in RUPP rats and preeclampsia. Although PlGF and vascular endothelial growth factor are both natural ligands for sFlt-1, vascular endothelial growth factor also has high affinity to VEGFR2 (Flk-1) causing side effects like edema. PlGF is specific for sFlt-1. We tested the hypothesis that PlGF treatment reduces placental ischemia-induced hypertension by antagonizing sFlt-1 without adverse consequences to the mother or fetus. On gestational day 14, rats were randomized to 4 groups: normal pregnant or RUPP±infusion of recombinant human PlGF (180 μg/kg per day; AG31, a purified, recombinant human form of PlGF) for 5 days via intraperitoneal osmotic minipumps. On day 19, mean arterial blood pressure and plasma sFlt-1 were higher and glomerular filtration rate lower in RUPP than normal pregnant rats. Infusion of recombinant human PlGF abolished these changes seen with RUPP along with reducing oxidative stress. These data indicate that the increased sFlt-1 and reduced PlGF resulting from placental ischemia contribute to maternal hypertension. Our novel finding that recombinant human PlGF abolishes placental ischemia-induced hypertension, without major adverse consequences, suggests a strong therapeutic potential for this growth factor in preeclampsia.

  14. Lectin-like domain of thrombomodulin binds to its specific ligand Lewis Y antigen and neutralizes lipopolysaccharide-induced inflammatory response

    Science.gov (United States)

    Shi, Chung-Sheng; Hsiao, Shi-Ming; Kao, Yuan-Chung; Kuo, Kuan-Lin; Ma, Chih-Yuan; Kuo, Cheng-Hsiang; Chang, Bi-Ing; Chang, Chuan-Fa; Lin, Chun-Hung; Wong, Chi-Huey

    2008-01-01

    Thrombomodulin (TM), a widely expressing glycoprotein originally identified in vascular endothelium, is an important cofactor in the protein C anticoagulant system. TM appears to exhibit anti-inflammatory ability through both protein C–dependent and –independent pathways. We presently have demonstrated that recombinant N-terminal lectinlike domain of TM (rTMD1) functions as a protective agent against sepsis caused by Gram-negative bacterial infections. rTMD1 caused agglutination of Escherichia coli and Klebsiella pneumoniae and enhanced the macrophage phagocytosis of these Gram-negative bacteria. Moreover, rTMD1 bound to the Klebsiella pneumoniae and lipopolysaccharide (LPS) by specifically interacting with Lewis Y antigen. rTMD1 inhibited LPS-induced inflammatory mediator production via interference with CD14 and LPS binding. Furthermore, rTMD1 modulated LPS-induced mitogen-activated protein kinase and nuclear factor-κB signaling pathway activations and inducible nitric oxide synthase expression in macrophages. Administration of rTMD1 protected the host by suppressing inflammatory responses induced by LPS and Gram-negative bacteria, and enhanced LPS and bacterial clearance in sepsis. Thus, rTMD1 can be used to defend against bacterial infection and inhibit LPS-induced inflammatory responses, suggesting that rTMD1 may be valuable in the treatment of severe inflammation in sepsis, especially in Gram-negative bacterial infections. PMID:18711002

  15. Altered placental development in undernourished rats: role of maternal glucocorticoids

    Directory of Open Access Journals (Sweden)

    Chen Chun-Hung

    2011-08-01

    Full Text Available Abstract Maternal undernutrition (MUN during pregnancy may lead to fetal intrauterine growth restriction (IUGR, which itself predisposes to adult risk of obesity, hypertension, and diabetes. IUGR may stem from insufficient maternal nutrient supply or reduced placental nutrient transfer. In addition, a critical role for maternal stress-induced glucocorticoids (GCs has been suggested to contribute to both IUGR and the ensuing risk of adult metabolic syndrome. While GC-induced fetal organ defects have been examined, there have been few studies on placental responses to MUN-induced maternal stress. Therefore, we hypothesize that 50% MUN associates with increased maternal GC levels and decreased placental HSD11B. This in turn leads to decreased placental and fetal growth, hence the need to investigate nutrient transporters. We measured maternal serum levels of corticosterone, and the placental basal and labyrinth zone expression of glucocorticoid receptor (NR3C1, 11-hydroxysteroid dehydrogenase B 1 (HSD11B-1 predominantly activates cortisone to cortisol and 11-dehydrocorticosterone (11-DHC to corticosterone, although can sometimes drive the opposing (inactivating reaction, and HSD11B-2 (only inactivates and converts corticosterone to 11-DHC in rodents in control and MUN rats at embryonic day 20 (E20. Moreover, we evaluated the expression of nutrient transporters for glucose (SLC2A1, SLC2A3 and amino acids (SLC38A1, 2, and 4. Our results show that MUN dams displayed significantly increased plasma corticosterone levels compared to control dams. Further, a reduction in fetal and placental weights was observed in both the mid-horn and proximal-horn positions. Notably, the placental labyrinth zone, the site of feto-maternal exchange, showed decreased expression of HSD11B1-2 in both horns, and increased HSD11B-1 in proximal-horn placentas, but no change in NR3C1. The reduced placental GCs catabolic capacity was accompanied by downregulation of SLC2A3, SLC

  16. Imaging and assessment of placental function.

    LENUS (Irish Health Repository)

    Moran, Mary

    2011-09-01

    The placenta is the vital support organ for the developing fetus. This article reviews current ultrasound (US) methods of assessing placental function. The ability of ultrasound to detect placental pathology is discussed. Doppler technology to investigate the fetal, placental, and maternal circulations in both high-risk and uncomplicated pregnancies is discussed and the current literature on the value of three-dimensional power Doppler studies to assess placental volume and vascularization is also evaluated. The article highlights the need for further research into three-dimensional ultrasound and alternative methods of placental evaluation if progress is to be made in optimizing placental function assessment.

  17. Combination therapy with sivelestat and recombinant human soluble thrombomodulin for ARDS and DIC patients

    Directory of Open Access Journals (Sweden)

    Miyoshi S

    2014-09-01

    Full Text Available Seigo Miyoshi,1 Ryoji Ito,1 Hitoshi Katayama,1 Kentaro Dote,2 Mayuki Aibiki,3 Hironobu Hamada,1,4 Takafumi Okura,1 Jitsuo Higaki1 1Department of Cardiology, Pulmonology, Hypertension and Nephrology, Ehime University Graduate School of Medicine, 2Intensive Care Division, Ehime University Hospital, 3Department of Emergency and Critical Care Medicine, School of Medicine, Ehime University, Shitsukawa, Toon, Ehime, 4Department of Physical Analysis and Therapeutic Sciences, Graduate School of Biomedical and Health Sciences, Hiroshima University, Kasumi, Minami-ku, Hiroshima, Japan Background: Neutrophil elastase, alveolar thrombin generation, and fibrin deposition play crucial roles in the development of acute respiratory distress syndrome (ARDS and disseminated intravascular coagulation (DIC. However, the usefulness of combination therapy with a selective neutrophil elastase inhibitor, sivelestat, and recombinant human soluble thrombomodulin (rhTM for patients with ARDS and DIC remains unknown. Methods: We conducted a retrospective data analysis of 142 ARDS patients with DIC to assess the effects of sivelestat combined with rhTM. Patients were divided into four groups: control (no sivelestat or rhTM treatment, sivelestat treatment alone, rhTM treatment alone, and combined treatment with sivelestat and rhTM. A Cox proportional hazard model was used to assess subject mortality rates. The efficacy of these drugs was evaluated based on survival rate, number of ventilator-free days, and change in PaO2/FIO2 (P/F ratios and DIC scores before and at 7 days after a diagnosis of ARDS with DIC. Results: Multivariate analysis showed that patient age, combination therapy, gas exchange, organ failure, cause, associated disease score, and serum C-reactive protein levels were predictors of mortality for patients with ARDS and DIC. As compared with untreated controls, combination therapy significantly improved the 60-day survival rate of patients with ARDS and DIC

  18. Altered feto-placental vascularization, feto-placental malperfusion and fetal growth restriction in mice with Egfl7 loss of function.

    Science.gov (United States)

    Lacko, Lauretta A; Hurtado, Romulo; Hinds, Samantha; Poulos, Michael G; Butler, Jason M; Stuhlmann, Heidi

    2017-07-01

    EGFL7 is a secreted angiogenic factor produced by embryonic endothelial cells. To understand its role in placental development, we established a novel Egfl7 knockout mouse. The mutant mice have gross defects in chorioallantoic branching morphogenesis and placental vascular patterning. Microangiography and 3D imaging revealed patchy perfusion of Egfl7(-/-) placentas marked by impeded blood conductance through sites of narrowed vessels. Consistent with poor feto-placental perfusion, Egfl7 knockout resulted in reduced placental weight and fetal growth restriction. The placentas also showed abnormal fetal vessel patterning and over 50% reduction in fetal blood space. In vitro, placental endothelial cells were deficient in migration, cord formation and sprouting. Expression of genes involved in branching morphogenesis, Gcm1, Syna and Synb, and in patterning of the extracellular matrix, Mmrn1, were temporally dysregulated in the placentas. Egfl7 knockout did not affect expression of the microRNA embedded within intron 7. Collectively, these data reveal that Egfl7 is crucial for placental vascularization and embryonic growth, and may provide insight into etiological factors underlying placental pathologies associated with intrauterine growth restriction, which is a significant cause of infant morbidity and mortality. © 2017. Published by The Company of Biologists Ltd.

  19. Placental leptin gene methylation and macrosomia during normal pregnancy.

    Science.gov (United States)

    Xu, Xinyun; Yang, Xinjun; Liu, Ziwei; Wu, Kele; Liu, Zheng; Lin, Chong; Wang, Yuhuan; Yan, Hongtao

    2014-03-01

    The present study examined the placental leptin (LEP) DNA methylation and mRNA levels in macrosomic infants from normal pregnancies. In total, 49 neonates with macrosomia, i.e., high birth weights of ≥ 4,000 g, and 52 neonates with normal birth weights between 2,500 g and 4,000 g were recruited from The Second Affiliated Hospital of Wenzhou Medical University (Wenzhou, Zhejiang) in China. Placental LEP promoter methylation and LEP transcript levels were determined by Sequenom MassARRAY and quantitative PCR, respectively. LEP promoter methylation and mRNA levels were not significantly different between the individuals with macrosomia and the controls. However, stratification revealed that individual CpG dinucleotides were hypermethylated in macrosomia (Pmacrosomia following a normal pregnancy and under certain conditions. However, placental LEP expression was not affected.

  20. DETECTION AND CLINICAL SIGNIFICANCE OF THROMBOMODULIN IN BOTH PLASMA AND TISSUE EXTRACTS OF CANCER PATIENTS

    Institute of Scientific and Technical Information of China (English)

    许晓华; 卢兴国; 徐根波; 朱蕾; 黄连生

    2004-01-01

    Objective: To study the changes of thrombomodulin (TM) in both plasma and tissue extracts of cancer patients for evaluating its clinical significance. Methods: Plasma TM levels were measured by enzyme-linked immunosorbent assay (ELISA) in both plasma of 188 cancer patients and 24 cancer tissue extracts including their adjacent non-cancer tissues. Results: The plasma TM levels both in cancer patients and in metastasis patients were significantly higher than that in controls [(33.47±14.25)μg/L, (41.68±16.96)μg/L, vs(20.40±7.22)μg/L,P0.05). The TM levels in cancer tissue extracts were significantly lower than that in their adjacent non-cancer tissue extracts [(647.71±317.51)μg/L vs (1455.63±772.22)μg/L, P<0.01]. On the contrary, the plasma TM levels in these cancers were significantly higher than that in controls. Conclusion: The rise of plasma TM levels in cancer patients was associated with metastasis and diffusion of cancers. The TM levels can be served as an sensitive index for judging progression and metastasis of cancers.

  1. Expression of variant surface antigens by Plasmodium falciparum parasites in the peripheral blood of clinically immune pregnant women indicates ongoing placental infection

    DEFF Research Database (Denmark)

    Ofori, Michael F; Staalsoe, Trine; Bam, Victoria

    2003-01-01

    Placenta-sequestered Plasmodium falciparum parasites that cause pregnancy-associated malaria (PAM) in otherwise clinically immune women express distinct variant surface antigens (VSA(PAM)) not expressed by parasites in nonpregnant individuals. We report here that parasites from the peripheral blood...... of clinically immune pregnant women also express VSA(PAM), making them a convenient source of VSA(PAM) expressors for PAM vaccine research....

  2. Molecules consolidate the placental mammal tree

    NARCIS (Netherlands)

    Springer, M.S.; Stanhope, M.J.; Madsen, O.; Jong, W.W.W. de

    2004-01-01

    Deciphering relationships among the orders of placental mammals remains an important problem in evolutionary biology and has implications for understanding patterns of morphological character evolution, reconstructing the ancestral placental genome, and evaluating the role of plate tectonics and dis

  3. Molecules consolidate the placental mammal tree

    NARCIS (Netherlands)

    Springer, M.S.; Stanhope, M.J.; Madsen, O.; Jong, W.W.W. de

    2004-01-01

    Deciphering relationships among the orders of placental mammals remains an important problem in evolutionary biology and has implications for understanding patterns of morphological character evolution, reconstructing the ancestral placental genome, and evaluating the role of plate tectonics and

  4. Placental lactogen levels in diabetic pregnancy.

    Science.gov (United States)

    Ursell, W; Brudenell, M; Chard, T

    1973-04-14

    A prospective study has been carried out of placental lactogen levels in pregnancy complicated by diabetes mellitus. The levels were higher than those in normal pregnant subjects; the higher levels were related to increased placental and fetal weight but more closely to the former; and lower levels were found when there was clinical evidence of placental dysfunction. Those patients requiring the largest insulin increment for the control of their diabetes in the pregnancy have placental lactogen levels in the higher range.

  5. Intrapritoneal Hemorrhage after Placental Abruption

    Directory of Open Access Journals (Sweden)

    Nahid Sakhavar

    2012-06-01

    Full Text Available A placental abruption or abruptio placentae (where in the placental lining has separated from the uterus of the mother is one of the complications caused by trauma during pregnancy. It lets the blood flow to infiltrate in the uterine lining and to develop Couvelaire uterus (also known as uteroplacental apoplexy and uterine atony (a condition in which a woman's uterine muscles lose the ability to contract after childbirth; however, it rarely develops considerable hemoperitoneum which needs hysterectomy. In this report, a unique case of placental abruption caused by trauma in a 28-year-old Afghan woman is introduced in which severity and duration of trauma because of delay in reaching health equipped center led to developing massive hemoperitoneum (infiltration of great amount of blood into the abdominal cavity and its complications.

  6. Plasma placental lactogen in pregnancy.

    Science.gov (United States)

    Raghuramulu, N

    1978-01-01

    Plasma placental lactogen (HPL) and urinary oestrogen levels were investigated in pregnant women belonging to low and high socio-economic groups. Plasma HPL levels increased progressively with increasing gestation in women of both the socio-economic groups. The mean values in the two groups were not statistically different at any period of gestation. No correlation was observed between the birth weight of the infant and the maternal plasma placental lactogen levels at term. A positive correlation was observed between urinary oestrogen excretion and plasma HPL concentration.

  7. Expressions of TGF-β1 and PLGF and their correlation in placental trophoblastic cells of patients with preeclampsia%子痫前期患者胎盘滋养细胞中TGF-β1与PLGF的表达及相关性

    Institute of Scientific and Technical Information of China (English)

    辛英; 温彦静; 马天辉; 郭影

    2011-01-01

    Objective: To explore the expressions of transforming growth factor - β1 ( TGF - β1 ) and placental growth factor ( PLGF) in placental trophoblastic cells of patients with preeclampsia, and their roles in pathogenesis of preeclampsia. Methods: Immunohistochemical method was used to detect the expression levels of TGF - β1 and PLGF in placental trophoblastic cells of 30 normal pregnant women and 68 patients with preeclampsia. Results: The expression level of TGF - β1 in severe preeclampsia group was significantly higher than those in normal pregnancy group and mild preeclampsia group (P <0. 05 ); the expression level of PLGF in severe preeclampsia group was significantly lower than those in normal pregnancy group and mild preeclampsia group ( P < 0. 05 ); there was negative correlation between TGF - β1 expression and PLGF expression in the three groups. Conclusion: TGF - β1 and PLGF are related to placental shallow implantation of patients with preeclampsia, and they participate in the regulation of growth, development and differentiation of placental chorionic trophoblastic cells and vascular endothelial cells in patients with preeclampsia, which play important roles in the course of occurrence and development of preeclampsia.%目的:探讨转化生长因子-β1(TGF-β1)与胎盘生长因子(PLGF)在子痫前期患者胎盘滋养细胞中的表达及两者在发病机制中的作用.方法:采用免疫组化法检测30例正常妊娠及68例子痫前期患者TGF-βl与PLGF的表达强度.结果:重度子痫前期组TGF-β1的表达强度明显高于正常妊娠组、轻度子痫前期组(P<0.05),PLGF的表达强度明显低于正常妊娠组、轻度子痫前期组(P<0.05),TGF-β1与PLGF的表达在各组中呈负相关.结论:TGF-β1与PLGF不仅与子痫前期患者胎盘浅着床有关,并且还参与调节了子痫前期患者胎盘绒毛滋养细胞和血管内皮细胞的生长发育分化过程,并在疾病的发生、发展过程中发挥了重要作用.

  8. Placental diversity in malagasy tenrecs

    DEFF Research Database (Denmark)

    Enders, A C; Blankenship, T N; Goodman, S M;

    2007-01-01

    Placentation in tenrecs of the subfamily Oryzorictinae, family Tenrecidae, has not been described previously. The structure of the placenta of this group and especially of the genus Microgale was investigated to determine its similarity or dissimilarity to previously described placentas of the te...

  9. PLACENTAL SIZE AND PERINATAL OUTCOMES

    Directory of Open Access Journals (Sweden)

    Nagamani

    2015-03-01

    Full Text Available BACKGROUND : The human placenta, a transient organ or pregnancy provides information about fetal well - being and pregnancy outcome . AIMS: To study the placental ultrasound characters in relation to perinatal outcomes . SETTINGS: Tertiary care hospital in southern India . METHODS AND MATERIAL S: The study sample comprised 500 consecutive women who presented to the Depart ment of Obstetrics and Gynecology at the King George Hospital who met the inclusion criteria. Ultrasonographic study was performed using a transabdominal 3.5 MHz volume transducer. Post natally the weight of the baby and of the placenta was recorded. Perina tal outcome was assessed by birth weight, APGAR score and the need for admission in neonatal intensive care unit. STATISTICAL ANALYSIS : Pearson’s correlation analysis and Chi square test was used. Statistical significance was considered at a p value <0.05 . RESULTS: The mean placental thickness was 3.10 cm; 76% (n:380 had normal thickness. Mean placental diameter was 21.306 cm, and its weight varied from 310 women 62% (n:310. Correlation of placental thickness (normal and abnormal, with birth weight, the difference was significant ( <0.001. CONCLUSION: Ultrasound forms a readily available, fairly safe, effective non - invasive method to identify and prevent fetal malnutrition in a cost - effective way.

  10. Oxidative stress and maternal obesity: feto-placental unit interaction.

    Science.gov (United States)

    Malti, N; Merzouk, H; Merzouk, S A; Loukidi, B; Karaouzene, N; Malti, A; Narce, M

    2014-06-01

    To determine oxidative stress markers in maternal obesity during pregnancy and to evaluate feto-placental unit interaction, especially predictors of fetal metabolic alterations. 40 obese pregnant women (prepregnancy BMI > 30 kg/m²) were compared to 50 control pregnant women. Maternal, cord blood and placenta samples were collected at delivery. Biochemical parameters (total cholesterol and triglycerides) and oxidative stress markers (malondialdehyde, carbonyl proteins, superoxide anion expressed as reduced Nitroblue Tetrazolium, nitric oxide expressed as nitrite, reduced glutathione, catalase, superoxide dismutase) were assayed by biochemical methods. Maternal, fetal and placental triglyceride levels were increased in obese group compared to control. Maternal malondialdehyde, carbonyl proteins, nitric oxide and superoxide anion levels were high while reduced glutathione concentrations and superoxide dismutase activity were low in obesity. In the placenta and in newborns of these obese mothers, variations of redox balance were also observed indicating high oxidative stress. Maternal and placental interaction constituted a strong predictor of fetal redox variations in obese pregnancies. Maternal obesity compromised placental metabolism and antioxidant status which strongly impacted fetal redox balance. Oxidative stress may be one of the key downstream mediators that initiate programming of the offspring. Maternal obesity is associated with metabolic alterations and dysregulation of redox balance in the mother-placenta - fetus unit. These perturbations could lead to maternal and fetal complications and should be carefully considered. Copyright © 2014 Elsevier Ltd. All rights reserved.

  11. Association of Thrombomodulin Gene Polymorphisms with Susceptibility to Atherosclerotic Diseases: A Meta-Analysis.

    Science.gov (United States)

    Xu, Jie; Jin, Jun; Tan, Sheng

    2016-05-01

    Previous studies have proved that the dysfunction of thrombomodulin (TM) plays an important role in the pathogenesis of atherosclerotic diseases. In order to reveal their inherent relationship, we conducted a meta-analysis to uncover the association between two polymorphisms -33G/A and Ala455Val (c.1418C>T) in the TM gene and atherosclerotic diseases. We carried out a systematic search in PubMed, Science Direct, BIOSIS Previews, SpringerLink, the Cochrane library, the Chinese National Knowledge Infrastructure, the Chinese Biomedical Database, the Wei Pu database, and the Wanfang Database. Pooled odds ratios (ORs) and 95% confidence intervals (CIs) were computed to show the association. We included 22 eligible studies which involved 5472 patients and 7786 controls. There were statistically significant associations between -33G/A polymorphisms in TM and the MI group under the Allele and Recessive models in Asians (G vs. A: OR = 0.67, 95%CI = 0.56-0.78, P < 0.00001; GG vs. GA+AA: OR = 0.66, 95%CI = 0.56-0.78, P < 0.00001). However, these findings of the overall and subgroups showed that Ala455Val polymorphisms did not have any relationship with atherosclerotic diseases. After Bonferroni correction, the above associations remained statistically significant. This meta-analysis provides robust evidence of association between the -33G/A polymorphism in the TM gene and the risk of myocardial infarction in Asians. The A allele may increase the incidence of MI in Asians. However, the Ala455Val variant was not associated with atherosclerotic risk. Further studies with adequate sample size are needed to verify our findings.

  12. Circulating thrombomodulin and hematological alterations in type 2 diabetic patients with retinopathy.

    Science.gov (United States)

    Fujiwara, Y; Tagami, S; Kawakami, Y

    1998-01-01

    To clarify the relationship between circulating thrombomodulin (TM) and endothelial cell damage in diabetes mellitus, plasma levels of TM were quantitated by an enzyme linked immunoabsorbant assay (ELISA) in 164 type 2 diabetes mellitus and 72 normal control subjects, and these levels were compared with those of von Willebrand factor antigen (vWf: Ag), thrombin antithrombin III complexes (TAT), plasmin-alpha2-plasmin inhibitor complexes (PIC), fibrinogen, D-dimer, urinary albumin excretion rate (AER), intima-media thickness (IMT) and plaque score of the common carotid artery assessed with high resolution B-mode ultrasonography. Plasma levels of TM, vWf: Ag, TAT, PIC, AER, IMT and plaque score were significantly increased in the diabetic patients compared to the normal control subjects. Plasma TM levels showed significant correlation with vWf: Ag (r=0.350, pPIC (r = 0.450, p sex, systolic and diastolic blood pressure levels, HbA,1c, or plasma lipid levels, although the plasma levels of TM, vWf: Ag, TAT, PIC, AER, IMT and the plaque score in the patients with proliferative retinopathy were significantly higher than those of the healthy controls and patients with simple retinopathy. Among the 43 normoalbuminuric patients without intima-media thickness or thickened plaque (AERPIC were significantly higher in those patients with retinopathy than in those without retinopathy. Multivariate analysis showed TM, TAT and PIC levels to be independent predictors of diabetic retinopathy. In conclusion, circulating TM reflects endothelial cell damage in patients with diabetic retinopathy, and hypercoagulability might play an important role in endothelial cell damage.

  13. Anti-inflammatory effect of recombinant thrombomodulin for fulminant hepatic failure.

    Science.gov (United States)

    Kurokohchi, Kazutaka; Imataki, Osamu; Kubo, Fumiyoshi

    2015-07-14

    Fulminant hepatic failure (FHF) is a critical illness that can be comorbid to primary liver damage. FHF shows a high mortality rate, and patients with FHF require intensive therapy, including plasma apheresis. However, intensive care at the present is not enough to restore the severe liver damage or promote hepatocellular reproduction, and a standard therapy for the treatment of FHF has not been established. An 86-year-old female with FHF was admitted to our hospital. Her manifestation demonstrated a clinical situation of systemic inflammatory response syndrome (SIRS) and disseminated intravascular coagulation. A diagnosis of fulminant hepatitis was made according to the definition given in the position paper of the American Association for the Study of Liver Diseases. Her serum hepatocyte growth factor (HGF) level had increased to 11.84 ng/mL. The HGF level indicated massive liver damage as seen in FHF. Recombinant thrombomodulin (rTM) was administered daily from the admission day for 1 wk at 380 U/kg. The patient's white blood cells and C-reactive protein responded to the rTM treatment within a few days. The HGF level and PT recovered to the normal range. The levels of proinflammatory cytokines (tumor necrosis factor-α and interleukin-1β) were suppressed by the administration of rTM. The patient's hepatic function (e.g., PT and albumin) completely recovered without plasma exchange. rTM may modulate the over-response of SIRS with the improvement of proinflammatory cytokines. The underlying mechanism is thought to be the inhibitory effect of rTM on high-mobility group box 1 (HMBG1). The pathogenesis of HMBG1 protein in fulminant hepatic failure has been already known. A novel favorable effect of rTM for SIRS would be promising for FHF, and the wide application of rTM for SIRS should be considered.

  14. Early thrombomodulin-α administration outcome for acute disseminated intravascular coagulopathy in gastrointestinal surgery.

    Science.gov (United States)

    Konishi, Hirotaka; Okamoto, Kazuma; Shoda, Katsutoshi; Arita, Tomohiro; Kosuga, Toshiyuki; Morimura, Ryo; Komatsu, Shuhei; Murayama, Yasutoshi; Shiozaki, Atsushi; Kuriu, Yoshiaki; Ikoma, Hisashi; Nakanishi, Masayoshi; Ichikawa, Daisuke; Fujiwara, Hitoshi; Otsuji, Eigo

    2017-02-07

    To investigate the efficacy of thrombomodulin (TM)-α for treatment of disseminated intravascular coagulopathy (DIC) in the field of gastrointestinal surgery. Thirty-six peri-operative DIC patients in the field of gastrointestinal surgery who were treated with TM-α were retrospectively investigated. The relationships between patient demographics and the efficacy of TM-α were examined. Analysis of survival at 28 d was also performed on some parameters by means of the Kaplan-Meier method. Relationships between the initiation of TM-α and patient demographics were also evaluated. Abscess formation or bacteremia was the most frequent cause of DIC (33%), followed by digestive tract perforation (31%). Twenty-six patients developed DIC after surgery, frequently within 1 wk (81%). TM-α was most often administered within 1 d of the DIC diagnosis (72%) and was continued for more than 3 d (64%). Although bleeding tendency was observed in 7 patients (19%), a hemostatic procedure was not needed. DIC scores, systemic inflammatory response syndrome (SIRS) scores, quick-sequential organ failure assessment (qSOFA) scores, platelet counts, and prothrombin time ratios significantly improved after 1 wk (P SIRS and qSOFA) at 1 wk were significantly better prognostic factors for 28-d survival (P < 0.05, for all). TM-α was administered significantly earlier to patients with severe clinical symptoms, such as high qSOFA scores, sepsis, shock or high lactate values (P < 0.05, for all). Early administration of TM-α and improvements in each parameter were essential for treatment of DIC. The diagnosis of patients with mild symptoms requires further study.

  15. Placental Sequestration of Plasmodium falciparum Malaria Parasites Is Mediated by the Interaction Between VAR2CSA and Chondroitin Sulfate A on Syndecan-1.

    Science.gov (United States)

    Ayres Pereira, Marina; Mandel Clausen, Thomas; Pehrson, Caroline; Mao, Yang; Resende, Mafalda; Daugaard, Mads; Riis Kristensen, Anders; Spliid, Charlotte; Mathiesen, Line; E Knudsen, Lisbeth; Damm, Peter; G Theander, Thor; R Hansson, Stefan; A Nielsen, Morten; Salanti, Ali

    2016-08-01

    During placental malaria, Plasmodium falciparum infected erythrocytes sequester in the placenta, causing health problems for both the mother and fetus. The specific adherence is mediated by the VAR2CSA protein, which binds to placental chondroitin sulfate (CS) on chondroitin sulfate proteoglycans (CSPGs) in the placental syncytium. However, the identity of the CSPG core protein and the cellular impact of the interaction have remain elusive. In this study we identified the specific CSPG core protein to which the CS is attached, and characterized its exact placental location. VAR2CSA pull-down experiments using placental extracts from whole placenta or syncytiotrophoblast microvillous cell membranes showed three distinct CSPGs available for VAR2CSA adherence. Further examination of these three CSPGs by immunofluorescence and proximity ligation assays showed that syndecan-1 is the main receptor for VAR2CSA mediated placental adherence. We further show that the commonly used placental choriocarcinoma cell line, BeWo, express a different set of proteoglycans than those present on placental syncytiotrophoblast and may not be the most biologically relevant model to study placental malaria. Syncytial fusion of the BeWo cells, triggered by forskolin treatment, caused an increased expression of placental CS-modified syndecan-1. In line with this, we show that rVAR2 binding to placental CS impairs syndecan-1-related Src signaling in forskolin treated BeWo cells, but not in untreated cells.

  16. Placental Hypoxia During Early Pregnancy Causes Maternal Hypertension and Placental Insufficiency in the Hypoxic Guinea Pig Model.

    Science.gov (United States)

    Thompson, Loren P; Pence, Laramie; Pinkas, Gerald; Song, Hong; Telugu, Bhanu P

    2016-12-01

    Chronic placental hypoxia is one of the root causes of placental insufficiencies that result in pre-eclampsia and maternal hypertension. Chronic hypoxia causes disruption of trophoblast (TB) development, invasion into maternal decidua, and remodeling of maternal spiral arteries. The pregnant guinea pig shares several characteristics with humans such as hemomonochorial placenta, villous subplacenta, deep TB invasion, and remodeling of maternal arteries, and is an ideal animal model to study placental development. We hypothesized that chronic placental hypoxia of the pregnant guinea pig inhibits TB invasion and alters spiral artery remodeling. Time-mated pregnant guinea pigs were exposed to either normoxia (NMX) or three levels of hypoxia (HPX: 16%, 12%, or 10.5% O2) from 20 day gestation until midterm (39-40 days) or term (60-65 days). At term, HPX (10.5% O2) increased maternal arterial blood pressure (HPX 57.9 ± 2.3 vs. NMX 40.4 ± 2.3, P < 0.001), decreased fetal weight by 16.1% (P < 0.05), and increased both absolute and relative placenta weights by 10.1% and 31.8%, respectively (P < 0.05). At midterm, there was a significant increase in TB proliferation in HPX placentas as confirmed by increased PCNA and KRT7 staining and elevated ESX1 (TB marker) gene expression (P < 0.05). Additionally, quantitative image analysis revealed decreased invasion of maternal blood vessels by TB cells. In summary, this animal model of placental HPX identifies several aspects of abnormal placental development, including increased TB proliferation and decreased migration and invasion of TBs into the spiral arteries, the consequences of which are associated with maternal hypertension and fetal growth restriction.

  17. Intestinal and placental zinc transport pathways.

    Science.gov (United States)

    Ford, Dianne

    2004-02-01

    Mammalian members of the cation diffusion facilitator (CDF) and zrt-, irt-like protein (ZIP) families of Zn transporters, initially identified in Saccharomyces cerevisiae and Arabidopsis thalania spp., have been cloned during the last 8 years and have been classified as families SLC30 and SLC39 respectively. The cloning of human Zn transporters ZnT-like transporter 1 (hZTL1)/ZnT5 (SLC30A5) and hZIP4 (SLC39A4) were major advances in the understanding of the molecular mechanisms of dietary Zn absorption. Both transporters are localised at the enterocyte apical membrane and are, therefore, potentially of fundamental importance in dietary Zn uptake. hZTL1 mediates Zn uptake when expressed in Xenopus laevis oocytes and hZIP4 is mutated in most cases of the inherited Zn deficiency disease acrodermatitis enteropathica. Localisation of hZTL1/ZnT5 at the apical membrane of the placental syncytiotrophoblast indicates a fundamental role in the transfer of Slc30 Zn to the foetus. Observations in rodent models indicate that in the intestine increased Zn availability increases expression of Zn transporters. Human intestinal Caco-2 cells show a similar response to increasing the Zn2+ concentration of the nutrient medium in relation to the expression of mRNA corresponding to several Zn transporters and that of ZnT1 (SLC30A1) and hZTL1/ZnT5 proteins. In the human placental cell line JAR, however, expression at the mRNA level of a number of Zn transporters is not modified by Zn availability, whilst ZnT1 and hZTL1/ZnT5 proteins are reduced under Zn-supplemented conditions. These differences between Caco-2 and JAR cells in Zn transporter gene responses to Zn supply may reflect the different extracellular Zn concentrations encountered by the corresponding cell types in vitro.

  18. Placental ABC transporters, cellular toxicity and stress in pregnancy.

    Science.gov (United States)

    Aye, Irving L M H; Keelan, Jeffrey A

    2013-04-25

    The human placenta, in addition to its roles as a nutrient transfer and endocrine organ, functions as a selective barrier to protect the fetus against the harmful effects of exogenous and endogenous toxins. Members of the ATP-binding cassette (ABC) family of transport proteins limit the entry of xenobiotics into the fetal circulation via vectorial efflux from the placenta to the maternal circulation. Several members of the ABC family, including proteins from the ABCA, ABCB, ABCC and ABCG subfamilies, have been shown to be functional in the placenta with clinically significant roles in xenobiotic efflux. However, recent findings suggest that these transporters also protect placental tissue by preventing the cellular accumulation of cytotoxic compounds such as lipids, sterols and their derivatives. Such protective functions are likely to be particularly important in pregnancies complicated by inflammatory or oxidative stress, where the generation of toxic metabolites is enhanced. For example, ABC transporters have been shown to protect against the harmful effects of hypoxia and oxidative stress through increased expression and efflux of oxysterols and glutathione conjugated xenobiotics. However, this protective capacity may be diminished in response to the same stressors. Several studies in primary human trophoblast cells and animal models have demonstrated decreased expression and activity of placental ABC transporters with inflammatory, oxidative or metabolic stress. Several clinical studies in pregnancies complicated by inflammatory conditions such as preeclampsia and gestational diabetes support these findings, although further studies are required to determine the clinical relevance of the relationships between placental ABC transporter expression and activity, and placental function in stressed pregnancies. Such studies are necessary to fully understand the consequences of pregnancy disorders on placental function and viability in order to optimise pregnancy

  19. Activation of AP-1 Transcription Factors Differentiates FGF2 and Vascular Endothelial Growth Factor Regulation of Endothelial Nitric-oxide Synthase Expression in Placental Artery Endothelial Cells*

    Science.gov (United States)

    Mata-Greenwood, Eugenia; Liao, Wu-xiang; Wang, Wen; Zheng, Jing; Chen, Dong-bao

    2010-01-01

    FGF2 (fibroblast growth factor 2), but not vascular endothelial growth factor (VEGF), stimulates sustained activation of ERK2/1 for endothelial NOS3 (nitric-oxide synthase 3) protein expression in ovine fetoplacental artery endothelial cells (oFPAEC). We deciphered herein the downstream signaling of ERK2/1 responsible for NOS3 expression by FGF2 in oFPAEC. FGF2, but not VEGF, increased NOS3 mRNA levels without altering its degradation. FGF2, but not VEGF, trans-activated sheep NOS3 promoter, and this was dependent on ERK2/1 activation. FGF2 did not trans-activate NOS3 promoters with deletions upstream of the consensus AP-1 site (TGAGTC A, −678 to −685). Trans-activation of wild-type NOS3 promoter by FGF2 was significantly inhibited when either the AP-1 or the cAMP-response element (CRE)-like sequence (TGCGTCA, −752 to −758) was mutated and was completely blocked when both were mutated. EMSA analyses showed that FGF2, but not VEGF, stimulated AP-1 and CRE DNA-protein complexes primarily composed of JunB and Fra1. Chromatin immunoprecipitation assays confirmed JunB/Fra1 binding to NOS3 promoter AP-1 and CRE elements in intact cells. FGF2, but not VEGF, stimulated JunB and Fra1 expressions; all preceded NOS3 up-regulation and were inhibited by PD98059. Down-regulation of JunB or Fra-1, but not c-Jun, blocked FGF2 stimulation of NOS3 expression and NO production. AP-1 inhibition suppressed FGF2 stimulation of NOS3 expression in human umbilical vein EC and uterine artery endothelial cells. Thus, FGF2 induction of NOS3 expression is mainly mediated by AP-1-dependent transcription involving JunB and Fra1 up-regulation via sustained ERK2/1 activation in endothelial cells. PMID:20371606

  20. Effects of transcutaneous electrical nerve stimulation on fetal and placental development in an experimental model of placental insufficiency.

    Science.gov (United States)

    Guimarães, Camila S O; Gomes, Bruno B F; Oliveira, Rafael A; Yamamoto, Leandro R; Rocha, Laura P; Glória, Maria A; Machado, Juliana R; Câmara, Niels O S; Reis, Marlene A; Corrêa, Rosana R M

    2016-01-01

    To elucidate the effects of transcutaneous electrical nerve stimulation (TENS) in pregnancies with placental insufficiency. Pregnant rats were subjected to uterine artery ligation and to TENS according to the following groups: ligated stimulated (LS); ligated non-stimulated (LN), control stimulated (CS); and control non-stimulated (CN). Fetal external measurements, such as crown-rump length (CRL), fronto-occipital distance (FOD), thoracic ventral-dorsal (TVDD) and abdominal ventral-dorsal (AVDD) distances were analyzed together with the area occupied by fetal internal organs. Glucose transporter 1 (GLUT-1) expression was evaluated by immunohistochemistry in fetal organs. Thickness of junctional, labyrinth and intermediate placental zones was analyzed by morphometric evaluation in HE-stained slides, and placental hypoxia-inducible factor 1 alfa expression was measured by real-time polymerase chain reaction. In LN and CS groups compared to the CN group, CRL was reduced (27.51/28.95 versus 30.16 mm), as well as FOD (6.63/6.63 versus 7.36 mm), AVDD (7.38/8.00 versus 8.61 mm) and TVDD (6.46/6.87 versus 7.23 mm). Brain GLUT-1 expression was higher in LS (1.3%) and CS (1.8%). The area occupied by placental vessels in the labyrinth zone (29.67 ± 3.51 versus 20.83 ± 7.63) and intermediate zone (26.46 ± 10.21 versus 10.86 ± 8.94) was larger in the LS group than in the LN group. Our results suggest a negative effect of TENS on placental development, thus compromising the maintenance of adequate blood flow to the fetus.

  1. Placental sequestration of Plasmodium falciparum malaria parasites is mediated by the interaction between VAR2CSA and chondroitin sulfate A on syndecan-1

    DEFF Research Database (Denmark)

    Ayres Pereira, Marina; Mandel Clausen, Thomas; Pehrson, Caroline

    2016-01-01

    During placental malaria, Plasmodium falciparum infected erythrocytes sequester in the placenta, causing health problems for both the mother and fetus. The specific adherence is mediated by the VAR2CSA protein, which binds to placental chondroitin sulfate (CS) on chondroitin sulfate proteoglycans......-down experiments using placental extracts from whole placenta or syncytiotrophoblast microvillous cell membranes showed three distinct CSPGs available for VAR2CSA adherence. Further examination of these three CSPGs by immunofluorescence and proximity ligation assays showed that syndecan-1 is the main receptor...... for VAR2CSA mediated placental adherence. We further show that the commonly used placental choriocarcinoma cell line, BeWo, express a different set of proteoglycans than those present on placental syncytiotrophoblast and may not be the most biologically relevant model to study placental malaria. Syncytial...

  2. Placental Sequestration of Plasmodium falciparum Malaria Parasites Is Mediated by the Interaction Between VAR2CSA and Chondroitin Sulfate A on Syndecan-1

    DEFF Research Database (Denmark)

    Ayres Pereira, Marina; Mandel Clausen, Thomas; Pehrson, Caroline;

    2016-01-01

    During placental malaria, Plasmodium falciparum infected erythrocytes sequester in the placenta, causing health problems for both the mother and fetus. The specific adherence is mediated by the VAR2CSA protein, which binds to placental chondroitin sulfate (CS) on chondroitin sulfate proteoglycans......-down experiments using placental extracts from whole placenta or syncytiotrophoblast microvillous cell membranes showed three distinct CSPGs available for VAR2CSA adherence. Further examination of these three CSPGs by immunofluorescence and proximity ligation assays showed that syndecan-1 is the main receptor...... for VAR2CSA mediated placental adherence. We further show that the commonly used placental choriocarcinoma cell line, BeWo, express a different set of proteoglycans than those present on placental syncytiotrophoblast and may not be the most biologically relevant model to study placental malaria. Syncytial...

  3. Isolation and characterization of goat ovarian aromatase cDNA: assessment of the activity using an intact cell system and placental expression.

    Science.gov (United States)

    Bobes, Raúl José; Miranda, Carolina; Pérez-Martinez, Mario; Luu-The, Van; Romano, Marta C

    2004-08-01

    Goat ovarian follicles produce estrone and estradiol from androgens. The synthesis of C18 estrogens from C19 androgens requires cytochrome P450 aromatase, but little information about this key enzyme is available in the goat. We report here for the first time the cDNA sequence of the goat ovarian aromatase, the activity of the enzyme in a cell system, and its expression in the term goat placenta. A cDNA library from goat ovarian poly(A)+ RNA was constructed. Human aromatase cDNA was selected as probe to screen the library; several clones were isolated, but none was complete. The longest clone was 3.1 kb long, but it lacked the sequence coding for a few amino acids in the NH(2)-terminal. To obtain the missing sequence, we performed reverse amplification of the cDNA end (RACE). Sequence analysis indicated that goat aromatase possessed a very long 3'-untranslated region ( approximately 1790 bp), and a polyadenylation signal (AATAAA) located at position 3320 downstream from the ATG start codon. The coding region of goat cDNA was inserted in an expression vector and transfected into HEK-293 cells that were cultured in presence of [14C]-androstenedione, steroids extracted and further separated by TLC. The transfected cells efficiently transformed [14C]-androstenedione into estrone. This activity was inhibited by 4-hydroxyandrostenedione. We also investigated the presence of mRNA for P450 aromatase in the goat placenta, using reverse transcription-polymerase chain reaction (RT-PCR) and primers derived from the cDNA ovarian sequence and confirmed the expression of the mRNA in term placenta.

  4. [Expression of mRNA and protein of Klotho gene in placental tissue of macrosomia and its relationship with birth weight of neonates].

    Science.gov (United States)

    Shao, W J; Wang, D X; Wan, Q Y; Zhang, M M; Chen, M M; Song, W W

    2016-06-25

    To explore the the expression of Klotho mRNA and protein in placenta of macrosomia and its relationship with the birth weight of neonates. The cases were from November 2014 to March 2015 in Shengjing Hospital of China Medical University, divided into 4 groups: the gestational diabetes with macrosomia group (GM), the gestational diabetes with normal birth weight group (GN), the normal pregnancy with macrosomia group (NM) and the normal pregnancy with normal birth weight group (NN). Klotho mRNA and protein expression in the placenta were detected by immunohistochemistry SP method, real-time fluorescent quantitative PCR and western blot, respectively, and were compared among the 4 groups. (1) Immunohistochemical detection showed the positive rate of Klotho protein was significantly higher in the placenta of GM (93%,28/30) than in the GN (73%,22/30; P0.05). The up-regulation of Klotho gene may be associated with macrosomia. The relationship is not affected by the complication of gestational diabetes.

  5. Placental membrane aging and HMGB1 signaling associated with human parturition

    Science.gov (United States)

    Menon, Ramkumar; Behnia, Faranak; Polettini, Jossimara; Saade, George R; Campisi, Judith; Velarde, Michael

    2016-01-01

    Aging is associated with the onset of several diseases in various organ systems; however, different tissues may age differently, rendering some of them dysfunctional sooner than others. Placental membranes (fetal amniochorionic membranes) protect the fetus throughout pregnancy, but their longevity is limited to the duration of pregnancy. The age-associated dysfunction of these membranes is postulated to trigger parturition. Here, we investigated whether cellular senescence—the loss of cell division potential as a consequence of stress—is involved in placental membrane function at term. We show telomere reduction, p38 MAPK activation, increase in p21 expression, loss of lamin B1 loss, increase in SA-β-galactosidase, and senescence-associated secretory phenotype (SASP) gene expression in placental membranes after labor and delivery (term labor [TL]) compared to membranes prior to labor at term (term, not-in-labor [TNIL]). Exposing TNIL placental membranes to cigarette smoke extract, an oxidative stress inducer, also induced markers of cellular senescence similar to those in TL placental membranes. Bioinformatics analysis of differentially expressed SASP genes revealed HMGB1 signaling among the top pathways involved in labor. Further, we show that recombinant HMGB1 upregulates the expression of genes associated with parturition in myometrial cells. These data suggest that the natural physiologic aging of placental tissues is associated with cellular senescence and human parturition. PMID:26851389

  6. Placental membrane aging and HMGB1 signaling associated with human parturition.

    Science.gov (United States)

    Menon, Ramkumar; Behnia, Faranak; Polettini, Jossimara; Saade, George R; Campisi, Judith; Velarde, Michael

    2016-02-01

    Aging is associated with the onset of several diseases in various organ systems; however, different tissues may age differently, rendering some of them dysfunctional sooner than others. Placental membranes (fetal amniochorionic membranes) protect the fetus throughout pregnancy, but their longevity is limited to the duration of pregnancy. The age-associated dysfunction of these membranes is postulated to trigger parturition. Here, we investigated whether cellular senescence-the loss of cell division potential as a consequence of stress-is involved in placental membrane function at term. We show telomere reduction, p38 MAPK activation, increase in p21 expression, loss of lamin B1 loss, increase in SA-β-galactosidase , and senescence-associated secretory phenotype (SASP) gene expression in placental membranes after labor and delivery (term labor [TL]) compared to membranes prior to labor at term (term, not-in-labor [TNIL]). Exposing TNIL placental membranes to cigarette smoke extract, an oxidative stress inducer, also induced markers of cellular senescence similar to those in TL placental membranes. Bioinformatics analysis of differentially expressed SASP genes revealed HMGB1 signaling among the top pathways involved in labor. Further, we show that recombinant HMGB1 upregulates the expression of genes associated with parturition in myometrial cells. These data suggest that the natural physiologic aging of placental tissues is associated with cellular senescence and human parturition.

  7. Notch signalling in placental development and gestational diseases.

    Science.gov (United States)

    Haider, S; Pollheimer, J; Knöfler, M

    2017-01-16

    Activation of Notch signalling upon cell-cell contact of neighbouring cells controls a plethora of cellular processes such as stem cell maintenance, cell lineage determination, cell proliferation, and survival. Accumulating evidence suggests that the pathway also critically regulates these events during placental development and differentiation. Herein, we summarize our present knowledge about Notch signalling in murine and human placentation and discuss its potential role in the pathophysiology of gestational disorders. Studies in mice suggest that Notch controls trophectoderm formation, decidualization, placental branching morphogenesis and endovascular trophoblast invasion. In humans, the particular signalling cascade promotes formation of the extravillous trophoblast lineage and regulates trophoblast proliferation, survival and differentiation. Expression patterns as well as functional analyses indicate distinct roles of Notch receptors in different trophoblast subtypes. Altered effects of Notch signalling have been detected in choriocarcinoma cells, consistent with its role in cancer development and progression. Moreover, deregulation of Notch signalling components were observed in pregnancy disorders such as preeclampsia and fetal growth restriction. In summary, Notch plays fundamental roles in different developmental processes of the placenta. Abnormal signalling through this pathway could contribute to the pathogenesis of gestational diseases with aberrant placentation and trophoblast function.

  8. Placental mitochondrial content and function in intrauterine growth restriction and preeclampsia.

    Science.gov (United States)

    Mandò, C; De Palma, C; Stampalija, T; Anelli, G M; Figus, M; Novielli, C; Parisi, F; Clementi, E; Ferrazzi, E; Cetin, I

    2014-02-15

    Intrauterine growth restriction (IUGR) and pregnancy hypertensive disorders such as preeclampsia (PE) associated with IUGR share a common placental phenotype called "placental insufficiency", originating in early gestation when high availability of energy is required. Here, we assess mitochondrial content and the expression and activity of respiratory chain complexes (RCC) in placental cells of these pathologies. We measured mitochondrial (mt)DNA and nuclear respiratory factor 1 (NRF1) expression in placental tissue and cytotrophoblast cells, gene and protein expressions of RCC (real-time PCR and Western blotting) and their oxygen consumption, using the innovative technique of high-resolution respirometry. We analyzed eight IUGR, six PE, and eight uncomplicated human pregnancies delivered by elective cesarean section. We found lower mRNA levels of complex II, III, and IV in IUGR cytotrophoblast cells but no differences at the protein level, suggesting a posttranscriptional compensatory regulation. mtDNA was increased in IUGR placentas. Both mtDNA and NRF1 expression were instead significantly lower in their isolated cytotrophoblast cells. Finally, cytotrophoblast RCC activity was significantly increased in placentas of IUGR fetuses. No significant differences were found in PE placentas. This study provides genuine new data into the complex physiology of placental oxygenation in IUGR fetuses. The higher mitochondrial content in IUGR placental tissue is reversed in cytotrophoblast cells, which instead present higher mitochondrial functionality. This suggests different mitochondrial content and activity depending on the placental cell lineage. Increased placental oxygen consumption might represent a limiting step in fetal growth restriction, preventing adequate oxygen delivery to the fetus.

  9. Ultrasound Determination of Gestational Age Using Placental Thickness in Female Dogs: An Experimental Study

    Directory of Open Access Journals (Sweden)

    André Luiz Louzada Maldonado

    2012-01-01

    Full Text Available Objective. To verify if the placental thickness allows determining the gestational age, evaluating the correlation between the referred gestational age with the studied one, and the accuracy of the placental thickness measurement (biometry with fetal morphologic parameters in bitches. Methods. The placental thickness of 336 bitches of diverse breeds was evaluated. Bitches were divided in three groups by body weight: small, medium, and big large size. The gestations pregnancies were evaluated by ultrasound from the third week of gestation. An analysis was performed between the mean values of the gestational age obtained of placental thickness by adjustment of curves and the reported gestational age. Student's t-test was applied to compare the mean of reported and placental thickness gestational age. Significance was defined as P<0.05. Results. A positive and statistically significant correlation exists between the placental thickness and gestational age. The expression that presents the best correlation coefficient and explanation was thickness of placenta = 0.021x gestational age −0.314. Conclusion. It is possible to determine the gestational age in relation to the placental thickness measured by ultrasound in bitches with a satisfactory accuracy in relation to fetal morphologic parameters as gestational vesicle, ribs, or kidneys.

  10. Maternal fructose drives placental uric acid production leading to adverse fetal outcomes.

    Science.gov (United States)

    Asghar, Zeenat A; Thompson, Alysha; Chi, Maggie; Cusumano, Andrew; Scheaffer, Suzanne; Al-Hammadi, Noor; Saben, Jessica L; Moley, Kelle H

    2016-04-29

    Maternal metabolic diseases increase offspring risk for low birth weight and cardiometabolic diseases in adulthood. Excess fructose consumption may confer metabolic risks for both women and their offspring. However, the direct consequences of fructose intake per se are unknown. We assessed the impact of a maternal high-fructose diet on the fetal-placental unit in mice in the absence of metabolic syndrome and determined the association between maternal serum fructose and placental uric acid levels in humans. In mice, maternal fructose consumption led to placental inefficiency, fetal growth restriction, elevated fetal serum glucose and triglyceride levels. In the placenta, fructose induced de novo uric acid synthesis by activating the activities of the enzymes AMP deaminase and xanthine oxidase. Moreover, the placentas had increased lipids and altered expression of genes that control oxidative stress. Treatment of mothers with the xanthine oxidase inhibitor allopurinol reduced placental uric acid levels, prevented placental inefficiency, and improved fetal weights and serum triglycerides. Finally, in 18 women delivering at term, maternal serum fructose levels significantly correlated with placental uric acid levels. These findings suggest that in mice, excess maternal fructose consumption impairs placental function via a xanthine oxidase/uric acid-dependent mechanism, and similar effects may occur in humans.

  11. Characterization and expression analysis of SOLD1, a novel member of the retrotransposon-derived Ly-6 superfamily, in bovine placental villi.

    Directory of Open Access Journals (Sweden)

    Koichi Ushizawa

    Full Text Available BACKGROUND: Ly-6 superfamily members have a conserved Ly-6 domain that is defined by a distinct disulfide bonding pattern between eight or ten cysteine residues. These members are divided into membrane-type and secretory-type proteins. In the present study, we report the identification of a novel Ly-6 domain protein, secreted protein of Ly-6 domain 1 (SOLD1, from bovine placenta. PRINCIPAL FINDINGS: SOLD1 mRNA was expressed in trophoblast mononucleate cells and the protein was secreted into and localized in the extracellular matrix of the mesenchyme in cotyledonary villi. SOLD1 bound mainly with type I collagen telopeptide. We confirmed secretion of SOLD1 from the basolateral surface of a bovine trophoblast cell line (BT-1. It may be related to the organization of the extra-cellular matrix in the mesenchyme of fetal villi. Since trophoblast mononucleate cells are epithelial cells, their polar organization is expected to have a crucial role in the SOLD1 secretion system. We established that SOLD1 is an intronless bovine gene containing the Alu retrotransposon, which was integrated via cytoplasmic reverse transcription. CONCLUSION: We identified a novel retrotransposon-like Ly-6 domain protein in bovine placenta. SOLD1 is a crucial secreted protein that is involved in the organization of the mesenchyme of the cotyledonary villi. Furthermore, the gene encoding SOLD1 has an interesting genomic structure.

  12. Placental chimerism in early human pregnancy

    Directory of Open Access Journals (Sweden)

    Ashutosh Halder

    2005-01-01

    Full Text Available Background0 : Human chimerism is rare and usually uncovered through investigations of ambiguous genitalia or blood grouping or prenatal diagnosis. Most of the publications on placental chimerism are mainly case reports. There is no systematic search with sensitive techniques for placental chimerism in human. Aim0 : This study was aimed to asses placental chimerism through two sensitive molecular techniques i.e., interphase fluorescent in situ hybridization and quantitative fluorescent PCR. Material and methods0 : Placental chimerism was analyzed using X & Y dual color fluorescent in-situ hybridization onto 154 placentae from natural conceptions, obtained at termination of pregnancy between 7 to 16 weeks of gestation. Results0 : Three cases of placental sex chromosome chimerism were observed (1.95%. Exclusion of maternal contamination and diagnosis was confirmed later by quantitative fluorescent PCR. Conclusion0 : This finding indicates that placental chimerism in early human pregnancy is not rare.

  13. Altered fetal growth, placental abnormalities, and stillbirth.

    Science.gov (United States)

    Bukowski, Radek; Hansen, Nellie I; Pinar, Halit; Willinger, Marian; Reddy, Uma M; Parker, Corette B; Silver, Robert M; Dudley, Donald J; Stoll, Barbara J; Saade, George R; Koch, Matthew A; Hogue, Carol; Varner, Michael W; Conway, Deborah L; Coustan, Donald; Goldenberg, Robert L

    2017-01-01

    Worldwide, stillbirth is one of the leading causes of death. Altered fetal growth and placental abnormalities are the strongest and most prevalent known risk factors for stillbirth. The aim of this study was to identify patterns of association between placental abnormalities, fetal growth, and stillbirth. Population-based case-control study of all stillbirths and a representative sample of live births in 59 hospitals in 5 geographic areas in the U.S. Fetal growth abnormalities were categorized as small (90th percentile) for gestational age at death (stillbirth) or delivery (live birth) using a published algorithm. Placental examination by perinatal pathologists was performed using a standardized protocol. Data were weighted to account for the sampling design. Among 319 singleton stillbirths and 1119 singleton live births at ≥24 weeks at death or delivery respectively, 25 placental findings were investigated. Fifteen findings were significantly associated with stillbirth. Ten of the 15 were also associated with fetal growth abnormalities (single umbilical artery; velamentous insertion; terminal villous immaturity; retroplacental hematoma; parenchymal infarction; intraparenchymal thrombus; avascular villi; placental edema; placental weight; ratio birth weight/placental weight) while 5 of the 15 associated with stillbirth were not associated with fetal growth abnormalities (acute chorioamnionitis of placental membranes; acute chorioamionitis of chorionic plate; chorionic plate vascular degenerative changes; perivillous, intervillous fibrin, fibrinoid deposition; fetal vascular thrombi in the chorionic plate). Five patterns were observed: placental findings associated with (1) stillbirth but not fetal growth abnormalities; (2) fetal growth abnormalities in stillbirths only; (3) fetal growth abnormalities in live births only; (4) fetal growth abnormalities in stillbirths and live births in a similar manner; (5) a different pattern of fetal growth abnormalities in

  14. Placental oxygen transport estimated by the hyperoxic placental BOLD MRI response

    DEFF Research Database (Denmark)

    Sørensen, Anne Nødgaard; Sinding, Marianne; Peters, David A;

    2015-01-01

    cases of severe early onset FGR, placental BOLD MRI was performed in a 1.5 Tesla MRI system (TR:8000 msec, TE:50 msec, Flip angle:90). Placental histological examination was performed in the FGR cases. In normal pregnancies, the average hyperoxic placental BOLD response was 12.6 ± 5.4% (mean ± SD...

  15. Expresión de la integrina avß3 y de las subunidades de integrinas a3 y ß1 durante la placentación porcina Expression of avß3, and subunits a3 and ß1 during porcine placentation

    Directory of Open Access Journals (Sweden)

    D.M Williamson

    2009-06-01

    Full Text Available La placenta porcina es epiteliocorial, adecidua, plegada, difusa y no invasiva, por lo que expresa moléculas de adhesión que posibilitan la formación de la interfase feto/materna. Las integrinas son glicoproteínas que gobiernan las interacciones celulares con la matriz extracelular y participan en la implantación de varias especies. El objetivo de éste estudio fue analizar y comparar la expresión de αvβ3, α3 y β1 a fin de detectar la existencia de un patrón de expresión diferencial durante la placentación porcina. Se utilizaron placentas porcinas de ± 37, 60, 70, 80 y 114 días de gestación y útero vacío. La presencia de integrinas se determinó por inmunoperoxidasa indirecta. Durante la placentación αvβ3 se expresó cuantiosamente, disminuyendo a partir de los 80 días. La integrina β1 fue la que mayor positividad marcó en todos los tejidos placentarios estudiados, disminuyendo su expresión solo al final de la gestación. La subunidad α3 no se expresó en glándulas endometriales en ninguno de los períodos gestacionales estudiados. Los resultados de este estudio remarcan la importancia de la expresión de las integrinas durante la placentación porcina, particularmente β1, en el transcurso de la gestación para permitir la remodelación de las vellosidades placentarias y α3 de las zonas interareolares.Porcine placenta is epitheliochorial, diffuse, folded, adecidua, and non invasive, and express adhesion molecules different. Integrins are glycoproteins composed of a and ß subunits that govern cellular interactions with the extracellular matrix. Recent studies showed that integrins have been involved in implantation events in several species. The aim of this study was to compare the expression of αvβ3, α3 and β1 during placentation porcine. Placental tissue from porcine female of 37, 60, 70, 80 and 114 days of gestation, and empty uterus were used. The detection of the integrins was analyzed by indirect

  16. Animal Models of Human Placentation - A Review

    DEFF Research Database (Denmark)

    Carter, Anthony Michael

    2007-01-01

    This review examines the strengths and weaknesses of animal models of human placentation and pays particular attention to the mouse and non-human primates. Analogies can be drawn between mouse and human in placental cell types and genes controlling placental development. There are, however...... and endometrium is similar in macaques and baboons, as is the subsequent lacunar stage. The absence of interstitial trophoblast cells in the monkey is an important difference from human placentation. However, there is a strong resemblance in the way spiral arteries are invaded and transformed in the macaque...

  17. CD74-downregulation of placental macrophage-trophoblastic interactions in preeclampsia

    Science.gov (United States)

    Przybyl, Lukasz; Haase, Nadine; Golic, Michaela; Rugor, Julianna; Solano, Maria Emilia; Arck, Petra Clara; Gauster, Martin; Huppertz, Berthold; Emontzpohl, Christoph; Stoppe, Christian; Bernhagen, Jürgen; Leng, Lin; Bucala, Richard; Schulz, Herbert; Heuser, Arnd; Weedon-Fekjær, M. Susanne; Johnsen, Guro M.; Peetz, Dirk; Luft, Friedrich C; Staff, Anne Cathrine; Müller, Dominik N; Dechend, Ralf; Herse, Florian

    2017-01-01

    RATIONALE We hypothesized that Cluster of differentiation 74 (CD74) downregulation of placental macrophages, leading to altered macrophage-trophoblast interaction, is involved in preeclampsia. OBJECTIVE Preeclamptic pregnancies feature hypertension, proteinuria and placental anomalies. Feto-placental macrophages regulate villous trophoblast differentiation during placental development. Disturbance of this well-balanced regulation can lead to pathological pregnancies. METHODS AND RESULTS We performed whole genome expression analysis of placental tissue. CD74 was one of the most downregulated genes in placentas from preeclamptic women. By RT-PCR, we confirmed this finding in early onset (<34 gestational week, n=26) and late onset (≥34 gestational week, n=24) samples from preeclamptic women, compared to healthy pregnant controls (n=28). CD74 protein levels were analyzed by Western blot and flow cytometry. We identified placental macrophages to express CD74 by immunofluorescence, flow cytometry and RT-PCR. CD74-positive macrophages were significantly reduced in preeclamptic placentas compared to controls. CD74-silenced macrophages showed that the adhesion molecules ALCAM, ICAM4, and Syndecan-2, as well as macrophage adhesion to trophoblasts were diminished. Naïve and activated macrophages lacking CD74 showed a shift towards a pro-inflammatory signature with an increased secretion of TNFα, CCL5, and MCP-1, when co-cultured with trophoblasts compared to control macrophages. Trophoblasts stimulated by these factors express more CYP2J2, sFlt1, TNFα and IL-8. CD74-knockout mice showed disturbed placental morphology, reduced junctional zone, smaller placentas and impaired spiral artery remodeling with fetal growth restriction. CONCLUSIONS CD74 downregulation in placental macrophages is present in preeclampsia. CD74 downregulation leads to altered macrophage activation towards a pro-inflammatory signature and a disturbed crosstalk with trophoblasts. PMID:27199465

  18. Triazole fungicide tebuconazole disrupts human placental trophoblast cell functions.

    Science.gov (United States)

    Zhou, Jinghua; Zhang, Jianyun; Li, Feixue; Liu, Jing

    2016-05-05

    Triazole fungicides are one of the top ten classes of current-use pesticides. Although exposure to triazole fungicides is associated with reproductive toxicity in mammals, limited information is available regarding the effects of triazole fungicides on human placental trophoblast function. Tebuconazole (TEB) is a common triazole fungicide that has been extensively used for fungi control. In this work, we showed that TEB could reduce cell viability, disturb normal cell cycle distribution and induce apoptosis of human placental trophoblast cell line HTR-8/SVneo (HTR-8). Bcl-2 protein expression decreased and the level of Bax protein increased after TEB treatment in HTR-8 cells. The results demonstrated that this fungicide induced apoptosis of trophoblast cells via mitochondrial pathway. Importantly, we found that the invasive and migratory capacities of HTR-8 cells decreased significantly after TEB administration. TEB altered the expression of key regulatory genes involved in the modulation of trophoblast functions. Taken together, TEB suppressed human trophoblast invasion and migration through affecting the expression of protease, hormones, angiogenic factors, growth factors and cytokines. As the invasive and migratory abilities of trophoblast are essential for successful placentation and fetus development, our findings suggest a potential risk of triazole fungicides to human pregnancy.

  19. Somatic cell nuclear transfer in the sheep induces placental defects that likely precede fetal demise.

    Science.gov (United States)

    Fletcher, C J; Roberts, C T; Hartwich, K M; Walker, S K; McMillen, I C

    2007-01-01

    The efficiency of cloning by somatic cell nuclear transfer (SCNT) is poor in livestock with approximately 5% of transferred cloned embryos developing to term. SCNT is associated with gross placental structural abnormalities. We aimed to identify defects in placental histology and gene expression in failing ovine cloned pregnancies to better understand why so many clones generated by SCNT die in utero. Placentomes from SCNT pregnancies (n = 9) and age matched, naturally mated controls (n = 20) were collected at two gestational age ranges (105-134 days and 135-154 days; term = 147 days). There was no effect of cloning on total placental weight. However, cloning reduced the number of placentomes at both gestational ages (105-134 days: control 55.0 +/- 4.2, clone 44.7 +/- 8.0 and 135-154 days: control 72.2 +/- 5.1, clone 36.6 +/- 5.1; P clone 18.6 +/- 2.8 g and 135-154 days: control 6.6 +/- 0.6 g, clone 7.0 +/- 2.0 g; P cloned pregnancies had a significant volume of shed trophoblast and fetal villous hemorrhage, absent in controls, at both gestational age ranges (P clones. In addition, cloning reduced placental expression of key genes in placental differentiation and function. Thus, cloning by SCNT results in both gross and microscopic placental abnormalities. We speculate that trophoblast apoptosis, shedding, and hemorrhage may be causal in fetal death in ovine clones.

  20. Triazole fungicide tebuconazole disrupts human placental trophoblast cell functions

    Energy Technology Data Exchange (ETDEWEB)

    Zhou, Jinghua [Key Laboratory of Environmental Remediation and Ecological Health, Ministry of Education, Zhejiang University, Hangzhou 310058 (China); Zhang, Jianyun [Research Center for Air Pollution and Health, College of Environmental and Resource Sciences, Zhejiang University, Hangzhou 310058 (China); Li, Feixue [Zhejiang Key Laboratory of Organ Development and Regeneration, Institute of Developmental and Regenerative Biology, College of Life and Environmental Sciences, Hangzhou Normal University, Hangzhou 310036 (China); Liu, Jing, E-mail: jliue@zju.edu.cn [Key Laboratory of Environmental Remediation and Ecological Health, Ministry of Education, Zhejiang University, Hangzhou 310058 (China); Research Center for Air Pollution and Health, College of Environmental and Resource Sciences, Zhejiang University, Hangzhou 310058 (China)

    2016-05-05

    Highlights: • Tebuconazole (TEB) inhibited the proliferation of human placental trophoblasts. • TEB changed cell cycle distribution of G1 and G2 phases of trophoblasts. • TEB induced apoptosis of trophoblasts via mitochondrial pathway. • TEB decreased the invasive and migratory capacities of trophoblasts. • TEB altered the mRNA levels of key regulatory genes in trophoblasts - Abstract: Triazole fungicides are one of the top ten classes of current-use pesticides. Although exposure to triazole fungicides is associated with reproductive toxicity in mammals, limited information is available regarding the effects of triazole fungicides on human placental trophoblast function. Tebuconazole (TEB) is a common triazole fungicide that has been extensively used for fungi control. In this work, we showed that TEB could reduce cell viability, disturb normal cell cycle distribution and induce apoptosis of human placental trophoblast cell line HTR-8/SVneo (HTR-8). Bcl-2 protein expression decreased and the level of Bax protein increased after TEB treatment in HTR-8 cells. The results demonstrated that this fungicide induced apoptosis of trophoblast cells via mitochondrial pathway. Importantly, we found that the invasive and migratory capacities of HTR-8 cells decreased significantly after TEB administration. TEB altered the expression of key regulatory genes involved in the modulation of trophoblast functions. Taken together, TEB suppressed human trophoblast invasion and migration through affecting the expression of protease, hormones, angiogenic factors, growth factors and cytokines. As the invasive and migratory abilities of trophoblast are essential for successful placentation and fetus development, our findings suggest a potential risk of triazole fungicides to human pregnancy.

  1. Maternal Outcomes According to Placental Position in Placental Previa

    Directory of Open Access Journals (Sweden)

    Dong Gyu Jang, Ji Sun We, Jae Un Shin, Yun Jin Choi, Hyun Sun Ko, In Yang Park, Jong Chul Shin

    2011-01-01

    Full Text Available Purpose: The purpose of this retrospective cohort study was to elucidate whether the location of placenta below uterine incision in cesarean section is important in the development of maternal complications in placenta previa patients.Methods: The study was conducted on 409 patients 414 parturition at 3 hospitals in affiliation with the Catholic Medical Center, Seoul, Korea from May 1999 to December 2009. The subjects were divided to two groups: the group whose placenta was located in the anterior portion of the uterus (anterior group and the group whose placenta was located in the posterior portion of the uterus (posterior group. And then they are compared to each other. Logistic regression was used to control for confounding factors.Results: In the anterior group, regardless of confounding factors, the incidence of excessive blood loss (OR 2.97; 95% CI: 1.64-5.37, massive transfusion (OR 3.31; 95% CI: 1.33-8.26, placental accreta (OR 2.60, 95% CI: 1.40-4.83, and hysterectomy (OR 3.47, 95% CI: 1.39-8.68 was higher.Conclusion: Sonographic determination of the placental position where its location beneath the uterine incision is very important to predict maternal outcomes in placenta previa patients, and such cases, close attention should be paid for massive hemorrhage.

  2. INVESTIGATION OF THROMBOMODULIN AND PLASMINOGEN ACTIVATOR INHIBITOR TYPE-I IN PREGNANCY INDUCED HYPERTENSION AND ITS CLINICAL SIGNIFICANCE

    Institute of Scientific and Technical Information of China (English)

    马水清; 白春梅; 边旭明

    2001-01-01

    Objective. To measure tbe circulating levels of thrombomodulin (TM) and plasminogen activator inhibitor type-Ⅰ(PAI-I) in women with pregnancy induced hypertension (PIH).``Methods. Blood samples were drawn from 97 pregnant women in their third trimester, grouped as 25 mild PIH, 26 moderate PIH, 22 severe PIH and 24 normotensive healthy pregnant women for determining levels of TM by ELISA, PAI-I by colorimetric assay methods, and creatinine (Cr) in serum by biochemical method.``Results. Circulating levels of TM, PAId and TM/Cr ratio increased with increasing severity of PIH. There were no significant differences between mild and normotensive pregnant women. The parameters were significantly changed in the moderate and severe PIH groups.``Conclv, sion. TM and PAI-Ⅰ may serve as meaningful clinical markers for the assessment of the endothelial damage in PIH,which is very important in evaluating and following the development of PIH.

  3. INVESTIGATION OF THROMBOMODULIN AND PLASMINOGEN ACTIVATOR INHIBITOR TYPE-I IN PREGNANCY INDUCED HYPERTENSION AND ITS CLINICAL SIGNIFICANCE

    Institute of Scientific and Technical Information of China (English)

    马水清; 白春梅; 边旭明

    2001-01-01

    Objective. To measure the circulating levels of thrombomodulin (TM) and plasminogen activator inhibitor type-I (PAI-I) inwomen with pregnancy induced hypertension (PIH). Methods. Blood samples were drawn from 97 pregnant women in their third trimester, grouped as 25 mild PIH, 26 moderate PIH, 22 severe PIH and 24 normotensive healthy pregnant women for determining levels of TM by ELISA, PAI-I by colorimetric assay methods, and creatinine (Cr) in serum by biochemical method. Results. Circulating levels of TM, PAI-I and TM/Cr ratio increased with increasing severity of PIH. There were no significant differences between mild and normotensive pregnant women. The parameters were significantly changed in the moderate and severe PIH groups. Conclusion. TM and PAI-I may serve as meaningful clinical markers for the assessment of the endothelial damage in PIH,which is very important in evaluating and following the development of PIH.

  4. Successful Control of Disseminated Intravascular Coagulation by Recombinant Thrombomodulin during Arsenic Trioxide Treatment in Relapsed Patient with Acute Promyelocytic Leukemia

    Directory of Open Access Journals (Sweden)

    Motohiro Shindo

    2012-01-01

    Full Text Available Disseminated intravascular coagulation (DIC frequently occurs in patients with acute promyelocytic leukemia (APL. With the induction of therapy in APL using all-trans retinoic acid (ATRA, DIC can be controlled in most cases as ATRA usually shows immediate improvement of the APL. However, arsenic trioxide (ATO which has been used for the treatment of relapse in APL patients has shown to take time to suppress APL cells, therefore the control of DIC in APL with ATO treatment is a major problem. Recently, the recombinant soluble thrombomodulin fragment has received a lot of attention as the novel drug for the treatment of DIC with high efficacy. Here, we present a relapsed patient with APL in whom DIC was successfully and safely controlled by rTM during treatment with ATO.

  5. 面神经损伤后面神经核中神经型钙黏附分子及胎盘型钙黏附分子的表达%Expression of neuronal cadherin and placental cadherin in facial motoneurons after facial nerve injury

    Institute of Scientific and Technical Information of China (English)

    李雷激; 徐超然; 覃纲; 刘跃华; 祝琳

    2015-01-01

    背景:面神经周围性损伤后,首先涉及其中枢神经元轴突的逆行性反应,神经能否再生则取决于神经元胞体的存活及功能状态。  目的:检测面神经损伤后,面神经核中神经型钙黏附分子和胎盘型钙黏附分子的表达变化。  方法:将新西兰大白兔随机分为模型组(n=48)和对照组(n=8)。模型组兔建立右侧面神经压榨损伤模型。模型组分别于损伤后1,4,7,14,21,28 d各取8只兔进行检测。运用免疫组织化学SP法及实时定量PCR法检测兔右侧面神经核运动神经元中神经型钙黏附分子和胎盘型钙黏附分子蛋白及mRNA的表达水平。  结果与结论:对照组兔右侧面神经核运动神经元中无神经型钙黏附分子或胎盘型钙黏附分子标记的阳性神经元。模型组兔右侧面神经核运动神经元中存在神经型钙黏附分子和胎盘型钙黏附分子阳性神经元,2种阳性神经元数量均在第14天时达到峰值。与对照组相比,模型组损伤后4-28 d兔面神经核中神经型钙黏附分子mRNA的表达水平明显增加,损伤后1 d时兔面神经核中胎盘型钙黏附分子mRNA的表达水平明显下降,损伤后7-28 d时兔面神经核中胎盘型钙黏附分子mRNA的表达水平明显增加。提示面神经损伤的早期即出现2种分子的阳性表达,其中胎盘型钙黏附分子的表达自神经损伤后一直存在,而神经型钙黏附分子表达时间相对较短。在面神经损伤时,面神经核中神经型钙黏附分子和胎盘型钙黏附分子均表达增加,说明面神经再生可能与黏附分子的高表达有关。%BACKGROUND:Peripheral facial nerve injury first involves the retrograde reactions of central nervous system axons, and nerve regeneration wil depend on the survival and functional status of neuronal cel bodies. OBJECTIVE:To explore the expression of neuronal cadherin and placental cadherin in facial

  6. Microparasites and Placental Invasiveness in Eutherian Mammals.

    Directory of Open Access Journals (Sweden)

    Isabella Capellini

    Full Text Available Placental invasiveness-the number of maternal tissue layers separating fetal tissues from maternal blood-is variable across mammalian species. Although this diversity is likely to be functionally important, variation in placental invasiveness remains unexplained. Here we test the hypothesis that increased risk of transplacental transmission of pathogens from the mother to the fetus promotes the evolution of non-invasive placentation, the most likely derived condition in eutherian mammals. Specifically, we predict that non-invasive placentation is associated with increased microparasite species richness relative to more invasive placental types, based on the assumption that higher numbers of microparasites in a population reflects greater risk of transplacental transmission to fetuses. As predicted, higher bacteria species richness is associated with non-invasive placentation. Protozoa species richness, however, shows the opposite pattern. Because invasive placentae facilitate the transfer of maternal antibodies to the fetus, we propose that the ancestral condition of invasive placentation is retained under selection for protection of newborns from higher risk of postnatal protozoan infection. Hence, our findings suggest that a tradeoff exists between protection against bacterial infection prenatally and protozoan infection postnatally. Future studies are needed to investigate how maternal prevalence of infection and the relative pre- versus postnatal risk of fetal infection by different microparasite groups vary among mammalian hosts in relation to placental invasiveness.

  7. Placental urocortins and CRF in late gestation.

    NARCIS (Netherlands)

    Pepels, P.P.L.M.; Spaanderman, M.E.A.; Bulten, J.; Smits, P.; Hermus, A.R.M.M.; Lotgering, F.K.; Sweep, C.G.J.

    2009-01-01

    Placental corticotropin-releasing factor (CRF) are thought to induce labor via activation of CRF receptor type 1 (CRF-R1) leading to several feed forward mechanisms in the placental, fetal and maternal compartments. Recently, receptor type 2 (CRF-R2) selective ligands called urocortin 2 and 3 (Ucn

  8. Placental iron uptake and its regulation

    NARCIS (Netherlands)

    M. Bierings (Marc)

    1989-01-01

    textabstractIron transport in pregnancy is an active one-way process, from mother to fetus. Early in gestation fetal iron needs are low, and so is trans-placental transport, but as erythropoiesis develops, rising fetal iron needs are met by trans-placental iron transport. Apparently, the fetus is pr

  9. Placental development during early pregnancy in sheep: Effects of embryo origin on vascularization

    Science.gov (United States)

    Grazul-Bilska, Anna T.; Johnson, Mary Lynn; Borowicz, Pawel P.; Bilski, Jerzy J.; Cymbaluk, Taylor; Norberg, Spencer; Redmer, Dale A.; Reynolds, Lawrence P.

    2014-01-01

    Utero-placental growth and vascular development are critical for pregnancy establishment that may be altered by various factors including assisted reproductive technologies (ART), nutrition, or others, leading to compromised pregnancy. We hypothesized that placental vascularization and expression of angiogenic factors are altered early in pregnancies after transfer of embryos created using selected ART methods. Pregnancies were achieved through natural mating (NAT), or transfer of embryos from natural mating (NAT-ET), or in vitro fertilization (IVF) or activation (IVA). Placental tissues were collected on day 22 of pregnancy. In maternal caruncles (CAR), vascular cell proliferation was less (P<0.05) for IVA than other groups. Compared to NAT, density of blood vessels was less (P<0.05) for IVF and IVA in fetal membranes (FM), and for NAT-ET, IVF and IVA in CAR. In FM, mRNA expression was decreased (P<0.01–0.08) in NAT-ET, IVF and IVA compared to NAT for vascular endothelial growth factor (VEGF) and its receptor FLT-1, placental growth factor (PGF), neuropilin (NP) 1 and 2, angiopoietin (ANGPT) 1 and 2, endothelial nitric oxide synthase (NOS3), hypoxia inducible factor-1A (HIF1A), fibroblast growth factor (FGF) 2 and its receptor FGFR2. In CAR, mRNA expression was decreased (P<0.01–0.05) in NAT-ET, IVF and IVA compared to NAT for VEGF, FLT-1, PGF, ANGPT1 and TEK. Decreased mRNA expression for 12 of 14 angiogenic factors across FM and CAR in NAT-ET, IVF and IVA pregnancies was associated with reduced placental vascular development, which would lead to poor placental function and compromised fetal and placental growth and development. PMID:24472816

  10. Nomenclature and placental mammal phylogeny

    Directory of Open Access Journals (Sweden)

    Helgen Kristofer M

    2010-04-01

    Full Text Available Abstract An issue arising from recent progress in establishing the placental mammal Tree of Life concerns the nomenclature of high-level clades. Fortunately, there are now several well-supported clades among extant mammals that require unambiguous, stable names. Although the International Code of Zoological Nomenclature does not apply above the Linnean rank of family, and while consensus on the adoption of competing systems of nomenclature does not yet exist, there is a clear, historical basis upon which to arbitrate among competing names for high-level mammalian clades. Here, we recommend application of the principles of priority and stability, as laid down by G.G. Simpson in 1945, to discriminate among proposed names for high-level taxa. We apply these principles to specific cases among placental mammals with broad relevance for taxonomy, and close with particular emphasis on the Afrotherian family Tenrecidae. We conclude that no matter how reconstructions of the Tree of Life change in years to come, systematists should apply new names reluctantly, deferring to those already published and maximizing consistency with existing nomenclature.

  11. The Endocannabinoid System in the Postimplantation Period: A Role during Decidualization and Placentation

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    B. M. Fonseca

    2013-01-01

    Full Text Available Although the detrimental effects of cannabis consumption during gestation are known for years, the vast majority of studies established a link between cannabis consumption and foetal development. The complex maternal-foetal interrelationships within the placental bed are essential for normal pregnancy, and decidua definitively contributes to the success of this process. Nevertheless, the molecular signalling network that coordinates strategies for successful decidualization and placentation are not well understood. The discovery of the endocannabinoid system highlighted new signalling mediators in various physiological processes, including reproduction. It is known that endocannabinoids present regulatory functions during blastocyst development, oviductal transport, and implantation. In addition, all the endocannabinoid machinery was found to be expressed in decidual and placental tissues. Additionally, endocannabinoid’s plasmatic levels were found to fluctuate during normal gestation and to induce decidual cell death and disturb normal placental development. Moreover, aberrant endocannabinoid signalling during the period of placental development has been associated with pregnancy disorders. It indicates the existence of a possible regulatory role for these molecules during decidualization and placentation processes, which are known to be particularly vulnerable. In this review, the influence of the endocannabinoid system in these critical processes is explored and discussed.

  12. Prenatal caffeine exposure induced a lower level of fetal blood leptin mainly via placental mechanism.

    Science.gov (United States)

    Wu, Yi-Meng; Luo, Han-Wen; Kou, Hao; Wen, Yin-Xian; Shen, Lang; Pei, Ling-Guo; Zhou, Jin; Zhang, Yuan-Zhen; Wang, Hui

    2015-11-15

    It's known that blood leptin level is reduced in intrauterine growth retardation (IUGR) fetus, and placental leptin is the major source of fetal blood leptin. This study aimed to investigate the decreased fetal blood leptin level by prenatal caffeine exposure (PCE) and its underlying placental mechanisms. Pregnant Wistar rats were intragastrically administered caffeine (30-120 mg/kg day) from gestational day 9 to 20. The level of fetal serum leptin and the expression of placental leptin-related genes were analyzed. Furthermore, we investigated the molecular mechanism of the reduced placental leptin's expression by treatment with caffeine (0.8-20 μM) in the BeWo cells. In vivo, PCE significantly decreased fetal serum leptin level in caffeine dose-dependent manner. Meanwhile, placental mRNA expression of adenosine A2a receptor (Adora2a), cAMP-response element binding protein (CREB), a short-type leptin receptor (Ob-Ra) and leptin was reduced in the PCE groups. In vitro, caffeine significantly decreased the mRNA expression of leptin, CREB and ADORA2A in concentration and time-dependent manners. The addition of ADORA2A agonist or adenylyl cyclase (AC) agonist reversed the inhibition of leptin expression induced by caffeine. PCE induced a lower level of fetal blood leptin, which the primary mechanism is that caffeine inhibited antagonized Adora2a and AC activities to decreased cAMP synthesis, thus inhibited the expression of the transcription factor CREB and target gene leptin in the placenta. Meantime, the reduced transportation of maternal leptin by placental Ob-Ra also contributed to the reduced fetal blood leptin. Together, PCE decreased fetal blood leptin mainly via reducing the expression and transportation of leptin in the placenta.

  13. A stochastic model for early placental development.

    KAUST Repository

    Cotter, Simon L

    2014-08-01

    In the human, placental structure is closely related to placental function and consequent pregnancy outcome. Studies have noted abnormal placental shape in small-for-gestational-age infants which extends to increased lifetime risk of cardiovascular disease. The origins and determinants of placental shape are incompletely understood and are difficult to study in vivo. In this paper, we model the early development of the human placenta, based on the hypothesis that this is driven by a chemoattractant effect emanating from proximal spiral arteries in the decidua. We derive and explore a two-dimensional stochastic model, and investigate the effects of loss of spiral arteries in regions near to the cord insertion on the shape of the placenta. This model demonstrates that disruption of spiral arteries can exert profound effects on placental shape, particularly if this is close to the cord insertion. Thus, placental shape reflects the underlying maternal vascular bed. Abnormal placental shape may reflect an abnormal uterine environment, predisposing to pregnancy complications. Through statistical analysis of model placentas, we are able to characterize the probability that a given placenta grew in a disrupted environment, and even able to distinguish between different disruptions.

  14. Genetic recapitulation of human pre-eclampsia risk during convergent evolution of reduced placental invasiveness in eutherian mammals.

    Science.gov (United States)

    Elliot, Michael G; Crespi, Bernard J

    2015-03-05

    The relationship between phenotypic variation arising through individual development and phenotypic variation arising through diversification of species has long been a central question in evolutionary biology. Among humans, reduced placental invasion into endometrial tissues is associated with diseases of pregnancy, especially pre-eclampsia, and reduced placental invasiveness has also evolved, convergently, in at least 10 lineages of eutherian mammals. We tested the hypothesis that a common genetic basis underlies both reduced placental invasion arising through a developmental process in human placental disease and reduced placental invasion found as a derived trait in the diversification of Euarchontoglires (rodents, lagomorphs, tree shrews, colugos and primates). Based on whole-genome analyses across 18 taxa, we identified 1254 genes as having evolved adaptively across all three lineages exhibiting independent evolutionary transitions towards reduced placental invasion. These genes showed strong evidence of enrichment for associations with pre-eclampsia, based on genetic-association studies, gene-expression analyses and gene ontology. We further used in silico prediction to identify a subset of 199 genes that are likely targets of natural selection during transitions in placental invasiveness and which are predicted to also underlie human placental disorders. Our results indicate that abnormal ontogenies can recapitulate major phylogenetic shifts in mammalian evolution, identify new candidate genes for involvement in pre-eclampsia, imply that study of species with less-invasive placentation will provide useful insights into the regulation of placental invasion and pre-eclampsia, and recommend a novel comparative functional-evolutionary approach to the study of genetically based human disease and mammalian diversification. © 2015 The Author(s) Published by the Royal Society. All rights reserved.

  15. 组织因子及其抑制物在妊娠期高血压疾病患者胎盘中的表达及临床意义%Expression and clinical significance of placental tissue factor and tissue factor pathway inhibitor in pregnant women with hypertensive disorders

    Institute of Scientific and Technical Information of China (English)

    王晓丹; 韩翠欣; 班玲; 刘雅丽; 剧蕴慧; 梁霞; 田甜

    2016-01-01

    目的:探讨妊娠期高血压疾病患者胎盘组织中组织因子( TF)及其抑制物———组织因子途径抑制物( TFPI)的表达变化,探讨妊娠期高血压疾病的发生机制。方法采用免疫组化法检测妊娠期高血压患者、子痫前期患者及正常妊娠妇女胎盘组织中TF和TFPI的水平。结果与正常妊娠组相比,妊娠期高血压组胎盘表达TF有升高趋势,但差异无统计学意义( P>0.05);与正常妊娠组和妊娠期高血压组相比,子痫前期组胎盘表达TF明显升高,差异有统计学意义( P<0.05)。妊娠期高血压组与正常妊娠组相比,TFPI表达有下降趋势,但差异无统计学意义;子痫前期组胎盘表达TFPI明显下降,与正常妊娠组和妊娠期高血压组相比差异有统计学意义(P<0.05)。结论 TF、TFPI值的变化及其比例失调导致了胎盘内凝血功能的异常,可能与妊娠期高血压疾病的发生、发展有关。%Objective It is to explore whether hypertensive disorders complicating pregnancy was associated with changes of the maternal placental concentrations as well as its inhibitor-tissue factor pathway inhibitor (TFPI).Methods Placental tissue factor( TF) and TFPI expression from gestational hypertension patients, preeclampsia patients and healthy pregnant controls were determined by immunohystochemistry.Results Comparing to healthy pregnant women,TF placental levels in gestational hypertension patients increased but had no difference.TF placental levels were significantly higher in preeclampsia patients than that in gestational hypertension patients and the healthy controls.Comparing to gestational hypertension patients and healthy pregnant women, TFPI placental levels in preeclampsia patients were significantly lower,but the difference between the gestational hypertension patients and the healthy controls was not significantly.Conclusion The changes of plasma TF and TF

  16. The evolution of epitheliochorial placentation.

    Science.gov (United States)

    Carter, Anthony M; Enders, Allen C

    2013-01-01

    Epitheliochorial placentation is a derived condition and has evolved separately in strepsirrhine primates and laurasiatherians (pangolins, whales, and hoofed mammals). Usually it is associated with a long gestation period, small litters, and precocial young. Oxygen transfer is facilitated by indenting of the uterine and trophoblast epithelia by maternal and fetal capillaries, respectively. Histotrophic nutrition is important, and adaptations include areolas and hemophagous regions. In pigs and horses, for example, iron is transported as uteroferrin secreted from the uterine glands and taken up by areolas. In the horse, invasive trophoblast cells form cups within the endometrium that are the source of equine chorionic gonadotropin. In ruminants, binucleate trophoblast cells fuse with uterine epithelial cells to form trinucleate cells or plaques that secrete pregnancy hormones. There is evidence of immunosuppression in connection with these more invasive types of trophoblasts. The epitheliochorial condition may be advantageous for long pregnancies in large animals.

  17. A microphysiological model of the human placental barrier.

    Science.gov (United States)

    Blundell, Cassidy; Tess, Emily R; Schanzer, Ariana S R; Coutifaris, Christos; Su, Emily J; Parry, Samuel; Huh, Dongeun

    2016-08-02

    During human pregnancy, the fetal circulation is separated from maternal blood in the placenta by two cell layers - the fetal capillary endothelium and placental trophoblast. This placental barrier plays an essential role in fetal development and health by tightly regulating the exchange of endogenous and exogenous materials between the mother and the fetus. Here we present a microengineered device that provides a novel platform to mimic the structural and functional complexity of this specialized tissue in vitro. Our model is created in a multilayered microfluidic system that enables co-culture of human trophoblast cells and human fetal endothelial cells in a physiologically relevant spatial arrangement to replicate the characteristic architecture of the human placental barrier. We have engineered this co-culture model to induce progressive fusion of trophoblast cells and to form a syncytialized epithelium that resembles the syncytiotrophoblast in vivo. Our system also allows the cultured trophoblasts to form dense microvilli under dynamic flow conditions and to reconstitute expression and physiological localization of membrane transport proteins, such as glucose transporters (GLUTs), critical to the barrier function of the placenta. To provide a proof-of-principle for using this microdevice to recapitulate native function of the placental barrier, we demonstrated physiological transport of glucose across the microengineered maternal-fetal interface. Importantly, the rate of maternal-to-fetal glucose transfer in this system closely approximated that measured in ex vivo perfused human placentas. Our "placenta-on-a-chip" platform represents an important advance in the development of new technologies to model and study the physiological complexity of the human placenta for a wide variety of applications.

  18. ULTRASONOGRAPHIC CORRELATION OF PLACENTAL THICKNESS WITH FETAL GESTATIONAL AGE AND GRADING OF PLACENTAL MATURIT

    Directory of Open Access Journals (Sweden)

    Nagesh

    2016-03-01

    Full Text Available AIMS AND OBJECTIVES Comparative correlation of placental thickness with foetal gestational age, and evaluation of placental maturity by ultrasonography. MATERIALS AND METHODS The study includes 100 normal singleton gestations between 10 to 40 weeks of gestation referred to our centre for routine antenatal ultrasound examination. All the women were evaluated by transabdominal ultrasonography. Foetal gestational age in weeks was determined by crown rump length, biparietal diameter, head circumference, abdominal circumference and femoral length. Placental thickness was measured in millimeters. All the placentae were graded using ultrasonographic grading system. RESULTS Our observations revealed that the placental thickness gradually increased from 11.8 mm at 12 weeks to 38.5 mm at 39 weeks. Placental thickness almost corresponds to advancing gestational age exhibiting a linear and direct growth. Progressive maturity changes were noted in placenta with advancing gestational age. CONCLUSION Placental thickness measured at cord insertion site can be used as one of the parameter for estimating foetal gestational age. Placental thickness measurement can also be used to differentiate certain abnormal conditions related to thick and thin placenta. Ultrasonographic placental grading helps to rule out certain conditions associated with premature or delayed placental maturation

  19. Perspectives of SLIT/ROBO signaling in placental angiogenesis.

    Science.gov (United States)

    Liao, Wu-xiang; Wing, Deborah A; Geng, Jian-Guo; Chen, Dong-bao

    2010-09-01

    A novel family of evolutionally conserved neuronal guidance cues, including ligands (i.e., Slit, netrin, epherin, and semaphorin) and their corresponding receptors (i.e., Robo, DCC/Unc5, Eph and plexin/ neuropilin), has been identified to play a crucial role in axon pathfinding and branching as well as neuronal cell migration. The presence of commonalities in both neural and vascular developments has led to some exciting discoveries recently, which have extended the functions of these systems to vascular formation (vasculogenesis) and development (angiogenesis). Some of these ligands and receptors have been found to be expressed in the vasculature and surrounding tissues in physiological and pathological conditions. It is postulated that they regulate the formation and integrity of blood vessels. In particular, it has been shown that the Slit/Robo pair plays a novel role in angiogenesis during tumorigenesis and vascular formation during embryogenesis. Herein we summarize briefly the characteristics of this family of neuronal guidance molecules and discuss the extra-neural expression and function of the Slit/Robo pair in angiogenesis in physiological and pathological settings. We report expression of Robo1 protein in capillary endothelium and co-expression of Slit2 and Robo1 proteins in syncytiotrophoblast in healthy term human placental villi. These cellular expression patterns implicate that the Slit/Robo signaling plays an autocrine and/or paracrine role in angiogenesis and trophoblast functions. We also speculate a possible role of this system in pathophysiological placental angiogenesis.

  20. Hyperemesis gravidarum and placental dysfunction disorders

    NARCIS (Netherlands)

    Koudijs, Heleen M; Savitri, Ary I; Browne, Joyce L; Amelia, Dwirani; Baharuddin, Mohammad; Grobbee, Diederick E; Uiterwaal, Cuno S P M

    2016-01-01

    BACKGROUND: Evidence about the consequence of hyperemesis gravidarum (HG) on pregnancy outcomes is still inconclusive. In this study, we evaluated if occurrence of hyperemesis gravidarum is associated with placental dysfunction disorders and neonatal outcomes. METHODS: A prospective cohort study was

  1. Epigenetic modifications at DMRs of placental genes are subjected to variations in normal gestation, pathological conditions and folate supplementation

    Science.gov (United States)

    Rahat, Beenish; Mahajan, Aatish; Bagga, Rashmi; Hamid, Abid; Kaur, Jyotdeep

    2017-01-01

    Invasive placentation and cancer development shares many similar molecular and epigenetic pathways. Paternally expressed, growth promoting genes (SNRPN, PEG10 and MEST) which are known to play crucial role in tumorogenesis, are not well studied during placentation. This study reports for the first time of the impact of gestational-age, pathological conditions and folic acid supplementation on dynamic nature of DNA and histone methylation present at their differentially methylated regions (DMRs). Here, we reported the association between low DNA methylation/H3K27me3 and higher expression of SNRPN, PEG10 and MEST in highly proliferating normal early gestational placenta. Molar and preeclamptic placental villi, exhibited aberrant changes in methylation levels at DMRs of these genes, leading to higher and lower expression of these genes, respectively, in reference to their respective control groups. Moreover, folate supplementation could induce gene specific changes in mRNA expression in placental cell lines. Further, MEST and SNRPN DMRs were observed to show the potential to act as novel fetal DNA markers in maternal plasma. Thus, variation in methylation levels at these DMRs regulate normal placentation and placental disorders. Additionally, the methylation at these DMRs might also be susceptible to folic acid supplementation and has the potential to be utilized in clinical diagnosis. PMID:28098215

  2. Postpartum deaths: piglet, placental, and umbilical characteristics.

    Science.gov (United States)

    Rootwelt, V; Reksen, O; Farstad, W; Framstad, T

    2013-06-01

    The fetal growth of the piglet is highly dependent on its placenta, and the newborn piglet birth weight is highly associated with postpartum death. However, there is little information available in the literature on the assessment of the placenta in relation to postpartum death in piglets. The aim of this study was to evaluate the impact of the placental area and placental weight, status of the umbilical cord, and piglet birth characteristics, such as blood parameters, vitality score, and birth weight on postpartum death. All live born piglets in litters from 26 Landrace-Yorkshire sows were monitored during farrowing and the status of each was recorded, including placental area and placental weight and blood variables obtained from the piglets and umbilical veins. Out of the 386 live-born piglets, 16.8% died before weaning at 5 wk. Among these, 78.5% died within the first 3 d of life. Mean blood concentration of lactate was increased in piglets that did not survive to weaning (P = 0.003). Concentrations of hemoglobin and hematocrit were decreased (P Piglets born with a broken umbilical cord had a reduced vitality score vs. piglets born with an intact umbilical cord (P = 0.021), and they had an increased probability of dying before weaning (P = 0.050). Mean birth weight, body mass index, placental area (P piglets that died before weaning vs. those that survived. Birth weight and placental area were furthermore negatively associated with live litter size. Blood concentrations of IgG and albumin recorded at d 1 were decreased in piglets that died before weaning (P < 0.01), and blood concentration of albumin was positively associated with placental area (P < 0.001). We conclude that placental area and placental weight, status of the umbilical cord, birth weight, body mass index, blood concentrations of lactate, hemoglobin, and hematocrit recorded at birth, and blood concentrations of IgG and albumin recorded at d 1 were associated with postpartum death in this study

  3. Prediction of fetal acidemia in placental abruption

    OpenAIRE

    MATSUDA, Yoshio; OGAWA, Masaki; KONNO, Jun; MITANI, Minoru; MATSUI, Hideo

    2013-01-01

    Background To determine the major predictive factors for fetal acidemia in placental abruption. Methods A retrospective review of pregnancies with placental abruption was performed using a logistic regression model. Fetal acidemia was defined as a pH of less than 7.0 in umbilical artery. The severe abruption score, which was derived from a linear discriminant function, was calculated to determine the probability of fetal acidemia. Results Fetal acidemia was seen in 43 survivors (43/222, 19%)....

  4. Comparative aspects of trophoblast development and placentation

    Directory of Open Access Journals (Sweden)

    Enders Allen C

    2004-07-01

    Full Text Available Abstract Based on the number of tissues separating maternal from fetal blood, placentas are classified as epitheliochorial, endotheliochorial or hemochorial. We review the occurrence of these placental types in the various orders of eutherian mammals within the framework of the four superorders identified by the techniques of molecular phylogenetics. The superorder Afrotheria diversified in ancient Africa and its living representatives include elephants, sea cows, hyraxes, aardvark, elephant shrews and tenrecs. Xenarthra, comprising armadillos, anteaters and sloths, diversified in South America. All placentas examined from members of these two oldest superorders are either endotheliochorial or hemochorial. The superorder Euarchontoglires includes two sister groups, Glires and Euarchonta. The former comprises rodents and lagomorphs, which typically have hemochorial placentas. The most primitive members of Euarchonta, the tree shrews, have endotheliochorial placentation. Flying lemurs and all higher primates have hemochorial placentas. However, the lemurs and lorises are exceptional among primates in having epitheliochorial placentation. Laurasiatheria, the last superorder to arise, includes several orders with epitheliochorial placentation. These comprise whales, camels, pigs, ruminants, horses and pangolins. In contrast, nearly all carnivores have endotheliochorial placentation, whilst bats have endotheliochorial or hemochorial placentas. Also included in Laurasiatheria are a number of insectivores that have many conserved morphological characters; none of these has epitheliochorial placentation. Consideration of placental type in relation to the findings of molecular phylogenetics suggests that the likely path of evolution in Afrotheria was from endotheliochorial to hemochorial placentation. This is also a likely scenario for Xenarthra and the bats. We argue that a definitive epitheliochorial placenta is a secondary specialization and that it

  5. Efficacy of thrombomodulin for acute exacerbation of idiopathic pulmonary fibrosis and nonspecific interstitial pneumonia: a nonrandomized prospective study

    Directory of Open Access Journals (Sweden)

    Abe M

    2015-10-01

    Full Text Available Mitsuhiro Abe, Kenji Tsushima, Takuma Matsumura, Tsukasa Ishiwata, Yasunori Ichimura, Jun Ikari, Jiro Terada, Yuji Tada, Seiichirou Sakao, Nobuhiro Tanabe, Koichiro Tatsumi Department of Respirology, Graduate School of Medicine, Chiba University, Chiba, Japan Purpose: Acute exacerbation (AE is an important outcome of idiopathic pulmonary fibrosis (IPF and nonspecific interstitial pneumonia (NSIP. Recombinant human soluble thrombomodulin (rhTM is a new drug for the treatment of disseminated intravascular coagulation in Japan. The objective of this study was to evaluate the efficacy of rhTM for AE of IPF/NSIP.Methods: Twenty-two patients with AE-idiopathic interstitial pneumonia (16 patients with IPF and six patients with NSIP were enrolled in our study. Among them, eleven patients were treated with rhTM (rhTM group, and eleven patients were treated without rhTM (non-rhTM group. Patients admitted to our hospital prior to December 2013 were treated with rhTM, while those admitted after January 2014 were treated without rhTM. The primary endpoint was mortality at 90 days after AE treatment. The secondary endpoint was the safety of rhTM for AE-IPF/AE-NSIP. In addition, we examined prognostic factors of AE-IPF/AE-NSIP.Results: The mortality rate was significantly lower in the rhTM group than in the non-rhTM group (mortality rate at 90 days: 36% vs 90%, P=0.023; median survival time: not reached vs 15.0 days, P=0.019. A univariate analysis revealed the respiratory rate (hazard ratio [HR] 1.09, 95% confidence interval [CI] 1.00–1.18, P=0.039 and rhTM administration (HR 0.21, 95% CI 0.06–0.77, P=0.013 as predictors of mortality at 90 days, and a multivariate analysis identified rhTM administration (HR 0.025, 95% CI 0.0006–0.94, P=0.046 as an independent predictor of mortality at 90 days. No serious adverse events were observed.Conclusion: The administration of rhTM is associated with reductions in mortality in patients with AE

  6. Erasmus Darwin's enlightened views on placental function.

    Science.gov (United States)

    Pijnenborg, R; Vercruysse, L

    2007-01-01

    In his major work "Zoonomia", Erasmus Darwin (1731-1802) devoted one chapter to the placenta, in which the new knowledge of the recently discovered element oxygen was applied to the functioning of this organ. He considered the "cavities" or "lacunae" in the placenta as the main areas for oxygenation of the fetal blood, as he thought them to be structurally comparable to the lungs and the gills of fish. He obviously was aware of species differences in the uterine arterial blood supply to the placenta between humans and cows, assuming a higher contractility of the vasculature in the latter species. The new evidence for a primarily respiratory role overshadowed ideas of a possible nutritive function of the placenta. Since Hunter's definitive demonstration of separate maternal and fetal blood circulations, nutritive functions of the placenta needed to be explained by transmembrane transport processes, which were unknown at that time. Instead Erasmus Darwin erroneously considered the amniotic fluid as the main source of nutrients for the fetus. His understanding of placental respiration found expression in his long poem on the history of life on earth.

  7. The cumulative effect of assisted reproduction procedures on placental development and epigenetic perturbations in a mouse model.

    Science.gov (United States)

    de Waal, Eric; Vrooman, Lisa A; Fischer, Erin; Ord, Teri; Mainigi, Monica A; Coutifaris, Christos; Schultz, Richard M; Bartolomei, Marisa S

    2015-12-15

    Assisted reproductive technologies (ART) are associated with several complications including low birth weight, abnormal placentation and increased risk for rare imprinting disorders. Indeed, experimental studies demonstrate ART procedures independent of existing infertility induce epigenetic perturbations in the embryo and extraembryonic tissues. To test the hypothesis that these epigenetic perturbations persist and result in adverse outcomes at term, we assessed placental morphology and methylation profiles in E18.5 mouse concepti generated by in vitro fertilization (IVF) in two different genetic backgrounds. We also examined embryo transfer (ET) and superovulation procedures to ascertain if they contribute to developmental and epigenetic effects. Increased placental weight and reduced fetal-to-placental weight ratio were observed in all ART groups when compared with naturally conceived controls, demonstrating that non-surgical embryo transfer alone can impact placental development. Furthermore, superovulation further induced overgrowth of the placental junctional zone. Embryo transfer and superovulation defects were limited to these morphological changes, as we did not observe any differences in epigenetic profiles. IVF placentae, however, displayed hypomethylation of imprinting control regions of select imprinted genes and a global reduction in DNA methylation levels. Although we did not detect significant differences in DNA methylation in fetal brain or liver samples, rare IVF concepti displayed very low methylation and abnormal gene expression from the normally repressed allele. Our findings suggest that individual ART procedures cumulatively increase placental morphological abnormalities and epigenetic perturbations, potentially causing adverse neonatal and long-term health outcomes in offspring.

  8. Uterine Activin-Like Kinase 4 Regulates Trophoblast Development During Mouse Placentation.

    Science.gov (United States)

    Peng, Jia; Fullerton, Paul T; Monsivais, Diana; Clementi, Caterina; Su, Gloria H; Matzuk, Martin M

    2015-12-01

    The placenta is the first organ to develop after fertilization. It forms an interface between the maternal uterus and growing fetus to allow nutrient uptake, waste elimination, and gas exchange for a successful pregnancy in both mice and humans. In the past 2 decades, in vivo and in vitro approaches have been used to show that several members of the TGF-β superfamily regulate embryo implantation and placental development. Nodal, a TGF-β superfamily ligand, is essential for mesendoderm formation and left-right axis patterning during embryogenesis, and Nodal null mutants exhibit abnormal placental organization with expansion of trophoblast giant cells and a decrease of spongiotrophoblast and labyrinth. To better understand the importance of Nodal signaling in the uterus, we established a mouse model to conditionally ablate activin-like kinase 4 (ALK4; the Nodal type 1 receptor) using Cre recombinase driven by the progesterone receptor promoter sequences (Pgr-Cre). Alk4 conditional knockout females are subfertile due to placental abnormalities and fetal loss in pregnancy, with a placental disorganization phenotype similar to what is observed in Nodal null mice. Thus, Nodal likely functions as an indirect regulator of placental development by binding to type 1 and type 2 receptors on maternal decidual cells to stimulate expression of unknown regulators of placental development. Our findings not only describe the generation of a mouse model that enables study of Nodal signaling in placentation but also provides insights into the pathogenesis of pregnancy complications in humans, including spontaneous abortion, preeclampsia, intrauterine growth restriction, and preterm birth.

  9. The placental exposome: Placental determinants of fetal adiposity and postnatal body composition

    NARCIS (Netherlands)

    R.M. Lewis (R.); H. Demmelmair (Hans); R. Gaillard (Romy); N. Godfrey; S. Hauguel-De Mouzon (S.); B. Huppertz (B.); E. Larque (E.); R. Saffery (R.); M.E. Symonds (M.); G. Desoye (G.)

    2013-01-01

    textabstractOffspring of obese and diabetic mothers are at increased risk of being born with excess adiposity as a consequence of their intrauterine environment. Excessive fetal fat accretion reflects additional placental nutrient transfer, suggesting an effect of the maternal environment on placent

  10. The placental exposome: Placental determinants of fetal adiposity and postnatal body composition

    NARCIS (Netherlands)

    R.M. Lewis (R.); H. Demmelmair (Hans); R. Gaillard (Romy); N. Godfrey; S. Hauguel-De Mouzon (S.); B. Huppertz (B.); E. Larque (E.); R. Saffery (R.); M.E. Symonds (M.); G. Desoye (G.)

    2013-01-01

    textabstractOffspring of obese and diabetic mothers are at increased risk of being born with excess adiposity as a consequence of their intrauterine environment. Excessive fetal fat accretion reflects additional placental nutrient transfer, suggesting an effect of the maternal environment on placent

  11. Pathogenesis of disseminated intravascular coagulation in patients with acute promyelocytic leukemia, and its treatment using recombinant human soluble thrombomodulin.

    Science.gov (United States)

    Ikezoe, Takayuki

    2014-07-01

    Acute promyelocytic leukemia (APL) is an uncommon subtype of acute myelogenous leukemia characterized by the proliferation of blasts with distinct morphology, a specific balanced reciprocal translocation t(15;17), and life-threatening hemorrhage caused mainly by enhanced fibrinolytic-type disseminated intravascular coagulation (DIC). The introduction of all-trans retinoic acid (ATRA) into anthracycline-based induction chemotherapy regimens has dramatically improved overall survival of individuals with APL, although hemorrhage-related death during the early phase of therapy remains a serious problem. Moreover, population-based studies have shown that the incidence of early death during induction chemotherapy is nearly 30 %, and the most common cause of death is associated with hemorrhage. Thus, development of a novel treatment strategy to alleviate abnormal coagulation in APL patients is urgently required. Recombinant human soluble thrombomodulin (rTM) comprises the active extracellular domain of TM, and has been used for treatment of DIC since 2008 in Japan. Use of rTM in combination with remission induction chemotherapy, including ATRA, produces potent resolution of DIC without exacerbation of bleeding tendency in individuals with APL. This review article discusses the pathogenesis and features of DIC caused by APL, as well as the possible anticoagulant and anti-leukemic action of rTM in APL patients.

  12. Serum vascular endothelial cadherin and thrombomodulin are markers of non-alcoholic fatty liver disease in children.

    Science.gov (United States)

    Kan, Xuan; Liu, Geli; Yang, Yong; Yang, Qingyan; Li, Yapu; Wang, Feng

    2016-12-01

    The diagnosis of non-alcoholic fatty liver disease (NAFLD) is usually based on liver ultrasonography and serum alanine aminotransferase (ALT) levels. However, the serum ALT level is not sensitive for detecting NAFLD. If more serum markers are available, serum analysis may play a more important role in the diagnosis of NAFLD. Here, we have investigated whether vascular endothelial cadherin (VE-cad) and thrombomodulin (TM) are markers of NAFLD in children. After an examination of liver ultrasonography, 90 children were divided into a lean control group (n=32), an overweight/obese NAFLD group (group-NAFLD, n=34) and an overweight/obese non-NAFLD group (group-SOO, n=24). Two overweight/obese groups had similar obesity. However, serum VE-cad and TM levels were increased in group-NAFLD but not group-SOO. When data from all children were pooled, serum VE-cad and TM levels were positively correlated to body-mass index (BMI) and serum ALT levels. In conclusion, VE-cad and TM are markers of pediatric NAFLD.

  13. GDM alters paracrine regulation of feto-placental angiogenesis via the trophoblast.

    Science.gov (United States)

    Loegl, Jelena; Nussbaumer, Erika; Cvitic, Silvija; Huppertz, Berthold; Desoye, Gernot; Hiden, Ursula

    2017-04-01

    Feto-placental angiogenesis and vascular development are tightly regulated by pro- and anti-angiogenic factors. Villous trophoblast may be a major source of these factors. It forms the classical placental barrier between mother and fetus, and is thus exposed to maternal influences as well. Metabolic and hormonal derangements in gestational diabetes mellitus (GDM) affect feto-placental angiogenesis and vascular growth. Here we hypothesized that GDM alters the trophoblast secretome, which will modulate the paracrine regulation of feto-placental angiogenesis. Primary term trophoblasts were isolated from normal (n=6) and GDM (n=6) pregnancies. Trophoblast conditioned medium (CM) was used to investigate paracrine effects of normal and GDM-exposed trophoblasts on feto-placental endothelial cells (fpECs; n=7), using functional assays for 2D network formation, wound healing, chemotaxis, and proliferation. Gene expression of 23 pro- and anti-angiogenic factors was analyzed. Four trophoblast-derived paracrine regulators of angiogenesis were specifically measured in CM. CM from GDM trophoblasts increased 2D network formation of fpEC by 2.4-fold (P<0.001), whereas wound healing was attenuated by 1.8-fold (P=0.02) and chemo-attraction to the CM was reduced by 33±9% (P=0.02). The effect of CM on proliferation was unchanged between normal and GDM trophoblasts. Expression analysis of pro- and anti-angiogenic molecules in normal and GDM trophoblasts revealed significant differences in ANGPT2, HGF, KISS1 and PLGF expression. Analysis of secreted proteins demonstrated reduced pigment epithelium derived factor and tumor necrosis factor-α secretion by GDM trophoblasts. GDM alters the balance of trophoblast derived, angiogenesis modulating paracrine factors. This may contribute to GDM-associated changes in placental angiogenesis and vascular structure.

  14. Post-transcriptional down regulation of ICAM-1 in feto-placental endothelium in GDM.

    Science.gov (United States)

    Díaz-Pérez, Francisca Isidora; Hiden, Ursula; Gauster, Martin; Lang, Ingrid; Konya, Viktoria; Heinemann, Akos; Lögl, Jelena; Saffery, Richard; Desoye, Gernot; Cvitic, Silvija

    2016-03-03

    Maternal gestational diabetes (GDM) is associated with hyperglycaemia and hyperinsulinemia in the fetal circulation which consequently may induce endothelial dysfunction in the feto-placental vasculature. In fact, feto-placental vasculature reveals various morphological changes in response to GDM. The cell adhesion molecules (CAMs) ICAM-1, VCAM-1 and E-selectin promote attachment and trans-endothelial migration of leukocytes, and are up regulated in inflammation and endothelial dysfunction. Thus, we hypothesized that the GDM environment upregulates ICAM-1, VCAM-1 and E-selectin in the feto-placental endothelium. We isolated primary feto-placental endothelial cells (fpEC) after normal (n=18) and GDM pregnancy (n=11) and analyzed mRNA (RT-qPCR) and protein expression (Immunoblot) of ICAM-1, VCAM-1 and E-selectin. While other CAMs were unchanged on mRNA and protein levels, ICAM-1 protein was decreased by GDM. Further analysis revealed also a decrease in the release of soluble ICAM-1 (sICAM-1), whose levels correlated negatively with maternal BMI. We conclude that this reduction of ICAM-1 protein species is the result of post-translational regulation, since ICAM-1 mRNA expression was unchanged. In fact, miRNAs targeting ICAM-1 were upregulated in GDM fpEC. Immunohistochemistry showed weaker ICAM-1 staining in the placental endothelium after GDM pregnancies, and demonstrated ICAM-1 binding partners CD11a and CD18 expressed on leukocytes in fetal circulation and on placental tissue macrophages. This study identified reduction of ICAM-1 protein in fpEC in GDM pregnancy, which was regulated post-transcriptionally. Low ICAM-1 protein production may represent a protective, placenta-specific mechanism to avoid leukocyte transmigration into the placenta in response to GDM.

  15. The expression of the imprinted gene pleckstrin homology-like domain family A member 2 in placental tissues of preeclampsia and its effects on the proliferation, migration and invasion of trophoblast cells JEG-3.

    Science.gov (United States)

    Jin, Feng; Qiao, Chong; Luan, Nannan; Shang, Tao

    2015-11-01

    Preeclampsia (PE) is one of the most common hypertensive disorders and is a leading cause of morbidity and mortality for pregnant women and perinatal babies. Additionally, pleckstrin homology-like domain family A member 2 (PHLDA2) is associated with placental dysfunction. However, the effect of PHLDA2 on trophoblast cell proliferation, migration and invasion has not been investigated. In this study, 15 PE patients and 15 normal pregnant women were recruited and clinical characteristics were summarized. Pleckstrin homology-like domain family A member 2 levels in placental tissues were examined using real-time PCR and western blot. Overexpression plasmid and PHLDA2 siRNA was introduced into JEG-3 cells, respectively. Cell proliferation was measured using MTT assay and flow cytometry. Cell migration and invasion capacities were assessed by wound healing and Transwell assays. It was found that PE patients collectively presented proteinuria, elevated systolic blood pressure (SBP) and diastolic blood pressure (DBP), and lower gestational ages and birth weights. Pleckstrin homology-like domain family A member 2 levels in the preeclamptic placenta were significantly upregulated. Pleckstrin homology-like domain family A member 2 overexpression significantly arrested cells in the G0/G1 phase, inhibited cell proliferation and suppressed the migration and invasion of JEG-3 cells. Pleckstrin homology-like domain family A member 2 knockdown significantly blocked the cells in the S phase of the cell cycle. Knockdown of PHLDA2 alleviated the inhibition on the migration and invasion of trophoblast cells JEG-3. These findings illustrate that PHLDA2 may participate in PE pathogenesis and indicate its potential application in the early diagnosis of PE. © 2015 Wiley Publishing Asia Pty Ltd.

  16. Comparison of functional assays used in the clinical development of a placental malaria vaccine

    DEFF Research Database (Denmark)

    Pehrson, Caroline; Heno, Kristine K; Adams, Yvonne;

    2017-01-01

    are in clinical development. The purpose of this study was to evaluate the robustness and comparability of binding inhibition assays used in the clinical development of placental malaria vaccines. METHODS: The ability of sera from animals immunised with different VAR2CSA constructs to inhibit IE binding to CSA......BACKGROUND: Malaria in pregnancy is associated with significant morbidity in pregnant women and their offspring. Plasmodium falciparum infected erythrocytes (IE) express VAR2CSA that mediates binding to chondroitin sulphate A (CSA) in the placenta. Two VAR2CSA-based vaccines for placental malaria...

  17. Endocrine activity of extraembryonic membranes extends beyond placental amniotes.

    Directory of Open Access Journals (Sweden)

    Lori C Albergotti

    Full Text Available BACKGROUND: During development, all amniotes (mammals, reptiles, and birds form extraembryonic membranes, which regulate gas and water exchange, remove metabolic wastes, provide shock absorption, and transfer maternally derived nutrients. In viviparous (live-bearing amniotes, both extraembryonic membranes and maternal uterine tissues contribute to the placenta, an endocrine organ that synthesizes, transports, and metabolizes hormones essential for development. Historically, endocrine properties of the placenta have been viewed as an innovation of placental amniotes. However, an endocrine role of extraembryonic membranes has not been investigated in oviparous (egg-laying amniotes despite similarities in their basic structure, function, and shared evolutionary ancestry. In this study, we ask whether the oviparous chorioallantoic membrane (CAM of chicken (Gallus gallus has the capability to synthesize and receive signaling of progesterone, a major placental steroid hormone. METHODOLOGY/PRINCIPAL FINDINGS: We quantified mRNA expression of key steroidogenic enzymes involved in progesterone synthesis and found that 3beta-hydroxysteroid dehydrogenase, which converts pregnenolone to progesterone exhibited a 464 fold increase in the CAM from day 8 to day 18 of embryonic development (F(5, 68 = 89.282, p<0.0001. To further investigate progesterone synthesis, we performed explant culture and found that the CAM synthesizes progesterone in vitro in the presence of a steroid precursor. Finally, we quantified mRNA expression and performed protein immunolocalization of the progesterone receptor in the CAM. CONCLUSIONS/SIGNIFICANCE: Collectively, our data indicate that the chick CAM is steroidogenic and has the capability to both synthesize progesterone and receive progesterone signaling. These findings represent a paradigm shift in evolutionary reproductive biology by suggesting that endocrine activity of extraembryonic membranes is not a novel characteristic of

  18. Novel adenovirus encoded virus-like particles displaying the placental malaria associated VAR2CSA antigen

    DEFF Research Database (Denmark)

    Andersson, Anne-Marie C; dos Santos Marques Resende, Mafalda; Salanti, Ali

    2017-01-01

    The malaria parasite Plasmodium falciparum presents antigens on the infected erythrocyte surface that bind human receptors expressed on the vascular endothelium. The VAR2CSA mediated binding to a distinct chondroitin sulphate A (CSA) is a crucial step in the pathophysiology of placental malaria a...

  19. DREAM mediated regulation of GCM1 in the human placental trophoblast.

    Directory of Open Access Journals (Sweden)

    Dora Baczyk

    Full Text Available The trophoblast transcription factor glial cell missing-1 (GCM1 regulates differentiation of placental cytotrophoblasts into the syncytiotrophoblast layer in contact with maternal blood. Reduced placental expression of GCM1 and abnormal syncytiotrophoblast structure are features of hypertensive disorder of pregnancy--preeclampsia. In-silico techniques identified the calcium-regulated transcriptional repressor--DREAM (Downstream Regulatory Element Antagonist Modulator--as a candidate for GCM1 gene expression. Our objective was to determine if DREAM represses GCM1 regulated syncytiotrophoblast formation. EMSA and ChIP assays revealed a direct interaction between DREAM and the GCM1 promoter. siRNA-mediated DREAM silencing in cell culture and placental explant models significantly up-regulated GCM1 expression and reduced cytotrophoblast proliferation. DREAM calcium dependency was verified using ionomycin. Furthermore, the increased DREAM protein expression in preeclamptic placental villi was predominantly nuclear, coinciding with an overall increase in sumolylated DREAM and correlating inversely with GCM1 levels. In conclusion, our data reveal a calcium-regulated pathway whereby GCM1-directed villous trophoblast differentiation is repressed by DREAM. This pathway may be relevant to disease prevention via calcium-supplementation.

  20. Characterization of human placental glycosaminoglycans and regional binding to VAR2CSA in malaria infected erythrocytes

    DEFF Research Database (Denmark)

    Beaudet, Julie M; Mansur, Leandra; Joo, Eun Ji;

    2014-01-01

    expressing VAR2CSA on the erythrocyte surface. This protein adheres to a low-sulfated chondroitin sulfate-A found in placental tissue causing great harm to both mother and developing fetus. In rare cases, the localization of infected erythrocytes to the placenta can even result in the vertical transmission...

  1. Placental growth factor and vascular endothelial growth factor receptor-2 in human lung development.

    Science.gov (United States)

    Janér, Joakim; Andersson, Sture; Haglund, Caj; Karikoski, Riitta; Lassus, Patrik

    2008-08-01

    We examined the pulmonary expression of 2 proangiogenic factors, namely, placental growth factor and vascular endothelial growth factor receptor-2, during lung development and acute and chronic lung injury in newborn infants. Six groups were included in an immunohistochemical study of placental growth factor and vascular endothelial growth factor receptor-2, that is, 9 fetuses, 4 preterm and 8 term infants without lung injury who died soon after birth, 5 preterm infants with respiratory distress syndrome of 10 days, and 6 with bronchopulmonary dysplasia. Placental growth factor concentrations in tracheal aspirate fluid were measured in 70 samples from 20 preterm infants during the first postnatal week. In immunohistochemical analyses, placental growth factor staining was seen in bronchial epithelium and macrophages in all groups. Distal airway epithelium positivity was observed mostly in fetuses and in preterm infants who died soon after birth. Vascular endothelial growth factor receptor-2 staining was seen in vascular endothelium in all groups and also in lymphatic endothelium in fetuses. Vascular endothelial growth factor receptor-2 staining in arterial endothelium was associated with higher and staining in venous endothelium with lower gestational age. In capillaries, less vascular endothelial growth factor receptor-2 staining was seen in bronchopulmonary dysplasia. The mean placental growth factor protein concentration in tracheal aspirate fluid during the first postnatal week was 0.64 +/- 0.42 pg/mL per IgA-secretory component unit. Concentrations during the first postnatal week were stable. Lower placental growth factor concentrations correlated with chorioamnionitis and lactosyl ceramide positivity. The vascular endothelial growth factor receptor-2 staining pattern seems to reflect ongoing differentiation and activity of different endothelia. Lower vascular endothelial growth factor receptor-2 expression in capillary endothelium in bronchopulmonary dysplasia

  2. Relation between utero-placental and feto-placental circulations: a longitudinal study.

    Science.gov (United States)

    Flo, Kari; Wilsgaard, Tom; Acharya, Ganesh

    2010-10-01

    To explore the relation between total utero-placental (TQ(uta)) and feto-placental (Q(uv)) blood flows and establish longitudinal reference ranges for the TQ(uta)/Q(uv) ratio and the mean uterine artery and umbilical artery pulsatility (UtaPI/UAPI) and resistance index (UtaRI/UARI) ratios. Prospective longitudinal observational study. University hospital in Norway. Fifty-three low-risk pregnant women. Uterine artery and umbilical vein blood flow was measured using Doppler ultrasonography at 4-weekly intervals from 22(+0) to 39(+6) weeks of gestation. Ratios between utero-placental and feto-placental volume blood flows and between indices of uterine and umbilical artery impedance. The TQ(uta)/Q(uv) ratio had a significant association with the gestational age (p feto-placental circulations do not appear to be affected by each other under physiological conditions. We have established longitudinal reference ranges for the utero-placental and feto-placental blood flow and impedance ratios during the second half of pregnancy.

  3. PPAR Signaling in Placental Development and Function.

    Science.gov (United States)

    Barak, Yaacov; Sadovsky, Yoel; Shalom-Barak, Tali

    2008-01-01

    With the major attention to the pivotal roles of PPARs in diverse aspects of energy metabolism, the essential functions of PPARgamma and PPARbeta/delta in placental development came as a surprise and were often considered a nuisance en route to their genetic analysis. However, these findings provided an opportune entrée into placental biology. Genetic and pharmacological studies, primarily of knockout animal models and cell culture, uncovered networks of PPARgamma and PPARdelta, their heterodimeric RXR partners, associated transcriptional coactivators, and target genes, that regulate various aspects of placental development and function. These studies furnish both specific information about trophoblasts and the placenta and potential hints about the functions of PPARs in other tissues and cell types. They reveal that the remarkable versatility of PPARs extends beyond the orchestration of metabolism to the regulation of cellular differentiation, tissue development, and trophoblast-specific functions. This information and its implications are the subject of this review.

  4. Placental proteome alterations in women with intrahepatic cholestasis of pregnancy.

    Science.gov (United States)

    He, Pei; Wang, Furong; Jiang, Yan; Zhong, Yi; Lan, Yongfei; Chen, Shuqing

    2014-09-01

    To investigate differences in the placental proteomes of women with intrahepatic cholestasis of pregnancy (ICP) and those with a normal pregnancy. Ten pregnant women diagnosed with ICP were recruited at the First People's Hospital of Yuhang District from October 2011 to September 2012; 10 age-matched healthy pregnant women acted as controls. Total placental proteins were extracted and subjected to two-dimensional polyacrylamide gel electrophoresis followed by mass spectrometry to identify proteins that were differentially expressed in the two groups. In total, 37 protein spots with differentially expressed proteins were found. These comprised proteins involved in cytoskeleton activity, blood coagulation, and platelet activation as well as chaperones, heat shock proteins, RNA-binding and calcium-binding proteins, and various enzymes. The placentas of women with ICP displayed significant proteome differences compared with women with a normal pregnancy. The results indicate that a variety of mechanisms and proteins may contribute to the development of ICP. Further verification and research are required to elucidate the exact roles of these proteins in ICP pathogenesis. Copyright © 2014 International Federation of Gynecology and Obstetrics. Published by Elsevier Ireland Ltd. All rights reserved.

  5. Immunomodulator expression in trophoblasts from the feline immunodeficiency virus FIV infected cat

    Science.gov (United States)

    FIV infection frequently compromises pregnancy under experimental conditions and is accompanied by aberrant expression of some placental cytokines. Trophoblasts produce numerous immunomodulators that play a role in placental development and pregnancy maintenance. We hypothesized that FIV infection m...

  6. Confined placental mosaicism in short term culture

    Directory of Open Access Journals (Sweden)

    Petrović Bojana

    2016-01-01

    Full Text Available Finding of fetal chromosomal mosaicism complicates genetic counseling, as well as pregnancy management. The aim of this study was to determine the risk of confined placental mosaicism in short term culture of chorionic villous samples. We conducted a retrospective review of karyotype analysis results obtained after chorionic villous sampling (CVS in two years period. A 420 samples of chorionic villi were taken transabdominally and obtained by a semidirect method (overnight incubating culture. All fetuses with CVS mosaicism were under the intensive perinatal care. In all cases of chromosome mosaicism the additional karyotyping was performed from fetal blood samples after 22nd gestational week in order to exclude true fetal mosaicism. After delivery newborns were examined by experienced pediatrician. From 420 analyzed samples in 11 (2,6% cases we found placental mosaicism. No anomalies were seen in genetic sonogram of this fetuses and mosaicism was confirmed only in one case. Confined placental mosaicism (CPM was found in 2,1% (9/420 of all analyzed cases, and it made 90% of all placental mosaicism. In 60% (6/10 of placental mosaicism cases we found mosaicism with single aberrant cell. Trisomy 21 mosaicism was the most frequent aberration found in 30% of cases. Finding of mosaicism in chorionic villi sample is at special importance for genetic counseling, because every case has to be reveled individually regarding the type and level of mosaicism. Anyway, in every case of placental mosaicism intensive antenatal monitoring is necessary, with additional chromosome analysis from different tissue in consideration of previous findings.

  7. Glucose, Insulin, and Oxygen Interplay in Placental Hypervascularisation in Diabetes Mellitus

    Directory of Open Access Journals (Sweden)

    Silvija Cvitic

    2014-01-01

    Full Text Available The placental vasculature rapidly expands during the course of pregnancy in order to sustain the growing needs of the fetus. Angiogenesis and vascular growth are stimulated and regulated by a variety of growth factors expressed in the placenta or present in the fetal circulation. Like in tumors, hypoxia is a major regulator of angiogenesis because of its ability to stimulate expression of various proangiogenic factors. Chronic fetal hypoxia is often found in pregnancies complicated by maternal diabetes as a result of fetal hyperglycaemia and hyperinsulinemia. Both are associated with altered levels of hormones, growth factors, and proinflammatory cytokines, which may act in a proangiogenic manner and, hence, affect placental angiogenesis and vascular development. Indeed, the placenta in diabetes is characterized by hypervascularisation, demonstrating high placental plasticity in response to diabetic metabolic derangements. This review describes the major regulators of placental angiogenesis and how the diabetic environment in utero alters their expression. In the light of hypervascularized diabetic placenta, the focus was placed on proangiogenic factors.

  8. Placental ontogeny in Tasmanian snow skinks (genus Niveoscincus) (Lacertilia: Scincidae).

    Science.gov (United States)

    Stewart, James R; Thompson, Michael B

    2009-04-01

    Lizards of the viviparous genus Niveoscincus contributed importantly to a classic model for the evolution of placentation of squamate reptiles. This model predicts that: (1) placental function is correlated with placental structural complexity and (2) the type of chorioallantoic placenta attributed to three species of Niveoscincus (N. metallicus, N. ocellatus, N. pretiosus) is intermediate in complexity to a highly placentotrophic type of placenta. Recent studies of two of these species (N. metallicus, N. ocellatus) revealed additional variation in placental structure, as well as variation in the level of placentotrophy; N. metallicus is predominantly lecithotrophic, while N. ocellatus is highly placentotrophic. We used light microscopy to study placental ontogeny in two biennially reproducing species of Niveoscincus (N. greeni, N. microlepidotus) and placental morphology in late stage embryos of N. pretiosus. These data, in combination with prior studies, provide descriptions of placental structure for six of the eight species assigned to this lineage. The genus Niveoscincus has greater variation in placental structure than any other squamate lineage. We recognize four distinct groupings among these six species based on placental structure. The most highly placentotrophic species, N. ocellatus, has a complex placental morphology, yet shares these structures with a predominantly lecithotrophic species, N. microlepidotus. Thus, among species of Niveoscincus, placental structural complexity is not an infallible predictor of overall placental function.

  9. Quality assessment of a placental perfusion protocol

    DEFF Research Database (Denmark)

    Mathiesen, Line; Mose, Tina; Mørck, Thit Juul;

    2010-01-01

    the placental perfusion model in Copenhagen including control substances. The positive control substance antipyrine shows no difference in transport regardless of perfusion media used or of terms of delivery (n=59, pmarked dextran correspond with leakage criteria (...mlh(-1) from the fetal reservoir) when adding 2 (n=7) and 20mg (n=9) FITC-dextran/100ml fetal perfusion media. Success rate of the Copenhagen placental perfusions is provided in this study, including considerations and quality control parameters. Three checkpoints suggested to determine success rate...

  10. A new method to determine tissue specific tissue factor thrombomodulin activities: endotoxin and particulate air pollution induced disbalance

    Directory of Open Access Journals (Sweden)

    Gerlofs-Nijland Miriam E

    2008-10-01

    Full Text Available Abstract Background Increase in tissue factor (TF and loss in thrombomodulin (TM antigen levels has been described in various inflammatory disorders. The functional consequences of such changes in antigen concentrations in the coagulation balance are, however, not known. This study was designed to assess the consequences of inflammation-driven organ specific functional properties of the procoagulant response. Methods Tissue specific procoagulant activity was assessed by adding tissue homogenate to normal human pool plasma and recording of the thrombin generation curve. The new technique was subsequently applied on two inflammation driven animal models: 1 mouse lipopolysaccharide (LPS induced endotoxemia and 2 spontaneously hypertensive rats exposed to environmental air pollution (particulate matter (PM. Results Addition of lung tissue from untreated animals to human plasma suppressed the endogenous thrombin potential (ETP (175 ± 61 vs. 1437 ± 112 nM.min for control. This inhibitory effect was due to TM, because a it was absent in protein C deficient plasma and b lungs from TMpro/pro mice allowed full thrombin generation (ETP: 1686 ± 209 nM.min. The inhibitory effect of TM was lost after LPS administration to mice, which induced TF activity in lungs of C57Bl/6 mice as well as increased the ETP (941 ± 523 vs. 194 ± 159 nM.min for control. Another pro-inflammatory stimulus, PM dose-dependently increased TF in the lungs of spontaneously hypertensive rats at 4 and 48 hours after PM exposure. The ETP increased up to 48 hours at the highest concentration of PM (1441 ± 289 nM.min vs. saline: 164 ± 64 nM.min, p Conclusion Inflammation associated procoagulant effects in tissues are dependent on variations in activity of the TF-TM balance. The application of these novel organ specific functional assays is a useful tool to monitor inflammation-driven shifts in the coagulation balance within animal or human tissues.

  11. Anti-inflammatory and anti-fibrinolytic effects of thrombomodulin alfa through carboxypeptidase B2 in the presence of thrombin.

    Science.gov (United States)

    Tawara, Shunsuke; Sakai, Takumi; Matsuzaki, Osamu

    2016-11-01

    Thrombomodulin (TM) alfa, a recombinant human soluble TM, enhances activation of pro-carboxypeptidase B2 (pro-CPB2) by thrombin. Activated pro-CPB2 (CPB2) exerts anti-inflammatory and anti-fibrinolytic activities. Therefore, TM alfa may also have anti-inflammatory and anti-fibrinolytic effects through CPB2. However, these effects of TM alfa have not been elucidated. In the present study, we investigated the effects of TM alfa on inactivation of complement component C5a as an anti-inflammatory effect and prolongation of clot lysis time as an anti-fibrinolytic effect via CPB2 in vitro. CPB2 activity and tissue factor-induced thrombin generation was examined by a chromogenic assay. C5a inactivation was evaluated by C-terminal cleavage of C5a and inhibition of C5a-induced human neutrophil migration. Clot lysis time prolongation was examined by a tissue-type plasminogen activator-induced clot lysis assay. CPB2 activity in human plasma was increased by TM alfa and thrombin in a concentration-dependent manner. TM alfa inhibited tissue factor-induced thrombin generation and enhanced pro-CPB2 activation in human plasma simultaneously. The mass spectrum of C5a treated with TM alfa, thrombin, and pro-CPB2 was decreased at 156m/z, indicating that TM alfa enhanced the processing of C5a to C-terminal-cleaved C5a, an inactive form of C5a. C5a-induced human neutrophil migration was decreased after C5a treatment with TM alfa, thrombin, and pro-CPB2. TM alfa prolonged the clot lysis time in human plasma, and this effect was completely abolished by addition of a CPB2 inhibitor. TM alfa exerts anti-inflammatory and anti-fibrinolytic effects through CPB2 in the presence of thrombin in vitro. Copyright © 2016 Elsevier Ltd. All rights reserved.

  12. Missense mutations in the gene encoding prothrombin corresponding to Arg596 cause antithrombin resistance and thrombomodulin resistance.

    Science.gov (United States)

    Takagi, Yuki; Murata, Moe; Kozuka, Toshihiro; Nakata, Yukiko; Hasebe, Ryo; Tamura, Shogo; Takagi, Akira; Matsushita, Tadashi; Saito, Hidehiko; Kojima, Tetsuhito

    2016-11-30

    Antithrombin (AT) and thrombomodulin (TM) play important roles in the process of natural anticoagulation in vivo. Recently, we reported that the prothrombin Yukuhashi mutation (p.Arg596Leu) was associated with AT and TM resistance-related thrombophilia. To assess the AT and TM resistances associated with other missense mutations by single base substitution in the Arg596 codon, we generated recombinant variants (596Gln, 596Trp, 596Gly, and 596Pro) and investigated the effects on AT and TM anticoagulant functions. All variants except 596Pro were secreted in amounts comparable to that of the wild-type but exhibited variable procoagulant activities. After a 30-minute inactivation by AT, the relative residual activity of wild-type thrombin decreased to 15 ± 4.0 %, in contrast to values of all variants were maintained at above 80 %. The thrombin-AT complex formation, as determined by enzyme-linked immunosorbent assay, was reduced with all tested variants in the presence and absence of heparin. In the presence of soluble TM (sTM), the relative fibrinogen clotting activity of wild-type thrombin decreased to 16 ± 0.12 %, whereas that of tested variants was 37 %-56 %. In a surface plasmon resonance assay, missense Arg596 mutations reduced thrombin-TM affinity to an extent similar to the reduction of fibrinogen clotting inhibition. In the presence of sTM or cultured endothelial-like cells, APC generation was enhanced differently by variant thrombins in a thrombin-TM affinity-dependent manner. These data indicate that prothrombin Arg596 missense mutations lead to AT and TM resistance in the variant thrombins and suggest that prothrombin Arg596 is important for AT- and TM-mediated anticoagulation.

  13. Use of recombinant human soluble thrombomodulin in patients with sepsis-induced disseminated intravascular coagulation after intestinal perforation

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    Takashi eTagami

    2015-02-01

    Full Text Available Background: Anticoagulant therapy has been evaluated with respect to its potential usefulness in reducing the high mortality rates associated with severe sepsis, including sepsis-induced disseminated intravascular coagulation (DIC after intestinal perforation. We examined the hypothesis that recombinant human soluble thrombomodulin (rhTM is effective in the treatment of patients with septic shock with sepsis-induced DIC after laparotomy for intestinal perforation. Methods: We performed propensity-score and instrumental variable analyses of the Japanese Diagnosis Procedure Combination inpatient database, a nationwide administrative database. The main outcome was 28-day in-hospital all-cause mortality.Results: We categorized eligible patients (n = 2202 from 622 hospitals into the rhTM group (n = 726 and control group (n = 1476. Propensity-score matching created 621 matched pairs of patients with and without rhTM. There was no significant difference in 28-day mortality between the two groups in the unmatched analysis (rhTM vs. control, 25.3% vs. 23.4%, respectively; difference, 1.9%; 95%CI, −1.9 to 5.7, nor in the propensity-score matched analysis (rhTM vs. control, 26.1% vs. 24.8%, respectively; difference, 1.3%; 95%CI, −3.6 to 6.1. The logistic analysis showed no significant association between the use of rhTM and the mortality in propensity-score matched patients ((OR, 1.1; 95%CI, 0.82−1.4. The instrumental variable analyses, using the hospital rhTM-prescribing proportion as the variable, found that receipt of rhTM was not associated with the reduction in the mortality (risk difference, −6.7%; 95%CI, −16.4 to 3.0.Conclusions: We found no association between administration of rhTM and 28-day mortality in mechanically ventilated patients with septic shock and concurrent DIC after intestinal perforation.

  14. Levels of protein C and soluble thrombomodulin in critically ill patients with acute kidney injury: a multicenter prospective observational study.

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    Josée Bouchard

    Full Text Available Endothelial dysfunction contributes to the development of acute kidney injury (AKI in animal models of ischemia reperfusion injury and sepsis. There are limited data on markers of endothelial dysfunction in human AKI. We hypothesized that Protein C (PC and soluble thrombomodulin (sTM levels could predict AKI. We conducted a multicenter prospective study in 80 patients to assess the relationship of PC and sTM levels to AKI, defined by the AKIN creatinine (AKI Scr and urine output criteria (AKI UO. We measured marker levels for up to 10 days from intensive care unit admission. We used area under the curve (AUC and time-dependent multivariable Cox proportional hazard model to predict AKI and logistic regression to predict mortality/non-renal recovery. Protein C and sTM were not different in patients with AKI UO only versus no AKI. On intensive care unit admission, as PC levels are usually lower with AKI Scr, the AUC to predict the absence of AKI was 0.63 (95%CI 0.44-0.78. The AUC using log10 sTM levels to predict AKI was 0.77 (95%CI 0.62-0.89, which predicted AKI Scr better than serum and urine neutrophil gelatinase-associated lipocalin (NGAL and cystatin C, urine kidney injury molecule-1 and liver-fatty acid-binding protein. In multivariable models, PC and urine NGAL levels independently predicted AKI (p=0.04 and 0.02 and PC levels independently predicted mortality/non-renal recovery (p=0.04. In our study, PC and sTM levels can predict AKI Scr but are not modified during AKI UO alone. PC levels could independently predict mortality/non-renal recovery. Additional larger studies are needed to define the relationship between markers of endothelial dysfunction and AKI.

  15. 水通道蛋白-8在羊水过少产妇胎盘和胎膜组织中的表达及意义%Expressions and significances of aquaporin -8 in placental tissues and fetal membranes of parturient women with oligohydramnios

    Institute of Scientific and Technical Information of China (English)

    周岩; 王凤莲

    2011-01-01

    目的:探讨水通道蛋白-8在羊水过少和正常羊水量产妇胎盘和胎膜组织中的表达及意义.方法:采用免疫组化方法(SP法)检测15例羊水过少和15例正常羊水量产妇胎盘、胎膜组织中水通道蛋白-8 (AQP8)的蛋白表达水平.结果:AQP8蛋白在羊水过少组和正常羊水量组产妇的胎盘、胎膜组织中均有表达,主要分布于羊膜上皮细胞、绒毛膜滋养细胞和胎盘合体滋养细胞的细胞膜和细胞质中.羊水过少组羊膜、绒毛膜和胎盘组织中的AQP8蛋白表达水平分别为0.088±0.021、0.143±0.021、0.122±0.019,正常羊水量组分别为0.148±0.016、0.158±0.025、0.151±0.025.羊水过少组羊膜、绒毛膜和胎盘组织中AQP8蛋白表达水平均低于正常羊水量组,在羊膜、胎盘中的表达差异均有统计学意义(P<0.05);绒毛膜组织中AQP8蛋白表达水平虽低于对照组,但差异无统计学意义(P>0.05).结论:AQP8蛋白在羊水过少临床病例胎盘和胎膜组织中的表达显著减少,提示AQP8在产妇母胎液体交换和羊水膜内吸收途径中发挥重要作用.%Objective: To explore the expressions and significances of aquaporin -8 in placental tissues and fetal membranes of parturient women with oligohydramnios and parturient women with normal volume of amniotic fluid. Methods; Immunohistochemical SP method was used to detect the expression levels of aquaporin - 8 protein in placental tissues and fetal membranes of 15 parturient women with oligohydramnios and 15 parturient women with normal volume of amniotic fluid. Results: Aquaporin -8 protein expressed in placental tissues and fetal membranes of oligohydramnios group and normal amniotic fluid volume group-, mainly in the cell membrane and cytoplasm of amniotic epithelial cells, trophoblast cells and placental syncytiotrophoblastic cells. The expression levels of aquaporin - 8 protein in amniotic membrane, chorion and placenta were (0.088 ±0.021), (0. 143 ±0

  16. Placental lesions and outcome in preterm born children : the relation between placental lesions, neonatal morbidity and neurological development

    NARCIS (Netherlands)

    Roescher, Annemiek

    2014-01-01

    The placenta is the link between the mother and her fetus during pregnancy and plays a crucial role in fetal growth and development. A less than optimal placental function as a result of placental lesions, may lead to maternal and or fetal problems. It is known that placental lesions are an importan

  17. Effects of lead exposure on placental cellular apoptosis and endoplasmic reticulum stress in rats

    Institute of Scientific and Technical Information of China (English)

    Wang Yunying; Hu Haiyan; Li Hong; Ma Haiyan; Xu Fengsen; Qu Baoming

    2014-01-01

    Background Lead exposure during pregnancy contributes to fetal abortion and/or teratogenesis.Endoplasmic reticulum (ER) apoptosis can be induced by various pathological conditions when ER function is disturbed.However,it is unclear whether ER stress and apoptosis play a role in the etiology of lead-exposed disease status.We aimed to investigate whether lead induced placental apoptosis and subsequent toxicity is initiated by ER apoptosis via caspase-12.Methods Sixty-three female Wistar rats were exposed to lead in drinking water during various gestational periods.Blood lead level was determined by atomic absorption spectrophotometry.Placental cytoplasmic organelles were examined by electronic microscopy.Placental caspase-12 mRNA expression was evaluated by qRT-PCR.TUNEL assay was used to determine the placental apoptosis.Results Lead exposure significant induced ER apoptosis compared to that of the controls (P <0.05),accompanied with increased caspase-12 mRNA expression.Significant differences of caspase-12 mRNA expression levels were observed among the four groups (F=13.78,P <0.05).Apoptotic index (AI) was significantly increased in experimental groups compared to that of the controls (F=96.15,P <0.05).In lead-exposed groups,trophoblast cells underwent degeneration and fibrin deposition; Mitochondria were swollen and decreased in number; ER swelling,expansion,and vacuolization were observed.Conclusion Lead exposure contributes to placental apoptosis,as well as increased caspase-12 mRNA expression,which in turn promoted ER stress.

  18. Magnetic resonance imaging of the placenta identifies placental vascular abnormalities independently of Doppler ultrasound.

    Science.gov (United States)

    Messerschmidt, A; Baschat, A; Linduska, N; Kasprian, G; Brugger, P C; Bauer, A; Weber, M; Prayer, D

    2011-06-01

    To evaluate the relationship between placental vascular pathology detected by prenatal magnetic resonance imaging (MRI) and perinatal outcome. This was a retrospective, hospital-based, cross-sectional study in which all fetal MRI examinations of singleton pregnancies with vascular placental pathology (i.e. infarction with/without hemorrhage, subchorionic thrombi/hemorrhages, intervillous thrombi/hemorrhages, or retroplacental hematoma) in the period 2002-2007 were included. The extent of the pathology was expressed as a percentage of the total placental volume. Abnormalities of umbilical artery Doppler ultrasound examinations within 7 days between MRI and ultrasound examination were noted. Death in utero or postnatally was the primary outcome. Gestational age at MRI and at birth and the occurrence of intrauterine growth restriction (IUGR) were noted. Logistic regression analysis was performed to assess the impact of gestational age at MRI, extent of the vascular lesion and presence of pathological Doppler ultrasound measurements on the prediction of mortality. Fifty-nine structurally normal singleton pregnancies with placental vascular abnormalities were included in the analysis. Mortality rate was 36%; among the survivors, 87% were born before 37 + 0 gestational weeks and 50% suffered from IUGR. In 55% of the pregnancies pathological umbilical artery Doppler findings were identified, of which 27% were non-survivors. Mortality was predicted by earlier gestational age at fetal MRI for placental pathology (P < 0.05) and increasing extent of the vascular lesion (P < 0.05), but not by the presence of pathological Doppler ultrasound data. Accuracy of the prediction was 82%, sensitivity was 67% and specificity 89%. MRI-detected vascular placental pathologies may help to identify pregnancies at risk for adverse outcome and fetal death independently of umbilical artery Doppler status. Copyright © 2011 ISUOG. Published by John Wiley & Sons, Ltd.

  19. 胎盘基底板中玻连蛋白的表达及其与重度子痫前期发病的关系%Expression of vitronectin in placental basal plate and its relationship with the pathogenesis of severe preeclampsia

    Institute of Scientific and Technical Information of China (English)

    沈晶; 杨淑莉; 靖丽娟; 陈帅; 马晓艳; 崔满华

    2013-01-01

    Objective To investigate the expression of vitronectin (VN) in placental basal plate and its relationship with the pathogenesis of severe preeclampsia.Methods From March 2010 to December 2011,17 patients with early-onset severe preeclampsia who delivered in the Second Hospital of Jilin University were recruited as the early-onset severe preeclampsia group; and 16 women were recruited as the late-onset severe preeclampsia group.Meanwhile,15 healthy pregnant women who delivered before 34 weeks were defined as the early control group (termination of pregnancy was carried out because of fetal heart malformations),and 15 healthy pregnant women delivered after 34 weeks were defined as the late control group.Imnunohistochemistry and semi-quantitative reverse transcription (RT)-PCR were used to investigate the expression of VN protein and mRNA in the placental infarct center and its surrounding tissue of placental basal plate.The levels of serum prothrombin time (PT),part thromboplastin time (APTT) and fibrinogen (FIb) were detected and the international normalized ratio (INR) was calculated.The correlation of abnormal coagulation markers and VN expression levels in the early-onset severe preeclampsia group and the early control group was studied.Results (l) VN protein was detected in all placental basal plate of the four groups.It was highly expressed in the necrotic tissue of placental infarct center and weakly expressed in the tissue far from the infarcted area.(2) The mean levels of VN protein expression in placental basal plate of the early-onset severe preeclampsia group,the late-onset severe preeclampsia group,the late control group and the early control group were 0.152 ± 0.019,0.113 ± 0.023,0.095 ± 0.014 and 0.055 ± 0.010,respectively.And the differences between the groups were statistically significant (P < 0.01).The VN protein expression in placental infarct center,infarct edge,peri-infarct tissue and tissue far from the infarcted area gradually reduced

  20. Placental Development in Ongoing Pregnancy and Miscarriage

    NARCIS (Netherlands)

    A.D. Reus (Averil)

    2015-01-01

    markdownabstract__Abstract__ In this thesis three-dimensional ultrasound, three-dimensional power Doppler ultrasound, virtual reality and histologic examination of the chorionic villous vascularization were used to investigate early placental development in normal ongoing pregnancy as well as misca

  1. A RADIOIMMUNOASSAY FOR PLACENTAL PROTEIN PP5

    Institute of Scientific and Technical Information of China (English)

    WANGShui-Long; DUGuo-Guang; ZHENGShu-Rong; LIUXin-Jun; YANRen-Ying

    1989-01-01

    A radioimmunoasay of high sendtivity end smbility was developed For placental proteinPP5 (PP5), a syncytiotrophoblast product oF the human placenta. We measured 94 samples from 17 normal nonpregnant women, 47 normal pregnant women, and 30 samples

  2. Placental specializations in lecithotrophic viviparous squamate reptiles.

    Science.gov (United States)

    Stewart, James R

    2015-09-01

    Squamate reptiles have been thought to be predisposed to evolution of viviparity because embryos of most oviparous species undergo considerable development in the uterus prior to oviposition. A related hypothesis proposes that prolonged intrauterine gestation, an intermediate condition leading to viviparity, requires little or no physiological adjustment, other than reduction in thickness of the eggshell. This logical framework is often accompanied by an assumption that mode of parity (oviparity, viviparity) and pattern of embryonic nutrition (lecithotrophy, placentotrophy) are independent traits that evolve in sequence. Thus, specializations for viviparity should be absent in some lecithotrophic viviparous species. Studies of species of lizards with geographic variation in mode of parity challenge this scenario by demonstrating that placental specializations are correlated with viviparity. Uterine specializations for placental transport of calcium to viviparous embryos alter uterine physiology compared to oviparous females. In addition, comparative studies of oviparous and viviparous species, i.e., in which gene flow is disrupted, reveal that both uterine and embryonic structural modifications are commonly associated with viviparity, suggesting relatively rapid evolution of placental specializations. Studies of squamate reproductive biology support two hypotheses: 1) evolution of viviparity requires physiological adjustments of the uterine environment, and 2) evolution of viviparity promotes relatively rapid adaptations for placentation. Models for the evolution of viviparity from oviparity, or for reversals from viviparity to oviparity, should reflect current understanding of squamate reproductive biology and future studies should be designed to challenge these models.

  3. Pregnancy Complications: Placental Accreta, Increta and Percreta

    Science.gov (United States)

    ... Being 35 or older Being pregnant before Having placenta previa How can you reduce your risk for placental conditions? One way to reduce your chances for having these ... In some cases, the placenta doesn’t develop correctly or work as well ...

  4. Placental Malaria: From Infection to Malfunction

    OpenAIRE

    2013-01-01

    Malaria during pregnancy is a major factor in infant morbidity and mortality. In this issue of Cell Host and Microbe, Conroy et al. (2013) propose that C5a, a product of complement cascade activation, counteracts the placental vascular remodeling response induced by Plasmodium infection and contributes to fetal growth restriction. Fundação para a Ciência e Tecnologia.

  5. Placental Mesenchymal Dysplasia: A Case Report

    Directory of Open Access Journals (Sweden)

    Rachna Agarwal

    2012-01-01

    Full Text Available Introduction. A rare case of histologically proven placental mesenchymal dysplasia (PMD with fetal omphalocele in a 22-year-old patient is reported. Material and Methods. Antenatal ultrasound of this patient showed hydropic placenta with a live fetus of 17 weeks period of gestation associated with omphalocele. Cordocentesis detected the diploid karyotype of the fetus. Patient, when prognosticated, choose to terminate the pregnancy in view of high incidence of fetal and placental anomalies. Subsequent histopathological examination of placenta established the diagnosis to be placental mesenchymal dysplasia. Conclusion. On clinical and ultrasonic grounds, suspicion of P.M.D. arises when hydropic placenta with a live fetus presents in second trimester of pregnancy. Cordocentesis can detect the diploid karyotype of the fetus in such cases. As this condition is prognostically better than triploid partial mole, continuation of pregnancy can sometimes be considered after through antenatal screening and patient counseling. However, a definite diagnosis of P.M.D. is made only on placental histology by absence of trophoblast hyperplasia and trophoblastic inclusions.

  6. Evolution of factors affecting placental oxygen transfer

    DEFF Research Database (Denmark)

    Carter, A M

    2009-01-01

    states, are more amenable to analysis. This is exemplified by factors contributing, respectively, to blood oxygen affinity and placental diffusing capacity. Comparative genomics has given fresh insight into the evolution of the beta-globin gene complex. In higher primates, duplication of an embryonic...

  7. Recent progress towards understanding the role of DNA methylation in human placental development

    Science.gov (United States)

    Mayne, Benjamin T; Buckberry, Sam; Breen, James; Rodriguez Lopez, Carlos M; Roberts, Claire T

    2016-01-01

    Epigenetic modifications, and particularly DNA methylation, have been studied in many tissues, both healthy and diseased, and across numerous developmental stages. The placenta is the only organ that has a transient life of 9 months and undergoes rapid growth and dynamic structural and functional changes across gestation. Additionally, the placenta is unique because although developing within the mother, its genome is identical to that of the foetus. Given these distinctive characteristics, it is not surprising that the epigenetic landscape affecting placental gene expression may be different to that in other healthy tissues. However, the role of epigenetic modifications, and particularly DNA methylation, in placental development remains largely unknown. Of particular interest is the fact that the placenta is the most hypomethylated human tissue and is characterized by the presence of large partially methylated domains (PMDs) containing silenced genes. Moreover, how and why the placenta is hypomethylated and what role DNA methylation plays in regulating placental gene expression across gestation are poorly understood. We review genome-wide DNA methylation studies in the human placenta and highlight that the different cell types that make up the placenta have very different DNA methylation profiles. Summarizing studies on DNA methylation in the placenta and its relationship with pregnancy complications are difficult due to the limited number of studies available for comparison. To understand the key steps in placental development and hence what may be perturbed in pregnancy complications requires large-scale genome-wide DNA methylation studies coupled with transcriptome analyses. PMID:27026712

  8. PLACENTAL SECRETORY FACTORS INFLUENCE TO THP-1 CELLS PHENOTYPE AND THP-1 CELLS TRANSENDOTHELIAL MIGRATION

    Directory of Open Access Journals (Sweden)

    O. I. Stepanova

    2013-01-01

    Full Text Available Decidual and placental macrophage pools are renewed due to its transendothelial monocyte migration from peripheral blood. Tissue macrophages control placental development and provide fetomaternal immunological tolerance. Preeclamptic pregnancy is accompanied by increased monocyte migration to decidual tissue and local inflammatory events. Regulatory mechanisms of monocyte recruitment to placental and decidual tissues is still unclear. Therefore we investigated the influence soluble placental factors (SPFs during the first- and third-trimester normal pregnancy, as compared to effects of these factors in preeclamptic pregnancy. We studied biological actions of SPF upon transendothelial migration of monocyte-like THP-1 cells and their phenotypic pattern. Transendothelial migration of THP-1 cells was more intensive with firsttrimester SPFs from normal pregnancy, when compared with third-trimester samples, and it was accompanied by decreased CD11a expression. SPFs from pre-eclamptic pregnancy caused an increase in transendothelial migration of THP-1 cells, as compared to SPFs from normal pregnancies, being accompanied by increased CD11b expression. The present study was supported by grants ГК №  02.740.11.0711, НШ-3594.2010.7, МД-150.2011.7 and a grant from St.-Petersburg Goverment for young scientists.

  9. STEC:O111-HUS complicated by acute encephalopathy in a young girl was successfully treated with a set of hemodiafiltration, steroid pulse, and soluble thrombomodulin under plasma exchange.

    Science.gov (United States)

    Yada, Noritaka; Fujioka, Masayuki; Bennett, Charles L; Inoki, Kazuya; Miki, Toyokazu; Watanabe, Akihiko; Yoshida, Toshiko; Hayakawa, Masaki; Matsumoto, Masanori; Fujimura, Yoshihiro

    2015-04-01

    We report a 14-year-old girl, who developed shigatoxin-producing E. coli (STEC)-HUS complicated by encephalopathy. She was successfully treated with hemodiafiltration, high-dose methylprednisolone pulse therapy, and soluble recombinant thrombomodulin under plasma exchange. von Willebrand factor multimers analysis provides potential insights into how the administered therapies might facilitate successful treatment of STEC-HUS.

  10. PLACENTAL PATHOLOGY IN INTRA UTERINE GROWTH RETARDATION

    Directory of Open Access Journals (Sweden)

    Vijaya Sheela

    2015-04-01

    Full Text Available INTRODUCTION: The placental development is an essential step in developing effective strategies or the prediction of various maternal and fetal medical and developmental problems . Oxygen transfer and nutrients to the fetus will be actively regulated by the placenta . AIM AND OBJECTIVE: To study morphological changes of placenta in Intrauterine growth Retardation and to correlate morphological changes of placenta with fetal outcome . MATERIALS AND METHODS: Placental tissue samples were obtained from 50 pregnancies complicated by IUGR and 50 normal uncomplicated pregnancies with gestational age between 28 to 42 weeks attending King George hospital Visakhapatnam . INCLUSIVE CRITERIA : An IUGR fetuses whose estimated fetal weight less than those in 10 th percentile are included in the study . Birth weight percentiles were determined by previously published normal curves . EXCLUSIVE CRITERIA: fetuses with known syndromes , chromosomal anomalies and twins . For all patients included in the data set gestational age was estimated from the last menstrual period or early ultra - sonogram before the 12 th week of gestation . The final data set was composed of 50pregnancies complicated by IUGR and APGAR scores . Because preeclampsia is an important maternal factor associated with IUGR , these cases were further divided into t wo subgroups according to presence of hypertension . Samples were taken both from vaginal deliveries and caesarean sections . All the placentas were examined by pathologists . The placentas were weighed . For each case one or two samples from the umbilical cor ds , extra placental membrane , and parenchyma were taken . Gross pathological findings were confirmed by histology . Histological data included are ischemic necrosis , decidual vascularity , acute chorioamni oni tis , fibrinoid necrosis and choriangiosis . Appropriate statistical parameters were used . Chi - square test was conducted to compare placental pathological changes

  11. Doppler indicates of uterine artery Doppler velocimetry by placental location

    Energy Technology Data Exchange (ETDEWEB)

    Han, Sung Shik; Park, Yong Won; Cho, Jae Sung; Kwon, Hye Kyeung; Kim, Jae Wook [Yonsei University College of Medicine, Seoul (Korea, Republic of)

    2001-09-15

    Our purpose was to investigate the relation between the vascular resistance of uterine artery and placental location and to establish the reference value of Doppler index in uterine artery by placental location. Placental location and flow velocity waveforms of both uterine arteries in 7,016 pregnant women after 18 weeks gestation were examined using color Doppler ultrasonography. Placental location was classified as central and lateral placental and the uterine artery with lateral placental were divided into ipsilateral uterine artery (same side of the placental) and contralateral uterine artery (opposite side of the placenta). The uterine artery with central placental was classified as the central uterine artery. Systolic-Diastolic ratio (S/D ratio) of uterine arteries by gestational weeks were calculated and compared with the placental location and perinatal outcomes. In the lateral placental group, the S/D ratio of the contralateral uterine artery was higher than the ipsilateral one (mean=2.08+0.34 vs 1.89+0.34, p=0.0001). S/D ratio of the uterine artery decreased during second trimester and the ratio after 27 weeks was a tendency to have a constant values(ipsilateral: 1.85+ 0.34, central : 1.96+ 0.40, contralateral: 2.01+0.54). S/D ratio of the uterine artery was affected by placental location. So when we evaluate Doppler spectrum of uterine artery, placental location should be considered and we established the reference value of Doppler index of uterine artery by placental location.

  12. Placental programming of anxiety in adulthood revealed by Igf2-null models.

    Science.gov (United States)

    Mikaelsson, Mikael Allan; Constância, Miguel; Dent, Claire L; Wilkinson, Lawrence S; Humby, Trevor

    2013-01-01

    Imprinted, maternally silenced insulin-like growth factor-2 is expressed in both the foetus and placenta and has been shown to have roles in foetal and placental development in animal models. Here we compared mice engineered to be null for the placenta-specific P0 transcript (insulin-like growth factor-2-P0 KO) to mice with disruptions of all four insulin-like growth factor-2 transcripts, and therefore null for insulin-like growth factor-2 in both placenta and foetus (insulin-like growth factor-2-total KO). Both models lead to intrauterine growth restriction but dissociate between a situation where there is an imbalance between foetal demand and placental supply of nutrients (the insulin-like growth factor-2-P0 KO) and one where demand and supply is more balanced (the insulin-like growth factor-2-total KO). Increased reactivity to anxiety-provoking stimuli is manifested later in life only in those animals where there is a mismatch between placental supply and foetal demand for nutrients during gestation. Our findings further distinguish placental dysfunction from intrauterine growth restriction and reveal a role for the placenta in long-term programming of emotional behaviour.

  13. Plasmodium falciparum malaria elicits inflammatory responses that dysregulate placental amino acid transport.

    Directory of Open Access Journals (Sweden)

    Philippe Boeuf

    2013-02-01

    Full Text Available Placental malaria (PM can lead to poor neonatal outcomes, including low birthweight due to fetal growth restriction (FGR, especially when associated with local inflammation (intervillositis or IV. The pathogenesis of PM-associated FGR is largely unknown, but in idiopathic FGR, impaired transplacental amino acid transport, especially through the system A group of amino acid transporters, has been implicated. We hypothesized that PM-associated FGR could result from impairment of transplacental amino acid transport triggered by IV. In a cohort of Malawian women and their infants, the expression and activity of system A (measured by Na⁺-dependent ¹⁴C-MeAIB uptake were reduced in PM, especially when associated with IV, compared to uninfected placentas. In an in vitro model of PM with IV, placental cells exposed to monocyte/infected erythrocytes conditioned medium showed decreased system A activity. Amino acid concentrations analyzed by reversed phase ultra performance liquid chromatography in paired maternal and cord plasmas revealed specific alterations of amino acid transport by PM, especially with IV. Overall, our data suggest that the fetoplacental unit responds to PM by altering its placental amino acid transport to maintain adequate fetal growth. However, IV more profoundly compromises placental amino acid transport function, leading to FGR. Our study offers the first pathogenetic explanation for FGR in PM.

  14. The impact of cocaine and heroin on the placental transfer of methadone

    Directory of Open Access Journals (Sweden)

    Wenzinger Silvana

    2009-06-01

    Full Text Available Abstract Background Methadone is the therapeutic agent of choice for the treatment of opiate addiction in pregnancy. The co-consumption (heroin, cocaine which may influence the effects of methadone is frequent. Therefore, the impact of cocaine and heroin on the placental transfer of methadone and the placental tissue was investigated under in vitro conditions. Methods Placentae (n = 24 were ex-vivo perfused with medium (m (control, n = 6, m plus methadone (n = 6, m plus methadone and cocaine (n = 6 or m plus methadone and heroin (n = 6. Placental functionality parameters like antipyrine permeability, glucose consumption, lactate production, hormone production (hCG and leptin, microparticles release and the expression of P-glycoprotein were analysed. Results Methadone accumulated in placental tissue. Methadone alone decreased the transfer of antipyrine from 0.60 +/- 0.07 to 0.50 +/- 0.06 (fetal/maternal ratio, mean +/- SD, P Conclusion The combination of cocaine or heroin with methadone increase antipyrine permeability. Changes of MPs resemble findings seen in oxidative stress of syncytiotrophoblast.

  15. Human placental lactogen and intrauterine growth retardation.

    Science.gov (United States)

    Spellacy, W N; Buhi, W C; Birk, S A

    1976-04-01

    Serum human placental lactogen levels were measured after 36 weeks' gestation in 264 serum samples from 109 women with normal pregnancies and in 137 serum samples from 70 women with pregnancies complicated by fetal intrauterine growth retardation (IGR). The fetal and placental weights were significantly lower in the IGR groups while the maternal ages were not different. There was a significantly lower hPL value at each week from 36 to 41 (except for the 39th) in the IGR group. Sixty percent of the women with IGR had hPL values less than 6 mug/ml, and 18.6% were less than 4 mug/ml. It is suggested that a low serum hPL value obtained during the last month of pregnancy should alert the physician to the possibility of intrauterine problems, including IGR.

  16. Neurotrophins: Role in Placental Growth and Development.

    Science.gov (United States)

    Sahay, A S; Sundrani, D P; Joshi, S R

    2017-01-01

    Neurotrophins, a family of closely related proteins, were originally identified as growth factors for survival, development, and function of neurons in both the central and peripheral nervous systems. Subsequently, neurotrophins have been shown to have functions in immune and reproductive systems. Neurotrophins like nerve growth factor and brain-derived neurotrophic factor (BDNF) are known to play an important role during pregnancy in the process of placental angiogenesis and maturation. Several studies have demonstrated the presence of neurotrophins in the human placenta. The current chapter reviews studies demonstrating the role of neurotrophins during pregnancy particularly in placental development. This chapter also focuses on the regional changes in neurotrophins in the human placenta and its interactions with other growth factors. Future research is needed to understand the mechanisms through which neurotrophins influence the growth and development of the placenta and pregnancy outcome.

  17. Placentation in the Amazonian manatee (Trichechus inunguis)

    DEFF Research Database (Denmark)

    Carter, A M; Miglino, M A; Ambrosio, C E;

    2008-01-01

    Evidence from several sources supports a close phylogenetic relationship between elephants and sirenians. To explore whether this was reflected in similar placentation, we examined eight delivered placentae from the Amazonian manatee using light microscopy and immunohistochemistry. In addition......, the fetal placental circulation was described by scanning electron microscopy of vessel casts. The manatee placenta was zonary and endotheliochorial, like that of the elephant. The interhaemal barrier comprised maternal endothelium, cytotrophoblasts and fetal endothelium. We found columnar trophoblast...... beneath the chorionic plate and lining lacunae in this region, but there was no trace in the term placenta of haemophagous activity. The gross anatomy of the cord and fetal membranes was consistent with previous descriptions and included a four-chambered allantoic sac, as also found in the elephant...

  18. Preeclampsia, biomarkers, syncytiotrophoblast stress, and placental capacity.

    Science.gov (United States)

    Redman, Christopher W G; Staff, Anne Cathrine

    2015-10-01

    The maternal syndrome of preeclampsia is mediated by dysfunctional syncytiotrophoblast (STB). When this is stressed by uteroplacental malperfusion, its signaling to the mother changes, as part of a highly coordinated stress response. The STB signals are both proinflammatory and dysangiogenic such that the preeclamptic mother has a stronger vascular inflammatory response than normal, with an antiangiogenic bias. Angiogenic factors have limitations as preeclampsia biomarkers, especially for prediction and diagnosis of preeclampsia at term. However, if they are recognized as markers of STB stress, their physiological changes at term demonstrate that STB stress develops in all pregnancies. The biomarkers reveal that the duration of pregnancies is restricted by placental capacity, such that there is increasing placental dysfunction, at and beyond term. This capacity includes limitations imposed by the size of the uterus, the capacity of the uteroplacental circulation and, possibly, the supply of villous progenitor trophoblast cells. Limited placental capacity explains the increasing risks of postmaturity, including preeclampsia. Early-onset preeclampsia is predictable because STB stress and changes in its biomarkers are intrinsic to poor placentation, an early pregnancy pathology. Prediction of preeclampsia at term is not good because there is no early STB pathology. Moreover, biomarkers cannot accurately diagnose term preeclampsia against a background of universal STB dysfunction, which may or may not be clinically revealed before spontaneous or induced delivery. In this sense, postterm pregnancy is, at best, a pseudonormal state. However, the markers may prove useful in screening for women with more severe problems of postmaturity. Copyright © 2015 Elsevier Inc. All rights reserved.

  19. Placental lactogen levels in rhesus isoimmunization.

    Science.gov (United States)

    Ward, R H; Letchworth, A T; Niven, P A; Chard, T

    1974-03-02

    A prospective study of the plasma levels of human placental lactogen (HPL) in pregnancies complicated by rhesus isoimmunization showed that in mild and moderately affected cases the levels were normal, while in severely affected cases they were raised. Serial levels of HPL before the 26th week provide a valuable indication of fetal outcome, and we suggest that this estimation should be used routinely as an adjunct to other tests in the management of rhesus isoimmunization.

  20. Screening and analyzing genes associated with Amur tiger placental development.

    Science.gov (United States)

    Li, Q; Lu, T F; Liu, D; Hu, P F; Sun, B; Ma, J Z; Wang, W J; Wang, K F; Zhang, W X; Chen, J; Guan, W J; Ma, Y H; Zhang, M H

    2014-09-26

    The Amur tiger is a unique endangered species in the world, and thus, protection of its genetic resources is extremely important. In this study, an Amur tiger placenta cDNA library was constructed using the SMART cDNA Library Construction kit. A total of 508 colonies were sequenced, in which 205 (76%) genes were annotated and mapped to 74 KEGG pathways, including 29 metabolism, 29 genetic information processing, 4 environmental information processing, 7 cell motility, and 5 organismal system pathways. Additionally, PLAC8, PEG10 and IGF-II were identified after screening genes from the expressed sequence tags, and they were associated with placental development. These findings could lay the foundation for future functional genomic studies of the Amur tiger.

  1. Mono-2-ethylhexyl phthalate induces oxidative stress responses in human placental cells in vitro

    Energy Technology Data Exchange (ETDEWEB)

    Tetz, Lauren M., E-mail: ltetz@umich.edu [Department of Environmental Health Sciences, University of Michigan, 1415 Washington Heights, Ann Arbor, MI 48109-2029 (United States); Cheng, Adrienne A.; Korte, Cassandra S. [Department of Environmental Health Sciences, University of Michigan, 1415 Washington Heights, Ann Arbor, MI 48109-2029 (United States); Giese, Roger W.; Wang, Poguang [Department of Pharmaceutical Sciences, Northeastern University, 360 Huntingon Ave, Boston, MA 02115 (United States); Harris, Craig; Meeker, John D.; Loch-Caruso, Rita [Department of Environmental Health Sciences, University of Michigan, 1415 Washington Heights, Ann Arbor, MI 48109-2029 (United States)

    2013-04-01

    Di-2-ethylhexyl phthalate (DEHP) is an environmental contaminant commonly used as a plasticizer in polyvinyl chloride products. Exposure to DEHP has been linked to adverse pregnancy outcomes in humans including preterm birth, low birth-weight, and pregnancy loss. Although oxidative stress is linked to the pathology of adverse pregnancy outcomes, effects of DEHP metabolites, including the active metabolite, mono-2-ethylhexyl phthalate (MEHP), on oxidative stress responses in placental cells have not been previously evaluated. The objective of the current study is to identify MEHP-stimulated oxidative stress responses in human placental cells. We treated a human placental cell line, HTR-8/SVneo, with MEHP and then measured reactive oxygen species (ROS) generation using the dichlorofluorescein assay, oxidized thymine with mass-spectrometry, redox-sensitive gene expression with qRT-PCR, and apoptosis using a luminescence assay for caspase 3/7 activity. Treatment of HTR-8 cells with 180 μM MEHP increased ROS generation, oxidative DNA damage, and caspase 3/7 activity, and resulted in differential expression of redox-sensitive genes. Notably, 90 and 180 μM MEHP significantly induced mRNA expression of prostaglandin-endoperoxide synthase 2 (PTGS2), an enzyme important for synthesis of prostaglandins implicated in initiation of labor. The results from the present study are the first to demonstrate that MEHP stimulates oxidative stress responses in placental cells. Furthermore, the MEHP concentrations used were within an order of magnitude of the highest concentrations measured previously in human umbilical cord or maternal serum. The findings from the current study warrant future mechanistic studies of oxidative stress, apoptosis, and prostaglandins as molecular mediators of DEHP/MEHP-associated adverse pregnancy outcomes. - Highlights: ► MEHP increased reactive oxygen species, oxidative DNA damage, and caspase activity. ► MEHP induced expression of PTGS2, a gene

  2. Placentation in mammals once grouped as insectivores.

    Science.gov (United States)

    Carter, Anthony M; Enders, Allen C

    2010-01-01

    Interest in insectivoran grade mammals has been reawakened by taxonomic changes that place tenrecs and golden moles in a new order and separate hedgehogs from moles, shrews and solenodons. This survey of their placentation shows there is great variation even within families. As an example three subfamilies of tenrec have been examined. The interhemal region is cellular hemomonochorial in Echinops and Microgale but endotheliochorial in Micropotamogale. Golden moles, which are placed in the same order, have hemodichorial placentation. Many insectivores have complex arrangements for histotrophic nutrition involving columnar trophoblast cells. These range from areolae in moles through complexly folded hemophagous regions in tenrecs to the trophoblastic annulus in shrews. Of these placental characters, few offer support to current phylogenies. However, the case for placing hedgehogs and gymnures in a separate order (Erinaceomorpha) is bolstered by the presence of interstitial implantation, amniogenesis by cavitation, a hemochorial barrier and a prominent spongy zone; these features do not occur in shrews, moles or solenodons (Soricomorpha). Three insectivoran grade mammals deserve close attention as they have been selected for genome sequencing. One of these, the European hedgehog (Erinaceus europaeus), has not been studied with current methodology and renewed investigation of this or the closely related genus Atelerix should be a priority.

  3. PLACENTAL PATHOLOGY IN PREGNANCY INDUCED HYPERTENSION

    Directory of Open Access Journals (Sweden)

    Sreechithra

    2014-08-01

    Full Text Available BACKGROUND: Hypertensive disorders complicating pregnancy are common and form one of the deadly triad along with hemorrhage and infection, that results in a large number of maternal deaths and there of fetal deaths. Since all anabolites needed for foetal metabolism come from the mothers blood and foetal catabolites are passed back into the mothers circulation through the placenta, the examination of placenta gives a clear idea of what had happened with it, when it was in the mother, s womb and what is going to happen with the foetus in future. With this objective the present study was carried out. MATERIALS AND METHODS: Retrospective study was done for a period of 21 months from April1st 2008 to December 31st 2009..Fifty mothers with uncomplicated pregnancy (control group and 100 mothers (test group diagnosed as having pregnancy induced hypertension were selected from patients of our institution of the age range from 20-40 years, and parity –primi, para2 and 3.Placental morphometric parameters, gross and histopathological features were examined in both test and control groups. STATISTICAL ANALYSIS USED: Fishers exact test RESULTS: Placental morphometric parameters were significantly reduced in the control group. Acute atherosis, endothelial proliferation and fibrinoid necrosis were the significant histological findings noted in our study. CONCLUSION: Placental findings can be confirmatory of PIH, but its absence does not exclude the diseases. These findings will become more evident only when there is significant reduction in the uteroplacental bloodflow

  4. The placental mammal ancestor and the post-K-Pg radiation of placentals.

    Science.gov (United States)

    O'Leary, Maureen A; Bloch, Jonathan I; Flynn, John J; Gaudin, Timothy J; Giallombardo, Andres; Giannini, Norberto P; Goldberg, Suzann L; Kraatz, Brian P; Luo, Zhe-Xi; Meng, Jin; Ni, Xijun; Novacek, Michael J; Perini, Fernando A; Randall, Zachary S; Rougier, Guillermo W; Sargis, Eric J; Silcox, Mary T; Simmons, Nancy B; Spaulding, Michelle; Velazco, Paúl M; Weksler, Marcelo; Wible, John R; Cirranello, Andrea L

    2013-02-01

    To discover interordinal relationships of living and fossil placental mammals and the time of origin of placentals relative to the Cretaceous-Paleogene (K-Pg) boundary, we scored 4541 phenomic characters de novo for 86 fossil and living species. Combining these data with molecular sequences, we obtained a phylogenetic tree that, when calibrated with fossils, shows that crown clade Placentalia and placental orders originated after the K-Pg boundary. Many nodes discovered using molecular data are upheld, but phenomic signals overturn molecular signals to show Sundatheria (Dermoptera + Scandentia) as the sister taxon of Primates, a close link between Proboscidea (elephants) and Sirenia (sea cows), and the monophyly of echolocating Chiroptera (bats). Our tree suggests that Placentalia first split into Xenarthra and Epitheria; extinct New World species are the oldest members of Afrotheria.

  5. Rescue of placental phenotype in a mechanistic model of Beckwith-Wiedemann syndrome

    Directory of Open Access Journals (Sweden)

    Higgins Michael J

    2010-05-01

    Full Text Available Abstract Background Several imprinted genes have been implicated in the process of placentation. The distal region of mouse chromosome 7 (Chr 7 contains at least ten imprinted genes, several of which are expressed from the maternal homologue in the placenta. The corresponding paternal alleles of these genes are silenced in cis by an incompletely understood mechanism involving the formation of a repressive nuclear compartment mediated by the long non-coding RNA Kcnq1ot1 initiated from imprinting centre 2 (IC2. However, it is unknown whether some maternally expressed genes are silenced on the paternal homologue via a Kcnq1ot1-independent mechanism. We have previously reported that maternal inheritance of a large truncation of Chr7 encompassing the entire IC2-regulated domain (DelTel7 allele leads to embryonic lethality at mid-gestation accompanied by severe placental abnormalities. Kcnq1ot1 expression can be abolished on the paternal chromosome by deleting IC2 (IC2KO allele. When the IC2KO mutation is paternally inherited, epigenetic silencing is lost in the region and the DelTel7 lethality is rescued in compound heterozygotes, leading to viable DelTel7/IC2KO mice. Results Considering the important functions of several IC2-regulated genes in placentation, we set out to determine whether these DelTel7/IC2KO rescued conceptuses develop normal placentae. We report no abnormalities with respect to the architecture and vasculature of the DelTel7/IC2KO rescued placentae. Imprinted expression of several of the IC2-regulated genes critical to placentation is also faithfully recapitulated in DelTel7/IC2KO placentae. Conclusion Taken together, our results demonstrate that all the distal chromosome 7 imprinted genes implicated in placental function are silenced by IC2 and Kcnq1ot1 on the paternal allele. Furthermore, our results demonstrate that the methylated maternal IC2 is not required for the regulation of nearby genes. The results show the potential for

  6. Elevated placental adenosine signaling contributes to the pathogenesis of preeclampsia.

    Science.gov (United States)

    Iriyama, Takayuki; Sun, Kaiqi; Parchim, Nicholas F; Li, Jessica; Zhao, Cheng; Song, Anren; Hart, Laura A; Blackwell, Sean C; Sibai, Baha M; Chan, Lee-Nien L; Chan, Teh-Sheng; Hicks, M John; Blackburn, Michael R; Kellems, Rodney E; Xia, Yang

    2015-02-24

    Preeclampsia is a prevalent hypertensive disorder of pregnancy and a leading cause of maternal and neonatal morbidity and mortality worldwide. This pathogenic condition is speculated to be caused by placental abnormalities that contribute to the maternal syndrome. However, the specific factors and signaling pathways that lead to impaired placentas and maternal disease development remain elusive. Using 2 independent animal models of preeclampsia (genetically engineered pregnant mice with elevated adenosine exclusively in placentas and a pathogenic autoantibody-induced preeclampsia mouse model), we demonstrated that chronically elevated placental adenosine was sufficient to induce hallmark features of preeclampsia, including hypertension, proteinuria, small fetuses, and impaired placental vasculature. Genetic and pharmacological approaches revealed that elevated placental adenosine coupled with excessive A₂B adenosine receptor (ADORA2B) signaling contributed to the development of these features of preeclampsia. Mechanistically, we provided both human and mouse evidence that elevated placental CD73 is a key enzyme causing increased placental adenosine, thereby contributing to preeclampsia. We determined that elevated placental adenosine signaling is a previously unrecognized pathogenic factor for preeclampsia. Moreover, our findings revealed the molecular basis underlying the elevation of placental adenosine and the detrimental role of excess placental adenosine in the pathophysiology of preeclampsia, and thereby, we highlight novel therapeutic targets. © 2014 American Heart Association, Inc.

  7. Placental localization by scanning with indium 113m

    Energy Technology Data Exchange (ETDEWEB)

    Choi, Seung Wook; Choe, Yong Kyu; Choi, Byung Sook [Yonsei University College of Medicine, Seoul (Korea, Republic of)

    1972-09-15

    The application of radioactive tracers for placental localization has been introduced as the worthwhile diagnostic method in placenta previa. Recently {sup 113m}In has been applied as the broad spectrum agent for the visualization of various organs. The advantage of {sup 113m}In are a short half-life with 1.7 hours and no beta particle emission. During the period from May 1970 to August 1971, the placental scanning with {sup 113m}In was carried out at Yonsei Medical Center on 19 cases of Korean pregnant females who had painless vaginal bleeding with suspicious placenta previa or other placental lesions, clinically. Followings are the results of placental scanning with Indium-113m. 1) Eight cases out of 19 cases were suggested as placenta previa and the remaining 11 cases were turned out to be normal placental location. 2) Among these 8 case of positive scanning, placenta previa totalis was 6 cases, placental previa partialis was 1 case and placenta previa marginalis was also 1 case. 3) Among 11 cases of normal placental localization, right side placenta was 7 cases and left side, 4 cases. The placental scanning with Indium-113m is thought to be one of the simple, safe and rapid method with high accuracy for clinical diagnosis of the placenta previa and placental localization.

  8. Placental Abnormalities and Preeclampsia in Trisomy 13 Pregnancies

    Directory of Open Access Journals (Sweden)

    Chih-Ping Chen

    2009-03-01

    Full Text Available Women who are carrying a trisomy 13 fetus are prone to have an abnormal placenta as well as to develop preeclampsia in the second and third trimesters. This article provides a comprehensive review of placental abnormalities, such as small placental volume, reduced placental vascularization, a partial molar appearance of the placenta and placental mesenchymal dysplasia, and preeclampsia associated with trisomy 13 pregnancies. The candidate preeclampsia-causing genes on chromosome 13, such as sFlt1, COL4A2 and periostin, are discussed.

  9. Cesarean Delivery for a Life-threatening Preterm Placental Abruption

    Science.gov (United States)

    Okafor, II; Ugwu, EO

    2015-01-01

    Placental abruption is one of the major life-threatening obstetric conditions. The fetomaternal outcome of a severe placental abruption depends largely on prompt maternal resuscitation and delivery. A case of severe preterm placental abruption with intrauterine fetal death. Following a failed induction of labor with a deteriorating maternal condition despite resuscitation, emergency cesarean delivery was offered with good maternal outcome. Cesarean delivery could avert further disease progression and possible maternal death in cases of severe preterm placental abruption where vaginal delivery is not imminent. However, further studies are necessary before this could be recommended for routine clinical practice. PMID:27057388

  10. Clinical development of placental malaria vaccines and immunoassays harmonization

    DEFF Research Database (Denmark)

    Chêne, Arnaud; Houard, Sophie; Nielsen, Morten A;

    2016-01-01

    Placental malaria caused by Plasmodium falciparum infection constitutes a major health problem manifesting as severe disease and anaemia in the mother, impaired fetal development, low birth weight or spontaneous abortion. Prevention of placental malaria currently relies on two key strategies...... that are losing efficacy due to spread of resistance: long-lasting insecticide-treated nets and intermittent preventive treatment during pregnancy. A placental malaria vaccine would be an attractive, cost-effective complement to the existing control tools. Two placental malaria vaccine candidates are currently...

  11. Circulating placental proteins in pregnancies complicated by RH isoimmunization.

    Science.gov (United States)

    Lee, J N; Huang, S C; Ouyang, P C; Chard, T

    1984-07-01

    Nine pregnant women with Rh isoimmunization who delivered newborns with hydrops fetalis were studied. The placental proteins, pregnancy specific beta 1-glycoprotein (SP1), human placental lactogen, and placental protein 5 (PP5) were measured in maternal serum by radioimmunoassays. The results indicate that both the serum human placental lactogen and PP5 levels were significantly higher than those observed in normal pregnancy. The strikingly higher circulating PP5 levels found in all nine patients with Rh isoimmunization studied suggests that serum PP5 may be specifically elevated in pregnant patients with Rh isoimmunization and hydrops fetalis.

  12. Prevention of Defective Placentation and Pregnancy Loss by Blocking Innate Immune Pathways in a Syngeneic Model of Placental Insufficiency.

    Science.gov (United States)

    Gelber, Shari E; Brent, Elyssa; Redecha, Patricia; Perino, Giorgio; Tomlinson, Stephen; Davisson, Robin L; Salmon, Jane E

    2015-08-01

    Defective placentation and subsequent placental insufficiency lead to maternal and fetal adverse pregnancy outcome, but their pathologic mechanisms are unclear, and treatment remains elusive. The mildly hypertensive BPH/5 mouse recapitulates many features of human adverse pregnancy outcome, with pregnancies characterized by fetal loss, growth restriction, abnormal placental development, and defects in maternal decidual arteries. Using this model, we show that recruitment of neutrophils triggered by complement activation at the maternal/fetal interface leads to elevation in local TNF-α levels, reduction of the essential angiogenic factor vascular endothelial growth factor, and, ultimately, abnormal placentation and fetal death. Blockade of complement with inhibitors specifically targeted to sites of complement activation, depletion of neutrophils, or blockade of TNF-α improves spiral artery remodeling and rescues pregnancies. These data underscore the importance of innate immune system activation in the pathogenesis of placental insufficiency and identify novel methods for treatment of pregnancy loss mediated by abnormal placentation.

  13. Altered placental DNA methylation patterns associated with maternal smoking: current perspectives

    Directory of Open Access Journals (Sweden)

    Maccani JZ

    2015-05-01

    Full Text Available Jennifer ZJ Maccani, Matthew A Maccani Penn State Tobacco Center of Regulatory Science, College of Medicine, Department of Public Health Sciences, Hershey, PA, USA Abstract: The developmental origins of health and disease hypothesis states that adverse early life exposures can have lasting, detrimental effects on lifelong health. Exposure to maternal cigarette smoking during pregnancy is associated with morbidity and mortality in offspring, including increased risks for miscarriage, stillbirth, low birth weight, preterm birth, asthma, obesity, altered neurobehavior, and other conditions. Maternal cigarette smoking during pregnancy interferes with placental growth and functioning, and it has been proposed that this may occur through the disruption of normal and necessary placental epigenetic patterns. Epigenome-wide association studies have identified a number of differentially methylated placental genes that are associated with maternal smoking during pregnancy, including RUNX3, PURA, GTF2H2, GCA, GPR135, and HKR1. The placental methylation status of RUNX3 and NR3C1 has also been linked to adverse infant outcomes, including preterm birth and low birth weight, respectively. Candidate gene analyses have also found maternal smoking-associated placental methylation differences in the NR3C1, CYP1A1, HTR2A, and HSD11B2 genes, as well as in the repetitive elements LINE-1 and AluYb8. The differential methylation patterns of several genes have been confirmed to also exhibit altered gene expression patterns, including CYP1A1, CYP19A1, NR3C1, and HTR2A. Placental methylation patterns associated with maternal smoking during pregnancy may be largely gene-specific and tissue-specific and, to a lesser degree, involve global changes. It is important for future research to investigate the mechanistic roles that these differentially methylated genes may play in mediating the association between maternal smoking during pregnancy and disease in later life, as well

  14. Placental and cord blood brain derived neurotrophic factor levels are decreased in nondiabetic macrosomia.

    Science.gov (United States)

    Cai, Qian-Ying; Zhang, Heng-Xin; Wang, Chen-Chen; Sun, Hao; Sun, Shu-Qiang; Wang, Yu-Huan; Yan, Hong-Tao; Yang, Xin-Jun

    2017-08-01

    To measure levels of placental brain derived neurotrophic factor (BDNF) gene expression and umbilical cord blood BDNF in neonates with nondiabetic macrosomia and determine associations between these levels and macrosomia. This case-control study included 58 nondiabetic macrosomic and 59 normal birth weight mother-infant pairs. Data were collected from interviews and our hospital's database. BDNF gene expression was quantified in placental tissues using quantitative real-time polymerase chain reaction (n = 117). Umbilical cord blood BDNF levels were measured by enzyme-linked immunosorbent assay (n = 90). Multivariate logistic regression models were used to evaluate associations between BDNF levels and macrosomia. Placental BDNF gene expression (P = 0.026) and cord blood BDNF (P = 0.008) were lower in neonates with nondiabetic macrosomia than in normal birth weight controls. Cord blood BDNF was significantly lower in vaginally delivered macrosomic neonates than vaginally delivered controls (P = 0.014), but cord BDNF did not differ between vaginal and cesarean section delivery modes in macrosomic neonates. Cord blood BDNF was positively associated with gestational age in control neonates (r = 0.496, P macrosomia (adjusted odds ratio 0.992; 95% confidence interval 0.986-0.998). Both placental BDNF gene expression and cord blood BDNF were downregulated in neonates with nondiabetic macrosomia compared with normal birth weight neonates. Cord BDNF may partly derive from BDNF secreted by the placenta. Higher cord plasma BDNF levels protected against nondiabetic macrosomia.

  15. A role for GPR55 in human placental venous endothelial cells

    OpenAIRE

    Kremshofer, Julia; Siwetz, Monika; Berghold, Veronika M.; Lang, Ingrid; Huppertz, Berthold; Gauster, Martin

    2015-01-01

    Endocannabinoids and their G protein-coupled receptors have been suggested to play a key role in human pregnancy, by regulating important aspects such as implantation, decidualization, placentation and labour. G protein-coupled receptor 55 (GPR55) was previously postulated to be another cannabinoid receptor, since specific cannabinoids were shown to act independently of the classical cannabinoid receptors CB1 or CB2. Current knowledge about GPR55 expression and function in human placenta is v...

  16. Successful treatment of sepsis-induced disseminated intravascular coagulation in a patient with idiopathic thrombocytopenic purpura using recombinant human soluble thrombomodulin.

    Science.gov (United States)

    Koga, Tomohiro; Inoue, Daisuke; Okada, Akitomo; Aramaki, Toshiyuki; Yamasaki, Satoshi; Nakashima, Munetoshi; Kawakami, Atsushi; Eguchi, Katsumi

    2011-12-01

    Disseminated intravascular coagulation (DIC) may complicate a variety of disorders that contribute to mortality, particularly those related to bleeding. It is therefore very difficult to manage DIC in patients with known bleeding disorders. We treated a 62-year-old woman with idiopathic thrombocytopenic purpura (ITP) complicated with sepsis-induced DIC. She had been diagnosed with ITP 8 months prior to admission. Laboratory tests showed an elevation of d-dimer and endotoxin, while pyelonephritis was shown by abdominal computed tomography. Escherichia coli was detected by blood culture. Based on these findings, the patient was diagnosed with sepsis-induced DIC due to urinary tract infection. Thrombocytopenia was refractory despite the use of antibiotics and platelet transfusion, but it was promptly improved in response to recombinant human soluble thrombomodulin (rTM). We suggest that rTM provides a new therapeutic strategy for DIC patients with high hemorrhagic risk.

  17. Placental-mediated increased cytokine response to lipopolysaccharides: a potential mechanism for enhanced inflammation susceptibility of the preterm fetus

    Directory of Open Access Journals (Sweden)

    Ross MG

    2012-07-01

    Full Text Available Julie L Boles,1 Michael G Ross,1 Ron Beloosesky,2 Mina Desai,1 Louiza Belkacemi11Department of Obstetrics and Gynecology, Harbor-UCLA Medical Center, Los Angeles Biomedical Research Institute at Harbor-UCLA, David Geffen School of Medicine at UCLA, University of California, Los Angeles, Torrance, CA, USA; 2Department of Obstetrics and Gynecology, Rambam Medical Center, Haifa, IsraelBackground: Cerebral palsy is a nonprogressive motor impairment syndrome that has no effective cure. The etiology of most cases of cerebral palsy remains unknown; however, recent epidemiologic data have demonstrated an association between fetal neurologic injury and infection/inflammation. Maternal infection/inflammation may be associated with the induction of placental cytokines that could result in increased fetal proinflammatory cytokine exposure, and development of neonatal neurologic injury. Therefore, we sought to explore the mechanism by which maternal infection may produce a placental inflammatory response. We specifically examined rat placental cytokine production and activation of the Toll-like receptor 4 (TLR4 pathway in response to lipopolysaccharide exposure at preterm and near-term gestational ages.Methods: Preterm (e16 or near-term (e20 placental explants from pregnant rats were treated with 0, 1, or 10 µg/mL lipopolysaccharide. Explant integrity was assessed by lactate dehydrogenase assay. Interleukin-6 and tumor necrosis alpha levels were determined using enzyme-linked immunosorbent assay kits. TLR4 and phosphorylated nuclear factor kappa light chain enhancer of activated B cells (NFκB protein expression levels were determined by Western blot analysis.Results: At both e16 and e20, lactate dehydrogenase levels were unchanged by treatment with lipopolysaccharide. After exposure to lipopolysaccharide, the release of interleukin-6 and tumor necrosis alpha from e16 placental explants increased by 4-fold and 8–9-fold, respectively (P < 0.05 versus

  18. Relationship of hepatitis B virus infection of placental barrier and hepatitis B virus intra-uterine transmission mechanism

    Institute of Scientific and Technical Information of China (English)

    Han Bai; Lin Zhang; Li Ma; Xiao-Guang Dou; Guo-He Feng; Gui-Zhen Zhao

    2007-01-01

    AIM: To explore the mechanism of intra-uterine transmission, the HBV infection status of placental tissue and in vitro cultured placental trophoblastic cells was tested through in vivo and in vitro experiments.METHODS: A variety of methods, such as ELISA, RTPCR, IHC staining and immunofluorescent staining were employed to test the HBV marker positive pregnant women's placenta and in vitro cultured placental trophoblastic cells.RESULTS: The HBV DNA levels in pregnant women's serum and fetal cord blood were correlated. For those cord blood samples positive for HBV DNA, their maternal blood levels of HBV DNA were at a high level. The HBsAg IHC staining positive cells could be seen in the placental tissues and the presence of HBV DNA detected. After coincubating the trophoblastic cells and HBV DNA positive serum in vitro, the expressions of both HBsAg and HBV DNA could be detected.CONCLUSION: The mechanism of HBV intra-uterine infection may be due to that HBV breaches the placental barrier and infects the fetus.

  19. Pigment epithelium-derived factor (PEDF): a novel trophoblast-derived factor limiting feto-placental angiogenesis in late pregnancy.

    Science.gov (United States)

    Loegl, Jelena; Nussbaumer, Erika; Hiden, Ursula; Majali-Martinez, Alejandro; Ghaffari-Tabrizi-Wizy, Nassim; Cvitic, Silvija; Lang, Ingrid; Desoye, Gernot; Huppertz, Berthold

    2016-07-01

    The rapidly expanding feto-placental vasculature needs tight control by paracrine and endocrine mechanisms. Here, we focused on paracrine influence by trophoblast, the placental epithelium. We aimed to identify differences in regulation of feto-placental angiogenesis in early versus late pregnancy. To this end, the effect of conditioned media (CM) from early and late pregnancy human trophoblast was tested on network formation, migration and proliferation of human feto-placental endothelial cells. Only CM of late pregnancy trophoblast reduced network formation and migration. Screening of trophoblast transcriptome for anti-angiogenic candidates identified pigment epithelium-derived factor (PEDF) with higher expression and protein secretion in late pregnancy trophoblast. Addition of a PEDF-neutralizing antibody restored the anti-angiogenic effect of CM from late pregnancy trophoblast. Notably, human recombinant PEDF reduced network formation only in combination with VEGF. Also in the CAM assay, the combination of PEDF with VEGF reduced branching of vessels below control levels. Analysis of phosphorylation of ERK1/2 and FAK, two key players in VEGF-induced proliferation and migration, revealed that PEDF altered VEGF signaling, while PEDF alone did not affect phosphorylation of ERK1/2 and FAK. These data suggest that the trophoblast-derived anti-angiogenic molecule PEDF is involved in restricting growth and expansion of the feto-placental endothelium predominantly in late pregnancy and targets to modulate the intracellular effect of VEGF.

  20. Elevated expression levels of matrix metalloproteinase-9 in placental villi and tissue inhibitor of metalloproteinase-2 in decidua are associated with prolonged bleeding after mifepristone-misoprostol medical abortion.

    Science.gov (United States)

    Zhuang, Yaling; Qian, Zhida; Huang, Lili

    2014-01-01

    To determine whether the expression levels of matrix metalloproteinases 2 and 9 (MMP-2 and -9) and tissue inhibitors of metalloproteinases 1 and 2 (TIMP-1 and -2) in the villi and the decidua are associated with prolonged bleeding after medical abortion. Case-controlled study. University hospital. Mifepristone-misoprostol medical abortion patients were divided into two groups (20 women each) based on the length of time (>14 or ≤14 days) of bleeding after the abortion. Discharged villi and deciduas were collected. The expression levels of MMP-2 and -9 and TIMP-1 and -2 in the villi and deciduas were assessed with semiquantitative immunohistochemistry. The median semiquantitative immunohistochemistry staining index (SI) scores for MMP-9 expression in the villi were elevated in the bleeding group compared with the control group (median SI scores 0.31 and 0.03, respectively). TIMP-2 expression was elevated in the decidua in the bleeding group compared with the control group (median SI scores 1.00 and 0.20, respectively). No significant differences were observed between the two groups in the expression levels of MMP-2 in the villi or of MMP-2, MMP-9, or TIMP-1 or of the ratios of MMP-9/TIMP-1 or MMP-2/TIMP-2 in the decidua. Elevated expression levels of MMP-9 in the villi and of TIMP-2 in the decidua were associated with prolonged bleeding after medical abortion. Copyright © 2014. Published by Elsevier Inc.

  1. Placental immunopathology in the FIV-infected cat: a role for inflammation in compromised pregnancy?

    Science.gov (United States)

    Coats, Karen S; Boudreaux, Crystal E; Clay, Brittany T; Lockett, Nikki N; Scott, Veronica L

    2010-03-15

    In utero transmission of feline immunodeficiency virus (FIV) occurs frequently in queens experimentally infected with FIV-B-2542 and other FIV isolates. Fetal infection has been detected as early as 3-4 weeks gestation, and the incidence of fetal infection increases with progressing gestation. Reproductive failure occurs commonly, including fetal resorptions and developmentally-arrested fetuses, demonstrating that fetal demise occurs early in gestation. Precise, temporal immunomodulation within the placenta is essential for successful pregnancy. Placental Th1 and Th2 cytokines must be appropriately balanced, typically favoring Th2 cytokines at the maternal-fetal interface. Abnormal inflammatory cytokine expression often accompanies miscarriage. Regulatory T cells (Tregs) play an essential role in maternal tolerance of the semi-allogeneic fetus by suppressing inflammation. We are using the FIV-infected cat to examine the relationship between lentivirus-induced placental immunopathology and reproductive outcome. Using TaqMan real time reverse transcriptase (RT)-PCR, we measured relative expression of key immunomodulators in the placentas of FIV-B-2542-infected and control cats, including placentas from both viable and nonviable pregnancies. Our data associate significantly-increased expression of inflammatory cytokines with failed pregnancies, identify Treg markers in the placentas, and provide preliminary evidence that Tregs or other cells bearing similar activation markers may be involved in pregnancy maintenance. Our data suggest that placental inflammation in the FIV-infected cat may compromise pregnancy.

  2. Adhesion of Plasmodium falciparum infected erythrocytes in ex vivo perfused placental tissue

    DEFF Research Database (Denmark)

    Pehrson, Caroline; Mathiesen, Line; Heno, Kristine K;

    2016-01-01

    expressing VAR2CSA accumulated in perfused placental tissue whereas the EPCR binding and the transgenic parasite did not. Soluble CSA and antibodies specific against VAR2CSA inhibited binding of infected erythrocytes. CONCLUSION: The ex vivo model provides a novel way of studying receptor-ligand interactions...

  3. Differential induction of functional IgG using the Plasmodium falciparum placental malaria vaccine candidate VAR2CSA

    DEFF Research Database (Denmark)

    Pinto, Vera V; Ditlev, Sisse B; Jensen, Kamilla E

    2011-01-01

    In Plasmodium falciparum malaria endemic areas placental malaria (PM) is an important complication of malaria. The recurrence of malaria in primigravidae women irrespective of acquired protection during childhood is caused by the interaction between the parasite-expressed VAR2CSA antigen...

  4. Plasma concentrations and placental immunostaining of interleukin-10 and tumornecrosis factor-α as predictors of alterations in the embryo-fetal organism and the placental development of diabetic rats

    Directory of Open Access Journals (Sweden)

    Y.K. Sinzato

    2011-03-01

    Full Text Available Interleukin-10 (IL-10 appears to be the key cytokine for the maintenance of pregnancy and inhibits the secretion of inflammatory cytokines such as tumor necrosis factor-α (TNF-α. However, there are no studies evaluating the profile of these cytokines in diabetic rat models. Thus, our aim was to analyze IL-10 and TNF-α immunostaining in placental tissue and their respective concentrations in maternal plasma during pregnancy in diabetic rats in order to determine whether these cytokines can be used as predictors of alterations in the embryo-fetal organism and in placental development. These parameters were evaluated in non-diabetic (control; N = 15 and Wistar rats with streptozotocin (STZ-induced diabetes (N = 15. At term, the dams (100 days of life were killed under anesthesia and plasma and placental samples were collected for IL-10 and TNF-α determinations by ELISA and immunohistochemistry, respectively. The reproductive performance was analyzed. Plasma IL-10 concentrations were reduced in STZ rats compared to controls (7.6 ± 4.5 vs 20.9 ± 8.1 pg/mL. The placental scores of immunostaining intensity did not differ between groups (P > 0.05. Prevalence analysis showed that the IL-10 expression followed TNF-α expression, showing a balance between them. STZ rats also presented impaired reproductive performance and reduced plasma IL-10 levels related to damage during early embryonic development. However, the increased placental IL-10 as a compensatory mechanism for the deficit of maternal regulation permitted embryo development. Therefore, the data suggest that IL-10 can be used as a predictor of changes in the embryo-fetal organism and in placental development in pregnant diabetic rats.

  5. Placental lipases in pregnancies complicated by gestational diabetes mellitus (GDM.

    Directory of Open Access Journals (Sweden)

    Helen L Barrett

    Full Text Available Infants of women with gestational diabetes mellitus (GDM are more likely to be born large for gestational age with a higher percentage body fat. Elevated maternal lipids may contribute to this. Placental lipases such as lipoprotein lipase (LPL, endothelial lipase (EL and hormone sensitive lipase (HSL are involved in transferring lipids from mother to fetus. Previous studies of expression of these lipases in placentae in women with diabetes in pregnancy have reported divergent results. Intracellular lipases such as adipose triglyceride lipase (ATGL, and HSL are central to lipid droplet metabolism. The activities of these lipases are both influenced by Perilipin 1, and ATGL is also activated by a co-factor comparative gene identification-58 (CGI-58 and inhibited by G0/G1 switch gene 2 (GS02. None of these modifying factors or ATGL have been examined previously in placenta. The purpose of this study was therefore to examine the expression of ATGL, HSL, LPL, EL, as well as Perilipin 1, GS02 and CGI-58 in term pregnancies complicated by GDM. mRNA and protein expression of the lipases were measured in placentae from 17 women with GDM and 17 normoglycaemic pregnancies, matched for maternal BMI and gestational age of delivery. ATGL mRNA expression was increased and HSL mRNA expression reduced in placentae from GDM although there was no differences in protein expression of any of the lipases. All lipases were localised to trophoblasts and endothelial cells. The expression of Perilipin 1 and CGI-58 mRNA was increased and GS02 not altered in GDM. These results suggest that there is no difference in expression in these four lipases between GDM and normoglycaemic placentae, and therefore altered lipid transfer via these lipases does not contribute to large for gestational age in infants of women with GDM.

  6. Cross-talk between cAMP and MAPK pathways in HSD11B2 induction by hCG in placental trophoblasts.

    Directory of Open Access Journals (Sweden)

    Qun Shu

    Full Text Available Overexposure of the fetus to glucocorticoids in gestation is detrimental to fetal development. The passage of maternal glucocorticoids into the fetal circulation is governed by 11beta-Hydroxysteroid Dehydrogenase Type 2 (HSD11B2 in the placental syncytiotrophoblasts. Human chorionic gonadotropin (hCG plays an important role in maintaining placental HSD11B2 expression via activation of the cAMP pathway. In this study, we investigated the relationship between the activation of the cAMP pathway by hCG and subsequent phosphorylation of extracellular signal-regulated kinase1/2 (ERK1/2 or p38 mitogen-activated protein kinase (MAPK pathways in the regulation of placental HSD11B2 expression in human placental syncytiotrophoblasts. We found that treatment of the placental syncytiotrophoblasts with either hCG or dibutyl cAMP (dbcAMP could promote the phosphorylation of p38 and ERK1/2. Inhibition of p38 MAPK with SB203580 not only reduced the basal HSD11B2 mRNA and protein levels but also attenuated HSD11B2 levels induced by either hCG or dbcAMP. By contrast, inhibition of ERK1/2 with PD98059 increased the basal mRNA and protein levels of HSD11B2 and had no effect on HSD11B2 mRNA and protein levels induced by either hCG or dbcAMP. These data suggest that p38 MAPK is involved in both basal and hCG/cAMP-induced expression of HSD11B2, and ERK1/2 may play a role opposite to p38 MAPK at least in the basal expression of HSD11B2 in human placental syncytiotrophoblasts and that there is complicated cross-talk between hCG/cAMP and MAPK cascades in the regulation of placental HSD11B2 expression.

  7. The placental exposome: Placental determinants of fetal adiposity and postnatal body composition

    NARCIS (Netherlands)

    R.M. Lewis (R.); H. Demmelmair (Hans); R. Gaillard (Romy); N. Godfrey; S. Hauguel-De Mouzon (S.); B. Huppertz (B.); E. Larque (E.); R. Saffery (R.); M.E. Symonds (M.); G. Desoye (G.)

    2013-01-01

    textabstractOffspring of obese and diabetic mothers are at increased risk of being born with excess adiposity as a consequence of their intrauterine environment. Excessive fetal fat accretion reflects additional placental nutrient transfer, suggesting an effect of the maternal environment on

  8. Prenatal endotoxemia and placental drug transport in the mouse: placental size-specific effects.

    Directory of Open Access Journals (Sweden)

    Enrrico Bloise

    Full Text Available Lipopolysaccharide (LPS in high doses inhibits placental multidrug resistance P-glycoprotein (P-gp--Abcb1a/b and breast cancer resistance protein (BCRP--Abcg2. This potentially impairs fetal protection against harmful factors in the maternal circulation. However, it is unknown whether LPS exposure, at doses that mimic sub-lethal clinical infection, alters placental multidrug resistance. We hypothesized that sub-lethal (fetal LPS exposure reduces placental P-gp activity. Acute LPS (n = 19;150 µg/kg; ip or vehicle (n = 19 were given to C57BL/6 mice at E15.5 and E17.5. Placentas and fetal-units were collected 4 and 24 h following injection. Chronic LPS (n = 6; 5 µg/kg/day; ip or vehicle (n = 5 were administered from E11.5-15.5 and tissues were collected 4 h after final treatment. P-gp activity was assessed by [³H]digoxin accumulation. Placental Abcb1a/b, Abcg2, interleukin-6 (Il-6, Tnf-α, Il-10 and toll-like receptor-4 (Tlr-4 mRNA were measured by qPCR. Maternal plasma IL-6 was determined. At E15.5, maternal IL-6 was elevated 4 h after single (p<0.001 and chronic (p<0.05 LPS, but levels had returned to baseline by 24 h. Placental Il-6 mRNA was also increased after acute and chronic LPS treatments (p<0.05, whereas Abcb1a/b and Abcg2 mRNA were unaffected. However, fetal [³H]digoxin accumulation was increased (p<0.05 4 h after acute LPS, and maternal [³H]digoxin myocardial accumulation was increased (p<0.05 in mice exposed to chronic LPS treatments. There was a negative correlation between fetal [³H]digoxin accumulation and placental size (p<0.0001. Acute and chronic sub-lethal LPS exposure resulted in a robust inflammatory response in the maternal systemic circulation and placenta. Acute infection decreased placental P-gp activity in a time- and gestational age-dependent manner. Chronic LPS decreased P-gp activity in the maternal myocardium and there was a trend for fetuses with smaller placentas to accumulate more P

  9. Placental glucose dehydrogenase polymorphism in Koreans.

    Science.gov (United States)

    Kim, Y J; Paik, S G; Park, H Y

    1994-12-01

    The genetic polymorphism of placental glucose dehydrogenase (GDH) was investigated in 300 Korean placentae using horizontal starch gel electrophoresis. The allele frequencies for GDH1, GDH2 and GDH3 were 0.537, 0.440 and 0.005, respectively, which were similar to those in Japanese. We also observed an anodal allele which was similar to the GDH4 originally reported in Chinese populations at a low frequency of 0.015. An additional new cathodal allele (named GDH6) was observed in the present study with a very low frequency of 0.003.

  10. Hans Strahl's pioneering studies in comparative placentation

    DEFF Research Database (Denmark)

    Carter, Anthony Michael; Mess, A

    2010-01-01

    and relationship to maternal tissues. This greatly influenced the work of Otto Grosser, who became better known in part because his work was more accessible to other scientists and clinicians. Strahl described the development of the fetal membranes across a broad range of mammalian orders extending his...... observations beyond parturition to the post partum involution of the uterus. He paid close attention to structures designed for histotrophic nutrition including the areolae of moles, haemophagous organs of carnivores and tenrecs and chorionic vesicles of lemurs and lorises. We here provide a summary of some...... of the most important findings made by Strahl including work on placentation in carnivores and higher primates that remains unsurpassed....

  11. Placentation in mammals once grouped as insectivores

    DEFF Research Database (Denmark)

    Carter, Anthony; Enders, Allen

    2009-01-01

    Interest in insectivoran grade mammals has been reawakened by taxonomic changes that place tenrecs and golden moles in a new order and separate hedgehogs from moles, shrews and solenodons. This survey of their placentation shows there is great variation even within families. As an example three...... in a separate order (Erinaceomorpha) is bolstered by the presence of interstitial implantation, amniogenesis by cavitation, a hemochorial barrier and a prominent spongy zone; these features do not occur in shrews, moles or solenodons (Soricomorpha). Three insectivoran grade mammals deserve close attention...

  12. Placental characteristics in women with polycystic ovary syndrome

    NARCIS (Netherlands)

    Koster, Maria P H; de Wilde, Marlieke A; Veltman-Verhulst, Susanne M; Houben, ML; Nikkels, Peter G J; van Rijn, Bas B; Fauser, Bart C J M

    2015-01-01

    STUDY QUESTION: Are macroscopic and microscopic placental characteristics in a heterogeneous group of women diagnosed with polycystic ovary syndrome (PCOS) different from those of a low-risk general population? SUMMARY ANSWER: Women with PCOS have significantly different microscopic placental charac

  13. Placental vascular responses are dependent on surrounding tissue

    DEFF Research Database (Denmark)

    Brøgger, Torbjørn Halle

    Background: The placenta is the base for the exchange of nutrients, oxygen and waste products for the fetus. The placental vessels hold a crucial role in regulation the blood flow, and a compromised placental function leads to serious complications such as fetal death or growth retardation. An in...

  14. Placental vascular responses are dependent on surrounding tissue

    DEFF Research Database (Denmark)

    Brøgger, Torbjørn Halle

    Background. The placenta is the base for the exchange of nutrients, oxygen and waste products for the fetus.The placental vessels hold a crucial role in regulation the blood flow, and a compromised placental function leads to serious complications such as fetal death or growth retardation...

  15. Placental transport and in vitro effects of Bisphenol A

    DEFF Research Database (Denmark)

    Mørck, Thit J; Sorda, Giuseppina; Bechi, Nicoletta

    2010-01-01

    Bisphenol A (BPA), an estrogen-like chemical, leaches from consumer products potentially causing human exposure. To examine the effects of BPA exposure during pregnancy, we performed studies using the BeWo trophoblast cell line, placental explant cultures, placental perfusions and skin diffusion...

  16. Of mice and women: rodent models of placental malaria

    DEFF Research Database (Denmark)

    Hviid, Lars; Marinho, Claudio R F; Staalsoe, Trine

    2010-01-01

    Pregnant women are at increased malaria risk. The infections are characterized by placental accumulation of infected erythrocytes (IEs) with adverse consequences for mother and baby. Placental IE sequestration in the intervillous space is mediated by variant surface antigens (VSAs) selectively ex...

  17. Arrangement of collagen fibers in human placental stem villi

    NARCIS (Netherlands)

    Sati, Leyla; Demir, Ayse Yasemin; Sarikcioglu, Levent; Demir, Ramazan

    2008-01-01

    The aim of the study was to investigate the arrangements and related localization patterns of different collagen types in the stroma of placental stem villi by immunohistochemistry and electron microscopy. A total of 14 normal human term placental tissue samples were studied. Immunohistochemistry wa

  18. Arrangement of collagen fibers in human placental stem villi

    NARCIS (Netherlands)

    Sati, Leyla; Demir, Ayse Yasemin; Sarikcioglu, Levent; Demir, Ramazan

    2008-01-01

    The aim of the study was to investigate the arrangements and related localization patterns of different collagen types in the stroma of placental stem villi by immunohistochemistry and electron microscopy. A total of 14 normal human term placental tissue samples were studied. Immunohistochemistry

  19. Providing a Placental Transfusion in Newborns Who Need Resuscitation

    Science.gov (United States)

    Katheria, Anup C.; Brown, Melissa K.; Rich, Wade; Arnell, Kathy

    2017-01-01

    Over the past decade, there have been several studies and reviews on the importance of providing a placental transfusion to the newborn. Allowing a placental transfusion to occur by delaying the clamping of the umbilical cord is an extremely effective method of enhancing arterial oxygen content, increasing cardiac output, and improving oxygen delivery. However, premature and term newborns who require resuscitation have impaired transitional hemodynamics and may warrant different methods to actively provide a placental transfusion while still allowing for resuscitation. In this review, we will provide evidence for providing a placental transfusion in these circumstances and methods for implementation. Several factors including cord clamping time, uterine contractions, umbilical blood flow, respirations, and gravity play an important role in determining placental transfusion volumes. Finally, while many practitioners agree that a placental transfusion is beneficial, it is not always straightforward to implement and can be performed using different methods, making this basic procedure important to discuss. We will review three placental transfusion techniques: delayed cord clamping, intact umbilical cord milking, and cut-umbilical cord milking. We will also review resuscitation with an intact cord and the evidence in term and preterm newborns supporting this practice. We will discuss perceived risks versus benefits of these procedures. Finally, we will provide key straightforward concepts and implementation strategies to ensure that placental-to-newborn transfusion can become routine practice at any institution. PMID:28180126

  20. Longitudinal study of serum placental GH in 455 normal pregnancies

    DEFF Research Database (Denmark)

    Chellakooty, Marla; Skibsted, Lillian; Skouby, Sven Olaf

    2002-01-01

    Placental GH is thought to be responsible for the rise in maternal IGF-I during pregnancy and is considered to be important for fetal growth. In this prospective longitudinal study of healthy pregnant women, we investigated determinants of placental GH in maternal serum. Serum was obtained from 4...

  1. Granuloma anular: distribuição tecidual dos dendrócitos dérmicos fator XIIIa+, das células dérmicas trombomodulina+ e de macrófagos CD68+ Granuloma annulare: tissue distribution of factor XIIIa+ dermal dendrocytes, thrombomodulin+ dermal cells and CD68+ macrophages

    Directory of Open Access Journals (Sweden)

    Claudia Regina Wanderley Soub

    2003-06-01

    expresses the pro-coagulation factor XIIIa, while others express the anti-coagulation cofactor thrombomodulin. These cells can be involved in inflammatory and reparative tissue events. OBJETIVES: We investigated the participation of factor XIIIa+ dermal cells and thrombomodulin+ (TM+ dermal cells in the histopathological picture of granuloma annulare which is characterized by collagen necrobiosis and macrophagic infiltrate. METHODS: The histopathological picture of granuloma annulare observed in 23 skin biopsies was classified according to presence of complete or incomplete collagen degeneration and distribution of dermal infiltrate. Factor XIIIa+ dermal dendrocytes and thrombomodulin+ dermal cells were recognized by specific antibodies applied in immunohistochemical protocols; a macrophage marker (CD68 was also used. Distribution of distinct cell subsets were observed and semiquantitative analysis performed. RESULTS: Factor XIIIa+ dendrocytes were rarely detected in the lesion while thrombomodulin+ and CD68+ cells represented a considerable part of cell infiltrate. They were seen at its periphery (palisade arrangement, among degenerated collagen or diffusely distributed. A tendency was noted for association between higher semiquantification of thrombomodulin+ cells and both lower semiquantification of FXIIIa+ dendrocytes and histological type II. Dermal dendrocyte hyperplasia around the lesion was detected. CONCLUSION: The different tissue distribution of the FXIIIa+ cells and TM+ cells could reflect their distinct and complementary roles in the recovery of dermal tissue and in the lesion evolutive process in granuloma annulare.

  2. Use of magnetic resonance imaging in evaluation of placental invasion

    Energy Technology Data Exchange (ETDEWEB)

    Teo, T.H. [Department of Diagnostic Radiology, Singapore General Hospital (Singapore)], E-mail: thteo76@gmail.com; Law, Y.M.; Tay, K.H.; Tan, B.S.; Cheah, F.K. [Department of Diagnostic Radiology, Singapore General Hospital (Singapore)

    2009-05-15

    Aim: To review and describe the magnetic resonance imaging (MRI) features in patients with suspected placental invasion and correlate the findings with surgery and pathology findings. Materials and Methods: A retrospective review was undertaken of the MRI images of seven consecutive patients with ultrasound findings suspicious for placental invasion. Two experienced MRI radiologists, blinded to the pathology and surgery findings, reviewed the MRI. The pathology or surgical findings were used as the reference standard to establish accuracy and concordance with the MRI findings. Results: Three MRI features described in an earlier series were consistently present in the patients with placental invasion: lower uterine bulging, heterogeneous placenta, and dark intraplacental linear bands on T2-weighted images. Conclusion: MRI features, which were described in patients with placental invasion in an earlier series, were useful in establishing the presence and depth of placental invasion.

  3. Clinical development of placental malaria vaccines and immunoassays harmonization

    DEFF Research Database (Denmark)

    Chêne, Arnaud; Houard, Sophie; Nielsen, Morten A

    2016-01-01

    Placental malaria caused by Plasmodium falciparum infection constitutes a major health problem manifesting as severe disease and anaemia in the mother, impaired fetal development, low birth weight or spontaneous abortion. Prevention of placental malaria currently relies on two key strategies...... that are losing efficacy due to spread of resistance: long-lasting insecticide-treated nets and intermittent preventive treatment during pregnancy. A placental malaria vaccine would be an attractive, cost-effective complement to the existing control tools. Two placental malaria vaccine candidates are currently...... in Phase Ia/b clinical trials. During two workshops hosted by the European Vaccine Initiative, one in Paris in April 2014 and the other in Brussels in November 2014, the main actors in placental malaria vaccine research discussed the harmonization of clinical development plans and of the immunoassays...

  4. Multimodality imaging of placental masses: a pictorial review.

    Science.gov (United States)

    Jha, Priyanka; Paroder, Viktoriya; Mar, Winnie; Horowtiz, Jeanne M; Poder, Liina

    2016-12-01

    Placental masses are uncommonly identified at the time of obstetric ultrasound evaluation. Understanding the pathologies presenting as placental masses is key for providing a differential diagnosis and guiding subsequent management, which may include additional imaging with magnetic resonance (MR) imaging. Potential benign entities include chorioangiomas and teratomas. Larger chorioangiomas can cause fetal cardiovascular issues from volume overload. Placental mesenchymal dysplasia has an association with fetal anomalies and detailed fetal evaluation should be performed when it is suspected. Identifying other cystic masses such as partial and complete moles is crucial to prevent erroneous pregnancy termination. This review addresses normal imaging appearance of the placenta on ultrasound and MR imaging and describes various trophoblastic and nontrophoblastic placental masses. Potential placental mass mimics including uterine contractions and thrombo-hematomas are also presented.

  5. Placental Growth during Normal Pregnancy - A Magnetic Resonance Imaging Study

    DEFF Research Database (Denmark)

    Langhoff, Lasse; Grønbeck, Lene; von Huth, Sebastian

    2017-01-01

    was 640 g (range 500-787 g). All pregnancies were carried to term, resulting in the delivery of healthy infants with good correlation between placental size and birth weight (R = 0.56, p = 0.009). CONCLUSION: Placental growth was measured systematically in a longitudinal study through the second and third......OBJECTIVE: To investigate normal human placental growth longitudinally throughout the second and third trimesters using MRI. METHODS: Twenty normal, first-time singleton pregnancies were scanned 7 times between the 14th and 38th week of gestation, at 4-week intervals, using MRI. Placental volumes...... were measured in both sagittal and transversal slices. All placentas were weighed after delivery to make a comparative study. RESULTS: Sixteen of the 20 women had increasing placental volumes from the 14th to 38th week of gestation. The 6th and 7th scan showed that 4 women had placentas of the same...

  6. Placental Vesicles Carry Active Endothelial Nitric Oxide Synthase and Their Activity is Reduced in Preeclampsia.

    Science.gov (United States)

    Motta-Mejia, Carolina; Kandzija, Neva; Zhang, Wei; Mhlomi, Vuyane; Cerdeira, Ana Sofia; Burdujan, Alexandra; Tannetta, Dionne; Dragovic, Rebecca; Sargent, Ian L; Redman, Christopher W; Kishore, Uday; Vatish, Manu

    2017-08-01

    Preeclampsia, a multisystem hypertensive disorder of pregnancy, is associated with increased systemic vascular resistance. Placentae from patients with preeclampsia have reduced levels of endothelial nitric oxide synthase (eNOS) and, thus, less nitric oxide (NO). Syncytiotrophoblast extracellular vesicles (STBEV), comprising microvesicles (STBMV) and exosomes, carry signals from the syncytiotrophoblast to the mother. We hypothesized that STBEV-bound eNOS (STBEV-eNOS), capable of producing NO, are released into the maternal circulation. Dual-lobe ex vivo placental perfusion and differential centrifugation was used to isolate STBEV from preeclampsia (n=8) and normal pregnancies (NP; n=11). Plasma samples of gestational age-matched preeclampsia and NP (n=6) were used to isolate circulating STBMV. STBEV expressed placental alkaline phosphatase, confirming placental origin. STBEV coexpressed eNOS, but not inducible nitric oxide synthase, confirmed using Western blot, flow cytometry, and immunodepletion. STBEV-eNOS produced NO, which was significantly inhibited by N  (G)-nitro-l-arginine methyl ester (eNOS inhibitor; Ppreeclampsia-perfused placentae had lower levels of STBEV-eNOS (STBMV; Ppreeclampsia women had lower STBEV-eNOS expression compared with that from NP women (Ppreeclampsia placentae, as well as in plasma. The lower STBEV-eNOS NO production seen in preeclampsia may contribute to the decreased NO bioavailability in this disease. © 2017 The Authors.

  7. Localization and the possible role of plasminogen activators and inhibitors in early stages of placentation

    Institute of Scientific and Technical Information of China (English)

    2000-01-01

    The distribution of mRNAs of tissue type (t) and urokinase type (u) plasminogen activator (PA) plus their corresponding inhibitors, type-1 (PAI-1) and type-2 (PAI-2) have been studied in the tissues of human first and second trimester placentae by in situ hybridization. The results show that: (ⅰ) All the molecules, tPA, uPA, PAI-1 and PAI-2, were identified in the blood vessels, the majority of extravillous trophoblastic cells of the decidual layer between Rohr's and Nitabuch's stria and in the trophoblast cells lining the chorionic plate, basal plate, intercotyledonary septae and cytotrophoblast cells of the chorionic villous tree. (ⅱ) No expression of such probes was observed in the basal and chorionic plate, glandular cells of the decidua, the septal tissues or the villous core mesenchyme. The co-distribution of the molecules observed suggests that the co-ordinated expression of the activators and inhibitors in various cells of the placental tissue may play a role in angiogenesis related to conversion of spiral arteries into utero-placental arteries and establishment of a chorio-decidual blood flow during early stages of placentation.

  8. Forkhead factor FoxO1 is essential for placental morphogenesis in the developing embryo

    Science.gov (United States)

    Ferdous, Anwarul; Morris, Jesse; Abedin, Mohammad Joynal; Collins, Shandon; Richardson, James A.; Hill, Joseph A.

    2011-01-01

    Forkhead box O1 (FoxO1), a member of the Forkhead box-containing O family of transcription factors, is a key regulator of numerous genes that govern a wide array of cellular functions, including differentiation, homeostasis, and survival. However, the role of FoxO1 in development remains elusive. Here, we describe an essential and previously undefined role for FoxO1 in placental development. We demonstrate that FoxO1-null embryos up to embryonic day 9.0 (E9.0) are indistinguishable, including their morphology, cardiovascular structure, and vascular gene expression, from wild-type (WT) littermates. However, FoxO1-nulls manifested a profoundly swollen/hydropic allantois, which failed to fuse with the chorion, a phenotype that leads to subsequent cardiovascular malformation, progressive apoptotic cell death, and embryonic lethality at E10.5. Quantitative RT-PCR analysis of genes involved in placental development revealed significant attenuation of VCAM1 expression in FoxO1-null embryos. Using immunohistochemical, transcriptional, and chromatin immunoprecipitation assays, we further discovered that FoxO1 is an essential upstream regulator of the VCAM1 gene. Collectively, our findings provide critical molecular insight into a unique FoxO1–VCAM1 axis that governs placental morphogenesis, a process that is essential for subsequent normal cardiovascular development and fetal life. PMID:21930913

  9. Maternal obesity alters feto-placental cytochrome P4501A1 activity.

    Science.gov (United States)

    DuBois, B N; O'Tierney-Ginn, P; Pearson, J; Friedman, J E; Thornburg, K; Cherala, G

    2012-12-01

    Cytochrome P4501A1 (CYP1A1), an important drug metabolizing enzyme, is expressed in human placenta throughout gestation as well as in fetal liver. Obesity, a chronic inflammatory condition, is known to alter CYP enzyme expression in non-placental tissues. In the present study, we test the hypothesis that maternal obesity alters the distribution of CYP1A1 activity in feto-placental unit. Placentas were collected from non-obese (BMI 30) women at term. Livers were collected from gestation day 130 fetuses of non-human primates fed either control diet or high-fat diet (HFD). Cytosol and microsomes were collected using differential centrifugation, and incubated with 7-ethoxyresorufin. The CYP1A1 specific activity (pmoles of resorufin formed/min/mg of protein) was measured at excitation/emission wavelength of 530/590 nm. Placentas of obese women had significantly reduced microsomal CYP1A1 activity compared to non-obese women (0.046 vs. 0.082; p feto-placental growth and thereby well-being of fetus. Copyright © 2012 Elsevier Ltd. All rights reserved.

  10. In vitro fertilization and embryo culture strongly impact the placental transcriptome in the mouse model.

    Directory of Open Access Journals (Sweden)

    Patricia Fauque

    Full Text Available BACKGROUND: Assisted Reproductive Technologies (ART are increasingly used in humans; however, their impact is now questioned. At blastocyst stage, the trophectoderm is directly in contact with an artificial medium environment, which can impact placental development. This study was designed to carry out an in-depth analysis of the placental transcriptome after ART in mice. METHODOLOGY/PRINCIPAL FINDINGS: Blastocysts were transferred either (1 after in vivo fertilization and development (control group or (2 after in vitro fertilization and embryo culture. Placentas were then analyzed at E10.5. Six percent of transcripts were altered at the two-fold threshold in placentas of manipulated embryos, 2/3 of transcripts being down-regulated. Strikingly, the X-chromosome harbors 11% of altered genes, 2/3 being induced. Imprinted genes were modified similarly to the X. Promoter composition analysis indicates that FOXA transcription factors may be involved in the transcriptional deregulations. CONCLUSIONS: For the first time, our study shows that in vitro fertilization associated with embryo culture strongly modify the placental expression profile, long after embryo manipulations, meaning that the stress of artificial environment is memorized after implantation. Expression of X and imprinted genes is also greatly modulated probably to adapt to adverse conditions. Our results highlight the importance of studying human placentas from ART.

  11. Human placental development is impaired by abnormal human chorionic gonadotropin signaling in trisomy 21 pregnancies.

    Science.gov (United States)

    Pidoux, Guillaume; Gerbaud, Pascale; Marpeau, Olivier; Guibourdenche, Jean; Ferreira, Fatima; Badet, Josette; Evain-Brion, Danièle; Frendo, Jean-Louis

    2007-11-01

    Placental development is markedly abnormal in women bearing a fetus with trisomy 21, with defective syncytiotrophoblast (ST) formation and function. The ST occurs from cytotrophoblast (CT) fusion and plays an essential role by secreting human chorionic gonadotropin (hCG), which is essential to placental development. In trisomy of chromosome 21 (T21) pregnancies, CTs do not fuse and differentiate properly into STs, leading to the secretion of an abnormal and weakly bioactive hCG. In this study we report for the first time, a marked decrease in the number of mature hCG receptor (LH/CG-R) molecules expressed at the surface of T21-affected CTs. The LH/CG-R seems to be functional based on sequencing that revealed no mutations or deletions and binding of recombinant hCG as well as endogenous hCG. We hypothesize that weakly bioactive hCG and lower LH/CG-R expression may be involved in the defect of ST formation. Interestingly, the defective ST formation is mimicked in normal CT cultures by using LH/CG-R small interfering RNA, which result in a lower hCG secretion. Furthermore, treatment of T21-affected CTs with recombinant hCG overcomes in vitro the T21 phenotype, allowing CTs to fuse and form a large ST. These results illustrate for the first time in trisomy 21 pathology, how abnormal endogenous hCG signaling impairs human placental development.

  12. Maternal Pre-Pregnancy Obesity Is Associated with Altered Placental Transcriptome

    Science.gov (United States)

    Segura, Maria Teresa; Esteban, Francisco J.; Bartel, Sabine; Brandi, Pilar; Irmler, Martin; Beckers, Johannes; Demmelmair, Hans; López-Sabater, Carmen; Koletzko, Berthold; Krauss-Etschmann, Susanne; Campoy, Cristina

    2017-01-01

    Maternal obesity has a major impact on pregnancy outcomes. There is growing evidence that maternal obesity has a negative influence on placental development and function, thereby adversely influencing offspring programming and health outcomes. However, the molecular mechanisms underlying these processes are poorly understood. We analysed ten term placenta’s whole transcriptomes in obese (n = 5) and normal weight women (n = 5), using the Affymetrix microarray platform. Analyses of expression data were carried out using non-parametric methods. Hierarchical clustering and principal component analysis showed a clear distinction in placental transcriptome between obese and normal weight women. We identified 72 differentially regulated genes, with most being down-regulated in obesity (n = 61). Functional analyses of the targets using DAVID and IPA confirm the dysregulation of previously identified processes and pathways in the placenta from obese women, including inflammation and immune responses, lipid metabolism, cancer pathways, and angiogenesis. In addition, we detected new molecular aspects of obesity-derived effects on the placenta, involving the glucocorticoid receptor signalling pathway and dysregulation of several genes including CCL2, FSTL3, IGFBP1, MMP12, PRG2, PRL, QSOX1, SERPINE2 and TAC3. Our global gene expression profiling approach demonstrates that maternal obesity creates a unique in utero environment that impairs the placental transcriptome. PMID:28125591

  13. Altered cytokine network in gestational diabetes mellitus affects maternal insulin and placental-fetal development.

    Science.gov (United States)

    Wedekind, Lauren; Belkacemi, Louiza

    2016-01-01

    Pregnancy is characterized by an altered inflammatory profile, compared to the non-pregnant state with an adequate balance between pro-and anti-inflammatory cytokines needed for normal development. Cytokines are small secreted proteins expressed mainly in immunocompetent cells in the reproductive system. From early developmental stages onward, the secretory activity of placenta cells clearly contributes to increase local as well as systemic levels of cytokines. The placental production of cytokines may affect mother and fetus independently. In turn because of this unique position at the maternal fetal interface, the placenta is also exposed to the regulatory influence of cytokines from maternal and fetal circulations, and hence, may be affected by changes in any of these. Gestational diabetes mellitus (GDM) is associated with an overall alteration of the cytokine network. This review discusses the changes that occur in cytokines post GDM and their negative effects on maternal insulin and placental-fetal development.

  14. An integrative view on the physiology of human early placental villi.

    Science.gov (United States)

    Huppertz, Berthold; Ghosh, Debabrata; Sengupta, Jayasree

    2014-01-01

    The placenta is an indispensable organ for intrauterine protection, development and growth of the embryo and fetus. It provides tight contact between mother and conceptus, enabling the exchange of gas, nutrients and waste products. The human placenta is discoidal in shape, and bears a hemo-monochorial interface as well as villous materno-fetal interdigitations. Since Peter Medawar's astonishment to the paradoxical nature of the mother-fetus relationship in 1953, substantial knowledge in the domain of placental physiology has been gathered. In the present essay, an attempt has been made to build an integrated understanding of morphological dynamics, cell biology, and functional aspects of genomic and proteomic expression of human early placental villous trophoblast cells followed by a commentary on the future directions of research in this field.

  15. Effect of prostaglandin E2 on multidrug resistance transporters in human placental cells.

    Science.gov (United States)

    Mason, Clifford W; Lee, Gene T; Dong, Yafeng; Zhou, Helen; He, Lily; Weiner, Carl P

    2014-12-01

    Prostaglandin (PG) E2, a major product of cyclooxygenase (COX)-2, acts as an immunomodulator at the maternal-fetal interface during pregnancy. It exerts biologic function through interaction with E-prostanoid (EP) receptors localized to the placenta. The activation of the COX-2/PGE2/EP signal pathway can alter the expression of the ATP-binding cassette (ABC) transporters, multidrug resistance protein 1 [P-glycoprotein (Pgp); gene: ABCB1], and breast cancer resistance protein (BCRP; gene: ABCG2), which function to extrude drugs and xenobiotics from cells. In the placenta, PGE2-mediated changes in ABC transporter expression could impact fetal drug exposure. Furthermore, understanding the signaling cascades involved could lead to strategies for the control of Pgp and BCRP expression levels. We sought to determine the impact of PGE2 signaling mechanisms on Pgp and BCRP in human placental cells. The treatment of placental cells with PGE2 up-regulated BCRP expression and resulted in decreased cellular accumulation of the fluorescent substrate Hoechst 33342. Inhibiting the EP1 and EP3 receptors with specific antagonists attenuated the increase in BCRP. EP receptor signaling results in activation of transcription factors, which can affect BCRP expression. Although PGE2 decreased nuclear factor κ-light chain-enhancer of activated B activation and increased activator protein 1, chemical inhibition of these inflammatory transcription factors did not blunt BCRP up-regulation by PGE2. Though PGE2 decreased Pgp mRNA, Pgp expression and function were not significantly altered. Overall, these findings suggest a possible role for PGE2 in the up-regulation of placental BCRP expression via EP1 and EP3 receptor signaling cascades. Copyright © 2014 by The American Society for Pharmacology and Experimental Therapeutics.

  16. Thyroid hormones and their placental deiodination in normal and pre-eclamptic pregnancy.

    Science.gov (United States)

    Kurlak, L O; Mistry, H D; Kaptein, E; Visser, T J; Broughton Pipkin, F

    2013-05-01

    Pre-eclampsia is associated with lower serum selenium concentrations and glutathione peroxidase expression/activity; total thyroid hormones are also lower. We hypothesised that the placental selenoprotein deiodinase (D3) will be protected in pre-eclampsia due to the hierarchy of selenoprotein biosynthesis in selenium deficiency. Venous blood and tissue from three standardised placental sites were obtained at delivery from 27 normotensive and 23 pre-eclamptic women. mRNA expression and enzyme activity were assessed for both deiodinases (D2 and D3); protein expression/localisation was also measured for D3. FT4, FT3 and TSH concentrations were measured in maternal and umbilical cord blood. No significant differences in D3 mRNA or protein expression between normotensive and pre-eclamptic pregnancies. There was a significant effect of sampling site on placental D3 activity only in pre-eclamptic women (P = 0.034; highest activity nearest the cord). A strong correlation between D3 mRNA expression and enzyme activity existed only in the pre-eclamptic group; further strengthened when controlling for maternal selenium (P thyroid hormones; umbilical TSH concentrations were significantly higher in the pre-eclamptic samples (P < 0.001). D3 mRNA and protein expression appear to be independent of selenium status. Nevertheless, the positive correlation between D3 mRNA expression and activity evident only in pre-eclampsia, suggests that in normotensive controls, where selenium is higher, translation is not affected, but in pre-eclampsia, where selenium is low, enzyme regulation may be altered. The raised umbilical TSH concentrations in pre-eclampsia may be an adaptive fetal response to maximise iodide uptake. Copyright © 2013 Elsevier Ltd. All rights reserved.

  17. Expression of hypoxia-inducible factor-1α in placental tissues in patients with placenta previa%缺氧诱导因子-1α在前置胎盘患者胎盘组织中的表达及意义

    Institute of Scientific and Technical Information of China (English)

    谢家滨

    2012-01-01

    Objective To study the expression of hypoxia-inducible factor-1 α (HIF-1 α) in patients with placenta previa, and explore the effect in the pathophysiology of placenta previa. Methods The expression of HIF-1 α was detected in patients with placenta previa (group A) and normal pregnant women (group B) by using immunohisto-chemistry. Then the results were compared between the two groups. Results In group A, the positive expression rate of HIF-1α was 73.33% (22/30) and the average optical density was (202.87±18.54), significantly higher than those in group B [23.33% (7/30) and (118.51±10.62)], P<0.01. Conclusion The expression of HIF-la in placental tissues in patients with placenta previa was significantly higher than normal, which could serves as an important indicator for the early diagnosis of placenta previa.%目的 研究缺氧诱导因子-1α(HIF-1α)在前置胎盘患者胎盘组织中的表达,探讨其在前置胎盘发病及病理生理过程中的作用.方法 采用免疫组化法检测并比较前置胎盘患者及正常孕妇的胎盘组织中HIF-1α的表达情况.结果 前置胎盘孕妇组胎盘HIF-1α阳性表达率为73.33%(22/30),光密度值平均为(2 02.87+18.54),均明显高于正常孕妇组水平[HIF-1α阳性表达率为23.33%(7/30),光密度值平均为(118.51±10.62)],差异均具有极显著统计学意义(P<0.01).结论 HIF-1α前置胎盘患者胎盘组织中表达明显升高,有可能成为前置胎盘早期诊断的重要指标.

  18. 子痫前期患者胎盘组织中HSP70和NF-κB的表达及意义%Expression of HSP70 and NF-κB in the placental trophoblasts of preg-nant women complicated with preeclampsia

    Institute of Scientific and Technical Information of China (English)

    林培红; 胡继芬

    2016-01-01

    Objective To investigate the difference and significance between the expression of HSP70 and NF-κB in the placenta tissues of normal pregnancy and preeclampsia patients, in order to find out the relation between HSP70 and NF-κB. Methods From December 2013 to January 2015, 65 pregnant patients in the First Affiliated Hospital of Fujian Medical University were selected. There were 25 healthy pregnant women (normal pregnant group), 17 mild preeclampsia patients (mild preeclampsia group) and 23 severe preeclampsia patients (severe preeclampsia group). The expressions of HSP70 and NF-κB in the placental tissues were measured using immunohistochemistry methods and re-al-time fluorescence quantitative PCR technique. Results HSP70 and NF-κB immunohistochemical results suggested that the staining degree of the normal pregnant group, the mild and severe preeclampsia group increased gradually. The differences of the expressions of HSP70 and NF-κB between the mild, severe preeclampsia group and the normal preg-nant group were significant (P 0.05); the results of HSP70 and NF-κB real-time fluorescence quantitative PCR suggested that, the level of the expression increased in mild preeclampsia group and severe preeclampsia group, as compared with the normal pregnant group, the difference between the mild preeclampsia group, severe preeclampsia group and the normal pregnant group was statistically significant (P0.05);实时荧光定量PCR结果提示:与正常妊娠组比较, HSP70及NF-κB在轻度子痫前期组及轻度子痫前期组中的表达水平增高, 轻度子痫前期组及重度子痫前期组与正常妊娠组两两比较差异有高度统计学意义(P<0.01).相关性分析结果显示,HSP70与NF-κB呈正相关(r=0.692, P<0.01). 结论 子痫前期患者胎盘组织中HSP70和NF-κB表达增加,可能与子痫前期的发生、发展有关.

  19. 胎盘型谷胱甘肽S-转移酶在喉肿瘤组织的表达%Study of expression of placental glutathione S-transferase in laryngeal tumors

    Institute of Scientific and Technical Information of China (English)

    高冰; 汤文学; 陈向东; 何健伶; 王曼

    2000-01-01

    目的:检测胎盘型谷胱甘肽S-转移酶(GST-π)在喉鳞状细胞癌、喉乳头状瘤、声带息肉的表达及意义。方法:病理诊断确诊的喉鳞状细胞癌标本34例,喉乳头状瘤31例,声带息肉38例,用免疫胶体金方法检测GST-π在喉肿瘤组织的表达。结果:34例喉鳞状细胞癌组织GST-π表达100%阳性,其中有3例化疗后表达强度增强;31例喉乳头状瘤组织12.9%弱阳性表达;38例声带息肉全部为阴性。结论:GST-π对喉部良、恶性肿瘤的检测及化疗耐药性的产生方面有重要意义。%Objective: The experiment is to study the expression of glutathione S-transferase (GST-π) in laryngeal tumors,suchas squamous cell cancer,papilloma and polyp. Methods: Expression of GST-π was studied immunohistochemically(glue-goldmethod) in routinely processed tissues from 34 eases of squamous cell cancer,31 cases of papilloma,38 cases of polyp of vocalcard. Results: The expression rates of GST-π in squamous cell cancer were 100%. The expression of GST-π in 3 eases ofsquamous cell cancer got stranger after chemical therapy. The expression rates of GST-π in papilloma were 12.9% but thestaining were light. All the larynx polyps were negative for GST-π. Conclusion: GST-π has the important significance for distinguishing benign and malignant tumors and producing chemotherapeutic resistance.

  20. Confined placental mosaicisms and uniparental disomy

    Energy Technology Data Exchange (ETDEWEB)

    Kalousek, D.K.; Langlois, S.; Harrison, K.J. [Univ. of British Columbia, Vancouver (Canada)] [and others

    1994-09-01

    Approximately 2% of pregnancies studied with chorionic villous sampling (CVS) show confined placental mosaicism (CPM) which persists to term in 50-70% of cases. An increased frequency of complications, such as intrauterine fetal growth restriction or intrauterine death, is observed in these pregnancies. As trisomic zygote rescue is a common mechanism responsible for CPM, fetal uniparental disomy (UPD), resulting from the loss of the extra trisomic chromosome in the embryonic stem cells, would be expected to occur in a proportion of pregnancies with CPM. We have studied 27 pregnancies with CPM involving trisomies for chromosomes 2, 7, 9, 10, 12, and 16 for involvement of specific cell lineage(s) and levels of mosaicism in term placentas. Also, DNA from the parents and infant was analyzed for UPD or biparental disomy (BPD). Five infants with UPD for chromosome 16 and one infant with UPD for chromosome 7 were detected. All other infants showed BPD for the chromosome involved in CPM. For trisomy 16 mosaic gestations, a close correlation between high levels of trisomic cells in placenta and intrauterine fetal growth restriction has been found irrespective of the type of disomy present in the infant. The effect of other trisomies (2, 7, 9, 10, 12) on placental function appears to be similar, but the low numbers of pregnancies studied and lack of detection of UPD for chromosomes 2, 9, 10 and 12 does not allow a definitive conclusion.

  1. The Role of Placental Tryptophan Catabolism

    Science.gov (United States)

    Sedlmayr, Peter; Blaschitz, Astrid; Stocker, Roland

    2014-01-01

    This review discusses the mechanisms and consequences of degradation of tryptophan (Trp) in the placenta, focusing mainly on the role of indoleamine 2,3-dioxygenase-1 (IDO1), one of three enzymes catalyzing the first step of the kynurenine pathway of Trp degradation. IDO1 has been implicated in regulation of feto-maternal tolerance in the mouse. Local depletion of Trp and/or the presence of metabolites of the kynurenine pathway mediate immunoregulation and exert antimicrobial functions. In addition to the decidual glandular epithelium, IDO1 is localized in the vascular endothelium of the villous chorion and also in the endothelium of spiral arteries of the decidua. Possible consequences of IDO1-mediated catabolism of Trp in the endothelium encompass antimicrobial activity and immunosuppression, as well as relaxation of the placental vasotonus, thereby contributing to placental perfusion and growth of both placenta and fetus. It remains to be evaluated whether other enzymes mediating Trp oxidation, such as indoleamine 2,3-dioxygenase-2, Trp 2,3-dioxygenase, and Trp hydroxylase-1 are of relevance to the biology of the placenta. PMID:24904580

  2. Transport of nanoparticles through the placental barrier.

    Science.gov (United States)

    Kulvietis, Vytautas; Zalgeviciene, Violeta; Didziapetriene, Janina; Rotomskis, Ricardas

    2011-12-01

    Nanoparticles (NP) are organic or inorganic substances, the size of which ranges from 1 to 100 nm, and they possess specific properties which are different from those of the bulk materials in the macroscopic scale. In a recent decade, NP were widely applied in biomedicine as potential probes for imaging, drug-delivery systems and regenerative medicine. However, rapid development of nanotechnologies and their applications in clinical research have raised concerns about the adverse effects of NP on human health and environment. In the present review, special attention is paid to the fetal exposure to NP during the period of pregnancy. The ability to control the beneficial effects of NP and to avoid toxicity during treatment requires comprehensive knowledge about the distribution of NP in maternal body and possible penetration through the maternal-fetal barrier that might impair the embryogenesis. The initial in vivo and ex vivo studies imply that NP are able to cross the placental barrier, but the passage to the fetus depends on the size and the surface coating of NP as well as on the experimental model. The toxicity assays indicate that NP might induce adverse physiological effects and impede embryogenesis. The molecular transport mechanisms which are responsible for the transport of nanomaterials across the placental barrier are still poorly understood, and there is a high need for further studies in order to resolve the NP distribution patterns in the organism and to control the beneficial effects of NP applications during pregnancy without impeding the embryogenesis.

  3. A Case of Placental Mesenchymal Dysplasia

    Directory of Open Access Journals (Sweden)

    Shigeki Taga

    2013-01-01

    Full Text Available Placental mesenchymal dysplasia (PMD rarely complicates with pregnancy. A 30-year-old woman, gravida 3, para 3, presenting with placentomegaly, was referred to our department at 18 weeks of gestation. An ultrasonography revealed a normal fetus with a large multicystic placenta, measuring 125 × 42 × 80 mm. The border between the lesion and normal region was not clear. Color doppler revealed little blood flow in the lesion. Magnetic resonance imaging revealed normal fetus and a large multicystic placenta. Serum human chorionic gonadotropin level was 20124.97 U/L, which was normal at 20 weeks of gestation. Thus, placental mesenchymal dysplasia rather than hydatidiform mole with coexistent fetus was suspected. Then, routine checkup was continued. Because she had the history of Cesarean section, an elective Cesarean section was performed at 37 weeks of gestation, and 2520 g female infant with apgar score 8/9 was delivered. The baby was normal with no evidence of Beckwith-Wiedemann syndrome. Placenta of 20 × 16 × 2 cm, weighing 720 g, was bulky with grape like vesicles involving whole placenta. Microscopic examination revealed dilated villi and vessels with thick wall which was lacking trophoblast proliferation. Large hydropic stem villi with myxomatous struma and cistern formation were seen. PMD was histopathologically confirmed.

  4. The impact of cocaine and heroin on the placental transfer of methadone

    Science.gov (United States)

    Malek, Antoine; Obrist, Cristina; Wenzinger, Silvana; von Mandach, Ursula

    2009-01-01

    Background Methadone is the therapeutic agent of choice for the treatment of opiate addiction in pregnancy. The co-consumption (heroin, cocaine) which may influence the effects of methadone is frequent. Therefore, the impact of cocaine and heroin on the placental transfer of methadone and the placental tissue was investigated under in vitro conditions. Methods Placentae (n = 24) were ex-vivo perfused with medium (m) (control, n = 6), m plus methadone (n = 6), m plus methadone and cocaine (n = 6) or m plus methadone and heroin (n = 6). Placental functionality parameters like antipyrine permeability, glucose consumption, lactate production, hormone production (hCG and leptin), microparticles release and the expression of P-glycoprotein were analysed. Results Methadone accumulated in placental tissue. Methadone alone decreased the transfer of antipyrine from 0.60 +/- 0.07 to 0.50 +/- 0.06 (fetal/maternal ratio, mean +/- SD, P < 0.01), whereas the combination with cocaine or heroin increased it (0.56 +/- 0.08 to 0.68 +/- 0.13, P = 0.03 and 0.58 +/- 0.21 to 0.71 +/- 0.24; P = 0.18). Microparticles (MPs) released from syncytiotrophoblast into maternal circuit increased by 30% after cocaine or heroin (P < 0.05) and the expression of P-glycoprotein in the tissue increased by ≥ 49% after any drug (P < 0.05). All other measured parameters did not show any significant effect when methadone was combined with cocaine or heroine. Conclusion The combination of cocaine or heroin with methadone increase antipyrine permeability. Changes of MPs resemble findings seen in oxidative stress of syncytiotrophoblast. PMID:19519880

  5. Maternal distress associates with placental genes regulating fetal glucocorticoid exposure and IGF2: Role of obesity and sex.

    Science.gov (United States)

    Mina, Theresia H; Räikkönen, Katri; Riley, Simon C; Norman, Jane E; Reynolds, Rebecca M

    2015-09-01

    Maternal emotional distress symptoms, including life satisfaction, anxiety and depressed mood, are worse in Severely Obese (SO) than lean pregnancy and may alter placental genes regulating fetal glucocorticoid exposure and placental growth. We hypothesised that the associations between increased maternal distress symptoms and changes in placental gene expression including IGF2 and genes regulating fetal glucocorticoid exposure are more pronounced in SO pregnancy. We also considered whether there were sex-specific effects. Placental mRNA levels of 11β-HSDs, NR3C1-α, NR3C2, ABC transporters, mTOR and the IGF2 family were measured in term placental samples from 43 lean (BMI≤25kg/m(2)) and 50 SO (BMI≥40kg/m(2)) women, in whom distress symptoms were prospectively evaluated during pregnancy. The mRNA levels of genes with a similar role in regulating fetal glucocorticoid exposure were strongly inter-correlated. Increased maternal distress symptoms associated with increased NR3C2 and IGF2 isoform 1(IGF2-1) in both lean and SO group (p≤0.05). Increased distress was associated with higher ABCB1 and ABCG2 mRNA levels in SO but lower ABCB1 and higher 11β-HSD1 mRNA levels in lean (p≤0.05) suggesting a protective adaptive response in SO placentas. Increased maternal distress associated with reduced mRNA levels of ABCB1, ABCG2, 11β-HSD2, NR3C1-α and IGF2-1 in placentas of female but not male offspring. The observed sex differences in placental responses suggest greater vulnerability of female fetuses to maternal distress with potentially greater fetal glucocorticoid exposure and excess IGF2. Further studies are needed to replicate these findings and to test whether this translates to potentially greater negative outcomes of maternal distress in female offspring in early childhood.

  6. Placental glucose and amino acid transport in calorie-restricted wild-type and Glut3 null heterozygous mice.

    Science.gov (United States)

    Ganguly, Amit; Collis, Laura; Devaskar, Sherin U

    2012-08-01

    Calorie restriction (CR) decreased placenta and fetal weights in wild-type (wt) and glucose transporter (Glut) 3 heterozygous null (glut3(+/-)) mice. Because placental nutrient transport is a primary energy determinant of placentofetal growth, we examined key transport systems. Maternal CR reduced intra- and transplacental glucose and leucine transport but enhanced system A amino acid transport in wt mice. These transport perturbations were accompanied by reduced placental Glut3 and leucine amino acid transporter (LAT) family member 2, no change in Glut1 and LAT family member 1, but increased sodium coupled neutral amino acid transporter (SNAT) and SNAT2 expression. We also noted decreased total and active phosphorylated forms of mammalian target of rapamycin, which is the intracellular nutrient sensor, the downstream total P70S6 kinase, and pS6 ribosomal protein with no change in total and phosphorylated 4E-binding protein 1. To determine the role of placental Glut3 in mediating CR-induced placental transport changes, we next investigated the effect of gestational CR in glut3(+/-) mice. In glut3(+/-) mice, a key role of placental Glut3 in mediating transplacental and intraplacental glucose transport was established. In addition, reduced Glut3 results in a compensatory increase of leucine and system A transplacental transport. On the other hand, diminished Glut3-mediated intraplacental glucose transport reduced leucine transport and mammalian target of rapamycin and preserved LAT and enhancing SNAT. CR in glut3(+/-) mice further reduced transplacental glucose transport and enhanced system A amino acid transport, although the increased leucine transport was lost. In addition, increased Glut3 was seen and preserved Glut1, LAT, and SNAT. These placental changes collectively protect survival of wt and glut3(+/-) fetuses against maternal CR-imposed reduction of macromolecular nutrients.

  7. Chronic tempol prevents hypertension, proteinuria, and poor feto-placental outcomes in BPH/5 mouse model of preeclampsia.

    Science.gov (United States)

    Hoffmann, Darren S; Weydert, Christine J; Lazartigues, Eric; Kutschke, William J; Kienzle, Martha F; Leach, Jenny E; Sharma, Jennifer A; Sharma, Ram V; Davisson, Robin L

    2008-04-01

    Recently we described a mouse model, BPH/5, that spontaneously develops the hallmark clinical features of preeclampsia. BPH/5 exhibit impaired placentation before the onset of hypertension and proteinuria, supporting a causal role for the placenta in the pathogenesis of preeclampsia. Here we tested the hypothesis that an increase in reactive oxygen species (ROS) early in pregnancy results in placental abnormalities leading to the maternal symptoms of preeclampsia. We further hypothesized that chronic antioxidant therapy would ameliorate both feto-placental abnormalities and maternal symptoms. ROS levels measured by dihydroethidium revealed significant increases in oxidative stress in BPH/5 placentas at midgestation compared with C57 controls. This increase in ROS was correlated with reduced expression and activity of cytoplasmic superoxide dismutase in early and midgestation BPH/5 placentas. These abnormalities in placental oxidant factors occurred before the onset of maternal symptoms, suggesting a possible causal link between increased ROS and maternal and feto-placental pathology in this model. In support of this, chronic treatment of BPH/5 with the superoxide dismutase-mimetic Tempol throughout gestation significantly improved fetal growth and survival. Furthermore, Tempol ameliorated pregnancy-induced increases in blood pressure and proteinuria in BPH/5 mothers. We confirmed that Tempol radical was present in plasma, and it normalized ROS levels in all placental zones in BPH/5. These data for the first time demonstrate an important causative role for increased ROS in the placenta in the pathogenesis of preeclampsia in a model that spontaneously develops the disease. The results also strongly suggest the potential utility of antioxidant therapy in treating preeclampsia.

  8. Prenatal Exposure to Sodium Arsenite Alters Placental Glucose 1, 3, and 4 Transporters in Balb/c Mice

    Directory of Open Access Journals (Sweden)

    Daniela Sarahí Gutiérrez-Torres

    2015-01-01

    Full Text Available Inorganic arsenic (iAs exposure induces a decrease in glucose type 4 transporter (GLUT4 expression on the adipocyte membrane, which may be related to premature births and low birth weight infants in women exposed to iAs at reproductive age. The aim of this study was to analyze the effect of sodium arsenite (NaAsO2 exposure on GLUT1, GLUT3, and GLUT4 protein expression and on placental morphology. Female Balb/c mice (n=15 were exposed to 0, 12, and 20 ppm of NaAsO2 in drinking water from 8th to 18th day of gestation. Morphological changes and GLUT1, GLUT3, and GLUT4 expression were evaluated in placentas by immunohistochemical and image analysis and correlated with iAs and arsenical species concentration, which were quantified by atomic absorption spectroscopy. NaAsO2 exposure induced a significant decrease in fetal and placental weight (P<0.01 and increases in infarctions and vascular congestion. Whereas GLUT1 expression was unchanged in placentas from exposed group, GLUT3 expression was found increased. In contrast, GLUT4 expression was significantly lower (P<0.05 in placentas from females exposed to 12 ppm. The decrease in placental GLUT4 expression might affect the provision of adequate fetal nutrition and explain the low fetal weight observed in the exposed groups.

  9. IFPA meeting 2015 workshop report I: placental mitochondrial function, transport systems and epigenetics.

    Science.gov (United States)

    Bianco-Miotto, T; Blundell, C; Buckberry, S; Chamley, L; Chong, S; Cottrell, E; Dawson, P; Hanna, C; Holland, O; Lewis, R M; Moritz, K; Myatt, L; Perkins, A V; Powell, T; Saffery, R; Sferruzzi-Perri, A; Sibley, C; Simmons, D; O'Tierney-Ginn, P F

    2016-12-01

    Workshops are an important part of the IFPA annual meeting as they allow for discussion of specialized topics. At IFPA meeting 2015 there were twelve themed workshops, three of which are summarized in this report. These workshops covered areas of placental regulation and nutrient handling: 1) placental epigenetics; 2) placental mitochondrial function; 3) placental transport systems.

  10. Pseudo-placentational endometrial cysts in a bitch.

    Science.gov (United States)

    Bartel, C; Schönkypl, S; Walter, I

    2010-02-01

    Cystic alterations of the canine endometrium compromise reproduction and fertility of the bitch and may lead to life-threatening diseases, such as pyometra. Even without clinical evidence, reduction of the uterine lumen by cysts implicates disturbances during migration, nidation and development of the embryo. Several studies point to the high variability of morphology of uterine endometrial cysts but they lack detailed analyses of alterations. In the present study, immunohistochemistry was used to investigate the expression of steroid hormone receptors (oestrogen, progesterone), proliferation activity, inflammation and infection in the cystic affected tissue regions in contrast to the normal endometrium. Oestrogen receptor expression showed a high density of receptors throughout the surface epithelial cells, crypt epithelial cells, glandular epithelial cells and stromal cells of the normal endometrium as well as the cystic affected regions. Proliferation in the cysts was verified in the middle and basal cells of the crypts. Neither in the endometrium nor in the cysts inflammatory processes or evidence of infection could be detected. Furthermore, lectin histochemistry and electron microscopic methods showed that lectin binding patterns and cell morphology of internal epithelial lining and surface epithelium of the cysts can be used to characterize and distinguish different types of cystic alterations. Analogies between epithelial cells of the glandular chambers of the canine placenta and the cystic cellular morphology, steroid hormone receptor distribution as well as lectin binding patterns of the endometrial cysts, as observed in this study, suggest to introduce the term 'pseudo-placentational endometrial cysts'.

  11. Monocarboxylate transporter 8 modulates the viability and invasive capacity of human placental cells and fetoplacental growth in mice.

    OpenAIRE

    Vasilopoulou, E.; Loubière, LS; Heuer, H.; Trajkovic-Arsic, M; Darras, VM; Visser, TJ; Lash, GE; Whitley, GS; McCabe, CJ; Franklyn, JA; Kilby, MD; Chan, SY

    2013-01-01

    textabstractMonocarboxylate transporter 8 (MCT8) is a well-established thyroid hormone (TH) transporter. In humans, MCT8 mutations result in changes in circulating TH concentrations and X-linked severe global neurodevelopmental delay. MCT8 is expressed in the human placenta throughout gestation, with increased expression in trophoblast cells from growth-restricted pregnancies. We postulate that MCT8 plays an important role in placental development and transplacental TH transport. We investiga...

  12. Associations between intrapartum death and piglet, placental, and umbilical characteristics.

    Science.gov (United States)

    Rootwelt, V; Reksen, O; Farstad, W; Framstad, T

    2012-12-01

    Intrapartum death in multiparous gestations in sows (Sus scrofa) is often caused by hypoxia. There is little information in the literature on the assessment of the placenta in relation to intrapartum death in piglets. The aim of this study was to evaluate the impact of the placental area and weight upon piglet birth characteristics and intrapartum death. Litters from 26 Landrace-Yorkshire sows were monitored during farrowing and the status of each piglet was recorded, including blood parameters of piglets and their umbilical veins. Of 413 piglets born, 6.5% were stillborn. Blood concentrations of glucose, lactate, and CO(2) partial pressure were increased in the stillborn piglets (P piglets, whereas pH and base excess were decreased (P piglets born dead vs. live (P piglets born dead was not different from live-born piglets (P = 0.631), whereas mean body mass index was reduced (P piglets were not different from live-born piglets (P = 0.662 and P = 0.253, respectively). Blood concentrations of lactate, hemoglobin, and hematocrit recorded in all piglets pooled were associated with placental area (P 0.2). Piglet BW was positively correlated with placental area and placental weight (P piglet birth weight, but not with the probability of being born dead. Placental area was a better predictor of piglet vitality than placental weight. Because umbilical cord rupture and prolonged birth time were associated with being born dead, umbilical cord rupture and placental detachment seem to be probable causes of intrapartum death.

  13. Placental exosomes in normal and complicated pregnancy.

    Science.gov (United States)

    Mitchell, Murray D; Peiris, Hassendrini N; Kobayashi, Miharu; Koh, Yong Q; Duncombe, Gregory; Illanes, Sebastian E; Rice, Gregory E; Salomon, Carlos

    2015-10-01

    While there is considerable contemporary interest in elucidating the role of placenta-derived extracellular vesicles in normal and complicated pregnancies and their utility as biomarkers and therapeutic interventions, progress in the field is hindered by a lack of standardized extracellular vesicle taxonomy and isolation protocols. The term "extracellular vesicle" is nonspecific and refers to all membrane-bound vesicles from nanometer to micrometer diameters and of different biogenic origins. To meaningfully ascribe biological function and/or diagnostic and therapeutic utility to extracellular vesicles, and in particular exosomes, greater specificity and vesicle characterization is required. The current literature relating to exosome biology must be interpreted in this context. Exosomes are a subtype of extracellular vesicle that are specifically defined by an endosomal biogenesis and particle size (40-120 nm) and density (1.13-1.19 g/mL(-1)). Exosomes are specifically package with signaling molecules (including protein, messenger RNA, microRNA, and noncoding RNA) and are released by exocytosis into biofluid compartments. Exosomes regulate the activity of both proximal and distal target cells, including translational activity, angiogenesis, proliferation, metabolism, and apoptosis. As such, exosomal signaling represents an integral pathway mediating intercellular communication. During pregnancy, the placenta releases exosomes into the maternal circulation from as early as 6 weeks of gestation. Release is regulated by factors that include both oxygen tension and glucose concentration and correlates with placental mass and perfusion. The concentration of placenta-derived exosomes in maternal plasma increases progressively during gestation. Exosomes isolated from maternal plasma are bioactive in vitro and are incorporated into target cells by endocytosis. While the functional significance of placental exosomes in pregnancy remains to be fully elucidated, available

  14. Developmental programing: impact of testosterone on placental differentiation.

    Science.gov (United States)

    Beckett, E M; Astapova, O; Steckler, T L; Veiga-Lopez, A; Padmanabhan, V

    2014-08-01

    Gestational testosterone treatment causes maternal hyperinsulinemia, intrauterine growth retardation (IUGR), low birth weight, and adult reproductive and metabolic dysfunctions. Sheep models of IUGR demonstrate placental insufficiency as an underlying cause of IUGR. Placental compromise is probably the cause of fetal growth retardation in gestational testosterone-treated sheep. This study tested whether testosterone excess compromises placental differentiation by its androgenic action and/or via altered insulin sensitivity. A comparative approach of studying gestational testosterone (aromatizable androgen) against dihydrotestosterone (non-aromatizable androgen) or testosterone plus androgen antagonist, flutamide, was used to determine whether the effects of testosterone on placental differentiation were programed by its androgenic actions. Co-treatment of testosterone with the insulin sensitizer, rosiglitazone, was used to establish whether the effects of gestational testosterone on placentome differentiation involved compromised insulin sensitivity. Parallel cohorts of pregnant females were maintained for lambing and the birth weight of their offspring was recorded. Placental studies were conducted on days 65, 90, or 140 of gestation. Results indicated that i) gestational testosterone treatment advances placental differentiation, evident as early as day 65 of gestation, and culminates in low birth weight, ii) placental advancement is facilitated at least in part by androgenic actions of testosterone and is not a function of disrupted insulin homeostasis, and iii) placental advancement, while helping to increase placental efficiency, was insufficient to prevent IUGR and low-birth-weight female offspring. Findings from this study may be of relevance to women with polycystic ovary syndrome, whose reproductive and metabolic phenotype is captured by the gestational testosterone-treated offspring. © 2014 Society for Reproduction and Fertility.

  15. Risk of placental abruption in relation to migraines and headaches

    Directory of Open Access Journals (Sweden)

    Ananth Cande V

    2010-10-01

    Full Text Available Abstract Background Migraine, a common chronic-intermittent disorder of idiopathic origin characterized by severe debilitating headaches and autonomic nervous system dysfunction, and placental abruption, the premature separation of the placenta, share many common pathophysiological characteristics. Moreover, endothelial dysfunction, platelet activation, hypercoagulation, and inflammation are common to both disorders. We assessed risk of placental abruption in relation to maternal history of migraine before and during pregnancy in Peruvian women. Methods Cases were 375 women with pregnancies complicated by placental abruption, and controls were 368 women without an abruption. During in-person interviews conducted following delivery, women were asked if they had physician-diagnosed migraine, and they were asked questions that allowed headaches and migraine to be classified according to criteria established by the International Headache Society. Logistic regression procedures were used to calculate odds ratios (aOR and 95% confidence intervals (CI adjusted for confounders. Results Overall, a lifetime history of any headaches or migraine was associated with an increased odds of placental abruption (aOR = 1.60; 95% CI 1.16-2.20. A lifetime history of migraine was associated with a 2.14-fold increased odds of placental abruption (aOR = 2.14; 95% CI 1.22-3.75. The odds of placental abruption was 2.11 (95% CI 1.00-4.45 for migraineurs without aura; and 1.59 (95% 0.70-3.62 for migraineurs with aura. A lifetime history of tension-type headache was also increased with placental abruption (aOR = 1.61; 95% CI 1.01-2.57. Conclusions This study adds placental abruption to a growing list of pregnancy complications associated with maternal headache/migraine disorders. Nevertheless, prospective cohort studies are needed to more rigorously evaluate the extent to which migraines and/or its treatments are associated with the occurrence of placental abruption.

  16. Paradoxical increase in maternal plasma leptin levels in food-restricted gestation: contribution by placental and adipose tissue.

    Science.gov (United States)

    Jelks, Andrea; Belkacemi, Louiza; Han, Guang; Chong, Wei-Lin; Ross, Michael G; Desai, Mina

    2009-07-01

    Maternal food restriction (FR) during pregnancy results in decreased body weight with increased plasma leptin. To address this paradox, we investigated the effects of FR during pregnancy on growth and leptin levels in maternal, placental, and fetal sites. From embryonic day E10, control pregnant rats received ad libitum (AdLib) food, whereas study rats were 50% FR. At gestational ages, E16 and E20, the alterations in maternal body composition, retroperitoneal versus subcutaneous adipose leptin expression, and plasma leptin levels were studied. Furthermore, these changes were related to non-pregnant (NP) status and placental/fetal growth and leptin levels. As compared to NP, both FR and AdLib dams showed a progressive increase in body and lean body mass. However, total body fat was reduced in FR dams but remained unchanged in AdLib dams. Furthermore, plasma leptin levels in FR dams were markedly increased at E20 unlike AdLib dams, which showed moderate increments at E16 and E20. Additionally, FR dams showed significantly decreased leptin expression in subcutaneous and notably unaltered levels in retroperitoneal adipose tissue, suggesting an alternate source of elevated maternal plasma leptin. More importantly, the FR dams had reduced placental weights with paradoxical increased leptin expression at both gestations. Thus, increased plasma leptin levels at E20 in maternal FR pregnancies may be explained, in part, by upregulation of placental leptin. Despite maternal and placental hyperleptinemia during FR pregnancies, the growth-restricted FR fetus had reduced leptin levels. These findings have important implications for pregnancy outcome and fetal growth.

  17. HSPC117 deficiency in cloned embryos causes placental abnormality and fetal death

    Energy Technology Data Exchange (ETDEWEB)

    Wang, Yingying [Department of Reproduction and Development, Kunming Institute of Zoology and Kunming Primate Research Center, Chinese Academy of Sciences, Kunming 650223 (China); State Key Laboratory of Reproductive Biology, Institute of Zoology, Chinese Academy of Sciences, Beijing 100080 (China); Graduate University of Chinese Academy of Sciences, Beijing 100049 (China); Hai, Tang; Liu, Zichuan; Zhou, Shuya; Lv, Zhuo [State Key Laboratory of Reproductive Biology, Institute of Zoology, Chinese Academy of Sciences, Beijing 100080 (China); Graduate University of Chinese Academy of Sciences, Beijing 100049 (China); Ding, Chenhui; Liu, Lei [State Key Laboratory of Reproductive Biology, Institute of Zoology, Chinese Academy of Sciences, Beijing 100080 (China); Niu, Yuyu [Department of Reproduction and Development, Kunming Institute of Zoology and Kunming Primate Research Center, Chinese Academy of Sciences, Kunming 650223 (China); Zhao, Xiaoyang; Tong, Man [State Key Laboratory of Reproductive Biology, Institute of Zoology, Chinese Academy of Sciences, Beijing 100080 (China); Graduate University of Chinese Academy of Sciences, Beijing 100049 (China); Wang, Liu [State Key Laboratory of Reproductive Biology, Institute of Zoology, Chinese Academy of Sciences, Beijing 100080 (China); Jouneau, Alice [INRA, UMR 1198, ENVA, CNRS, FRE 2857, Biologie du Developpement et Reproduction, Jouy en Josas F-78350 (France); Zhang, Xun [Neuroendocrine Unit, Massachusetts General Hospital and Harvard Medical School, Boston, MA 02114 (United States); Ji, Weizhi, E-mail: wji@mail.kiz.ac.cn [Department of Reproduction and Development, Kunming Institute of Zoology and Kunming Primate Research Center, Chinese Academy of Sciences, Kunming 650223 (China); Zhou, Qi, E-mail: qzhou@ioz.ac.cn [State Key Laboratory of Reproductive Biology, Institute of Zoology, Chinese Academy of Sciences, Beijing 100080 (China)

    2010-07-02

    Somatic cell nuclear transfer (SCNT) has been successfully used in many species to produce live cloned offspring, albeit with low efficiency. The low frequency of successful development has usually been ascribed to incomplete or inappropriate reprogramming of the transferred nuclear genome. Elucidating the genetic differences between normal fertilized and cloned embryos is key to understand the low efficiency of SCNT. Here, we show that expression of HSPC117, which encodes a hypothetical protein of unknown function, was absent or very low in cloned mouse blastocysts. To investigate the role of HSPC117 in embryo development, we knocked-down this gene in normal fertilized embryos using RNA interference. We assessed the post-implantation survival of HSPC117 knock-down embryos at 3 stages: E9 (prior to placenta formation); E12 (after the placenta was fully functional) and E19 (post-natal). Our results show that, although siRNA-treated in vivo fertilized/produced (IVP) embryos could develop to the blastocyst stage and implanted without any difference from control embryos, the knock-down embryos showed substantial fetal death, accompanied by placental blood clotting, at E12. Furthermore, comparison of HSPC117 expression in placentas of nuclear transfer (NT), intracytoplasmic sperm injection (ICSI) and IVP embryos confirmed that HSPC117 deficiency correlates well with failures in embryo development: all NT embryos with a fetus, as well as IVP and ICSI embryos, had normal placental HSPC117 expression while those NT embryos showing reduced or no expression of HSPC117 failed to form a fetus. In conclusion, we show that HSPC117 is an important gene for post-implantation development of embryos, and that HSPC117 deficiency leads to fetal abnormalities after implantation, especially following placental formation. We suggest that defects in HSPC117 expression may be an important contributing factor to loss of cloned NT embryos in vivo.

  18. Longitudinal study of serum placental GH in 455 normal pregnancies

    DEFF Research Database (Denmark)

    Chellakooty, Marla; Skibsted, Lillian; Skouby, Sven O

    2002-01-01

    women with normal singleton pregnancies at approximately 19 and 28 wk gestation. Serum placental GH concentrations were measured by a highly specific immunoradiometric assay, and fetal size was measured by ultrasound. Data on birth weight, gender, prepregnancy body mass index (BMI), parity, and smoking.......002). Placental GH at second examination was positively correlated with gestational age (P = 0.002) and negatively correlated with prepregnancy BMI (P = 0.039). Placental GH correlated with fetal weight at approximately 28 wk gestation (P = 0.002) but did not predict birth weight at term. Our study supports...

  19. [How to stimulate the placental function (author's transl)].

    Science.gov (United States)

    Fanard, A; Picazo, J J

    1976-01-01

    Imminent abortion, habitual abortion and threatened premature labor, all constitute difficult clinical problems. Those cases require on every occasion a diagnosis as acurate as possible, and unfortunately our present methods of biochemical determinations only represent a means to evaluate placental function. On those cases where a faulty placental function is detected thru the tests presently available, the authors recommend the utilization of a placentotropic substance, Gestanon, that is capable to stimulate and normalize the placental function, a is demostrated by the statistical results published in the international medical bibliography.

  20. Peri-Implantation Hormonal Milieu: Elucidating Mechanisms of Abnormal Placentation and Fetal Growth1

    Science.gov (United States)

    Mainigi, Monica A.; Olalere, Devvora; Burd, Irina; Sapienza, Carmen; Bartolomei, Marisa; Coutifaris, Christos

    2013-01-01

    ABSTRACT Assisted reproductive technologies (ART) have been associated with several adverse perinatal outcomes involving placentation and fetal growth. It is critical to examine each intervention individually in order to assess its relationship to the described adverse perinatal outcomes. One intervention ubiquitously used in ART is superovulation with gonadotropins. Superovulation results in significant changes in the hormonal milieu, which persist during the peri-implantation and early placentation periods. Epidemiologic evidence suggests that the treatment-induced peri-implantation maternal environment plays a critical role in perinatal outcomes. In this study, using the mouse model, we have isolated the exposure to the peri-implantation period, and we examine the effect of superovulation on placentation and fetal growth. We report that the nonphysiologic peri-implantation maternal hormonal environment resulting from gonadotropin stimulation appears to have a direct effect on fetal growth, trophoblast differentiation, and gene expression. This appears to be mediated, at least in part, through trophoblast expansion and invasion. Although the specific molecular and cellular mechanism(s) leading to these observations remain to be elucidated, identifying this modifiable risk factor will not only allow us to improve perinatal outcomes with ART, but help us understand the pathophysiology contributing to these outcomes. PMID:24352558

  1. The peroxisome proliferator-activated receptors under epigenetic control in placental metabolism and fetal development.

    Science.gov (United States)

    Lendvai, Ágnes; Deutsch, Manuel J; Plösch, Torsten; Ensenauer, Regina

    2016-05-15

    The placental metabolism can adapt to the environment throughout pregnancy to both the demands of the fetus and the signals from the mother. Such adaption processes include epigenetic mechanisms, which alter gene expression and may influence the offspring's health. These mechanisms are linked to the diversity of prenatal environmental exposures, including maternal under- or overnutrition or gestational diabetes. The peroxisome proliferator-activated receptors (PPARs) are nuclear receptors that contribute to the developmental plasticity of the placenta by regulating lipid and glucose metabolism pathways, including lipogenesis, steroidogenesis, glucose transporters, and placental signaling pathways, thus representing a link between energy metabolism and reproduction. Among the PPAR isoforms, PPARγ appears to be the main modulator of mammalian placentation. Certain fatty acids and lipid-derived moieties are the natural activating PPAR ligands. By controlling the amounts of maternal nutrients that go across to the fetus, the PPARs play an important regulatory role in placenta metabolism, thereby adapting to the maternal nutritional status. As demonstrated in animal studies, maternal nutrition during gestation can exert long-term influences on the PPAR methylation pattern in offspring organs. This review underlines the current state of knowledge on the relationship between environmental factors and the epigenetic regulation of the PPARs in placenta metabolism and offspring development. Copyright © 2016 the American Physiological Society.

  2. Factors affecting the placental transfer of actinides

    Energy Technology Data Exchange (ETDEWEB)

    Sikov, M.R.; Kelman, B.J. (Pacific Northwest Laboratory, Richland, WA (USA))

    1989-01-01

    The primary goal of this paper is to consider factors that affect the availability and transport of actinides from maternal blood, through the placenta, to the conceptus. These factors, of particular importance in scaling results from animals to man, include the route and temporal pattern of administration, the mass and physicochemical state of material administered, metabolism of the pregnant animal and fetal organs or tissue, and species-specific changes in placental structure relative to stage of gestation at exposure. Preliminary concepts for descriptive and kinetic models are proposed to integrate these results, to identify additional information required for developing more comprehensive models, and to provide a basis for scaling to human pregnancies for purposes of radiation dosimetry.

  3. MyD88 Signaling Is Directly Involved in the Development of Murine Placental Malaria

    Science.gov (United States)

    Barboza, Renato; Reis, Aramys Silva; da Silva, Leandro Gustavo; Hasenkamp, Lutero; Pereira, Keitty Raquel Benevides; Câmara, Niels Olsen Saraiva; Costa, Fabio Trindade Maranhão; Lima, Maria Regina D'Império; Alvarez, José Maria; Boscardin, Silvia Beatriz; Epiphanio, Sabrina

    2014-01-01

    Malaria is a widespread infectious disease caused by the parasite Plasmodium. During pregnancy, malaria infection leads to a range of complications that can affect both the mother and fetus, including stillbirth, infant mortality, and low birth weight. In this study, we utilized a mouse model of placental malaria (PM) infection to determine the importance of the protein MyD88 in the host immune response to Plasmodium during pregnancy. Initially, we demonstrated that Plasmodium berghei NK65GFP adhered to placental tissue via chondroitin sulfate A and induced PM in mice with a C57BL/6 genetic background. To evaluate the involvement of MyD88 in the pathology of PM, we performed a histopathological analysis of placentas obtained from MyD88−/− and wild-type (WT) mice following infection on the 19th gestational day. Our data demonstrated that the detrimental placental alterations observed in the infected mice were correlated with the expression of MyD88. Moreover, in the absence of this protein, production of interleukin 6 (IL-6) and tumor necrosis factor alpha (TNF-α) was significantly reduced in the infected mice. More importantly, in contrast to fetuses from infected WT mice, which exhibited a reduction in body weight, the fetuses from infected MyD88−/− mice did not display significant weight loss compared to their noninfected littermates. In addition, we observed a decrement of maternal care associated with malaria infection, which was attenuated in the MyD88-deficient mice. Collectively, the results of this study illustrate the pivotal importance of the MyD88 signaling pathway in the pathogenesis of placental malaria, thus presenting new possibilities for targeting MyD88 in therapeutic interventions. PMID:24478096

  4. Plasmodium vivax adherence to placental glycosaminoglycans.

    Directory of Open Access Journals (Sweden)

    Kesinee Chotivanich

    Full Text Available BACKGROUND: Plasmodium vivax infections seldom kill directly but do cause indirect mortality by reducing birth weight and causing abortion. Cytoadherence and sequestration in the microvasculature are central to the pathogenesis of severe Plasmodium falciparum malaria, but the contribution of cytoadherence to pathology in other human malarias is less clear. METHODOLOGY: The adherence properties of P. vivax infected red blood cells (PvIRBC were evaluated under static and flow conditions. PRINCIPAL FINDINGS: P. vivax isolates from 33 patients were studied. None adhered to immobilized CD36, ICAM-1, or thrombospondin, putative ligands for P. falciparum vascular cytoadherence, or umbilical vein endothelial cells, but all adhered to immobilized chondroitin sulphate A (CSA and hyaluronic acid (HA, the receptors for adhesion of P. falciparum in the placenta. PvIRBC also adhered to fresh placental cells (N = 5. Pre-incubation with chondroitinase prevented PvIRBC adherence to CSA, and reduced binding to HA, whereas preincubation with hyaluronidase prevented adherence to HA, but did not reduce binding to CSA significantly. Pre-incubation of PvIRBC with soluble CSA and HA reduced binding to the immobilized receptors and prevented placental binding. PvIRBC adhesion was prevented by pre-incubation with trypsin, inhibited by heparin, and reduced by EGTA. Under laminar flow conditions the mean (SD shear stress reducing maximum attachment by 50% was 0.06 (0.02 Pa but, having adhered, the PvIRBC could then resist detachment by stresses up to 5 Pa. At 37 °C adherence began approximately 16 hours after red cell invasion with maximal adherence at 30 hours. At 39 °C adherence began earlier and peaked at 24 hours. SIGNIFICANCE: Adherence of P. vivax-infected erythrocytes to glycosaminoglycans may contribute to the pathogenesis of vivax malaria and lead to intrauterine growth retardation.

  5. Human placental multipotent mesenchymal stromal cells modulate placenta angiogenesis through Slit2-Robo signaling.

    Science.gov (United States)

    Chen, Cheng-Yi; Tsai, Chin-Han; Chen, Chia-Yu; Wu, Yi-Hsin; Chen, Chie-Pein

    2016-03-03

    The objective of this study was to investigate whether human placental multipotent mesenchymal stromal cell (hPMSC)-derived Slit2 and endothelial cell Roundabout (Robo) receptors are involved in placental angiogenesis. The hPMSC-conditioned medium and human umbilical vein endothelial cells were studied for Slit2 and Robo receptor expression by immunoassay and RT-PCR. The effect of the conditioned medium of hPMSCs with or without Slit2 depletion on endothelial cells was investigated by in vitro angiogenesis using growth factor-reduced Matrigel. hPMSCs express Slit2 and both Robo1 and Robo4 are present in human umbilical vein endothelial cells. Human umbilical vein endothelial cells do not express Robo2 and Robo3. The hPMSC-conditioned medium and Slit2 recombinant protein significantly inhibit the endothelial cell migration, but not by the hPMSC-conditioned medium with Slit2 depletion. The hPMSC-conditioned medium and Slit2 significantly enhance endothelial tube formation with increased cumulated tube length, polygonal network number and vessel branching point number compared to endothelial cells alone. The tube formation is inhibited by the depletion of Slit2 from the conditioned medium, or following the expression of Robo1, Robo4, and both receptor knockdown using small interfering RNA. Furthermore, co-immunoprecipitation reveals Slit2 binds to Robo1 and Robo4. Robo1 interacts and forms a heterodimeric complex with Robo4. These results suggest the implication of both Robo receptors with Slit2 signaling, which is involved in endothelial cell angiogenesis. Slit2 in the conditioned medium of hPMSCs has functional effect on endothelial cells and may play a role in placental angiogenesis.

  6. Placental polyp: a rare cause of iron deficiency anemia

    Directory of Open Access Journals (Sweden)

    Fernando Peixoto Ferraz de Campos

    2011-12-01

    Full Text Available Placental polyps are defined as pedunculated or polypoid fragments of placentaor ovular membranes retained for an indefinite period of time into the uterus afterabortion or child birth. An important cause of retention is placental accretism, anabnormal adherence of the placenta into the uterine wall. Chronic cases are rarelyreported in the literature. In these cases, the placental retention in the immediatepostpartum is not followed by heavy bleeding what makes the diagnosischallenging. We report a rare case of iron-deficiency anemia in a multiparous29-year-old female patient two years after the last delivery. She sought medicalcare with clinical symptoms of anemia and recent menses alterations. Therewas no history of abortion. On gynecological examination, there was a twofoldenlarged uterus, and the pelvic ultrasound revealed an image compatible with anendometrial polyp. She underwent open hysterectomy because of uncontrollablebleeding followed by hypotension after curettage. The histolopathologicexamination revealed a partially hyalinized and necrotic placental polyp.

  7. The effect of smoking on serum human placental lactogen levels.

    Science.gov (United States)

    Spellacy, W N; Buhi, W C; Birk, S A

    1977-02-01

    Serial serum samples (162) were drawn weekly from normal pregnant women (53) during the last month of gestation and measurements were made of the human placental lactogen (HPL) content. The women were interviewed as to their smoking habits and divided into nonsmokers (32) and smokers of from one to two packages of cigarettes per day (21). The infant birth weight and placental weights were not significantly different. The HPL levels were elevated in the women who smoked and the differences were significant at the thirty-sixth and thirty-eighth weeks. The importance of this in interpreting HPL as a placental function test and in terms of the biology of placental function and the control of protein hormone synthesis is emphasized.

  8. Placental loctogen levels associated with gross fetal abnormality.

    Science.gov (United States)

    Gau, G S; Cadle, G

    1977-02-01

    Four cases of severe congenital abnormality associated with persistently low maternal serum human placental lactogen levels are described. It is thought that this pattern might act as a warning of severe fetal abnormality.

  9. Comparative Placentation: Some Interesting Modifications for Histotrophic Nutrition - A Review

    DEFF Research Database (Denmark)

    Enders; Carter, Anthony M.

    2006-01-01

    In considering the diversity of Eutherian mammalian placental structure, it is helpful to keep in mind that both phylogenetically and ontogenetically a functional yolk sac placenta precedes development of the chorioallantoic placenta. Usually the chorioallantoic placenta progressively displaces t...

  10. Placental fetal vascular thrombosis lesions and maternal thrombophilia

    NARCIS (Netherlands)

    Beeksma, F. A.; Erwich, J. J. H. M.; Khong, T. Y.

    Aims: Following intrauterine fetal death (IUFD), the placental fetal vessels undergo regressive changes. These changes are virtually indistinguishable from lesions that are the result of fetal vascular thrombosis (FVT). This study investigated the relation between these lesions and maternal

  11. The new framework for understanding placental mammal evolution.

    Science.gov (United States)

    Asher, Robert J; Bennett, Nigel; Lehmann, Thomas

    2009-08-01

    An unprecedented level of confidence has recently crystallized around a new hypothesis of how living placental mammals share a pattern of common descent. The major groups are afrotheres (e.g., aardvarks, elephants), xenarthrans (e.g., anteaters, sloths), laurasiatheres (e.g., horses, shrews), and euarchontoglires (e.g., humans, rodents). Compared with previous hypotheses this tree is remarkably stable; however, some uncertainty persists about the location of the placental root, and (for example) the position of bats within laurasiatheres, of sea cows and aardvarks within afrotheres, and of dermopterans within euarchontoglires. A variety of names for sub-clades within the new placental mammal tree have been proposed, not all of which follow conventions regarding priority and stability. More importantly, the new phylogenetic framework enables the formulation of new hypotheses and testing thereof, for example regarding the possible developmental dichotomy that seems to distinguish members of the newly identified southern and northern radiations of living placental mammals.

  12. Monocarboxylate transporter 8 modulates the viability and invasive capacity of human placental cells and fetoplacental growth in mice.

    Science.gov (United States)

    Vasilopoulou, Elisavet; Loubière, Laurence S; Heuer, Heike; Trajkovic-Arsic, Marija; Darras, Veerle M; Visser, Theo J; Lash, Gendie E; Whitley, Guy S; McCabe, Christopher J; Franklyn, Jayne A; Kilby, Mark D; Chan, Shiao Y

    2013-01-01

    Monocarboxylate transporter 8 (MCT8) is a well-established thyroid hormone (TH) transporter. In humans, MCT8 mutations result in changes in circulating TH concentrations and X-linked severe global neurodevelopmental delay. MCT8 is expressed in the human placenta throughout gestation, with increased expression in trophoblast cells from growth-restricted pregnancies. We postulate that MCT8 plays an important role in placental development and transplacental TH transport. We investigated the effect of altering MCT8 expression in human trophoblast in vitro and in a Mct8 knockout mouse model. Silencing of endogenous MCT8 reduced T3 uptake into human extravillous trophoblast-like cells (SGHPL-4; 40%, PMCT8 over-expression transiently increased T3 uptake (SGHPL-4∶30%, PMCT8 did not significantly affect SGHPL-4 invasion, but with MCT8 over-expression T3 treatment promoted invasion compared with no T3 (3.3-fold; PMCT8 silencing increased cytotrophoblast viability (∼20%, PMCT8 over-expression reduced cytotrophoblast viability independently of T3 (∼20%, PMct8 knockout reduced fetal:placental weight ratios compared with wild-type controls at gestational day 18 (25%, Pfetal and placental weights were not significantly different. The volume fraction of the labyrinthine zone of the placenta, which facilitates maternal-fetal exchange, was reduced in Mct8 knockout placentae (10%, PMCT8 makes a significant contribution to T3 uptake into human trophoblast cells and has a role in modulating human trophoblast cell invasion and viability. In mice, Mct8 knockout has subtle effects upon fetoplacental growth and does not significantly affect placental cell viability probably due to compensatory mechanisms in vivo.

  13. Maternal serum placental growth hormone, but not human placental lactogen or insulin growth factor-1, is positively associated with fetal growth in the first half of pregnancy

    DEFF Research Database (Denmark)

    Pedersen, N G; Juul, A; Christiansen, M

    2010-01-01

    To investigate if maternal levels of human placental lactogen (hPL), placental growth hormone (PGH) and insulin-like growth factor-1 (IGF-1) are associated with growth rate of the biparietal diameter (BPD) in the first half of pregnancy.......To investigate if maternal levels of human placental lactogen (hPL), placental growth hormone (PGH) and insulin-like growth factor-1 (IGF-1) are associated with growth rate of the biparietal diameter (BPD) in the first half of pregnancy....

  14. Prenatal testosterone-induced fetal growth restriction is associated with down-regulation of rat placental amino acid transport

    Directory of Open Access Journals (Sweden)

    Hankins Gary DV

    2011-08-01

    Full Text Available Abstract Background Exposure of pregnant mothers to elevated concentrations of circulating testosterone levels is associated with fetal growth restriction and delivery of small-for-gestational-age babies. We examined whether maternal testosterone crosses the placenta to directly suppress fetal growth or if it modifies placental function to reduce the capacity for transport of nutrients to the fetus. Methods Pregnant rats were exposed to testosterone propionate (TP; 0.5 mg/kg by daily subcutaneous injection from gestational days (GD 15-19. Maternal and fetal testosterone levels, placental nutrient transport activity and expression of transporters and birth weight of pups and their anogenital distances were determined. Results This dose of TP doubled maternal testosterone levels but had no effect on fetal testosterone levels. Maternal daily weight gain was significantly lower only on GD 19 in TP treated dams compared to controls. Placental weight and birth weight of pups were significantly reduced, but the anogenital distance of pups were unaffected by TP treatment. Maternal plasma amino acids concentrations were altered following testosterone exposure, with decreases in glutamine, glycine, tyrosine, serine, proline, and hydroxyproline and increases in asparagine, isoleucine, leucine, lysine, histidine and arginine. In the TP dams, placental system A amino acid transport activity was significantly reduced while placental glucose transport capacity was unaffected. Decreased expression of mRNA and protein levels of slc38a2/Snat2, an amino acid transporter, suggests that reduced transporter proteins may be responsible for the decrease in amino acid transport activity. Conclusions Taken together, these data suggest that increased maternal testosterone concentrations do not cross the placenta to directly suppress fetal growth but affects amino acid nutrient delivery to the fetus by downregulating specific amino acid transporter activity.

  15. A thrombomodulin mutation that impairs active protein C generation is detrimental in severe pneumonia-derived gram-negative sepsis (melioidosis.

    Directory of Open Access Journals (Sweden)

    Liesbeth M Kager

    2014-04-01

    Full Text Available BACKGROUND: During severe (pneumosepsis inflammatory and coagulation pathways become activated as part of the host immune response. Thrombomodulin (TM is involved in a range of host defense mechanisms during infection and plays a pivotal role in activation of protein C (PC into active protein C (APC. APC has both anticoagulant and anti-inflammatory properties. In this study we investigated the effects of impaired TM-mediated APC generation during melioidosis, a common form of community-acquired Gram-negative (pneumosepsis in South-East Asia caused by Burkholderia (B. pseudomallei. METHODOLOGY/PRINCIPAL FINDINGS: (WT mice and mice with an impaired capacity to activate protein C due to a point mutation in their Thbd gene (TMpro/pro mice were intranasally infected with B. pseudomallei and sacrificed after 24, 48 or 72 hours for analyses. Additionally, survival studies were performed. When compared to WT mice, TMpro/pro mice displayed a worse survival upon infection with B. pseudomallei, accompanied by increased coagulation activation, enhanced lung neutrophil influx and bronchoalveolar inflammation at late time points, together with increased hepatocellular injury. The TMpro/pro mutation had limited if any impact on bacterial growth and dissemination. CONCLUSION/SIGNIFICANCE: TM-mediated protein C activation contributes to protective immunity after infection with B. pseudomallei. These results add to a better understanding of the regulation of the inflammatory and procoagulant response during severe Gram-negative (pneumosepsis.

  16. Improvement of blood compatibility on polysulfone-polyvinylpyrrolidone blend films as a model membrane of dialyzer by physical adsorption of recombinant soluble human thrombomodulin (ART-123).

    Science.gov (United States)

    Omichi, Masaaki; Matsusaki, Michiya; Maruyama, Ikuro; Akashi, Mitsuru

    2012-01-01

    ART-123 is a recombinant soluble human thrombomodulin (hTM) with potent anticoagulant activity, and is available for developing antithrombogenic surfaces by immobilization. We focused on improving blood compatibility on the dialyzer surface by the physical adsorption of ART-123 as a safe yet simple method without using chemical reagents. The physical adsorption mechanism and anticoagulant activities of adsorbed hTM on the surface of a polysulfone (PSF) membrane containing polyvinylpyrrolidone (PVP) as a model dialyzer were investigated in detail. The PVP content of the PSF-PVP films was saturated at 20 wt% after immersion in Tris-HCl buffer, even with the addition of over 20 wt% PVP. The surface morphology of the PSF-PVP films was strongly influenced by the PVP content, because PVP covered the outermost surface of the PSF-PVP films. The adsorption speed of hTM slowed dramatically with increasing PVP content up to 10 wt%, but the maximum adsorption amount of hTM onto the PSF-PVP film surface was almost the same, regardless of the PVP content. The PSF-PVP film with the physically adsorbed hTM showed higher protein C activity as compared to the PSF film, it showed excellent blood compatibility due to the protein C activity and the inhibition properties of platelet adhesion. The physical adsorption of hTM can be useful as a safe yet simple method to improve the blood compatibility of a dialyzer surface.

  17. Analysis of homeobox gene action may reveal novel angiogenic pathways in normal placental vasculature and in clinical pregnancy disorders associated with abnormal placental angiogenesis.

    Directory of Open Access Journals (Sweden)

    Padma eMurthi

    2014-06-01

    Full Text Available Homeobox genes are essential for both the development of the blood and lymphatic vascular systems, as well as for their maintenance in the adult. Homeobox genes comprise an important family of transcription factors, which are characterised by a well conserved DNA binding motif; the homeodomain. The specificity of the homeodomain allows the transcription factor to bind to the promoter regions of batteries of target genes and thereby regulates their expression. Target genes identified for homeodomain proteins have been shown to control fundamental cell processes such as proliferation, differentiation and apoptosis. We and others have reported that homeobox genes are expressed in the placental vasculature, but our knowledge of their downstream target genes is limited. This review highlights the importance of studying the cellular and molecular mechanisms by which homeobox genes and their downstream targets may regulate important vascular cellular processes such as proliferation, migration, and endothelial tube formation, which are essential for placental vasculogenesis and angiogenesis. A better understanding of the molecular targets of homeobox genes may lead to new therapies for aberrant angiogenesis associated with clinically important pregnancy pathologies, including fetal growth restriction and preeclampsia.

  18. Placental Vascular Tree as Biomarker of Autism/ASD Risk

    Science.gov (United States)

    2013-09-01

    Carolyn M. Salafia, MD, MS, NYS Institute for Basic Research in Developmental Disabilities (IBR), 1050 Forest Hill Road, Staten Island, NY, 10314. Co...Carolyn M Salafia, MD, Institute for Basic Research (IBR), 1050 Forest Hill Road, Staten Island, NY, 10314. Co-Investigators: Michael Yampolsky, PhD...computer platforms; and Maplesoft Maple 9.0 Math & Engineering software. Placental histopathology diagnoses Placental disease was characterized by gross

  19. Multiscale modelling of the feto–placental vasculature

    Science.gov (United States)

    Clark, A. R.; Lin, M.; Tawhai, M.; Saghian, R.; James, J. L.

    2015-01-01

    The placenta provides all the nutrients required for the fetus through pregnancy. It develops dynamically, and, to avoid rejection of the fetus, there is no mixing of fetal and maternal blood; rather, the branched placental villi ‘bathe’ in blood supplied from the uterine arteries. Within the villi, the feto–placental vasculature also develops a complex branching structure in order to maximize exchange between the placental and maternal circulations. To understand the development of the placenta, we must translate functional information across spatial scales including the interaction between macro- and micro-scale haemodynamics and account for the effects of a dynamically and rapidly changing structure through the time course of pregnancy. Here, we present steps towards an anatomically based and multiscale approach to modelling the feto–placental circulation. We assess the effect of the location of cord insertion on feto–placental blood flow resistance and flow heterogeneity and show that, although cord insertion does not appear to directly influence feto–placental resistance, the heterogeneity of flow in the placenta is predicted to increase from a 19.4% coefficient of variation with central cord insertion to 23.3% when the cord is inserted 2 cm from the edge of the placenta. Model geometries with spheroidal and ellipsoidal shapes, but the same volume, showed no significant differences in flow resistance or heterogeneity, implying that normal asymmetry in shape does not affect placental efficiency. However, the size and number of small capillary vessels is predicted to have a large effect on feto–placental resistance and flow heterogeneity. Using this new model as an example, we highlight the importance of taking an integrated multi-disciplinary and multiscale approach to understand development of the placenta. PMID:25844150

  20. Multiscale modelling of the feto-placental vasculature.

    Science.gov (United States)

    Clark, A R; Lin, M; Tawhai, M; Saghian, R; James, J L

    2015-04-06

    The placenta provides all the nutrients required for the fetus through pregnancy. It develops dynamically, and, to avoid rejection of the fetus, there is no mixing of fetal and maternal blood; rather, the branched placental villi 'bathe' in blood supplied from the uterine arteries. Within the villi, the feto-placental vasculature also develops a complex branching structure in order to maximize exchange between the placental and maternal circulations. To understand the development of the placenta, we must translate functional information across spatial scales including the interaction between macro- and micro-scale haemodynamics and account for the effects of a dynamically and rapidly changing structure through the time course of pregnancy. Here, we present steps towards an anatomically based and multiscale approach to modelling the feto-placental circulation. We assess the effect of the location of cord insertion on feto-placental blood flow resistance and flow heterogeneity and show that, although cord insertion does not appear to directly influence feto-placental resistance, the heterogeneity of flow in the placenta is predicted to increase from a 19.4% coefficient of variation with central cord insertion to 23.3% when the cord is inserted 2 cm from the edge of the placenta. Model geometries with spheroidal and ellipsoidal shapes, but the same volume, showed no significant differences in flow resistance or heterogeneity, implying that normal asymmetry in shape does not affect placental efficiency. However, the size and number of small capillary vessels is predicted to have a large effect on feto-placental resistance and flow heterogeneity. Using this new model as an example, we highlight the importance of taking an integrated multi-disciplinary and multiscale approach to understand development of the placenta.

  1. [Fetal circulation in normal pregnancy and in placental insufficiency].

    Science.gov (United States)

    Ivanov, B; Malinova, M

    2010-01-01

    The fetal circulation is different from the adult circulation. One of the quite common conditions that are challenging to the developing fetus is placental hypoxia. Regardless of its cause, placental vascular insufficiency is commonly assumed to be an important factor in the development of intrauterine growth retardation. Several mechanisms are involved in the fetal adaptation to the decompensation during hypoxemia. Doppler Ultrasound technologies can help to evaluate of the fetal wellbeing.

  2. Role of mouse Wdr13 in placental growth; a genetic evidence for lifetime body weight determination by placenta during development.

    Science.gov (United States)

    Singh, Vijay Pratap; Alex, Jomini Liza; Lakshmi, B Jyothi; Sailasree, S Purnima; Raj, T Avinash; Kumar, Satish

    2015-08-26

    Placental development is essential for implantation and growth of foetus in the uterus of eutherian mammals. Numerous growth factors are responsible for placental development and cell lineage differentiation. Gene knockout mice have shown role of various genes in the placenta. Here using Wdr13 knockout mice, we show that this gene is important for proper placental development. Wdr13, a X-linked gene, expresses in multiple trophoblast cell types of placenta and the mutant placenta had reduced size after 17.5 dpc due to reduction of junctional zone (JZ) and labyrinth zone (LZ). We observed reduction in levels of angiopoietin-2 and cd44 mRNA in Wdr13 mutant placenta as compared to that in the wild type. Our findings show that Wdr13 is required for normal placental development and cell differentiation. Wdr13 heterozygous female placenta when the mutant allele was of maternal origin showed similar defects as those in case of Wdr13 null placenta. Using two types of heterozygous females carrying either maternally and paternally derived mutant Wdr13 allele we provide genetic evidence that development of placenta determines body weight of mice for the entire life.

  3. Placental-derived stem cells: Culture, differentiation andchallenges

    Institute of Scientific and Technical Information of China (English)

    2015-01-01

    Stem cell therapy is a promising approach to clinicalhealing in several diseases. A great variety of tissues(bone marrow, adipose tissue, and placenta) arepotentially sources of stem cells. Placenta-derivedstem cells (p-SCs) are in between embryonic andmesenchymal stem cells, sharing characteristics withboth, such as non-carcinogenic status and property todifferentiate in all embryonic germ layers. Moreover,their use is not ethically restricted as fetal membranesare considered medical waste after birth. In this context,the present review will be focused on the biologicalproperties, culture and potential cell therapy usesof placental-derived stem cells. Immunophenotypecharacterization, mainly for surface marker expression,and basic principles of p-SC isolation and culture(mechanical separation or enzymatic digestion ofthe tissues, the most used culture media, cell platingconditions) will be presented. In addition, somepreclinical studies that were performed in differentmedical areas will be cited, focusing on neurological,liver, pancreatic, heart, muscle, pulmonary, and bonediseases and also in tissue engineering field. Finally,some challenges for stem cell therapy applications willbe highlighted. The understanding of the mechanismsinvolved in the p-SCs differentiation and the achievementof pure cell populations (after differentiation) arekey points that must be clarified before bringing thepreclinical studies, performed at the bench, to themedical practice.

  4. Placental Growth Factor Promotes Cardiac Muscle Repair via Enhanced Neovascularization

    Directory of Open Access Journals (Sweden)

    Jianfeng Zhang

    2015-06-01

    Full Text Available Background/Aims: Transplantation of mesenchymal stem cells (MSCs improves post-injury cardiac muscle repair using ill-defined mechanisms. Recently, we have shown that production and secretion of placental growth factor (PLGF by MSCs play a critical role in the MSCs-mediated post-injury cardiac muscle repair. In this study, we addressed the underlying molecular mechanisms, focusing specifically on the interactions between MSCs, macrophages and endothelial cells. Methods: We isolated macrophages (BM-MΦ from mouse bone-marrow derived cells based on F4/80 expression by flow cytometry. BM-MΦ were treated with different doses of PLGF. Cell number was analyzed by a MTT assay. Macrophage polarization was examined based on CD206 expression by flow cytometry. PLGF levels in macrophage subpopulations were analyzed by RT-qPCR and ELISA. Effects of macrophages on vascularization were evaluated by a collagen gel assay using Human umbilical vein endothelial cells (HUVECs co-cultured with PLGF-treated macrophages. Results: PLGF did not increase macrophage number, but dose-dependently polarized macrophages into a M2 subpopulation. M2 macrophages expressed high levels of PLGF. PLGF-polarized M2 macrophages significantly increased tubular structures in the collagen gel assay. Conclusion: Our data suggest that MSCs-derived PLGF may induce macrophage polarization into a M2 subpopulation, which in turn releases more PLGF to promote local neovascularization for augmenting post-injury cardiac muscle repair. This study thus sheds novel light on the role of PLGF in cardiac muscle regeneration.

  5. Elastase induces lung epithelial cell autophagy through placental growth factor

    Science.gov (United States)

    Hou, Hsin-Han; Cheng, Shih-Lung; Chung, Kuei-Pin; Kuo, Mark Yen-Ping; Yeh, Cheng-Chang; Chang, Bei-En; Lu, Hsuan-Hsuan; Wang, Hao-Chien; Yu, Chong-Jen

    2014-01-01

    Chronic obstructive pulmonary disease (COPD) is a devastating disease, which is associated with increasing mortality and morbidity. Therefore, there is a need to clearly define the COPD pathogenic mechanism and to explore effective therapies. Previous studies indicated that cigarette smoke (CS) induces autophagy and apoptosis in lung epithelial (LE) cells. Excessive ELANE/HNE (elastase, neutrophil elastase), a factor involved in protease-antiprotease imbalance and the pathogenesis of COPD, causes LE cell apoptosis and upregulates the expression of several stimulus-responsive genes. However, whether or not elastase induces autophagy in LE cell remains unknown. The level of PGF (placental growth factor) is higher in COPD patients than non-COPD controls. We hypothesize that elastase induces PGF expression and causes autophagy in LE cells. In this study, we demonstrated that porcine pancreatic elastase (PPE) induced PGF expression and secretion in LE cells in vitro and in vivo. The activation of MAPK8/JNK1 (mitogen-activated protein kinase 8) and MAPK14/p38alpha MAPK signaling pathways was involved in the PGF mediated regulation of the TSC (tuberous sclerosis complex) pathway and autophagy in LE cells. Notably, PGF-induced MAPK8 and MAPK14 signaling pathways mediated the inactivation of MTOR (mechanistic target of rapamycin), the upregulation of MAP1LC3B/LC3B (microtubule-associated protein 1 light chain 3 β) and the increase of autophagosome formation in mice. Furthermore, the PPE-induced autophagy promotes further apoptosis in vitro and in vivo. In summary, elastase-induced autophagy promotes LE cell apoptosis and pulmonary emphysema through the upregulation of PGF. PGF and its downstream MAPK8 and MAPK14 signaling pathways are potential therapeutic targets for the treatment of emphysema and COPD. PMID:24988221

  6. PLACENTAL LOCATION AT SECOND TRIMESTER AND PREGNANCY OUTCOMES

    Directory of Open Access Journals (Sweden)

    Seadati N

    2013-04-01

    Full Text Available The aimed of this study was to find association between location of placental at second trimester and pregnancy outcomes. It was a descriptive -analytic epidemiological study which has performed on 250 pregnant women by simple random sampling in Razi hospital and Imam Khomeini hospital during July 2011 – October 2012 in Ahvaz city, Iran. Placental location was determined by sonography at 18 - 22 weeks of gestation, and it was classified to high / low category and anterior / posterior category. In this study has been assessed placental location with incidence of preeclampsia, intrauterine growth restriction and preterm birth. The incidence of preeclampsia and intrauterine growth restriction was 5.6%, 1.6% respectively, these parameters were not associated with placental location (p=0.84, p=0.69. The incidence of preterm birth was 7.2% and it was associated with low placental location (p=0.01.There was no significant difference between anterior and posterior placenta in all of outcomes. Low placental location was associated with increased risk of preterm labor and preterm delivery.

  7. Metabolism of bupropion by baboon hepatic and placental microsomes.

    Science.gov (United States)

    Wang, Xiaoming; Abdelrahman, Doaa R; Fokina, Valentina M; Hankins, Gary D V; Ahmed, Mahmoud S; Nanovskaya, Tatiana N

    2011-08-01

    The aim of this investigation was to determine the biotransformation of bupropion by baboon hepatic and placental microsomes, identify the enzyme(s) catalyzing the reaction(s) and determine its kinetics. Bupropion was metabolized by baboon hepatic and placental microsomes to hydroxybupropion (OH-BUP), threo- (TB) and erythrohydrobupropion (EB). OH-bupropion was the major metabolite formed by hepatic microsomes (Km 36±6 μM, Vmax 258±32 pmol mg protein(-1) min(-1)), however the formation of OH-BUP by placental microsomes was below the limit of quantification. The apparent Km values of bupropion for the formation of TB and EB by hepatic and placental microsomes were similar. The selective inhibitors of CYP2B6 (ticlopidine and phencyclidine) and monoclonal antibodies raised against human CYP2B6 isozyme caused 80% inhibition of OH-BUP formation by baboon hepatic microsomes. The chemical inhibitors of aldo-keto reductases (flufenamic acid), carbonyl reductases (menadione), and 11β-hydroxysteroid dehydrogenases (18β-glycyrrhetinic acid) significantly decreased the formation of TB and EB by hepatic and placental microsomes. Data indicate that CYP2B of baboon hepatic microsomes is responsible for biotransformation of bupropion to OH-BUP, while hepatic and placental short chain dehydrogenases/reductases and to a lesser extent aldo-keto reductases are responsible for the reduction of bupropion to TB and EB.

  8. Progesterone and testosterone production by dispersed rat placental cells.

    Science.gov (United States)

    Matt, D W; Gibney, J A; Malamed, S; Macdonald, G J

    1986-04-01

    Isopycnic separation and unit gravity sedimentation were employed to identify the rat placental cell types capable of producing progesterone and testosterone. Subdivision of Day 12-dispersed placental cells in Percoll gradients revealed that fractions (less than 1.048 g/ml) containing giant cytotrophoblast cells produced greater quantities of progesterone (p less than 0.01) than did fractions (greater than 1.048 g/ml) with equal numbers of placental cells but void of giant cytotrophoblasts. Unit gravity sedimentation of Day 16-dispersed placental cells revealed that when incubated, isolated giant cytotrophoblast cells were capable of producing both progesterone and testosterone. Both of the separation studies strongly suggested that other cell types also produce steroids. However, the biosynthetic capacity of the giant cytotrophoblast cell appeared to be 1000-fold greater than that of the other cell types. Incubation of Day 12-dispersed placental cells with human chorionic gonadotropin or 3',5'-cyclic adenosine monophosphate did not further increase progesterone production as compared to untreated control incubates, suggesting rat placental steroidogenesis is not under trophic hormone control. Electron microscopic observations of giant cytotrophoblast cells revealed a complex ultrastructure suggesting a variety of physiological functions.

  9. Microvessel density in the placental bed among preeclampsia patients

    Directory of Open Access Journals (Sweden)

    Tarcisio Mota Coelho

    Full Text Available CONTEXT AND OBJECTIVE: Morphological changes in the spiral arteries of the placental bed have been studied in patients with preeclampsia, one of the largest causes of maternal and perinatal morbidity and mortality. The reports show that vasospasm and vascular endothelial injury were two major pathological conditions for preeclampsia. The aim of this study was to investigate the microvessel density of spiral arteries in the placental bed, in pregnancies complicated by hypertension and proteinuria, and in normal pregnancies. DESIGN AND SETTING: This was a cross-sectional survey of immunohistochemical studies on biopsies from the spiral arteries of the placental bed, among women undergoing cesarean sections for clinical and obstetrical reasons at Universidade Federal de São Paulo, São Paulo, Brazil. METHODS: Placental bed biopsies were obtained during cesarean section after placenta removal, with direct viewing of the central area of placenta insertion. The microvessel density of spiral arteries was measured by immunohistochemical methods in decidual and myometrial segments, using CD34 antibody. RESULTS: Biopsies containing spiral arteries were obtained from 34 hypertensive pregnant women with proteinuria, and 26 normotensive pregnant women. The microvessel densities in decidual and myometrial segments of the placental bed were compared between the groups. It was observed that, with increasing blood pressure and proteinuria, the microvessel density gradually decreased. CONCLUSION: The presence of high levels of hypertension and proteinuria may be associated with a progressive decrease in microvessel density in the placental bed.

  10. Fetal insulin and IGF-II contribute to gestational diabetes mellitus (GDM)-associated up-regulation of membrane-type matrix metalloproteinase 1 (MT1-MMP) in the human feto-placental endothelium.

    Science.gov (United States)

    Hiden, U; Lassance, L; Tabrizi, N Ghaffari; Miedl, H; Tam-Amersdorfer, C; Cetin, I; Lang, U; Desoye, G

    2012-10-01

    Gestational diabetes mellitus (GDM)-associated hormonal and metabolic derangements in mother and fetus affect placental development and function. Indeed, in GDM, placentas are characterized by hypervascularization and vascular dysfunction. The membrane-type matrix metalloproteinase 1 (MT1-MMP) is a key player in angiogenesis and vascular expansion. Here, we hypothesized elevated placental MT1-MMP levels in GDM induced by components of the diabetic environment. Therefore, we measured placental MT1-MMP in normal vs. GDM pregnancies, identified potential functional consequences, and investigated the contribution of hyperglycemia and the insulin/IGF axis. Immunohistochemistry identified placental cell types expressing MT1-MMP. MT1-MMP was compared between normal and GDM placentas by immunoblotting. Quantitative PCR of MT1-MMP in primary feto-placental endothelial cells (fpEC) and trophoblasts isolated from both normal and GDM placentas identified the cells contributing to the GDM-associated changes. A putative MT1-MMP role in angiogenesis was determined using blocking antibodies for in vitro angiogenesis assays. Potential GDM-associated factors and signaling pathways inducing MT1-MMP up-regulation in fpEC were identified using kinase inhibitors. Total and active MT1-MMP was increased in GDM placentas (+51 and 54%, respectively, Pfeto-placental endothelium, and insulin and IGF-II contribute. This may account for GDM-associated changes in the feto-placental vasculature.

  11. 1,25(OH)2D3 Induces Placental Vascular Smooth Muscle Cell Relaxation by Phosphorylation of Myosin Phosphatase Target Subunit 1Ser507: Potential Beneficial Effects of Vitamin D on Placental Vasculature in Humans.

    Science.gov (United States)

    Jia, Xiuyue; Gu, Yang; Groome, Lynn J; Al-Kofahi, Mahmoud; Alexander, J Steven; Li, Weimin; Wang, Yuping

    2016-05-01

    Placental vascular dysfunction has been linked to insufficiency/deficiency of maternal vitamin D levels during pregnancy. In contrast, sufficient maternal vitamin D levels have shown beneficial effects on pregnancy outcomes. To study the role of vitamin D in pregnancy, we tested our hypothesis that vitamin D exerts beneficial effects on placental vasculature. We examined expression of CYP2R1, CYP27B1, vitamin D receptor (VDR), and CYP24A1 in placental vascular smooth muscle cells (VSMCs) in response to 1,25(OH)2D3 We found that VDR expression was inducible, CYP27B1 expression was dose-dependently down-regulated, and CYP24A1 expression was dose-dependently up-regulated in cells treated with 1,25(OH)2D3 These data suggest a feedback autoregulatory system of vitamin D existing in placental VSMCs. Using a VSMC/collagen-gel contraction assay, we evaluated the effect of 1,25(OH)2D3 on placental VSMC contractility. We found that, similar to losartan, 1,25(OH)2D3 could diminish angiotensin II-induced cell contractility. The mechanism of 1,25(OH)2D3-mediated VSMC relaxation was further explored by examination of Rho-associated protein kinase 1 (ROCK1)/phosphorylation of myosin phosphatase target subunit 1 (MYPT1) pathway molecules. Our results showed that p-MYPT1(Thr853) and p-MYPT1(Thr696) were undetectable. However, p-MYPT1(Ser507), but not p-MYPT1(Ser668), was significantly up-regulated in cells treated with losartan plus angiotensin II. Similar effects were also seen in cells treated with 1,25(OH)2D3 plus angiotensin II or 1,25(OH)2D3 plus losartan plus angiotensin II. Because MYPT1 serine phosphorylation could activate myosin light chain phosphatase (MLCP), and MLCP activation is an important regulatory machinery of smooth muscle cell relaxation, up-regulation of MYPT1(Ser507) phosphorylation could be a mechanism of vitamin D and/or losartan mediated placental VSMC relaxation.

  12. Low birth weight in response to salt restriction during pregnancy is not due to alterations in uterine-placental blood flow or the placental and peripheral renin-angiotensin system.

    Science.gov (United States)

    Leandro, Sandra Márcia; Furukawa, Luzia Naôko Shinohara; Shimizu, Maria Heloisa Massola; Casarini, Dulce Elena; Seguro, Antonio Carlos; Patriarca, Giuliana; Coelho, Michella Soares; Dolnikoff, Miriam Sterman; Heimann, Joel Claudio

    2008-09-03

    A number of studies conducted in humans and in animals have observed that events occurring early in life are associated with the development of diseases in adulthood. Salt overload and restriction during pregnancy and lactation are responsible for functional (hemodynamic and hormonal) and structural alterations in adult offspring. Our group observed that lower birth weight and insulin resistance in adulthood is associated with salt restriction during pregnancy. On the other hand, perinatal salt overload is associated with higher blood pressure and higher renal angiotensin II content in adult offspring. Therefore, we hypothesised that renin-angiotensin system (RAS) function is altered by changes in sodium intake during pregnancy. Such changes may influence fetoplacental blood flow and thereby fetal nutrient supply, with effects on growth in utero and, consequently, on birth weight. Female Wistar rats were fed low-salt (LS), normal-salt (NS), or high-salt (HS) diet, starting before conception and continuing until day 19 of pregnancy. Blood pressure, heart rate, fetuses and dams' body weight, placentae weight and litter size were measured on day 19 of pregnancy. Cardiac output, uterine and placental blood flow were also determined on day 19. Expressions of renin-angiotensin system components and of the TNF-alpha gene were evaluated in the placentae. Plasma renin activity (PRA) and plasma and tissue angiotensin-converting enzyme (ACE) activity, as well as plasma and placental levels of angiotensins I, II, and 1-7 were measured. Body weight and kidney mass were greater in HS than in NS and LS dams. Food intake did not differ among the maternal groups. Placental weight was lower in LS dams than in NS and HS dams. Fetal weight was lower in the LS group than in the NS and HS groups. The PRA was greater in LS dams than in NS and HS dams, although ACE activity (serum, cardiac, renal, and placental) was unaffected by the level of sodium intake. Placental levels of

  13. Imbalance of placental regulatory T cell and Th17 cell population dynamics in the FIV-infected pregnant cat

    Directory of Open Access Journals (Sweden)

    Boudreaux Crystal E

    2012-05-01

    Full Text Available Abstract Background An appropriate balance in placental regulatory T cells (Tregs, an immunosuppressive cell population, and Th17 cells, a pro-inflammatory cell population, is essential in allowing tolerance of the semi-allogeneic fetus. TGF-β and IL-6 are cytokines that promote differentiation of Tregs and Th17 cells from a common progenitor; aberrant expression of the cytokines may perturb the balance in the two cell populations. We previously reported a pro-inflammatory placental environment with decreased levels of FoxP3, a Treg marker, and increased levels of IL-6 in the placentas of FIV-infected cats at early pregnancy. Thus, we hypothesized that FIV infection in the pregnant cat causes altered placental Treg and Th17 cell populations, possibly resulting in placental inflammation. Methods We examined the effect of FIV infection on Treg and Th17 populations in placentas at early pregnancy using quantitative confocal microscopy to measure FoxP3 or RORγ, a Th17 marker, and qPCR to quantify expression of the key cytokines TGF-β and IL-6. Results FoxP3 and RORγ were positively correlated in FIV-infected placentas at early pregnancy, but not placentas from normal cats, indicating virus-induced alteration in the balance of these cell populations. In control cats the expression of IL-6 and RORγ was positively correlated as predicted, but this relationship was disrupted in infected animals. TGF-β was reduced in infected queens, an occurrence that could dysregulate both Treg and Th17 cell populations. Co-expression analyses revealed a highly significant positive correlation between IL-6 and TGF-β expression in control animals that did not occur in infected animals. Conclusion Collectively, these data point toward potential disruption in the balance of Treg and Th17 cell populations that may contribute to FIV-induced inflammation in the feline placenta.

  14. What do placental function tests predict? Observations on placental lactogen levels in growth retardation and fetal distress.

    Science.gov (United States)

    Obiekwe, B C; Chard, T

    1982-11-01

    Single blood samples were obtained from an unselected population of 527 women between 36 and 40 wk gestation. Serum placental lactogen levels were lower than normal in patients whose infants were growth retarded or developed fetal distress in labor. These associations were independent; the fetal distress group did not contain an excess of subjects with growth retardation. Thus, the results of a biochemical test reflect dynamic aspects of placental function and not simply the overall growth of fetus and placenta.

  15. Placentation in the colugos Cynocephalus volans and Galeopterus variegatus (Dermoptera) and the transition from labyrinthine to villous placentation in primates

    DEFF Research Database (Denmark)

    Carter, A. M.; Mess, A. M.

    2017-01-01

    Introduction Phylogenetics and genomics place colugos as the sister group to primates. Therefore their placentation is of interest in an evolutionary perspective. Previous accounts are fragmentary, not readily accessible and sometimes contradictory. Methods We have examined archival material...... covering the early development of fetal membranes and placenta, the fate of the yolk sac and definitive placentation. Results Initially the trophoblast extended over a rather broad but shallow area, enclosing maternal blood spaces. After expansion of the exocoelom it became covered by somatic mesoderm...

  16. Investigating the effect of excess caffeine exposure on placental angiogenesis using chicken 'functional' placental blood vessel network.

    Science.gov (United States)

    Ma, Zheng-Lai; Wang, Guang; Lu, Wen-Hui; Cheng, Xin; Chuai, Manli; Lee, Kenneth Ka Ho; Yang, Xuesong

    2016-02-01

    It is now known that over-consumption of caffeine by pregnant mothers could have detrimental effects on normal fetal development. However, it remains obscure how caffeine's harmful effect impacts directly or indirectly on the developing embryo/fetus through damaging placenta development. In this study, we demonstrated the morphological similarities between the yolk sac and chorioallantoic membranes (CAM) of chick embryos and the villi of the mammalian placenta. Using the chick yolk sac and the CAM as a model, we found that 5-15 µmol per egg of caffeine exposure inhibited angiogenesis. Under the same condition, cell proliferation in extraembryonic mesoderm was reduced while apoptosis was enhanced. Semi-quantitative RT-PCR analysis revealed that caffeine treatment down-regulated VEGF, VEGFR2, PIGF, IGF2 and NRP1 expression, but up-regulated Ang1 and Ang2 expression. We performed in situ hybridization to show VE-cadherin expression and as to demonstrate the blood vessels in the CAM and yolk sac membranes. This distribution of the VE-cadherin(+) blood vessels was determined to be reduced after caffeine treatment. Furthermore, MDA activity was induced after caffeine exposure, but GSH-PX activity was inhibited after caffeine exposure; SOD activity was unchanged as compared with the control. In summary, our results suggest that caffeine exposure could negatively impact on angiogenesis in the chick yolk sac and CAM by targeting angiogenesis-related genes. Some of these genes are also involved in regulating excess ROS generation. The results implied that the negative impact of caffeine on fetal development was partly attributed to impaired placental angiogenesis.

  17. Evolutionary perspectives into placental biology and disease

    Directory of Open Access Journals (Sweden)

    Edward B. Chuong

    2013-12-01

    Full Text Available In all mammals including humans, development takes place within the protective environment of the maternal womb. Throughout gestation, nutrients and waste products are continuously exchanged between mother and fetus through the placenta. Despite the clear importance of the placenta to successful pregnancy and the health of both mother and offspring, relatively little is understood about the biology of the placenta and its role in pregnancy-related diseases. Given that pre- and peri-natal diseases involving the placenta affect millions of women and their newborns worldwide, there is an urgent need to understand placenta biology and development. Here, we suggest that the placenta is an organ under unique selective pressures that have driven its rapid diversification throughout mammalian evolution. The high divergence of the placenta complicates the use of non-human animal models and necessitates an evolutionary perspective when studying its biology and role in disease. We suggest that diversifying evolution of the placenta is primarily driven by intraspecies evolutionary conflict between mother and fetus, and that many pregnancy diseases are a consequence of this evolutionary force. Understanding how maternal–fetal conflict shapes both basic placental and reproductive biology – in all species – will provide key insights into diseases of pregnancy.

  18. Human placental lactogen levels in multiple pregnancies.

    Science.gov (United States)

    Spellacy, W N; Buhi, W C; Birk, S A

    1978-08-01

    Serum human placental lactogen (hPL) levels were measured in duplicate with a radioimmunoassay in 206 serum samples at 30 and 36 weeks' gestation from women with normal singleton pregnancies (75) or pregnancies with twins (37). One triplet pregnancy was also studied. The results show a significant elevation of hPL in the women with twin pregnancies at both the 30th (7.0 vs 6.0 microgram/ml) and the 36th (9.2 vs 7.4 microgram/ml) weeks. One-third of the twin pregnancies had values of hPL in excess of 8.0 microgram/ml at 30 weeks and more than half had values in excess of 9.0 microgram/ml at 36 weeks. The triplet pregnancy had an hPL value of 11.0 microgram/ml at 36 weeks' gestation. These data support the potential usefulness of serum hPL measurements in the screening profile for the detection of high-risk pregnancies.

  19. Increasing maternal body mass index is associated with systemic inflammation in the mother and the activation of distinct placental inflammatory pathways.

    Science.gov (United States)

    Aye, Irving L M H; Lager, Susanne; Ramirez, Vanessa I; Gaccioli, Francesca; Dudley, Donald J; Jansson, Thomas; Powell, Theresa L

    2014-06-01

    Obese pregnant women have increased levels of proinflammatory cytokines in maternal circulation and placental tissues. However, the pathways contributing to placental inflammation in obesity are largely unknown. We tested the hypothesis that maternal body mass index (BMI) was associated with elevated proinflammatory cytokines in maternal and fetal circulations and increased activation of placental inflammatory pathways. A total of 60 women of varying pre-/early pregnancy BMI, undergoing delivery by Cesarean section at term, were studied. Maternal and fetal (cord) plasma were collected for analysis of insulin, leptin, IL-1beta, IL-6, IL-8, monocyte chemoattractant protein (MCP) 1, and TNFalpha by multiplex ELISA. Activation of the inflammatory pathways in the placenta was investigated by measuring the phosphorylated and total protein expression of p38-mitogen-activated protein kinase (MAPK), c-Jun-N-terminal kinase (JNK)-MAPK, signal transducer-activated transcription factor (STAT) 3, caspase-1, IL-1beta, IkappaB-alpha protein, and p65 DNA-binding activity. To determine the link between activated placental inflammatory pathways and elevated maternal cytokines, cultured primary human trophoblast (PHT) cells were treated with physiological concentrations of insulin, MCP-1, and TNFalpha, and inflammatory signaling analyzed by Western blot. Maternal BMI was positively correlated with maternal insulin, leptin, MCP-1, and TNFalpha, whereas only fetal leptin was increased with BMI. Placental phosphorylation of p38-MAPK and STAT3, and the expression of IL-1beta protein, were increased with maternal BMI; phosphorylation of p38-MAPK was also correlated with birth weight. In contrast, placental NFkappaB, JNK and caspase-1 signaling, and fetal cytokine levels were unaffected by maternal BMI. In PHT cells, p38-MAPK was activated by MCP-1 and TNFalpha, whereas STAT3 phosphorylation was increased following TNFalpha treatment. Maternal BMI is associated with elevated maternal

  20. Alterations of placental cytochrome P450 1A1 and P-glycoprotein in tobacco-induced intrauterine growth retardation in rats

    Institute of Scientific and Technical Information of China (English)

    You-e YAN; Hui WANG; Ying-hong FENG

    2005-01-01

    Aim: To investigate the alterations of placental P-glycoprotein (P-gp) and cytochrome P450 1A1 (CYP1A1) at different gestational days (GD), and to explore the possible significance of placental P-gp and CYP1A1 in tobacco smoke-induced intrauterine growth retardation (IUGR) in rats. Methods: An IUGR model was produced by passive tobacco smoking from GD 7 to parturition (GD 21) and predicted using fetal development parameters. Placental structure and function were monitored by observing pathological alteration and antioxidative function, including the content of malondialdehyde and the activities of superoxide dismutase and catalase (CAT). The expressions of CYP1A1 and P-gp (mdr 1a and mdr 1b)were detected using a reverse transcription polymerase chain reaction and immunohistochemistry. Results: Placental pathological changes occurred and the malondialdehyde content increased, whereas the activities ofsuperoxide dismutase and CAT lowered, when compared to their controls. In the rat placenta of the tobacco group, the level of CYP1A1 mRNA increased significantly; the level of mdr1a mRNA increased significantly at GD 21 but not at GD 14, whereas the level of mdr1b mRNA in different term remained stable; the expression of P-gp increased significantly only in full-term placenta. Conclusion: The expression of placental CYP1A1 and P-gp increased in tobacco-induced IUGR. Overexpression of placental CYP1A1 can attribute to the metabolism of tobacco and the generation of reactive metabolites, which can trigger IUGR. As a compulsory mechanism,upregulation of P-gp might decrease tobacco exposure to a developing fetus with IUGR.

  1. Cholinergic urethral brush cells are widespread throughout placental mammals.

    Science.gov (United States)

    Deckmann, Klaus; Krasteva-Christ, Gabriela; Rafiq, Amir; Herden, Christine; Wichmann, Judy; Knauf, Sascha; Nassenstein, Christina; Grevelding, Christoph G; Dorresteijn, Adriaan; Chubanov, Vladimir; Gudermann, Thomas; Bschleipfer, Thomas; Kummer, Wolfgang

    2015-11-01

    We previously identified a population of cholinergic epithelial cells in murine, human and rat urethrae that exhibits a structural marker of brush cells (villin) and expresses components of the canonical taste transduction signaling cascade (α-gustducin, phospholipase Cβ2 (PLCβ2), transient receptor potential cation channel melanostatin 5 (TRPM5)). These cells serve as sentinels, monitoring the chemical composition of the luminal content for potentially hazardous compounds such as bacteria, and initiate protective reflexes counteracting further ingression. In order to elucidate cross-species conservation of the urethral chemosensory pathway we investigated the occurrence and molecular make-up of urethral brush cells in placental mammals. We screened 11 additional species, at least one in each of the five mammalian taxonomic units primates, carnivora, perissodactyla, artiodactyla and rodentia, for immunohistochemical labeling of the acetylcholine synthesizing enzyme, choline acetyltransferase (ChAT), villin, and taste cascade components (α-gustducin, PLCβ2, TRPM5). Corresponding to findings in previously investigated species, urethral epithelial cells with brush cell shape were immunolabeled in all 11 mammals. In 8 species, immunoreactivities against all marker proteins and ChAT were observed, and double-labeling immunofluorescence confirmed the cholinergic nature of villin-positive and chemosensory (TRPM5-positive) cells. In cat and horse, these cells were not labeled by the ChAT antiserum used in this study, and unspecific reactions of the secondary antiserum precluded conclusions about ChAT-expression in the bovine epithelium. These data indicate that urethral brush cells are widespread throughout the mammalian kingdom and evolved not later than about 64.5millionyears ago.

  2. Hofbauer cells of M2a, M2b and M2c polarization may regulate feto-placental angiogenesis.

    Science.gov (United States)

    Loegl, J; Hiden, U; Nussbaumer, E; Schliefsteiner, C; Cvitic, S; Lang, I; Wadsack, C; Huppertz, B; Desoye, G

    2016-11-01

    The human placenta comprises a special type of tissue macrophages, the Hofbauer cells (HBC), which exhibit M2 macrophage phenotype. Several subtypes of M2-polarized macrophages (M2a, M2b and M2c) exist in almost all tissues. Macrophage polarization depends on the way of macrophage activation and leads to the expression of specific cell surface markers and the acquisition of specific functions, including tissue remodeling and the promotion of angiogenesis. The placenta is a highly vascularized and rapidly growing organ, suggesting a role of HBC in feto-placental angiogenesis. We here aimed to characterize the specific polarization and phenotype of HBC and investigated the role of HBC in feto-placental angiogenesis. Therefore, HBC were isolated from third trimester placentas and their phenotype was determined by the presence of cell surface markers (FACS analysis) and secretion of cytokines (ELISA). HBC conditioned medium (CM) was analyzed for pro-angiogenic factors, and the effect of HBC CM on angiogenesis, proliferation and chemoattraction of isolated primary feto-placental endothelial cells (fpEC) was determined in vitro Our results revealed that isolated HBC possess an M2 polarization, with M2a, M2b and M2c characteristics. HBC secreted the pro-angiogenic molecules VEGF and FGF2. Furthermore, HBC CM stimulated the in vitro angiogenesis of fpEC. However, compared with control medium, chemoattraction of fpEC toward HBC CM was reduced. Proliferation of fpEC was not affected by HBC CM. These findings demonstrate a paracrine regulation of feto-placental angiogenesis by HBC in vitro Based on our collective results, we propose that the changes in HBC number or phenotype may affect feto-placental angiogenesis. © 2016 Society for Reproduction and Fertility.

  3. Placental Cadmium Levels Are Associated with Increased Preeclampsia Risk.

    Science.gov (United States)

    Laine, Jessica E; Ray, Paul; Bodnar, Wanda; Cable, Peter H; Boggess, Kim; Offenbacher, Steven; Fry, Rebecca C

    2015-01-01

    Environmental exposure to heavy metals is a potentially modifiable risk factor for preeclampsia (PE). Toxicologically, there are known interactions between the toxic metal cadmium (Cd) and essential metals such as selenium (Se) and zinc (Zn), as these metals can protect against the toxicity of Cd. As they relate to preeclampsia, the interaction between Cd and these essential metals is unknown. The aims of the present study were to measure placental levels of Cd, Se, and Zn in a cohort of 172 pregnant women from across the southeast US and to examine associations of metals levels with the odds of PE in a nested case-control design. Logistic regressions were performed to assess odds ratios (OR) for PE with exposure to Cd controlling for confounders, as well as interactive models with Se or Zn. The mean placental Cd level was 3.6 ng/g, ranging from 0.52 to 14.5 ng/g. There was an increased odds ratio for PE in relationship to placental levels of Cd (OR = 1.5; 95% CI: 1.1-2.2). The Cd-associated OR for PE increased when analyzed in relationship to lower placental Se levels (OR = 2.0; 95% CI: 1.1-3.5) and decreased with higher placental Se levels (OR = 0.98; 95% CI: 0.5-1.9). Similarly, under conditions of lower placental Zn, the Cd-associated OR for PE was elevated (OR = 1.8; 95% CI: 0.8-3.9), whereas with higher placental Zn it was reduced (OR = 1.3; 95% CI: 0.8-2.0). Data from this pilot study suggest that essential metals may play an important role in reducing the odds of Cd-associated preeclampsia and that replication in a larger cohort is warranted.

  4. Transferência placentária de drogas Placental drug transfer

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    Ricardo de Carvalho Cavalli

    2006-09-01

    Full Text Available Grávidas podem depender do uso de medicações para minimizar os agravos da doença preexistente. A gravidez, por si só, pode causar situações que comprometem o bem-estar materno, como náuseas e vômitos, as quais necessitam de tratamento. O obstetra deve estar atento à transferência placentária de drogas e à exposição do feto a agentes teratogênicos ou tóxicos, que podem comprometer o seu desenvolvimento ou mesmo sua vida futura.O transporte através da placenta envolve o movimento de moléculas entre três compartimentos: sangue materno, citoplasma do sinciciotrofoblasto e sangue fetal. Esse movimento pode ocorrer pelos seguintes mecanismos: difusão simples, difusão facilitada, transporte ativo, bombas classe P, V, F e grande família ABC e endocitose. Com o uso de anticonvulsivantes a incidência de malformações maiores em recém-nascidos expostos é de 4 a 6%, comparado com 2 a 4% na população geral. A politerapia é mais lesiva, especialmente se o ácido valpróico e a hidantoína fazem parte da associação. Para as pacientes epilépticas clinicamente assintomáticas há dois anos recomenda-se a suspensão da drogas em uso, porém se apresentam crises, torna-se prudente consultar neurologista para discussão da terapia anticonvulsivante com melhores benefícios e menores efeitos colaterais. Os anestésicos locais e os opióides são largamente utilizados durante a resolução da gestação. A lidocaína utilizada como anestésico por via perineal para episiotomia, na dose fixa de 400 mg, apresenta alta concentração plasmática materna e alta taxa de transferência placentária no momento do nascimento, que vem alertar para o cuidado no uso de doses repetidas. A bupivacaína administrada por via epidural representa anestésico seguro, apresentando-se na forma racêmica e com transferência placentária em torno de 30%. A fentanila, anestésico opióide, utilizado por via epidural na resolução por cesariana, na dose

  5. Placental FKBP5 genetic and epigenetic variation is associated with infant neurobehavioral outcomes in the RICHS cohort.

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    Alison G Paquette

    Full Text Available Adverse maternal environments can lead to increased fetal exposure to maternal cortisol, which can cause infant neurobehavioral deficits. The placenta regulates fetal cortisol exposure and response, and placental DNA methylation can influence this function. FK506 binding protein (FKBP5 is a negative regulator of cortisol response, FKBP5 methylation has been linked to brain morphology and mental disorder risk, and genetic variation of FKBP5 was associated with post-traumatic stress disorder in adults. We hypothesized that placental FKBP5 methylation and genetic variation contribute to gene expression control, and are associated with infant neurodevelopmental outcomes assessed using the Neonatal Intensive Care Unit (NICU Network Neurobehavioral Scales (NNNS. In 509 infants enrolled in the Rhode Island Child Health Study, placental FKBP5 methylation was measured at intron 7 using quantitative bisulfite pyrosequencing. Placental FKBP5 mRNA was measured in a subset of 61 infants by quantitative PCR, and the SNP rs1360780 was genotyped using a quantitative allelic discrimination assay. Relationships between methylation, expression and NNNS scores were examined using linear models adjusted for confounding variables, then logistic models were created to determine the influence of methylation on membership in high risk groups of infants. FKBP5 methylation was negatively associated with expression (P = 0.08, r = -0.22; infants with the TT genotype had higher expression than individuals with CC and CT genotypes (P = 0.06, and those with CC genotype displayed a negative relationship between methylation and expression (P = 0.06, r = -0.43. Infants in the highest quartile of FKBP5 methylation had increased risk of NNNS high arousal compared to infants in the lowest quartile (OR 2.22, CI 1.07-4.61. TT genotype infants had increased odds of high NNNS stress abstinence (OR 1.98, CI 0.92-4.26. Placental FKBP5 methylation reduces expression in

  6. Maternal risk factors for abnormal placental growth: The national collaborative perinatal project

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    Nicholson Wanda K

    2008-09-01

    Full Text Available Abstract Background Previous studies of maternal risk factors for abnormal placental growth have focused on placental weight and placental ratio as measures of placental growth. We sought to identify maternal risk factors for placental weight and two neglected dimensions of placental growth: placental thickness and chorionic plate area. Methods We conducted an analysis of 24,135 mother-placenta pairs enrolled in the National Collaborative Perinatal Project, a prospective cohort study of pregnancy and child health. We defined growth restriction as th percentile and hypertrophy as > 90th percentile for three placental growth dimensions: placental weight, placental thickness and chorionic plate area. We constructed parallel multinomial logistic regression analyses to identify (a predictors of restricted growth (vs. normal and (b predictors of hypertrophic growth (vs. normal. Results Black race was associated with an increased likelihood of growth restriction for placental weight, thickness and chorionic plate area, but was associated with a reduced likelihood of hypertrophy for these three placental growth dimensions. We observed an increased likelihood of growth restriction for placental weight and chorionic plate area among mothers with hypertensive disease at 24 weeks or beyond. Anemia was associated with a reduced likelihood of growth restriction for placental weight and chorionic plate area. Pre-pregnancy BMI and pregnancy weight gain were associated with a reduced likelihood of growth restriction and an increased likelihood of hypertrophy for all three dimensions of placental growth. Conclusion Maternal risk factors are either associated with placental growth restriction or placental hypertrophy not both. Our findings suggest that the placenta may have compensatory responses to certain maternal risk factors suggesting different underlying biological mechanisms.

  7. Differential regulation of placental amino acid transport by saturated and unsaturated fatty acids.

    Science.gov (United States)

    Lager, Susanne; Jansson, Thomas; Powell, Theresa L

    2014-10-15

    Fatty acids are critical for normal fetal development but may also influence placental function. We have previously reported that oleic acid (OA) stimulates amino acid transport in primary human trophoblasts (PHTs). In other tissues, saturated and unsaturated fatty acids have distinct effects on cellular signaling, for instance, palmitic acid (PA) but not OA reduces IκBα expression. We hypothesized that saturated and unsaturated fatty acids differentially affect trophoblast amino acid transport and cellular signaling. To test this hypothesis, PHTs were cultured in docosahexaenoic acid (DHA; 50 μM), OA (100 μM), or PA (100 μM). DHA and OA were also combined to test whether DHA could counteract the OA stimulatory effect on amino acid transport. The effects of fatty acids were compared against a vehicle control. Amino acid transport was measured by isotope-labeled tracers. Activation of inflammatory-related signaling pathways and the mechanistic target of rapamycin (mTOR) pathway were determined by Western blot analysis. Exposure of PHTs to DHA for 24 h reduced amino acid transport and phosphorylation of p38 MAPK, STAT3, mTOR, eukaryotic initiation factor 4E-binding protein 1, and ribosomal protein (rp)S6. In contrast, OA increased amino acid transport and phosphorylation of ERK, mTOR, S6 kinase 1, and rpS6. The combination of DHA with OA increased amino acid transport and rpS6 phosphorylation. PA did not affect amino acid transport but reduced IκBα expression. In conclusion, these fatty acids differentially regulated placental amino acid transport and cellular signaling. Taken together, these findings suggest that dietary fatty acids could alter the intrauterine environment by modifying placental function, thereby having long-lasting effects on the developing fetus.

  8. Prolonged endoplasmic reticulum stress alters placental morphology and causes low birth weight

    Energy Technology Data Exchange (ETDEWEB)

    Kawakami, Takashige, E-mail: tkawakami@ph.bunri-u.ac.jp; Yoshimi, Masaki; Kadota, Yoshito; Inoue, Masahisa; Sato, Masao; Suzuki, Shinya

    2014-03-01

    The role of endoplasmic reticulum (ER) stress in pregnancy remains largely unknown. Pregnant mice were subcutaneously administered tunicamycin (Tun), an ER stressor, as a single dose [0, 50, and 100 μg Tun/kg/body weight (BW)] on gestation days (GDs) 8.5, 12.5, and 15.5. A high incidence (75%) of preterm delivery was observed only in the group treated with Tun 100 μg/kg BW at GD 15.5, indicating that pregnant mice during late gestation are more susceptible to ER stress on preterm delivery. We further examined whether prolonged in utero exposure to ER stress affects fetal development. Pregnant mice were subcutaneously administered a dose of 0, 20, 40, and 60 μg Tun/kg from GD 12.5 to 16.5. Tun treatment decreased the placental and fetal weights in a dose-dependent manner. Histological evaluation showed the formation of a cluster of spongiotrophoblast cells in the labyrinth zone of the placenta of Tun-treated mice. The glycogen content of the fetal liver and placenta from Tun-treated mice was lower than that from control mice. Tun treatment decreased mRNA expression of Slc2a1/glucose transporter 1 (GLUT1), which is a major transporter for glucose, but increased placental mRNA levels of Slc2a3/GLUT3. Moreover, maternal exposure to Tun resulted in a decrease in vascular endothelial growth factor receptor-1 (VEGFR-1), VEGFR-2, and placental growth factor. These results suggest that excessive and exogenous ER stress may induce functional abnormalities in the placenta, at least in part, with altered GLUT and vascular-related gene expression, resulting in low infant birth weight. - Highlights: • Maternal exposure to excessive ER stress induced preterm birth and IUGR. • Prolonged excessive ER stress altered the formation of the placental labyrinth. • ER stress decreased GLUT1 mRNA expression in the placenta, but increased GLUT3. • ER stress-induced IUGR causes decreased glycogen and altered glucose transport.

  9. Bidirectional Transfer Study of Polystyrene Nanoparticles across the Placental Barrier in an ex Vivo Human Placental Perfusion Model

    Science.gov (United States)

    Grafmueller, Stefanie; Manser, Pius; Diener, Liliane; Diener, Pierre-André; Maeder-Althaus, Xenia; Maurizi, Lionel; Jochum, Wolfram; Krug, Harald F.; Buerki-Thurnherr, Tina; von Mandach, Ursula

    2015-01-01

    Background Nanoparticle exposure in utero might not be a major concern yet, but it could become more important with the increasing application of nanomaterials in consumer and medical products. Several epidemiologic and in vitro studies have shown that nanoparticles can have potential toxic effects. However, nanoparticles also offer the opportunity to develop new therapeutic strategies to treat specifically either the pregnant mother or the fetus. Previous studies mainly addressed whether nanoparticles are able to cross the placental barrier. However, the transport mechanisms underlying nanoparticle translocation across the placenta are still unknown. Objectives In this study we examined which transport mechanisms underlie the placental transfer of nanoparticles. Methods We used the ex vivo human placental perfusion model to analyze the bidirectional transfer of plain and carboxylate modified polystyrene particles in a size range between 50 and 300 nm. Results We observed that the transport of polystyrene particles in the fetal to maternal direction was significantly higher than for the maternal to fetal direction. Regardless of their ability to cross the placental barrier and the direction of perfusion, all polystyrene particles accumulated in the syncytiotrophoblast of the placental tissue. Conclusions Our results indicate that the syncytiotrophoblast is the key player in regulating nanoparticle transport across the human placenta. The main mechanism underlying this translocation is not based on passive diffusion, but is likely to involve an active, energy-dependent transport pathway. These findings will be important for reproductive toxicology as well as for pharmaceutical engineering of new drug carriers. Citation Grafmueller S, Manser P, Diener L, Diener PA, Maeder-Althaus X, Maurizi L, Jochum W, Krug HF, Buerki-Thurnherr T, von Mandach U, Wick P. 2015. Bidirectional transfer study of polystyrene nanoparticles across the placental barrier in an ex vivo human

  10. Thrombomodulin-dependent effect of factor V Leiden mutation on the cross-linking of α2-plasmin inhibitor to fibrin and its consequences on fibrinolysis.

    Science.gov (United States)

    Koncz, Zsuzsa; Bagoly, Zsuzsa; Haramura, Gizella; Mezei, Zoltán A; Muszbek, László

    2012-09-01

    It has been shown that thrombomodulin (TM) considerably delays factor XIII (FXIII) activation and this effect is abrogated by Factor V Leiden (FV(Leiden)) mutation. The aim of the study was to explore the effect of TM on the cross-linking of α(2)-plasmin inhibitor (α(2)-PI) to fibrin in plasma samples of different FV genotypes and how this effect is related to the impaired fibrinolysis of FV(Leiden) carriers. In the plasma samples of fifteen individuals with different FV genotypes and in FV deficient plasma supplemented with wild type FV or FV(Leiden) coagulation was initiated by recombinant human tissue factor and phospholipids with or without recombinant human TM (rhTM). In the recovered clots the extent of α(2)-PI-fibrin cross-linking was evaluated by Western blotting and quantitative densitometry. The effect of rhTM on tissue plasminogen activator (tPA) induced clot lysis was measured by turbidimetric method. rhTM significantly delayed the formation of α(2)-PI-fibrin α-chain heterodimers/oligomers in plasma samples containing wild type FV. This effect of rhTM was impaired in the presence of FV(Leiden). rhTM delayed tPA-induced clot lysis and this effect of rhTM was more pronounced in plasma containing FV(Leiden). When TAFIa was inhibited by potato carboxypeptidase inhibitor, rhTM accelerated clot lysis in the presence of wild type FV, which is explained by the delayed α(2)-PI-fibrin cross-linking. This effect of rhTM did not prevail in the presence of FV(Leiden). FV(Leiden) abrogates the delaying effect of rhTM on α(2)-PI-fibrin cross-linking, which contributes to the impaired fibrinolysis observed in FV(Leiden) carriers. Copyright © 2012 Elsevier Ltd. All rights reserved.

  11. The roles of selected arginine and lysine residues of TAFI (Pro-CPU) in its activation to TAFIa by the thrombin-thrombomodulin complex.

    Science.gov (United States)

    Wu, Chengliang; Kim, Paul Y; Manuel, Reg; Seto, Marian; Whitlow, Marc; Nagashima, Mariko; Morser, John; Gils, Ann; Declerck, Paul; Nesheim, Michael E

    2009-03-13

    Thrombomodulin (TM) increases the catalytic efficiency of thrombin (IIa)-mediated activation of thrombin-activable fibrinolysis inhibitor (TAFI) 1250-fold. Negatively charged residues of the C-loop of TM-EGF-like domain 3 are required for TAFI activation. Molecular models suggested several positively charged residues of TAFI with which the C-loop residues could interact. Seven TAFI mutants were constructed to determine if these residues are required for efficient TAFI activation. TAFI wild-type or mutants were activated in the presence or absence of TM and the kinetic parameters of TAFI activation were determined. When the three consecutive lysine residues in the activation peptide of TAFI were substituted with alanine (K42/43/44A), the catalytic efficiencies for TAFI activation with TM decreased 8-fold. When other positively charged surface residues of TAFI (Lys-133, Lys-211, Lys-212, Arg-220, Lys-240, or Arg-275) were mutated to alanine, the catalytic efficiencies for TAFI activation with TM decreased by 1.7-2.7-fold. All decreases were highly statistically significant. In the absence of TM, catalytic efficiencies ranged from 2.8-fold lower to 1.24-fold higher than wild-type. None of these, except the 2.8-fold lower value, was statistically significant. The average half-life of the TAFIa mutants was 8.1+/-0.6 min, and that of wild type was 8.4+/-0.3 min at 37 degrees C. Our data show that these residues are important in the activation of TAFI by IIa, especially in the presence of TM. Whether the mutated residues promote a TAFI-TM or TAFI-IIa interaction remains to be determined. In addition, these residues do not influence spontaneous inactivation of TAFIa.

  12. Correlation of Serum Concentrations of Soluble Thrombomodulin, Soluble Vascular Cell Adhesion Molecule-1,Intracellular Adhesion Molecule -1 And E-Selectin In Patients WithSystemic Lupus Erythematosus

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    Malak., A. Mohsen*, Magda.A.Gamil*,Maha. I.Shehata

    2003-09-01

    Full Text Available To date no specific serological parameters are available to assess disease activity in systemic lupus erythematosus (SLE. The objective of this study was to correlate serum levels of thrombomodulin (TM, intracellular adhesion molecule-1 sICAM-1, vascular cell adhesion molecule-1 sVCAM-1, and E-selectin with standard laboratory tests and clinical indices of disease activity in 40 patients with SLE and 20 apparently healthy persons as controls. According to British Isles Lupus Assessment Group (BILAG disease activity index, the 40 patients were divided into two groups, the first consisted of 22 with active disease, and the second consisted of 18 patients with inactive SLE. Serum sTM, sICAM-1, sVCAM-I, and E-selectin were measured in their sera, using enzyme linked immuonosorbent assay (ELISA technique.C-reactiv protein (CRP, Erythrocyte sedimentation rates (ESR and serum creatinines were measured by standard laboratory tests. Total leukocytic count and hemoglobin concentration were detected by coulter counter. Levels of sTM and sVCAM were highly elevated in the group of patients with active SLE as compared to the inactive one (P0.05. In SLE, the BILAG disease activity index, ESR and serum creatinine correlated best with sTM, sVCAM-1 and E-selectin levels while there was a weak association between CRP levels and the adhesion molecules, and no correlation between CRP level and disease activity. In conclusion, sTM and sVCAM were the most important serological indices of disease activity in SLE and might be valuable serological parameters for monitoring therapy.

  13. Histopathological placental lesions in mild gestational hyperglycemic and diabetic women

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    Rudge Marilza VC

    2011-08-01

    Full Text Available Abstract Objective To investigate and compare the incidence of histopathological placental lesions in mild gestational hyperglycemia, gestational diabetes and overt diabetes at term and preterm gestation. Research design and methods One-hundred-and-thirty-one placental samples were collected from Diabetes mellitus (DM positive screened patients. Two diagnostic tests, glycemic profile and 100 g oral glucose tolerance test (OGTT in parallel identified 4 groups normoglycemic, mild gestational hyperglycemia (MGH, gestational DM (GDM or overt DM (DM. Placental tissue specimens and sections from 4 groups were obtained by uniform random sampling and stained with hematoxylin-eosin. Results Placentas from MGH group presented 17 types of histopathological change and higher rates of syncytial nodes and endarteritis. GDM placentas presented only nine types of histopathological change, high rates of dysmaturity, low rates of calcification and no syncytial nodes. Overt DM placentas showed 22 types of histopathological change, 21 of which were present in the preterm period. There were histopathological similarities between MGH and DM placentas, but the former exhibited a higher incidence of endarteritis, which has been described as a "post-mortem" phenomenon. Conclusion Our results confirmed that the distinct placental changes associated with DM and MGH depend on gestational period during which the diabetic insult occurs. It may reasonably be inferred that subclinical maternal hyperglycemia during pregnancy, as showed in MGH group, is responsible for increased placental endarteritis, a postmortem lesion in the live fetus.

  14. Adenylate kinase locus 1 polymorphism and feto-placental development.

    Science.gov (United States)

    Fulvia, Gloria-Bottini; Antonio, Pietroiusti; Anna, Neri; Patrizia, Saccucci; Ada, Amante; Egidio, Bottini; Andrea, Magrini

    2011-12-01

    Recently our group has found that the correlation between birth weight and placental weight - an index of a balanced feto-placental unit development - is influenced by genetic factors. Since adenylate kinase locus 1 (AK₁) is a polymorphic enzyme that plays an important role in the synthesis of nucleotides required for many metabolic functions, we have investigated the possible role of its genetic variability in the correlation between birth weight and placental weight. 342 consecutive healthy newborn infants from the population of Rome (Italy) and 286 puerperae from another population from Central Italy were studied. The correlation coefficient between birth weight and placental weight is much higher in infants with low activity AK₁2-1 phenotype than in those with high activity AK₁1 phenotype. The difference between AK₁ and AK₁2-1 is well marked only in newborns with a gestational age greater than 38 weeks and it is not influenced by sex, maternal age and maternal smoking. A similar pattern is observed with maternal AK₁ phenotype. These results suggest that the difference in enzymatic activity between AK₁ phenotypes influencing the equilibrium among ATP, ADP, AMP and adenosine could have an important role in a balanced development of feto-placental unit. Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.

  15. Important aspects of placental-specific gene transfer.

    Science.gov (United States)

    Kaufman, Melissa R; Albers, Renee E; Keoni, Chanel; Kulkarni-Datar, Kashmira; Natale, David R; Brown, Thomas L

    2014-10-15

    The placenta is a unique and highly complex organ that develops only during pregnancy and is essential for growth and survival of the developing fetus. The placenta provides the vital exchange of gases and wastes, the necessary nutrients for fetal development, acts as immune barrier that protects against maternal rejection, and produces numerous hormones and growth factors that promote fetal maturity to regulate pregnancy until parturition. Abnormal placental development is a major underlying cause of pregnancy-associated disorders that often result in preterm birth. Defects in placental stem cell propagation, growth, and differentiation are the major factors that affect embryonic and fetal well-being and dramatically increase the risk of pregnancy complications. Understanding the processes that regulate placentation is important in determining the underlying factors behind abnormal placental development. The ability to manipulate genes in a placenta-specific manner provides a unique tool to analyze development and eliminates potentially confounding results that can occur with traditional gene knockouts. Trophoblast stem cells and mouse embryos are not overly amenable to traditional gene transfer techniques. Most viral vectors, however, have a low infection rate and often lead to mosaic transgenesis. Although the traditional method of embryo transfer is intrauterine surgical implantation, the methodology reported here, combining lentiviral blastocyst infection and nonsurgical embryo transfer, leads to highly efficient and placental-specific gene transfer. Numerous advantages of our optimized procedures include increased investigator safety, a reduction in animal stress, rapid and noninvasive embryo transfer, and higher a rate of pregnancy and live birth.

  16. Compensatory placental growth after restricted maternal nutrition in early pregnancy.

    Science.gov (United States)

    Lumey, L H

    1998-01-01

    This study examined the effects of undernutrition in pregnancy on fetal and placental growth among infants born in 1944-1946 in The Netherlands, including infants born during the war-induced Dutch famine of 1944-1945. There was an increase in placental weight, but not in birthweight, in infants whose mothers' nutrition was compromised around conception or in the first trimester of pregnancy. Therefore, the placental index was also increased. Compared to pre-famine controls, the relative increase after first trimester exposure to undernutrition was larger in the northern part of the country (5.2 per cent, 95 per cent confidence interval 1.4, 9.0) where nutritional deprivation was presumably moderate compared to the west (3.5 per cent, 95 per cent confidence interval 0.2, 7.2) where nutritional deprivation was severe. The increase in placental weight is interpreted as compensatory for the reduction in maternal caloric intake. Whereas this suggests that pregnancy undernutrition can stimulate compensatory placental growth, the latter was only seen after first trimester undernutrition, which does not affect infant size at birth. For these infants, therefore, birthweight is not an appropriate proxy measure of undernutrition in pregnancy. These factors need to be considered in future studies relating pregnancy nutrition to adult health outcomes.

  17. Placental pathologies in fetal MRI with pathohistological correlation.

    Science.gov (United States)

    Linduska, N; Dekan, S; Messerschmidt, A; Kasprian, G; Brugger, P C; Chalubinski, K; Weber, M; Prayer, D

    2009-06-01

    The purpose of this study was to evaluate whether currently available fetal Magnetic Resonance Imaging (MRI/MR) techniques are sufficient for the assessment of placental pathologies. We hypothesized that placental pathologies as detected and evaluated by MRI, would correlate with histological findings. In a retrospective study, 45 singleton pregnancies from 19 to 35 gestational weeks, with placental pathologies on MR scans, were included. MRI was performed on a 1.5T unit using T2-, T1-, and diffusion-weighted and echo-planar sequences. Pathologies were categorized into infarction with/without hemorrhagic components, subchorionic/intervillous thrombi/hemorrhages, retroplacental hematoma, massive perivillous fibrin deposition, and chorioamnionitis. Pathohistological examination was performed postnatally within a median of seven days between MR examination and delivery. Pathologically, 26 placentas showed infarctions (96.2% on MR scans), two retroplacental hematomas were detected by MRI and confirmed by pathology, and 9 of 14 subchorionic hematomas were confirmed. Six of eight intervillous hemorrhages were seen on MRI, and three of six cases of severe chorioamnionitis were diagnosed prenatally. Placental hemorrhages (retroplacental hematoma, intervillous thrombi, subchorionic hematoma), and ischemic lesions could be detected with fetal MRI, while chorioamnionitis and even massive perivillous fibrin deposition showed few signal changes, probably reflecting small macroscopic changes in the placenta. Fetal MRI, therefore, seems to be a promising tool for the assessment of placental insufficiency.

  18. A higher-level MRP supertree of placental mammals

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    Bininda-Emonds Olaf RP

    2006-11-01

    Full Text Available Abstract Background The higher-level phylogeny of placental mammals has long been a phylogenetic Gordian knot, with disagreement about both the precise contents of, and relationships between, the extant orders. A recent MRP supertree that favoured 'outdated' hypotheses (notably, monophyly of both Artiodactyla and Lipotyphla has been heavily criticised for including low-quality and redundant data. We apply a stringent data selection protocol designed to minimise these problems to a much-expanded data set of morphological, molecular and combined source trees, to produce a supertree that includes every family of extant placental mammals. Results The supertree is well-resolved and supports both polyphyly of Lipotyphla and paraphyly of Artiodactyla with respect to Cetacea. The existence of four 'superorders' – Afrotheria, Xenarthra, Laurasiatheria and Euarchontoglires – is also supported. The topology is highly congruent with recent (molecular phylogenetic analyses of placental mammals, but is considerably more comprehensive, being the first phylogeny to include all 113 extant families without making a priori assumptions of suprafamilial monophyly. Subsidiary analyses reveal that the data selection protocol played a key role in the major changes relative to a previously published higher-level supertree of placentals. Conclusion The supertree should provide a useful framework for hypothesis testing in phylogenetic comparative biology, and supports the idea that biogeography has played a crucial role in the evolution of placental mammals. Our results demonstrate the importance of minimising poor and redundant data when constructing supertrees.

  19. Heterogeneous models place the root of the placental mammal phylogeny.

    Science.gov (United States)

    Morgan, Claire C; Foster, Peter G; Webb, Andrew E; Pisani, Davide; McInerney, James O; O'Connell, Mary J

    2013-09-01

    Heterogeneity among life traits in mammals has resulted in considerable phylogenetic conflict, particularly concerning the position of the placental root. Layered upon this are gene- and lineage-specific variation in amino acid substitution rates and compositional biases. Life trait variations that may impact upon mutational rates are longevity, metabolic rate, body size, and germ line generation time. Over the past 12 years, three main conflicting hypotheses have emerged for the placement of the placental root. These hypotheses place the Atlantogenata (common ancestor of Xenarthra plus Afrotheria), the Afrotheria, or the Xenarthra as the sister group to all other placental mammals. Model adequacy is critical for accurate tree reconstruction and by failing to account for these compositional and character exchange heterogeneities across the tree and data set, previous studies have not provided a strongly supported hypothesis for the placental root. For the first time, models that accommodate both tree and data set heterogeneity have been applied to mammal data. Here, we show the impact of accurate model assignment and the importance of data sets in accommodating model parameters while maintaining the power to reject competing hypotheses. Through these sophisticated methods, we demonstrate the importance of model adequacy, data set power and provide strong support for the Atlantogenata over other competing hypotheses for the position of the placental root.

  20. Monocarboxylate transporter 8 modulates the viability and invasive capacity of human placental cells and fetoplacental growth in mice.

    Directory of Open Access Journals (Sweden)

    Elisavet Vasilopoulou

    Full Text Available Monocarboxylate transporter 8 (MCT8 is a well-established thyroid hormone (TH transporter. In humans, MCT8 mutations result in changes in circulating TH concentrations and X-linked severe global neurodevelopmental delay. MCT8 is expressed in the human placenta throughout gestation, with increased expression in trophoblast cells from growth-restricted pregnancies. We postulate that MCT8 plays an important role in placental development and transplacental TH transport. We investigated the effect of altering MCT8 expression in human trophoblast in vitro and in a Mct8 knockout mouse model. Silencing of endogenous MCT8 reduced T3 uptake into human extravillous trophoblast-like cells (SGHPL-4; 40%, P<0.05 and primary cytotrophoblast (15%, P<0.05. MCT8 over-expression transiently increased T3 uptake (SGHPL-4∶30%, P<0.05; cytotrophoblast: 15%, P<0.05. Silencing MCT8 did not significantly affect SGHPL-4 invasion, but with MCT8 over-expression T3 treatment promoted invasion compared with no T3 (3.3-fold; P<0.05. Furthermore, MCT8 silencing increased cytotrophoblast viability (∼20%, P<0.05 and MCT8 over-expression reduced cytotrophoblast viability independently of T3 (∼20%, P<0.05. In vivo, Mct8 knockout reduced fetal:placental weight ratios compared with wild-type controls at gestational day 18 (25%, P<0.05 but absolute fetal and placental weights were not significantly different. The volume fraction of the labyrinthine zone of the placenta, which facilitates maternal-fetal exchange, was reduced in Mct8 knockout placentae (10%, P<0.05. However, there was no effect on mouse placental cell proliferation in vivo. We conclude that MCT8 makes a significant contribution to T3 uptake into human trophoblast cells and has a role in modulating human trophoblast cell invasion and viability. In mice, Mct8 knockout has subtle effects upon fetoplacental growth and does not significantly affect placental cell viability probably due to compensatory mechanisms in

  1. Differential Loss of Embryonic Globin Genes during the Radiation of Placental Mammals

    National Research Council Canada - National Science Library

    Juan C. Opazo; Federico G. Hoffmann; Jay F. Storz

    2008-01-01

    ...-globin gene family of placental mammals. By analyzing genomic sequence data from representatives of each of the main superordinal clades of placental mammals, we were able to reconstruct pathways of gene family evolution during the basal...

  2. Social disparity affects the incidence of placental abruption among multiparous but not nulliparous women

    DEFF Research Database (Denmark)

    Räisänen, Sari; Gissler, Mika; Nielsen, Henriette Svarre

    2013-01-01

    To identify risk factors for placental abruption and to evaluate associations between adverse perinatal outcomes and placental abruption stratified by parity among women with singleton births from 1991 to 2010 in Finland.......To identify risk factors for placental abruption and to evaluate associations between adverse perinatal outcomes and placental abruption stratified by parity among women with singleton births from 1991 to 2010 in Finland....

  3. Role of the endothelium in placental dysfunction after fetal cardiac bypass.

    Science.gov (United States)

    Reddy, V M; McElhinney, D B; Rajasinghe, H A; Liddicoat, J R; Hendricks-Munoz, K; Fineman, J R; Hanley, F L

    1999-02-01

    Fetal cardiac bypass causes placental dysfunction, characterized by increased placental vascular resistance, decreased placental blood flow, hypoxia, and acidosis. Vasoactive factors produced by the vascular endothelium, such as nitric oxide and endothelin 1, are important regulators of placental vascular tone and may contribute to this placental dysfunction. To investigate the role of the vascular endothelium in placental dysfunction related to fetal cardiac bypass, we studied 3 groups of fetal sheep. In the first group (n = 7) we determined placental hemodynamic responses before and after bypass to an endothelium-dependent vasodilator (acetylcholine), an endothelium-independent vasodilator (nitroprusside), and endothelin 1. In the second group (n = 8) a nonspecific endothelin receptor blocker (PD 145065) was administered and placental hemodynamic values were measured before and after bypass. In the third group (n = 5) endothelin 1 levels were measured before and after bypass. Before fetal cardiac bypass exogenous endothelin 1 decreased placental blood flow by 9% and increased placental resistance by 9%. After bypass endothelin 1 decreased placental flow by 47% and increased resistance by 106%. There was also a significant attenuation of the placental vascular relaxation response to acetylcholine after bypass, whereas the response to nitroprusside was not significantly altered. In fetuses that received the PD 145065, placental vascular resistance increased significantly less than in control fetuses (28% versus 62%). Similarly, placental blood flow decreased significantly more (from 6. 3 +/- 3.1 to 28.3 +/- 10.4 pg/mL; P =.01) in control fetuses than in fetuses receiving PD 145065 (33% versus 20%). Umbilical venous endothelin 1 levels increased significantly in fetuses exposed to fetal bypass but did not change in control fetuses. The basal endothelial regulatory mechanisms of placental vascular tone were deranged after fetal cardiac bypass. Endothelin receptor

  4. Blocking Endogenous Leukemia Inhibitory Factor During Placental Development in Mice Leads to Abnormal Placentation and Pregnancy Loss.

    Science.gov (United States)

    Winship, Amy; Correia, Jeanne; Krishnan, Tara; Menkhorst, Ellen; Cuman, Carly; Zhang, Jian-Guo; Nicola, Nicos A; Dimitriadis, Evdokia

    2015-08-14

    The placenta forms the interface between the maternal and fetal circulation and is critical for the establishment of a healthy pregnancy. Specialized trophoblast cells derived from the embryonic trophectoderm play a pivotal role in the establishment of the placenta. Leukemia inhibitory factor (LIF) is one of the predominant cytokines present in the placenta during early pregnancy. LIF has been shown to regulate trophoblast adhesion and invasion in vitro, however its precise role in vivo is unknown. We hypothesized that LIF would be required for normal placental development in mice. LIF and LIFRα were immunolocalized to placental trophoblasts and fetal vessels in mouse implantation sites during mid-gestation. Temporally blocking LIF action during specific periods of placental development via intraperitoneal administration of our specific LIFRα antagonist, PEGLA, resulted in abnormal placental trophoblast and vascular morphology and reduced activated STAT3 but not ERK. Numerous genes regulating angiogenesis and oxidative stress were altered in the placenta in response to LIF inhibition. Pregnancy viability was also significantly compromised in PEGLA treated mice. Our data suggest that LIF plays an important role in placentation in vivo and the maintenance of healthy pregnancy.

  5. Indications of anti-HY immunity in recurrent placental abruption

    DEFF Research Database (Denmark)

    Nielsen, Henriette Svarre; Mogensen, Marie; Steffensen, Rudi

    2007-01-01

    PROBLEM: Placental abruption is a potential life-threatening condition for both the fetus and the mother, being significantly more common in pregnancies with male fetuses. The pathogenesis of placental abruption remains unknown. However, some recent reports point toward a maternal immune response...... the fetus died. Seven patients (88%) had first-born boys, and 15 abruptions (68%) involved male fetuses. All patients with a first-born boy, except one, had HLA-class II alleles known to restrict CD4+ T-cell responses against male-specific minor histocompatibility (HY)-antigens (HLA-DRB1*15, HLA-DRB3...... abruption is exclusively almost preceded by the birth of a boy and the majority of patients have HLA-class II known to restrict CD4 T-cell reactions against HY-antigens. This indicates that maternal immunological responses against HY-antigens play a role in recurrent placental abruption. Udgivelsesdato...

  6. Non-placental causes of intrauterine growth restriction.

    Science.gov (United States)

    Hendrix, Nancy; Berghella, Vincenzo

    2008-06-01

    Placental insufficiency, in some form or fashion, is associated with the majority of cases of intrauterine growth restriction (IUGR). There are numerous causes of IUGR which are not caused primarily by placental insufficiency, but indirectly lead to it. The causes of IUGR can be subdivided into fetal and maternal etiologies. The fetal etiologies consist of genetic diseases, congenital malformations, infections, multiple gestations, and placental/cord abnormalities. The maternal etiologies are categorized as follows: (1) decreased uteroplacental blood flow, (2) reduced blood volume, (3) decreased oxygen carrying capacity, (4) nutrition status, (5) teratogens, and (6) miscellaneous causes such as short interpregnancy intervals, race, maternal age, and low socioeconomic status. Knowledge of the etiologies of fetal growth restriction is essential, so that future care can be targeted at prevention. There are several primary and secondary prevention strategies that can be adopted.

  7. The feto-placental endothelium in pregnancy pathologies.

    Science.gov (United States)

    Wadsack, Christian; Desoye, Gernot; Hiden, Ursula

    2012-05-01

    This review aims to provide a comprehensive summary of the aspects of endothelial and vascular dysfunction in the feto-placental vasculature occurring in pregnancy pathologies. This endothelium is continuous with the fetal circulation. Its function and potential dysfunction in pathologies will have a profound impact on fetal development. Gestational diabetes mellitus represents one of these pathologies, in which its associated metabolic derangements will alter feto-placental endothelial functions. These, in turn, may result in functional changes of the placenta, which may entail impaired fetal development. By contrast, changes in the feto-placental vasculature observed in cases of fetal growth restriction and preeclampsia may be causative (fetal growth restriction) or secondary (preeclampsia) for the pathology.

  8. Clinical use of placental hormones in pregnancy management.

    Science.gov (United States)

    De Bonis, M; Vellucci, F L; Di Tommaso, M; Voltolini, C; Torricelli, M; Petraglia, F

    2012-09-01

    Across human pregnancy, placenta represents a transit of oxygen and nutrients from the mother to the fetus and actively produces a large number of hormones that serve to regulate and balance maternal and fetal physiology. An abnormal secretion of placental hormones may be part of the pathogenesis of the main obstetric syndrome, from early to late pregnancy, in particular chromosomopathies, miscarriage, gestational trophoblastic diseases, preeclampsia, gestational diabetes, and pre-term delivery. The possibility to measure placental hormones represents an important tool not only for the diagnosis and management of gestational disorders, but it is also fundamental in the early identification of women at risk for these pregnancy complications. In the last decades, the use of ultrasound examination has provided additional biophysical markers, improving the early diagnosis of gestational diseases. In conclusion, while few placental hormones have sufficient sensitivity for clinical application, there are promising new biochemical and biophysical markers that, if used in combination, may provide a valid screening tool.

  9. Macrosomia has its roots in early placental development.

    Science.gov (United States)

    Schwartz, N; Quant, H S; Sammel, M D; Parry, S

    2014-09-01

    We sought to determine if early placental size, as measured by 3-dimensional ultrasonography, is associated with an increased risk of delivering a macrosomic or large-for-gestational age (LGA) infant. We prospectively collected 3-dimensional ultrasound volume sets of singleton pregnancies at 11-14 weeks and 18-24 weeks. Birth weights were collected from the medical records. After delivery, the ultrasound volume set were used to measure the placental volume (PV) and placental quotient (PQ = PV/gestational age), as well as the mean placental and chorionic diameters (MPD and MCD, respectively). Placental measures were analyzed as predictors of macrosomia (birth weight ≥4000 g) and LGA (birth weight ≥90th percentile). The 578 pregnancies with first trimester volumes included 44 (7.6%) macrosomic and 43 (7.4%) LGA infants. 373 subjects also had second trimester volumes available. A higher PV and PQ were both significantly associated with macrosomia and LGA in both the first and second trimesters. Second trimester MPD was significantly associated with both outcomes as well, while second trimester MCD was only associated with LGA. The above associations remained significant after adjusting for maternal demographic variables such as race, ethnicity, age and diabetes. Adjusted models yielded moderate prediction of macrosomia and LGA (AUC: 0.71-0.77). Sonographic measurement of the early placenta can identify pregnancies at greater risk of macrosomia and LGA. Macrosomia and LGA are already determined in part by early placental growth and development. Copyright © 2014 Elsevier Ltd. All rights reserved.

  10. Association between PAPP-A and placental thickness

    Directory of Open Access Journals (Sweden)

    Elaheh Mesdaghi-nia

    2016-06-01

    Full Text Available Background: Measuring of maternal serum pregnancy-associated plasma protein-A (PAPP-A in first trimester can be a way for early detection of adverse prenatal outcome due to faulty placenta. Objective: The aim was to Determination of association between placental thickness in second trimester with low level of PAPP-A in first trimester. Materials and Methods: In this cohort study, serum PAPP-A of 187 pregnant women was measured in the first trimester of pregnancy. Patients who had PAPP-A ≤0.8 MOM were in exposed and others who had PAPP-A >0.8 defined as unexposed group. The criteria of placental thickness in ultrasound study was thickness of 4 cm or more than 50% of placental length. Results: Of 187 patients, 87 patients had PAPP-A >0.8 and 93 patients had PAPP-A ≤0.8. Women with low levels of PAPP-A in the first trimester, had an increased incidence placental thickness of 34.4%, whereas another group had about 15% (p=0.002. Also, PAPP-A levels had acceptable sensitivity and specificity for placental thickness detection (71.1% and 54.8%, respectively. Conclusion: Our study showed that serum level of PAPP-A generally was low (≤0.8 in women with a thick placenta (>4 cm or >50% of placental length. The first trimester of pregnancy measurement of PAPP-A will be more predictable for healthy placenta.

  11. HIV-1 Nef breaches placental barrier in rat model.

    Science.gov (United States)

    Singh, Poonam; Agnihotri, Saurabh Kumar; Tewari, Mahesh Chandra; Kumar, Sadan; Sachdev, Monika; Tripathi, Raj Kamal

    2012-01-01

    The vertical transmission of HIV-1 from the mother to fetus is known, but the molecular mechanism regulating this transmission is not fully characterized. The fetus is highly protected by the placenta, which does not permit microbial pathogens to cross the placental barrier. In the present study, a rat model was established to observe the effect of HIV-1 protein Nef on placental barrier. Evans blue dye was used to assay permeability of placental barrier and fourteen day pregnant Sprague Dawley rats were injected intravenously with 2% Evans blue dye along with various concentrations of recombinant Nef. After an hour, animals were sacrificed and dye migration was observed through the assimilation of peripheral blood into fetus. Interestingly, traces of recombinant Nef protein were detected in the embryo as well as amniotic fluid and amniotic membrane along with placenta and uterus. Our study indicates that recombinant HIV-1-Nef protein breaches the placental barrier and allows the migration of Evans blue dye to the growing fetus. Further the concentration of Nef protein in blood is directly proportional to the intensity of dye migration and to the amount of Nef protein detected in uterus, placenta, amniotic membrane, amniotic fluid and embryo. Based on this study, it can be concluded that the HIV-1 Nef protein has a direct effect on breaching of the placental barrier in the model we have established in this study. Our observations will be helpful to understand the molecular mechanisms related to this breach of placental barrier by Nef in humans and may be helpful to identify specific Nef inhibitors.

  12. Transferência placentária de drogas Placental drug transfer

    OpenAIRE

    Ricardo de Carvalho Cavalli; Cláudia de Oliveira Baraldi; Sérgio Pereira da Cunha

    2006-01-01

    Grávidas podem depender do uso de medicações para minimizar os agravos da doença preexistente. A gravidez, por si só, pode causar situações que comprometem o bem-estar materno, como náuseas e vômitos, as quais necessitam de tratamento. O obstetra deve estar atento à transferência placentária de drogas e à exposição do feto a agentes teratogênicos ou tóxicos, que podem comprometer o seu desenvolvimento ou mesmo sua vida futura.O transporte através da placenta envolve o movimento de moléculas e...

  13. Placental transport of large molecules –a study using human ex vivo placental perfusion

    DEFF Research Database (Denmark)

    Mathiesen, Line

    2011-01-01

    To maintain a healthy pregnancy, the exchange of substances between mother and fetus is vital. All transport of these substances takes place through the placenta, which is a temporary organ that serves its purpose from the implantation of the blastula to the birth of the term fetus, supplying...... nutrients, gas and waste transport between the maternal blood and the developing fetus and maintaining pregnancy by producing hormones. The placenta consists of cells of both maternal and fetal origin and forms a complex barrier between the maternal and fetal blood that allows for passage of different...... within two hours of perfusion with a fetal flow rate of 3 mL/min. Negative controls are added to ensure that substance transfer is not due to leakage, e.g. high molecular weight substances that only pass the placental barrier with bulk flow through a leakage in the fetal system. Dextran (40kD) can...

  14. Ovine placental eluate immunoglobulins recognise isologous and third party acid-treated trophoblast microvesicle antigens in vitro

    Directory of Open Access Journals (Sweden)

    C.A. Omwandho

    2006-06-01

    Full Text Available