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Sample records for human placental tissue

  1. A Comparative Pathophysiological Study of Normal and Growth Retarded Human Placental Tissue

    Directory of Open Access Journals (Sweden)

    Adam Moyosore Afodun

    2014-01-01

    Full Text Available This study compares the pathophysiology of normal and growth retarded human placental tissues. Female patients were recruited from the Antenatal Clinic of Dolu Specialist Hospital, Mafoluku, Oshodi, Lagos, between 2008 and 2012. A total of 48 normal term placentas and 15 placentas of known IUGR cases were used for this study. IUGR cases were confirmed on the basis of ultrasound follow-up and diagnosis. Normal term placentas were collected at the point of delivery by a consultant gynaecologist, the cords were clamped, and membranes were then carefully trimmed after which each placenta was weighed. About 1 cm thickness of both normal and growth retarded placenta tissues was cut, processed for hematoxylin and eosin stain, while tissues for enzyme (ALP assay were homogenized in cold 0.5 M sucrose solution. Comparative analysis of the data was done using ANOVA; P<0.05 was taken as significant. The photomicrographs were observed/studied under light microscope, using the X150 and X600 magnifications. It was revealed therein that placental tissues are homogenous (regionally, compromised of maternal spiral arterioles and deregulated villous vasculogenesis, and that there is a significant difference in the level of alkaline phosphatase enzyme. We therefore concluded that there is a distinct difference between the normal and growth retarded human placenta tissue.

  2. The Effect of Cryopreserved Human Placental Tissues on Biofilm Formation of Wound-Associated Pathogens

    Directory of Open Access Journals (Sweden)

    Yong Mao

    2018-01-01

    Full Text Available Biofilm, a community of bacteria, is tolerant to antimicrobial agents and ubiquitous in chronic wounds. In a chronic DFU (Diabetic Foot Ulcers clinical trial, the use of a human cryopreserved viable amniotic membrane (CVAM resulted in a high rate of wound closure and reduction of wound-related infections. Our previous study demonstrated that CVAM possesses intrinsic antimicrobial activity against a spectrum of wound-associated bacteria under planktonic culture conditions. In this study, we evaluated the effect of CVAM and cryopreserved viable umbilical tissue (CVUT on biofilm formation of S. aureus and P. aeruginosa, the two most prominent pathogens associated with chronic wounds. Firstly, we showed that, like CVAM, CVUT released antibacterial activity against multiple bacterial pathogens and the devitalization of CVUT reduced its antibacterial activity. The biofilm formation was then measured using a high throughput method and an ex vivo porcine dermal tissue model. We demonstrate that the formation of biofilm was significantly reduced in the presence of CVAM- or CVUT-derived conditioned media compared to control assay medium. The formation of P. aeruginosa biofilm on CVAM-conditioned medium saturated porcine dermal tissues was reduced 97% compared with the biofilm formation on the control medium saturated dermal tissues. The formation of S. auerus biofilm on CVUT-conditioned medium saturated dermal tissues was reduced 72% compared with the biofilm formation on the control tissues. This study is the first to show that human cryopreserved viable placental tissues release factors that inhibit biofilm formation. Our results provide an explanation for the in vivo observation of their ability to support wound healing.

  3. The Effect of Cryopreserved Human Placental Tissues on Biofilm Formation of Wound-Associated Pathogens.

    Science.gov (United States)

    Mao, Yong; Singh-Varma, Anya; Hoffman, Tyler; Dhall, Sandeep; Danilkovitch, Alla; Kohn, Joachim

    2018-01-08

    Biofilm, a community of bacteria, is tolerant to antimicrobial agents and ubiquitous in chronic wounds. In a chronic DFU (Diabetic Foot Ulcers) clinical trial, the use of a human cryopreserved viable amniotic membrane (CVAM) resulted in a high rate of wound closure and reduction of wound-related infections. Our previous study demonstrated that CVAM possesses intrinsic antimicrobial activity against a spectrum of wound-associated bacteria under planktonic culture conditions. In this study, we evaluated the effect of CVAM and cryopreserved viable umbilical tissue (CVUT) on biofilm formation of S. aureus and P. aeruginosa, the two most prominent pathogens associated with chronic wounds. Firstly, we showed that, like CVAM, CVUT released antibacterial activity against multiple bacterial pathogens and the devitalization of CVUT reduced its antibacterial activity. The biofilm formation was then measured using a high throughput method and an ex vivo porcine dermal tissue model. We demonstrate that the formation of biofilm was significantly reduced in the presence of CVAM- or CVUT-derived conditioned media compared to control assay medium. The formation of P. aeruginosa biofilm on CVAM-conditioned medium saturated porcine dermal tissues was reduced 97% compared with the biofilm formation on the control medium saturated dermal tissues. The formation of S. auerus biofilm on CVUT-conditioned medium saturated dermal tissues was reduced 72% compared with the biofilm formation on the control tissues. This study is the first to show that human cryopreserved viable placental tissues release factors that inhibit biofilm formation. Our results provide an explanation for the in vivo observation of their ability to support wound healing.

  4. In vivo assessment of putative functional placental tissue volume in placental intrauterine growth restriction (IUGR) in human fetuses using diffusion tensor magnetic resonance imaging.

    Science.gov (United States)

    Javor, D; Nasel, C; Schweim, T; Dekan, S; Chalubinski, K; Prayer, D

    2013-08-01

    Intrauterine growth restriction (IUGR) is a diagnostic challenge, since ultrasound fetal biometry (UFB) provides only a 50% detection rate for IUGR. This may be attributable to the fact that UFB does not allow a direct evaluation of functional placental tissue. We hypothesized that direct assessment, using magnetic resonance diffusion tensor imaging (DT-MRI), can provide better detection of IUGR by reliably distinguishing between normal and non-functional placental tissue. Patients with normal placenta function (n = 21) and suspected IUGR (n = 14) according to UFB were examined. DT-MRI-based properties of areas of the placenta that were judged to represent normal functional tissue, in normal pregnancies, were used to perform volumetry of the putative functional placental tissue (PFPT) in a control- and an IUGR-group. Fractional anisotropy (FRC), as well as maximum and mean diffusivity were also calculated. PFPT volumetry showed a significant reduction of functional placental tissue in the IUGR group of up to 33%. Analysis of global PFPT, maximum diffusivity, mean diffusivity, and FRC also showed a significant difference. PFPT volume is dramatically reduced in IUGR. Several DT-MRI parameters suggest an additional placental micro-architecture disturbance in IUGR. PFPT volumetry appears to be a promising tool for improving the detection of IUGR. Copyright © 2013 Elsevier Ltd. All rights reserved.

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

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    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.

  6. Human placental alkaline phosphatase in liver and intestine.

    OpenAIRE

    Garattini, E; Margolis, J; Heimer, E; Felix, A.; Udenfriend, S

    1985-01-01

    Three distinct forms of human alkaline phosphatase, presumably isozymes, are known, each apparently associated with a specific tissue. These are placental, intestinal, and liver (kidney and bone). We have used a specific immunoassay and HPLC to show that placental alkaline phosphatase is also present in extracts of liver and intestine in appreciable amounts.

  7. 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

  8. Oxygen and tissue culture affect placental gene expression.

    Science.gov (United States)

    Brew, O; Sullivan, M H F

    2017-07-01

    Placental explant culture is an important model for studying placental development and functions. We investigated the differences in placental gene expression in response to tissue culture, atmospheric and physiologic oxygen concentrations. Placental explants were collected from normal term (38-39 weeks of gestation) placentae with no previous uterine contractile activity. Placental transcriptomic expressions were evaluated with GeneChip® Human Genome U133 Plus 2.0 arrays (Affymetrix). We uncovered sub-sets of genes that regulate response to stress, induction of apoptosis programmed cell death, mis-regulation of cell growth, proliferation, cell morphogenesis, tissue viability, and protection from apoptosis in cultured placental explants. We also identified a sub-set of genes with highly unstable pattern of expression after exposure to tissue culture. Tissue culture irrespective of oxygen concentration induced dichotomous increase in significant gene expression and increased enrichment of significant pathways and transcription factor targets (TFTs) including HIF1A. The effect was exacerbated by culture at atmospheric oxygen concentration, where further up-regulation of TFTs including PPARA, CEBPD, HOXA9 and down-regulated TFTs such as JUND/FOS suggest intrinsic heightened key biological and metabolic mechanisms such as glucose use, lipid biosynthesis, protein metabolism; apoptosis, inflammatory responses; and diminished trophoblast proliferation, differentiation, invasion, regeneration, and viability. These findings demonstrate that gene expression patterns differ between pre-culture and cultured explants, and the gene expression of explants cultured at atmospheric oxygen concentration favours stressed, pro-inflammatory and increased apoptotic transcriptomic response. Copyright © 2017 Elsevier Ltd. All rights reserved.

  9. 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 delivers poorly developed young. Guinea pig is a good alternative rodent model and among the few species known to develop pregnancy toxaemia. The sheep is well established as a model in fetal physiology but is of limited value for placental research. The ovine placenta is epitheliochorial...

  10. Extremely stable soluble high molecular mass multi-protein complex with DNase activity in human placental tissue.

    Directory of Open Access Journals (Sweden)

    Evgeniya E Burkova

    Full Text Available Human placenta is an organ which protects, feeds, and regulates the grooving of the embryo. Therefore, identification and characterization of placental components including proteins and their multi-protein complexes is an important step to understanding the placenta function. We have obtained and analyzed for the first time an extremely stable multi-protein complex (SPC, ∼ 1000 kDa from the soluble fraction of three human placentas. By gel filtration on Sepharose-4B, the SPC was well separated from other proteins of the placenta extract. Light scattering measurements and gel filtration showed that the SPC is stable in the presence of NaCl, MgCl2, acetonitrile, guanidinium chloride, and Triton in high concentrations, but dissociates efficiently in the presence of 8 M urea, 50 mM EDTA, and 0.5 M NaCl. Such a stable complex is unlikely to be a casual associate of different proteins. According to SDS-PAGE and MALDI mass spectrometry data, this complex contains many major glycosylated proteins with low and moderate molecular masses (MMs 4-14 kDa and several moderately abundant (79.3, 68.5, 52.8, and 27.2 kDa as well as minor proteins with higher MMs. The SPC treatment with dithiothreitol led to a disappearance of some protein bands and revealed proteins with lower MMs. The SPCs from three placentas efficiently hydrolyzed plasmid supercoiled DNA with comparable rates and possess at least two DNA-binding sites with different affinities for a 12-mer oligonucleotide. Progress in study of placental protein complexes can promote understanding of their biological functions.

  11. Kinetic comparison of tissue non-specific and placental human alkaline phosphatases expressed in baculovirus infected cells: application to screening for Down's syndrome

    Directory of Open Access Journals (Sweden)

    Grozdea Jean J

    2002-01-01

    Full Text Available Abstract Background In humans, there are four alkaline phosphatases, and each form exibits a characteristic pattern of tissue distribution. The availability of an easy method to reveal their activity has resulted in large amount of data reporting correlations between variations in activity and illnesses. For example, alkaline phosphatase from neutrophils of mothers pregnent with a trisomy 21 fetus (Down's syndrome displays significant differences both in its biochemical and immunological properties, and in its affinity for some specific inhibitors. Results To analyse these differences, the biochemical characteristics of two isozymes (non specific and placental alkaline phosphatases were expressed in baculovirus infected cells. Comparative analysis of the two proteins allowed us to estimate the kinetic constants of denaturation and sensitivity to two inhibitors (L-p-bromotetramisole and thiophosphate, allowing better discrimination between the two enzymes. These parameters were then used to estimate the ratio of the two isoenzymes in neutrophils of pregnant mothers with or without a trisomy 21 fetus. It appeared that the placental isozyme represented 13% of the total activity of neutrophils of non pregnant women. This proportion did not significantly increase with normal pregnancy. By contrast, in pregnancies with trisomy 21 fetus, the proportion reached 60–80% of activity. Conclusion Over-expression of the placental isozyme compared with the tissue-nonspecific form in neutrophils of mother with a trisomy 21 fetus may explain why the characteristics of the alkaline phosphatase in these cells is different from normal. Application of this knowledge could improve the potential of using alkaline phosphatase measurements to screen for Down's syndrome.

  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. 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

  14. Simplified matrix solid phase dispersion procedure for the determination of parabens and benzophenone-ultraviolet filters in human placental tissue samples.

    Science.gov (United States)

    Vela-Soria, F; Rodríguez, I; Ballesteros, O; Zafra-Gómez, A; Ballesteros, L; Cela, R; Navalón, A

    2014-12-05

    In recent decades, the industrial development has resulted in the appearance of a large amount of new chemicals that are able to produce disorders in the human endocrine system. These substances, so-called endocrine disrupting chemicals (EDCs), include many families of compounds, such as parabens and benzophenone-UV filters. Taking into account the demonstrated biological activity of these compounds, it is necessary to develop new analytical procedures to assess the exposure in order to establish, in an accurate way, relationships between EDCs and harmful health effects in population. In the present work, a new method based on a simplified sample treatment by matrix solid phase dispersion (MSPD) followed by ultrahigh performance liquid chromatography-tandem mass spectrometry (UHPLC-MS/MS) analysis, is validated for the determination of four parabens (methyl-, ethyl-, propyl- and butylparaben) and six benzophenone-UV filters (benzophenone-1, benzophenone-2, benzophenone-3, benzophenone-6, benzophenone-8 and 4-hydroxybenzophenone) in human placental tissue samples. The extraction parameters were accurately optimized using multivariate optimization strategies. Ethylparaben ring-13C6 and benzophenone-d10 were used as surrogates. The found limits of quantification ranged from 0.2 to 0.4 ng g(-1) and inter-day variability (evaluated as relative standard deviation) ranged from 5.4% to 12.8%. The method was validated using matrix-matched standard calibration followed by a recovery assay with spiked samples. Recovery rates ranged from 96% to 104%. The method was satisfactorily applied for the determination of compounds in human placental tissue samples collected at the moment of delivery from 10 randomly selected women. Copyright © 2014 Elsevier B.V. All rights reserved.

  15. Immunoblot analysis of the placental form of glutathione S-transferase in protein extracted from paraffin-embedded human glioma tissue.

    Science.gov (United States)

    Hara, A; Sakai, N; Yamada, H; Yoshimi, N; Tanaka, T; Mori, H

    1993-01-01

    Protein extracted from conventional formalin-fixed and paraffin-embedded tissue sections of human gliomas was examined for immunoblot analysis using antibody against the placental form of glutathione S-transferase (GST-pi). Four benign astrocytomas, five anaplastic astrocytomas and four glioblastomas were used in this study. The preliminary study demonstrated that immunoreactivity of GST-pi was well preserved in normal brain tissue and normal term placenta fixed in acetone, formalin or buffered formalin (pH 7.4). GST-pi in gliomas fixed in formalin also had a good immunoreactivity and showed clear bands on nitrocellulose membranes processed by the method of Western blotting using anti-GST-pi antibody. The results of immunoblot analysis for GST-pi indicate that the intensity of immunoreactivity of benign astrocytoma, anaplastic astrocytoma and glioblastoma increases with the advance of malignancy of these neoplasms. Western blot analysis for GST-pi can be performed using protein extracted from formalin-fixed and paraffin-embedded tissue sections, and the immunoreactive bands can be analyzed quantitatively by densitometric scanning.

  16. Placental perfusion - a human alternative

    DEFF Research Database (Denmark)

    Mose, Tina; Knudsen, Lisbeth E

    2006-01-01

    and represents a supplement and alternative to animal testing, bypassing the animal to human extrapolation. Placentas are readily obtainable from most births upon informed consent from the mothers and are considered a promising tissue alternative/supplement to animal experiments. The system is validated...

  17. Fetal gender specific expression of tandem-repeat galectins in placental tissue from normally progressed human pregnancies and intrauterine growth restriction (IUGR).

    Science.gov (United States)

    Hutter, Stefan; Knabl, Julia; Andergassen, Ulrich; Mayr, Doris; Hofmann, Simone; Kuhn, Christina; Mahner, Sven; Arck, Petra; Jeschke, Udo

    2015-12-01

    The tandem-repeat type galectins, which comprise of gal-4, -6, -8, -9, and -12, form a sub-family of galectins. Gal-6 is expressed only in rodents, whereas the other four galectins, tandem-repeat galectins, are also detectable in human tissue. The placental expression of individual members of the tandem-repeat gal family is increasingly known, however, systematic, comparative analysis especially in the human placenta from normal or pathological pregnancies is still lacking. Within this study, third trimester placentas obtained at delivery (n = 14 IUGR, n = 15 controls, equally divided in placentas from male and female fetuses) were analyzed for the expression of gal-4, -8, -9 and -12 by immunohistology and immunofluorescence, data were obtained by using a semiquantitative scoring system. Double immune-fluorescence with trophoblast specific markers was used to identify co-expression in the decidua. We identified dysregulation of tandem repeat galectins in IUGR placentas with a strong connection to the fetal gender. We identified a significantly lower expression of gal-4 and gal-9 in villous trophoblast tissue of IUGR placentas with male fetuses and a downregulation of gal-4 and gal-8 in extravillous trophoblast (EVT) from IUGR and male fetuses. Conversely, expression of gal-9 and gal-12 was higher in EVT of IUGR cases in placentas with female fetuses. Double immunofluorescence using cytokeratin-7 confirmed the expression of tandem-repeat galectins in EVT. The human placenta expresses tandem-repeat type galectins in villous trophoblasts, EVT, endothelial cells and decidual stromal cells. Summarizing all effects, there is significant down-regulation of gal-4, -8 and gal-9 in the IUGR trophoblast of male fetuses. In contrast, in IUGR pregnancies with female fetus gal-9 and gal-12 are upregulated in the EVT and in endothelial cells in the cases of gal-12. Therefore we propose a fetal-gender specific action of tandem repeat galectins in IUGR placentas. Copyright © 2015

  18. Human placental immunoglobulins show unique re-association ...

    African Journals Online (AJOL)

    Objective: To study re-association pattern of human placental eluate immunoglobulins with acid treated isologous and third party trophoblast derived placental microvesicles. Design: Laboratory based experimentation. Setting: Biological Sciences Department and Discipline for Reproductive Medicine University of ...

  19. Combined effects of mineral trioxide aggregate and human placental extract on rat pulp tissue and growth, differentiation and angiogenesis in human dental pulp cells.

    Science.gov (United States)

    Chang, Seok-Woo; Kim, Ji-Youn; Kim, Mi-Joo; Kim, Ga-Hyun; Yi, Jin-Kyu; Lee, Deok-Won; Kum, Kee-Yeon; Kim, Eun-Cheol

    2016-01-01

    The aim of this study was to evaluate the combined effects of mineral trioxide aggregate (MTA) and human placental extract (HPE) on cell growth, differentiation and in vitro angiogenesis of human dental pulp cells (HDPCs) and to identify underlying signal transduction mechanisms. In vivo dental pulp responses in rats for a pulp-capping agent were examined. MTS assay. ALP activity test, alizarin red S staining and RT-PCR for marker genes were carried out to evaluate cell growth and differentiation. HUVEC migration, mRNA expression and capillary tube formation were measured to evaluate angiogenesis. Signal transduction was analysed using Western blotting and confocal microscopy. The pulps of rat maxillary first molars were exposed and capped with either MTA or MTA plus HPE. Histologic observation and scoring were performed. Compared to treatment of HDPCs with either HPE or MTA alone, the combination of HPE and MTA increased cell growth, ALP activity, mineralized nodules and expression of marker mRNAs. Combination HPE and MTA increased migration, capillary tube formation and angiogenic gene expression compared with MTA alone. Activation of Akt, mammalian target of rapamycin (mTOR), p38, JNK and ERK MAPK, Akt, and NF-κB were significantly increased by combining HPE and MTA compared with MTA alone. Pulp capping with MTA plus HPE in rats showed superior dentin bridge formation, odontoblastic layers and dentinal tubules and lower inflammatory cell response, compared to the MTA alone group. This study demonstrates for the first time that the use of MTA with HPE promotes cell growth, differentiation and angiogenesis in HDPCs, which were associated with mTOR, MAPK and NF-κB pathways. Direct pulp capping with HPE plus MTA showed superior results when compared with MTA alone. Thus, the combination of MTA and HPE may be useful for regenerative endodontics.

  20. Heat shock protein-70 and 4-hydroxy-2-nonenal adducts in human placental villous tissue of normotensive, preeclamptic and intrauterine growth restricted pregnancies.

    Science.gov (United States)

    Hnat, Michael D; Meadows, Juliana W; Brockman, Diane E; Pitzer, Brad; Lyall, Fiona; Myatt, Leslie

    2005-09-01

    The purpose of this study was to compare immunohistochemical expression of heat shock protein-70 (hsp70), a marker for oxidative stress, and 4-hydroxy-2-nonenal adducts (HNE), a marker for lipid peroxidation, in placental villous tissue of normotensive, preeclampsia, and intrauterine growth restricted (IUGR) pregnancies. Placentas were collected and flash frozen in liquid nitrogen after delivery from normotensive pregnancies (n=5), and pregnancies complicated by preeclampsia (n=5), IUGR (n=5), and preeclampsia plus IUGR (n=4). Cryosections were cut and immunostained with polyclonal anti-hsp70 and monoclonal anti-HNE antibodies using Vectastain Elite ABC kit. Normal rabbit serum or mouse IgG were used as negative controls. Three independent observers, blinded to identity of tissue, examined each slide to identify cellular localization and intensity of the immunostaining. Western blot analysis and scanning densitometry were used to quantify and compare the amount of hsp70 and HNE adducts present in tissue homogenates. Positive immunostaining for both antibodies was observed in cytoplasm of syncytiotrophoblasts, extravillous trophoblasts, vascular smooth muscle, and endothelial cells for all groups. Expression of hsp70 and HNE adducts was reported as observers' mean stained intensity. Overall, kappa showed good agreement between observers. Immunostaining intensity was similar in all tissue types for each group with the exception that immunostaining was significantly more intense in the vascular endothelium of the preeclamptic group for HNE adducts (P=.02) and significantly less intense in the IUGR group for hsp70 (P=.013). Scanning densitometric analysis of the Western blots showed no significant difference in total hsp70 and HNE adducts expression in all 4 tissue groups. Immunohistochemistry showed local changes for oxidative stress and lipid peroxidation in the vascular endothelium from placentas of preeclamptic and IUGR pregnancies. However, these changes were

  1. Placental elasticity evaluation using virtual touch tissue quantification during pregnancy.

    Science.gov (United States)

    Ohmaru, Takako; Fujita, Yasuyuki; Sugitani, Maiko; Shimokawa, Mototsugu; Fukushima, Kotaro; Kato, Kiyoko

    2015-08-01

    Virtual touch tissue quantification (VTTQ) has been developed to evaluate tissue elasticity. Our previous study using delivered placentas showed increased elasticity in fetal growth restriction (FGR). Therefore, we investigated changes in placental elasticity during pregnancy, including complicated pregnancies. Based on complications, 199 women were divided into 5 groups (normal, FGR, pregnancy induced hypertension (PIH), diabetes mellitus and collagen disease), and shear wave velocity (SWV) of the placenta, measured using VTTQ, was compared. A cross-sectional study was performed with the 143 normal cases to construct the reference range. The association between placental SWV and the expression ratio of collagen fibers in the placenta stained with Masson's trichrome was determined. The SWV was safely measured for all participants. The correlation between SWV and gestational weeks was not significant. The mean ± SD SWVs in the normal, FGR, and PIH groups were 0.98 ± 0.21, 1.28 ± 0.39, and 1.60 ± 0.45 m/sec, respectively. The FGR and PIH groups had significantly higher SWVs than that of the normal group. SWV and the expression ratio of collagen fibers were significantly correlated. Based on the present findings, changes in SWV during pregnancy were associated with placental fibrosis, and increased SWV in PIH and/or FGR cases might be influenced by infarction, ischemic changes, and inflammation, as well as fibrosis. In conclusion, the measurement of placental SWV is potentially useful to evaluate the condition of the placenta during pregnancy. Copyright © 2015 Elsevier Ltd. All rights reserved.

  2. Prevalence and predictors of placental malaria in human ...

    African Journals Online (AJOL)

    2016-02-16

    Feb 16, 2016 ... Background: Human immunodeficiency virus (HIV)‑infected pregnant women have alterations in cellular and humoral immunity that increase the risks to placental malaria infection. Aim: This study aimed at determining the prevalence and predictors of placental malaria among HIV‑positive women.

  3. Prevalence and predictors of placental malaria in human ...

    African Journals Online (AJOL)

    Background: Human immunodeficiency virus (HIV)‑infected pregnant women have alterations in cellular and humoral immunity that increase the risks to placental malaria infection. Aim: This study aimed at determining the prevalence and predictors of placental malaria among HIV‑positive women in Nigeria. Materials and ...

  4. Arrangement of collagen fibers in human placental stem villi.

    Science.gov (United States)

    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 was performed in order to localize collagen types I, III, IV, V and cytokeratin 7 on tissue sections. Parallel tissue samples were examined by transmission electron microscopy. Semi-quantitative analysis of immunolabeling intensities was also performed to determine the distribution of fibers in stem villi stroma. All collagen types, especially collagen type V, were strongly immunopositive in the triangular areas of the stem villi stroma. However, there was no collagen type I or type III immunolabeling in the sub-trophoblastic regions. Membrane collagen type IV immunolabeling was also observed in the stroma of stem villi. Ultrastructurally, collagen fibers showed different configurations in cross, longitudinal, circular, oblique and parallel directions compared to the villous axis. We conclude that the organization of collagen fiber bundles in stem villi shows a very specific arrangement: a compact coat formed by fibrillar bundles between the vascular wall and extravascular stroma of stem villi correlated with the functional activity.

  5. Pathologic evaluation of normal and perfused term placental tissue

    DEFF Research Database (Denmark)

    Maroun, Lisa Leth; Mathiesen, Line; Hedegaard, Morten

    2014-01-01

    This study reports for the 1st time the incidence and interobserver variation of morphologic findings in a series of 34 term placentas from pregnancies with normal outcome used for perfusion studies. Histologic evaluation of placental tissue is challenging, especially when it comes to defining...... and selected findings were tested against success parameters from the perfusions. Finally, the criteria for frequent lesions with fair to poor interobserver variation in the nonperfused tissue were revised and reanalyzed. In the perfused tissue, the perfusion artefact "trophoblastic vacuolization," which...... with addition of antibiotics to the medium. In the "normal" tissue, certain lesions were very frequent and showed only fair or poor interobserver agreement. Revised minimum criteria for these lesions were defined and found reproducible. This study has emphasized the value of pathologic examination...

  6. Placental and stillbirth tissue lead concentrations in occupationally exposed women.

    Science.gov (United States)

    Khera, A K; Wibberley, D G; Dathan, J G

    1980-11-01

    The lead values in maternal and infant blood, in placental tissue, and in stillbirth liver, kidney, and rib- and skull-bones have been determined in samples from the Stoke-on-Trent area. The lead values in antenatal blood and placenta increase with occupational exposure; liver and kidney stillbirth lead values are lower than those of much older children and rib-bone lead values from stillbirths were on average three times as high as those from a control group comprised of cot deaths and early infant deaths from accidental causes.

  7. The 4-vessel Sampling Approach to Integrative Studies of Human Placental Physiology In Vivo.

    Science.gov (United States)

    Holme, Ane M; Holm, Maia B; Roland, Marie C P; Horne, Hildegunn; Michelsen, Trond M; Haugen, Guttorm; Henriksen, Tore

    2017-08-02

    The human placenta is highly inaccessible for research while still in utero. The current understanding of human placental physiology in vivo is therefore largely based on animal studies, despite the high diversity among species in placental anatomy, hemodynamics and duration of the pregnancy. The vast majority of human placenta studies are ex vivo perfusion studies or in vitro trophoblast studies. Although in vitro studies and animal models are essential, extrapolation of the results from such studies to the human placenta in vivo is uncertain. We aimed to study human placenta physiology in vivo at term, and present a detailed protocol of the method. Exploiting the intraabdominal access to the uterine vein just before the uterine incision during planned cesarean section, we collect blood samples from the incoming and outgoing vessels on the maternal and fetal sides of the placenta. When combining concentration measurements from blood samples with volume blood flow measurements, we are able to quantify placental and fetal uptake and release of any compound. Furthermore, placental tissue samples from the same mother-fetus pairs can provide measurements of transporter density and activity and other aspects of placental functions in vivo. Through this integrative use of the 4-vessel sampling method we are able to test some of the current concepts of placental nutrient transfer and metabolism in vivo, both in normal and pathological pregnancies. Furthermore, this method enables the identification of substances secreted by the placenta to the maternal circulation, which could be an important contribution to the search for biomarkers of placenta dysfunction.

  8. Review: The effects of oxygen on normal and pre-eclamptic placental tissue--insights from metabolomics.

    Science.gov (United States)

    Heazell, A E P; Brown, M; Worton, S A; Dunn, W B

    2011-03-01

    Placental dysfunction is central to many complications of human pregnancy including pre-eclampsia (PE), intra-uterine growth restriction (IUGR) and stillbirth. The precise molecular pathophysiology of placental dysfunction in these conditions is not known, although oxidative and nitrative stresses have been implicated. Metabolites are low molecular weight chemicals which play an important role in biological function, primarily through metabolism and regulation of biological processes. The holistic study of metabolites, defined as metabolomics or metabolic profiling, has the objective to detect and identify all, or a large complement of all metabolites. Metabolomics is applied to discover new knowledge regarding biological processes and systems. We hypothesised that a metabolomic strategy could (1) provide a reproducible technique to investigate the intracellular metabolism of placental tissue and also metabolites consumed from or secreted in to the extracellular 'metabolic footprint' of in vitro culture systems (2) identify metabolic related differences in placental tissue culture systems subjected to perturbations in oxygen tension and from pregnancies complicated by PE. We review our early studies which demonstrate that a reproducible experimental protocol is required, including the preparation of culture medium and the site of the placenta applied for sampling tissue. We have detected changes in the intracellular metabolome and metabolic footprint of placental tissue in response to altered oxygen tension and PE. We have demonstrated that placental tissue from uncomplicated pregnancies cultured in 1% oxygen (hypoxia) had metabolic similarities to explants from PE pregnancies cultured at 6% oxygen (normoxia). Metabolites requiring further study include lipids, glutamate and glutamine and metabolites related to tryptophan, leukotriene and prostaglandin metabolism. Metabolomics has the potential to identify changes in clinical conditions, such as PE, that are

  9. Mesenchymal stem cells in human placental chorionic villi reside in a vascular Niche

    NARCIS (Netherlands)

    Castrechini, N. M.; Murthi, P.; Gude, N. M.; Erwich, J. J. H. M.; Gronthos, S.; Zannettino, A.; Brennecke, S. R.; Kalionis, B.; Brennecke, S.P.

    The chorionic villi of human term placentae are a rich source of mesenchymal stem cells (PMSCs) The stem cell "niche" within the chorionic villi regulates how PMSCs participate in placental tissue generation, maintenance and repair, but the anatomic location of the niche has not been defined A

  10. Human papillomavirus infects placental trophoblast and Hofbauer cells, but appears not to play a causal role in miscarriage and preterm labor.

    Science.gov (United States)

    Ambühl, Lea M M; Leonhard, Anne K; Widen Zakhary, Carina; Jørgensen, Annemette; Blaakaer, Jan; Dybkaer, Karen; Baandrup, Ulrik; Uldbjerg, Niels; Sørensen, Suzette

    2017-10-01

    Recently, an association between human papillomavirus infection and both spontaneous abortion and spontaneous preterm delivery was suggested. However, the reported human papillomavirus prevalence in pregnant women varies considerably and reliable conclusions are difficult. We aimed to investigate human papillomavirus infection in placental tissue of a Danish study cohort. Furthermore, we studied the cellular localization of human papillomavirus. In this prospective case-control study, placental tissue was analyzed for human papillomavirus infection by nested PCR in the following four study groups: full-term delivery (n = 103), spontaneous preterm delivery (n = 69), elective abortion (n = 54), and spontaneous abortion (n = 44). Moreover, human papillomavirus cellular target was identified using in situ hybridization. Human papillomavirus prevalence in placental tissue was 8.7% in full-term deliveries, 8.8% in spontaneous preterm deliveries, 10.9% in spontaneous abortions, and 20.4% in elective abortions. Twelve different human papillomavirus types were detected, and placental human papillomavirus infection was associated to a disease history of cervical cancer. Human papillomavirus DNA was identified in trophoblast cells, cells of the placental villi mesenchyme including Hofbauer cells, and in parts of the encasing endometrium. Placental human papillomavirus infections are not likely to constitute a risk factor for spontaneous preterm labor or spontaneous abortions in the Danish population, although an effect of human papillomavirus DNA in placental cells cannot be excluded. © 2017 Nordic Federation of Societies of Obstetrics and Gynecology.

  11. Improvement of a tissue maceration technique for the determination of placental involvement in schistosomiasis.

    Science.gov (United States)

    Holtfreter, Martha Charlotte; Neubauer, Heinrich; Groten, Tanja; El-Adawy, Hosny; Pastuschek, Jana; Richter, Joachim; Häussinger, Dieter; Pletz, Mathias Wilhelm; Schleenvoigt, Benjamin Thomas

    2017-04-01

    Schistosomiasis in pregnancy may cause low birth weight, prematurity and stillbirth of the offspring. The placenta of pregnant women might be involved when schistosome ova are trapped in placental tissue. Standard histopathological methods only allow the examination of a limited amount of placental tissue and are therefore not sufficiently sensitive. Thus, placental schistosomiasis remains underdiagnosed and its role in contributing to schistosomiasis-associated pregnancy outcomes remains unclear. Here we investigated an advanced maceration method in order to recover a maximum number of schistosome ova from the placenta. We examined the effect of different potassium hydroxide (KOH) concentrations and different tissue fixatives with respect to maceration success and egg morphology. Placental tissue was kept either in 0.9% saline, 5% formalin or 70% ethanol and was macerated together with Schistosoma mansoni infested mouse livers and KOH 4% or 10%, respectively. We found that placenta maceration using 4% KOH at 37°C for 24 h was the most effective method: placental tissue was completely digested, egg morphology was well preserved and alkaline concentration was the lowest. Ethanol proved to be the best fixative for this method. Here we propose an improved maceration technique in terms of sensitivity, safety and required skills, which may enable its wider use also in endemic areas. This technique may contribute to clarifying the role of placental involvement in pregnant women with schistosomiasis.

  12. Paraquat inhibits progesterone synthesis in human placental mitochondria.

    Science.gov (United States)

    Milczarek, Ryszard; Sokołowska, Ewa; Rybakowska, Iwona; Kaletha, Krystian; Klimek, Jerzy

    2016-07-01

    Human placenta mitochondria produces huge amounts of progesterone necessary for maintaining the pregnancy. Lipid peroxidation in human placental mitochondria inhibits progesterone synthesis and that inhibition can be reversed by superoxide dismutase and other antioxidants. Paraquat (PQ) a highly toxic herbicide generates superoxide radical inside cells and induces lipid peroxidation. Hence, it is supposed to stimulate lipid peroxidation in human placental mitochondria and in consequence to inhibit a placental mitochondrial steroidogenesis. Placentas were obtained from normal pregnancies. All experiments were done using isolated human placental mitochondria. Mitochondrial lipid peroxidation was determined as tiobarbituric acid reactive substances (TBARS). A conversion of cholesterol to pregnenolone or pregnenolone to progesterone was measured using radiolabeled steroids and thin layer chromatography. PQ enhanced the iron-dependent lipid peroxidation as also PQ heightened the inhibitory action of this process on progesterone synthesis in isolated human placental mitochondria. Paradoxically, a superoxide dismutase (SOD) reversed the inhibition of progesterone synthesis only minimally although it strongly inhibited PQ stimulated iron-dependent lipid peroxidation. When iron was absent, PQ stimulated only negligible lipid peroxidation but strongly inhibited progesterone synthesis. SOD had no effect on inhibition of progesterone synthesis by PQ. PQ strongly inhibited of the conversion of cholesterol to pregnenolone but had not got any influence on the enzymatic activity of mitochondrial 3β-hydroxysteroid dehydrogenase. PQ strongly decreased the efficiency of NADPH-dependent cytochrome P450 reduction as well as it promoted the rapid oxidation of the pre-reduced mitochondrial cytochrome P450. However PQ has not inhibited combined activity of adrenodoxin reductase and adrenodoxin. We conclude that the most important reason of the inhibition of progesterone synthesis by PQ

  13. Applications for Research Concerning Fetal or Placental Tissue and Expected Institutional Review Board Responses.

    Science.gov (United States)

    Borgatta, Lynn; Kaufman, David; Kelly, Judith Parsells; Babaian, David; Banks, Mary

    2017-07-01

    Proposals for research concerning fetal and/or placental tissue may be refused institutional review board (IRB) review, effectively preventing the research from occurring. We conducted an anonymous electronic survey of IRB chairs to determine their assessment of the likely response to research projects using fetal/placental tissue obtained from various procedures. We found that proposals concerning tissue obtained from diagnostic procedures or miscarriage were anticipated to be considered at most institutions. Tissue obtained after abortion was likely to be refused consideration by more than 25% of respondents. Additional consultation during review was anticipated for up to 30% of scenarios. Responses for fetal and placental tissue were similar. The most frequently anticipated reason for refusal was institutional policy.

  14. Bacterial communities found in placental tissues are associated with severe chorioamnionitis and adverse birth outcomes.

    Directory of Open Access Journals (Sweden)

    Ronan M Doyle

    Full Text Available Preterm birth is a major cause of neonatal mortality and morbidity worldwide. Bacterial infection and the subsequent inflammatory response are recognised as an important cause of preterm birth. It is hypothesised that these organisms ascend the cervical canal, colonise placental tissues, cause chorioamnionitis and in severe cases infect amniotic fluid and the foetus. However, the presence of bacteria within the intrauterine cavity does not always precede chorioamnionitis or preterm birth. Whereas previous studies observing the types of bacteria present have been limited in size and the specificity of a few predetermined organisms, in this study we characterised bacteria found in placental tissues from a cohort of 1391 women in rural Malawi using 16S ribosomal RNA gene sequencing. We found that specific bacteria found concurrently on placental tissues associate with chorioamnionitis and delivery of a smaller newborn. Severe chorioamnionitis was associated with a distinct difference in community members, a higher bacterial load and lower species richness. Furthermore, Sneathia sanguinengens and Peptostreptococcus anaerobius found in both matched participant vaginal and placental samples were associated with a lower newborn length-for-age Z-score. This is the largest study to date to examine the placental microbiome and its impact of birth outcomes. Our results provide data on the role of the vaginal microbiome as a source of placental infection as well as the possibility of therapeutic interventions against targeted organisms during pregnancy.

  15. The surrounding tissue modifies the placental stem villous vascular responses

    DEFF Research Database (Denmark)

    Brøgger, Torbjørn; Forman, Axel; Aalkjær, Christian

    2014-01-01

    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 of blood flow, and compromised function may lead to complications like growth retardation and preeclampsia where no specific treatment...

  16. Differential expression of human placental PAPP-A2 over gestation and in preeclampsia.

    Science.gov (United States)

    Kramer, Anita W; Lamale-Smith, Leah M; Winn, Virginia D

    2016-01-01

    Pregnancy Associated Plasma Protein A2 (PAPP-A2) is a pregnancy related insulin-like growth factor binding protein-5 (IGFBP-5) protease, known to be elevated in preeclampsia. As the insulin-like growth factors are important in human implantation and placentation, we sought to determine the expression pattern of PAPP-A2 over human gestation in normal and preeclamptic pregnancies to evaluate its role in placental development and the pathogenesis of preeclampsia. Placental basal plate and chorionic villi samples, maternal and fetal cord blood sera were obtained from preeclamptic and control pregnancies. Formalin-fixed tissue sections from across gestation were stained for cytokeratin-7, HLA-G, and PAPP-A2. PAPP-A2 immunoblot analysis was also performed on protein lysates and sera. PAPP-A2 expression is predominately expressed by differentiated trophoblasts and fetal endothelium. Chorionic villi show strong expression in the first trimester, followed by a progressive decrease in the second trimester, which returns in the third trimester. PAPP-A2 expression is not impacted by labor. PAPP-A2 is increased in the basal plate, chorionic villi and maternal sera in preeclampsia compared to controls, but is not detectable in cord blood. PAPP-A2 is differentially expressed in different trophoblast populations and shows strong down regulation in the mid second trimester in chorionic villous samples. Both maternal sera and placental tissue from pregnancies complicated by preeclampsia show increased levels of PAPP-A2. PAPP-A2 levels are not altered by labor. Additionally, PAPP-A2 cannot be detected in cord blood demonstrating that the alterations in maternal and placental PAPP-A2 are not recapitulated in the fetal circulation. Published by Elsevier Ltd.

  17. 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.

  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. Copyright © 2016 Elsevier B.V. All rights reserved.

  19. Pomegranate juice and punicalagin attenuate oxidative stress and apoptosis in human placenta and in human placental trophoblasts.

    Science.gov (United States)

    Chen, Baosheng; Tuuli, Methodius G; Longtine, Mark S; Shin, Joong Sik; Lawrence, Russell; Inder, Terrie; Michael Nelson, D

    2012-05-15

    The human placenta is key to pregnancy outcome, and the elevated oxidative stress present in many complicated pregnancies contributes to placental dysfunction and suboptimal pregnancy outcomes. We tested the hypothesis that pomegranate juice, which is rich in polyphenolic antioxidants, limits placental trophoblast injury in vivo and in vitro. Pregnant women with singleton pregnancies were randomized at 35∼38 wk gestation to 8 oz/day of pomegranate juice or apple juice (placebo) until the time of delivery. Placental tissues from 12 patients (4 in the pomegranate group and 8 in the control group) were collected for analysis of oxidative stress. The preliminary in vivo results were extended to oxidative stress and cell death assays in vitro. Placental explants and cultured primary human trophoblasts were exposed to pomegranate juice or glucose (control) under defined oxygen tensions and chemical stimuli. We found decreased oxidative stress in term human placentas from women who labored after prenatal ingestion of pomegranate juice compared with apple juice as control. Moreover, pomegranate juice reduced in vitro oxidative stress, apoptosis, and global cell death in term villous explants and primary trophoblast cultures exposed to hypoxia, the hypoxia mimetic cobalt chloride, and the kinase inhibitor staurosporine. Punicalagin, but not ellagic acid, both prominent polyphenols in pomegranate juice, reduced oxidative stress and stimulus-induced apoptosis in cultured syncytiotrophoblasts. We conclude that pomegranate juice reduces placental oxidative stress in vivo and in vitro while limiting stimulus-induced death of human trophoblasts in culture. The polyphenol punicalagin mimics this protective effect. We speculate that antenatal intake of pomegranate may limit placental injury and thereby may confer protection to the exposed fetus.

  20. Pomegranate juice and punicalagin attenuate oxidative stress and apoptosis in human placenta and in human placental trophoblasts

    Science.gov (United States)

    Tuuli, Methodius G.; Longtine, Mark S.; Shin, Joong Sik; Lawrence, Russell; Inder, Terrie; Michael Nelson, D.

    2012-01-01

    The human placenta is key to pregnancy outcome, and the elevated oxidative stress present in many complicated pregnancies contributes to placental dysfunction and suboptimal pregnancy outcomes. We tested the hypothesis that pomegranate juice, which is rich in polyphenolic antioxidants, limits placental trophoblast injury in vivo and in vitro. Pregnant women with singleton pregnancies were randomized at 35∼38 wk gestation to 8 oz/day of pomegranate juice or apple juice (placebo) until the time of delivery. Placental tissues from 12 patients (4 in the pomegranate group and 8 in the control group) were collected for analysis of oxidative stress. The preliminary in vivo results were extended to oxidative stress and cell death assays in vitro. Placental explants and cultured primary human trophoblasts were exposed to pomegranate juice or glucose (control) under defined oxygen tensions and chemical stimuli. We found decreased oxidative stress in term human placentas from women who labored after prenatal ingestion of pomegranate juice compared with apple juice as control. Moreover, pomegranate juice reduced in vitro oxidative stress, apoptosis, and global cell death in term villous explants and primary trophoblast cultures exposed to hypoxia, the hypoxia mimetic cobalt chloride, and the kinase inhibitor staurosporine. Punicalagin, but not ellagic acid, both prominent polyphenols in pomegranate juice, reduced oxidative stress and stimulus-induced apoptosis in cultured syncytiotrophoblasts. We conclude that pomegranate juice reduces placental oxidative stress in vivo and in vitro while limiting stimulus-induced death of human trophoblasts in culture. The polyphenol punicalagin mimics this protective effect. We speculate that antenatal intake of pomegranate may limit placental injury and thereby may confer protection to the exposed fetus. PMID:22374759

  1. Expression pattern alterations of the serine protease HtrA1 in normal human placental tissues and in gestational trophoblastic diseases.

    Science.gov (United States)

    Marzioni, Daniela; Quaranta, Alexia; Lorenzi, Teresa; Morroni, Manrico; Crescimanno, Caterina; De Nictolis, Michele; Toti, Paolo; Muzzonigro, Giovanni; Baldi, Alfonso; De Luca, Antonio; Castellucci, Mario

    2009-10-01

    HtrA1 is a secreted protein which behaves as a molecular chaperone at low temperatures and as a serine protease at high temperatures. When the placenta escapes the normal growth control mechanisms, which are present during normal pregnancy, it may develop trophoblastic diseases, such as hydatidiform mole and choriocarcinoma. The aim of the study is to investigate the expression of HtrA1 in these gestational trophoblastic diseases and evaluate whether different HtrA1 expression might be associated with increasingly severe forms of disease. We used immunohistochemistry to assess the expression of HtrA1 in normal human placenta, hydatidiform mole (partial and complete) and choriocarcinoma. In addition to that we used the western blotting technique to quantify HtrA1 immunoreaction in normal human placentas. The most striking finding of our investigation is the decrease in immunostaining of this protease with increasing severity of gestational trophoblastic disease. For instance, in partial and complete moles HtrA1 is weakly expressed in the trophoblast. Moreover, absence of immunoreaction for HtrA1 is observable in the choriocarcinoma cells. In conclusion, we suggest that HtrA1 may play an important role in the pathogenesis and progression of hydatidiform moles and choriocarcinomas, and that HtrA1 may play an important role during the normal development of the placenta, as well as in trophoblastic diseases.

  2. Analysis of Placental Tissue in Fabry Disease With and Without Enzyme Replacement Therapy

    NARCIS (Netherlands)

    Bouwman, M. G.; Hollak, C. E. M.; van den Bergh Weerman, M. A.; Wijburg, F. A.; Linthorst, G. E.

    2010-01-01

    There are only a few reports on the histology of placental tissue of pregnancies from mothers with Fabry disease. Fabry disease is a lysosomal disorder caused by alpha-galactosidase A deficiency. Extensive glycosphingolipid (GSL) accumulation in fetal and maternal placenta tissue obtained from a

  3. Maternal-fetal transport kinetics of manganese in perfused human placental lobule in vitro.

    Science.gov (United States)

    Nandakumaran, Moorkath; Al-Sannan, Baydaa; Al-Sarraf, Hameed; Al-Shammari, Majed

    2016-01-01

    There have been no detailed reports relating to maternal-fetal transport kinetics of manganese, an essential trace element in the human pregnancies, and hence we have attempted to study the transport kinetics of this trace element in the human placenta in vitro. Human placentae from normal uncomplicated pregnancies were collected postpartum. Manganese chloride solution (GFS Chem Inc., Columbus, OH), 10 times the physiological concentrations, along with antipyrine (Sigma Chem Co., St. Louis, MO) as reference marker were then injected as a single bolus (100 µl) into the maternal arterial circulation of perfused placental lobules and perfusate samples collected from maternal and fetal circulations over a period of five minutes. National Culture and Tissue Collection medium, diluted with Earle's buffered salt solution was used as the perfusate and serial perfusate samples from fetal venous perfusate collected for a period of 30 min. Concentration of manganese in perfusate samples was assessed by atomic absorption spectrophotometry, while that of antipyrine was assessed by spectrophotometry. Transport kinetics of substances studied were computed using established permeation parameters. Differential transport rates of manganese and antipyrine in 12 perfusions differed significantly for 25.75, 90% efflux fractions (ANOVA test, p manganese averaged 54.9% of bolus dose in 12 perfusions, whereas that of antipyrine averaged 89% of bolus dose, representing 61.80% of reference marker TF. The difference observed in TF values of manganese and antipyrine was statistically significant (Student's t-test, p manganese compared to reference marker were significantly different (ANOVA test, p manganese in human placenta in vitro. Considering the restricted transfer of this essential trace element despite its small molecular weight, we hypothesize possibility of active transport of manganese across the human placental membrane. Further studies relating to manganese placental

  4. Modeling placental transport: correlation of in vitro BeWo cell permeability and ex vivo human placental perfusion

    DEFF Research Database (Denmark)

    Poulsen, Marie Sønnegaard; Rytting, Erik; Mose, Tina

    2009-01-01

    . Placental passage of benzoic acid, caffeine, and glyphosate in an ex vivo human perfusion system. J. Toxicol. Environ. Health, Part A 71, 984-991]. In this work, the transport of these same three compounds, plus the reference compound antipyrine, was investigated using BeWo (b30) cell monolayers. Transport......The placental passage of three compounds with different physicochemical properties was recently investigated in ex vivo human placental perfusion experiments (caffeine, benzoic acid, and glyphosate) [Mose, T., Kjaerstad, M.B., Mathiesen, L., Nielsen, J.B., Edelfors, S., Knudsen, L.E., 2008...... across the BeWo cells was observed in the rank order of caffeine>antipyrine>benzoic acid>glyphosate in terms of both the apparent permeability coefficient and the initial slope, defined as the linear rate of substance transferred to the fetal compartment as percent per time, a parameter used to compare...

  5. Human placental trophoblast invasion and differentiation: a particular focus on Wnt signalling

    Directory of Open Access Journals (Sweden)

    Martin eKnöfler

    2013-09-01

    Full Text Available Wingless ligands, a family of secreted proteins, are critically involved in organ development and tissue homeostasis by ensuring balanced rates of stem cell proliferation, cell death and differentiation. Wnt signalling components also play crucial roles in murine placental development controlling trophoblast lineage determination, chorioallantoic fusion and placental branching morphogenesis. However, the role of the pathway in human placentation, trophoblast development and differentiation is only partly understood. Here, we summarize our present knowledge about Wnt signalling in the human placenta and discuss its potential role in physiological and aberrant trophoblast invasion, gestational diseases and choriocarcinoma formation. Differentiation of proliferative first trimester cytotrophoblasts into invasive extravillous trophoblasts is associated with nuclear recruitment of β-catenin and induction of Wnt-dependent T-cell factor 4 suggesting that canonical Wnt signalling could be important for the formation and function of extravillous trophoblasts. Indeed, activation of the pathway was shown to promote trophoblast invasion in different in vitro trophoblast model systems as well as trophoblast cell fusion. Methylation-mediated silencing of inhibitors of Wnt signalling provided evidence for epigenetic activation of the pathway in placental tissues and choriocarcinoma cells. Similarly, abundant nuclear expression of β-catenin in invasive trophoblasts of complete hydatidiform moles suggested a role for hyper-activated Wnt signalling. In contrast, upregulation of Wnt inhibitors was noticed in placentae of women with preeclampsia, a disease characterized by shallow trophoblast invasion and incomplete spiral artery remodelling. Moreover, changes in Wnt signalling have been observed upon cytomegalovirus infection and in recurrent abortions. In summary, the current literature suggests a critical role of Wnt signalling in physiological and abnormal

  6. Comparing human and macaque placental transcriptomes to disentangle preterm birth pathology from gestational age effects.

    Science.gov (United States)

    Eidem, Haley R; Rinker, David C; Ackerman, William E; Buhimschi, Irina A; Buhimschi, Catalin S; Dunn-Fletcher, Caitlin; Kallapur, Suhas G; Pavličev, Mihaela; Muglia, Louis J; Abbot, Patrick; Rokas, Antonis

    2016-05-01

    A major issue in the transcriptomic study of spontaneous preterm birth (sPTB) in humans is the inability to collect healthy control tissue at the same gestational age (GA) to compare with pathologic preterm tissue. Thus, gene expression differences identified after the standard comparison of sPTB and term tissues necessarily reflect differences in both sPTB pathology and GA. One potential solution is to use GA-matched controls from a closely related species to tease apart genes that are dysregulated during sPTB from genes that are expressed differently as a result of GA effects. To disentangle genes whose expression levels are associated with sPTB pathology from those linked to GA, we compared RNA sequencing data from human preterm placentas, human term placentas, and rhesus macaque placentas at 80% completed gestation (serving as healthy non-human primate GA-matched controls). We first compared sPTB and term human placental transcriptomes to identify significantly differentially expressed genes. We then overlaid the results of the comparison between human sPTB and macaque placental transcriptomes to identify sPTB-specific candidates. Finally, we overlaid the results of the comparison between human term and macaque placental transcriptomes to identify GA-specific candidates. Examination of relative expression for all human genes with macaque orthologs identified 267 candidate genes that were significantly differentially expressed between preterm and term human placentas. 29 genes were identified as sPTB-specific candidates and 37 as GA-specific candidates. Altogether, the 267 differentially expressed genes were significantly enriched for a variety of developmental, metabolic, reproductive, immune, and inflammatory functions. Although there were no notable differences between the functions of the 29 sPTB-specific and 37 GA-specific candidate genes, many of these candidates have been previously shown to be dysregulated in diverse pregnancy-associated pathologies. By

  7. Immunohistochemical localization of retroviral-related antigens expressed in normal baboon placental villous tissue.

    Science.gov (United States)

    Langat, D K; Johnson, P M; Rote, N S; Wango, E O; Owiti, G O; Mwenda, J M

    1998-12-01

    Endogenous retroviral particles (ERVs) have been detected in the genome of all eukaryotes. They are generally non-pathogenic except in mice where they have been found to induce tumors and immunological disorders. The ERVs have morphological features consistent with type-C retroviral particles and are commonly expressed in normal placental villous tissues. ERVs may have a role in the regulation of placental gene expression, syncytiotrophoblast formation, or pregnancy-related immunosuppression. In this study, well-characterized antibodies (monoclonal and polyclonal antibodies) raised against retroviral proteins (anti-HIV and anti-SIV) and endogenous retroviral (ERV) particles were assessed for their cross-reactivity (by using immunohistochemistry) with normal baboon placental and other adult tissues. The monoclonal antibodies to exogenous retroviral proteins (anti-HIV-2 gp120, anti-HIV-1 gp41, anti-SIVmac p27, anti-HIV-1 RT, and anti-HIV-2 core protein) showed specific immunohistochemical reactivity with the syncytiotrophoblast. Antibodies to endogenous retroviral gene products (anti-ERV3 env, anti-HERV-K RT, and anti-HERV-K env) also reacted in a similar manner and did not cross-react with other adult tissues. These studies have shown that retroviral-cross-reactive proteins are expressed in baboon placental syncytiotrophoblast and may have a role to play at the feto-maternal interface.

  8. 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......, such as binding to immunoglobulins. Furthermore, other parasite antigens have been associated with placental malaria. These findings have important implications for placental malaria vaccine design. The objective of this study was to adapt and describe a biologically relevant model of parasite adhesion in intact...... 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...

  9. Banking placental tissue: An optimized collection procedure for genome-wide analysis of nucleic acids

    Science.gov (United States)

    Wolfe, L.M.; Thiagarajan, R.D.; Boscolo, F.; Taché, V.; Coleman, R.L.; Kim, J.; Kwan, W.K.; Loring, J.F.; Parast, M.; Laurent, L.C.

    2016-01-01

    Introduction Banking of high-quality placental tissue specimens will enable biomarker discovery and molecular studies on diseases involving placental dysfunction. Systematic studies aimed at developing feasible standardized methodology for placental collection in a typical clinical setting are lacking. Methods To determine the acceptable timeframe for placental collection, we collected multiple samples from first and third trimester placentas at serial timepoints in a 2-h window after delivery, simultaneously comparing the traditional snap-freeze technique to commercial solutions designed to preserve RNA (RNAlater™), and DNA (DNAgard®). The performance of RNAlater for preserving DNA was also tested. Nucleic acid quality was assessed by determining the RNA integrity number (RIN) and genome-wide microarray profiling for gene expression and DNA methylation. Results We found that samples collected in RNAlater had higher and more consistent RINs compared to snap-frozen tissue. Similar RINs were obtained for tissue collected in RNAlater as large (1 cm3) and small (∼0.1 cm3) pieces. RNAlater appeared to better stabilize the time zero gene expression profile compared to snap-freezing for first trimester placenta. DNA methylation profiles remained quite stable over a 2 h time period after removal of the placenta from the uterus, with DNAgard being superior to other treatments. Discussion and conclusion The collection of placental samples in RNAlater and DNAgard is simple, and eliminates the need for liquid nitrogen or a freezer on-site. Moreover, the quality of the nucleic acids and the resulting data from samples collected in these preservation solutions is higher than samples collected using the snap-freeze method and easier to implement in busy clinical environments. PMID:24951174

  10. Identification of Epigenetic Factor Proteins Expressed in Human Embryonic Stem Cell-Derived Trophoblasts and in Human Placental Trophoblasts.

    Science.gov (United States)

    Sarkar, Prasenjit; Mischler, Adam; Randall, Shan M; Collier, Timothy S; Dorman, Karen F; Boggess, Kim A; Muddiman, David C; Rao, Balaji M

    2016-08-05

    Human embryonic stem cells (hESCs) have been used to derive trophoblasts through differentiation in vitro. Intriguingly, mouse ESCs are prevented from differentiation to trophoblasts by certain epigenetic factor proteins such as Dnmt1, thus necessitating the study of epigenetic factor proteins during hESC differentiation to trophoblasts. We used stable isotope labeling by amino acids in cell culture and quantitative proteomics to study changes in the nuclear proteome during hESC differentiation to trophoblasts and identified changes in the expression of 30 epigenetic factor proteins. Importantly, the DNA methyltransferases DNMT1, DNMT3A, and DNMT3B were downregulated. Additionally, we hypothesized that nuclear proteomics of hESC-derived trophoblasts may be used for screening epigenetic factor proteins expressed by primary trophoblasts in human placental tissue. Accordingly, we conducted immunohistochemistry analysis of six epigenetic factor proteins identified from hESC-derived trophoblasts-DNMT1, DNMT3B, BAF155, BAF60A, BAF57, and ING5-in 6-9 week human placentas. Indeed, expression of these proteins was largely, though not fully, consistent with that observed in 6-9 week placental trophoblasts. Our results support the use of hESC-derived trophoblasts as a model for placental trophoblasts, which will enable further investigation of epigenetic factors involved in human trophoblast development.

  11. Decreased expression of phosphorylated placental heat shock protein 27 in human and ovine intrauterine growth restriction (IUGR).

    Science.gov (United States)

    Bahr, B; Galan, H L; Arroyo, J A

    2014-06-01

    Intrauterine growth restriction (IUGR) has been documented to increase placental apoptosis at term. HSP27 has been shown to be involved in the control of apoptosis. Our objective is to determine the expression of phosphorylated HSP27 (p-HSP27) in human IUGR, and to determine the role of HSP27 during gestation in an ovine hyperthermia induced model of IUGR. Human placenta tissue samples were collected at term to quantify p-HSP27. Pregnant sheep were placed in hyperthermic (HT) conditions to induce IUGR. Placental tissues were collected at 55 (early), 95 (mid-gestation) and 130 (near-term) days gestational age (dGA) to determined phosphorylated and total HSP27 across the development of IUGR. Phosphorylated HSP27 was significantly reduced in human placenta IUGR compared to controls at term. HSP27 was increased throughout gestation during the development of IUGR in the sheep. P-HSP27 was increased in early gestation (55 dGA), and decreased near term (130 dGA). The near term decrease was localized to the trophoblast cells of the placenta. We conclude that decreased p-HSP27 at term is present when placental apoptosis is increased during IUGR. This could be a factor leading to the decreased placental weight observed during IUGR. Copyright © 2014 Elsevier Ltd. All rights reserved.

  12. Increased ubiquitination and reduced plasma membrane trafficking of placental amino acid transporter SNAT-2 in human IUGR.

    Science.gov (United States)

    Chen, Yi-Yung; Rosario, Fredrick J; Shehab, Majida Abu; Powell, Theresa L; Gupta, Madhulika B; Jansson, Thomas

    2015-12-01

    Placental amino acid transport is decreased in intrauterine growth restriction (IUGR); however, the underlying mechanisms remain largely unknown. We have shown that mechanistic target of rapamycin (mTOR) signalling regulates system A amino acid transport by modulating the ubiquitination and plasma membrane trafficking of sodium-coupled neutral amino acid transporter 2 (SNAT-2) in cultured primary human trophoblast cells. We hypothesize that IUGR is associated with (1) inhibition of placental mTORC1 and mTORC2 signalling pathways, (2) increased amino acid transporter ubiquitination in placental homogenates and (3) decreased protein expression of SNAT-2 in the syncytiotrophoblast microvillous plasma membrane (MVM). To test this hypothesis, we collected placental tissue and isolated MVM from women with pregnancies complicated by IUGR (n=25) and gestational age-matched women with appropriately grown control infants (n=19, birth weights between the twenty-fifth to seventy-fifth percentiles). The activity of mTORC1 and mTORC2 was decreased whereas the protein expression of the ubiquitin ligase NEDD4-2 (neural precursor cell expressed developmentally down-regulated protein 4-2; +72%, Pcauses down-regulation of placental system A activity by shifting SNAT-2 trafficking towards proteasomal degradation, thereby contributing to decreased fetal amino acid availability and restricted fetal growth in IUGR. © 2015 Authors; published by Portland Press Limited.

  13. A proposed study on the transplacental transport of parabens in the human placental perfusion model.

    Science.gov (United States)

    Mathiesen, Line; Zuri, Giuseppina; Andersen, Maria H; Knudsen, Lisbeth E

    2013-12-01

    Human exposure to parabens as a preservative used in personal care products is of increasing concern, as there is evidence from in vivo and in vitro studies of hormone disruption in association with exposure to parabens. Transport across the placenta could be critical for risk assessment, but the available data are sparse. The aim is to develop a method for estimating fetal exposure, via the placenta, to the most commonly-used parabens, by using a human placental perfusion model. The use of human tissue is vital for determining human fetal exposure, because animal studies are of little relevance, since the placenta exhibits significant interspecies variation. An HPLC model is currently being established to simultaneously quantify four different parabens, namely, methylparaben, ethylparaben, propylparaben and butylparaben, and their main metabolite, p-hydroxybenzoic acid. With this model, we aim to determine the transport kinetics of these parabens across the human placenta, and to investigate placental metabolism, including differences in transport due to molecular characteristics. This will facilitate assessment of the risks associated with the use of paraben-containing products during pregnancy. 2013 FRAME.

  14. Placental vascular responses are dependent on surrounding tissue

    DEFF Research Database (Denmark)

    Brøgger, Torbjørn Halle

    . Materials and methods. From fresh born placentas, stem villi arteries were carefully dissected. The artery branches were divided. The surrounding tissue was removed from one end and was left untouched in the other end.Then, using wire myography, they were investigated in terms of contractility...

  15. Placental Vasculogenesis Is Regulated by Keratin-Mediated Hyperoxia in Murine Decidual Tissues

    Science.gov (United States)

    Kröger, Cornelia; Vijayaraj, Preethi; Reuter, Ursula; Windoffer, Reinhard; Simmons, David; Heukamp, Lukas; Leube, Rudolf; Magin, Thomas M.

    2011-01-01

    The mammalian placenta represents the interface between maternal and embryonic tissues and provides nutrients and gas exchange during embryo growth. Recently, keratin intermediate filament proteins were found to regulate embryo growth upstream of the mammalian target of rapamycin pathway through glucose transporter relocalization and to contribute to yolk sac vasculogenesis through altered bone morphogenetic protein 4 signaling. Whether keratins have vital functions in extraembryonic tissues is not well understood. Here, we report that keratins are essential for placental function. In the absence of keratins, we find hyperoxia in the decidual tissue directly adjacent to the placenta, because of an increased maternal vasculature. Hyperoxia causes impaired vasculogenesis through defective hypoxia-inducible factor 1α and vascular endothelial growth factor signaling, resulting in invagination defects of fetal blood vessels into the chorion. In turn, the reduced labyrinth, together with impaired gas exchange between maternal and embryonic blood, led to increased hypoxia in keratin-deficient embryos. We provide evidence that keratin-positive trophoblast secretion of prolactin-like protein a (Prlpa) and placental growth factor (PlGF) during decidualization are altered in the absence of keratins, leading to increased infiltration of uterine natural killer cells into placental vicinity and increased vascularization of the maternal decidua. Our findings suggest that keratin mutations might mediate conditions leading to early pregnancy loss due to hyperoxia in the decidua. PMID:21435445

  16. Virus-Free Human Placental Cell Lines To Study Genetic Functions | NCI Technology Transfer Center | TTC

    Science.gov (United States)

    The National Institute of Child Health and Human Development's Section on Cellular Differentiation is seeking statements of capability or interest from parties interested in collaborative research to further develop, evaluate, or commercialize immortalized virus-free human placental cell lines.The National Institute of Child Health and Human Development's Section on Cellular Differentiation is seeking statements of capability or interest from parties interested in collaborative research to further develop, evaluate, or commercialize immortalized virus-free human placental cell lines.

  17. Partial characterization of lysyl oxidase from several human tissues.

    OpenAIRE

    Kuivaniemi, H

    1985-01-01

    Lysyl oxidase activity was assayed in urea extracts of a number of human tissues, proving to be highest in skin. Antibodies to human placental lysyl oxidase completely inhibited the activity of crude lysyl oxidase from all the human tissues studied, with no significant differences in the amounts of antiserum required for 50% inhibition. By contrast, marked differences were found in this value between skin tissue samples from different species. The Mr of lysyl oxidase in crude extracts of huma...

  18. Placental transport of large molecules –a study using human ex vivo placental perfusion

    DEFF Research Database (Denmark)

    Mathiesen, Line

    2011-01-01

    and extrapolation to the in vivo situation critical. In my PhD study I have focused on validation and studies with placental perfusion of substances with a high molecular weight, which require transport or carrier molecules to be transported from the maternal to the fetal side, and longer perfusion time demanding...... 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...

  19. Differences in collagen ultrastructure of human first trimester decidua basalis and parietalis: Implications for trophoblastic invasion of the placental bed

    OpenAIRE

    Sinai Talaulikar, V; Kronenberger, K; Bax, BE; Moss, R; Manyonda, I

    2014-01-01

    AIM:\\ud The human embryo-maternal interface in the first trimester of pregnancy is an area of extensive tissue remodeling. Because collagen is the most abundant constituent of the extracellular matrix of the placental bed, successful invasion must involve its rapid turnover. We compared the nature and distribution of collagen fibrils in decidua basalis and parietalis.\\ud METHODS:\\ud We used a direct-vision hysteroscopic technique to obtain biopsies of the decidua basalis and parietalis from 1...

  20. Human placental growth hormone in ectopic pregnancy: Detection in maternal blood, immunohistochemistry and potential clinical implication.

    Science.gov (United States)

    Hübener, Christoph; Bidlingmaier, Martin; Wu, Zida; Diebold, Joachim; Strasburger, Christian J; Mahner, Sven; Hasbargen, Uwe; Delius, Maria

    2017-12-01

    To investigate human placental growth hormone (hGH-V) in ectopic pregnancy (EP): detection in maternal blood, correlation with immunohistochemistry and possible role as a marker for the course of EP. Women presenting in the outpatient or emergency department of a tertiary care university hospital with a positive pregnancy test and strong suspicion of EP by ultrasound and/or symptoms were eligible for the study (n=70). Tissue specimens from the surgically treated patients (n=50) were examined by histopathology as well as by a hGH-V specific immohistochemistry set-up. A highly sensitive hGH-V specific immunoassay was used to analyse serum samples collected before treatment, day 1 post surgery samples and serial samples for medical treatment. In EP patients' sera hGH-V was shown to be measurable for the first time (n=18). HGH-V however could not be detected in all patients' sera. HCG levels were significantly higher in the hGH-V serum positive group (p 0.001). HGH-V was localized to the syncytiotrophoblast in all specimens of EP examined by immunohistochemistry (n=10) regardless of the detection in the patient's blood. Placental growth hormone (hGH-V) was shown to be present both in ectopic pregnancy patients' sera and tissue. It may serve as a biomarker for monitoring the course and treatment of EP. Copyright © 2017 Elsevier Ltd. All rights reserved.

  1. Expression of HLA-E molecules in the placental tissue of women infected with HIV-1 and uninfected women.

    Science.gov (United States)

    Martinez, Juliana; Santiago, Mariana Rodrigues; Martelli-Palomino, Gustavo; Souza, Diego Agra de; Silva, Társia Giabardo Alves; Silva, Gyl Eanes Barros; Chahud, Fernando; Donadi, Eduardo Antônio; Fernandes, Ana Paula Morais

    2017-01-01

    Expression of HLA-E molecule in the placental extravillous trophoblast is associated with immune system cell inhibition, resulting in immune tolerance to fetus during pregnancy. HIV-1 can infect trophoblast cells and modify the expression of HLA-E, which may inhibit the cytotoxic activity of the immune system. The aim of this study was to evaluate HLA-E expression in third trimester placental tissue of women infected with HIV-1 and uninfected women. We performed an immunohistochemistry assay to evaluate HLA-E staining in the placental tissue of 99 HIV-1 infected and 85 uninfected women. A pathologist analyzed and classified the HLA-E expression in the placental cells. Irrespective of the HIV status, HLA-E staining was observed in the extravillous trophoblast cells, endothelial cells and Hofbauer cells, but not in the syncytiotrophoblast. HLA-E staining showed no significant difference between the placental tissue of women infected with HIV-1 and uninfected women (P = 0.76). Considering HIV-1 infected women, HLA-E staining was not influenced by HIV-1 viral load (P = 0.48), CD4+ T-cell count (P = 0.10) and antiretroviral therapy used during pregnancy (P = 0.54). Despite the presence of HIV-1 infection, the expression of HLA-E molecules in the placental tissue was not modified when the infection was under antiretroviral therapy control. Copyright © 2016. Published by Elsevier Ltd.

  2. Implication of Human Endogenous Retrovirus Envelope Proteins in Placental Functions

    Directory of Open Access Journals (Sweden)

    Adjimon Gatien Lokossou

    2014-11-01

    Full Text Available Human endogenous retroviruses (ERVs represent 8% of the total human genome. Although the majority of these ancient proviral sequences have only retained non-coding long terminal repeats (LTRs, a number of “endogenized” retroviral genes encode functional proteins. Previous studies have underlined the implication of these ERV-derived proteins in the development and the function of the placenta. In this review, we summarize recent findings showing that two ERV genes, termed Syncytin-1 and Syncytin-2, which encode former envelope (Env proteins, trigger fusion events between villous cytotrophoblasts and the peripheral multinucleated syncytiotrophoblast layer. Such fusion events maintain the stability of this latter cell structure, which plays an important role in fetal development by the active secretion of various soluble factors, gas exchange and regulation of fetomaternal immunotolerance. We also highlight new studies showing that these ERV proteins, in addition to their localization at the cell surface of cytotrophoblasts, are also incorporated on the surface of various extracellular microvesicles, including exosomes. Such exosome-associated proteins could be involved in the various functions attributed to these vesicles and could provide a form of tropism. Additionally, through their immunosuppressive domains, these ERV proteins could also contribute to fetomaternal immunotolerance in a local and more distal manner. These various aspects of the implication of Syncytin-1 and -2 in placental function are also addressed in the context of the placenta-related disorder, preeclampsia.

  3. Placental glucose transfer: a human in vivo study.

    Directory of Open Access Journals (Sweden)

    Ane M Holme

    Full Text Available The placental transfer of nutrients is influenced by maternal metabolic state, placenta function and fetal demands. Human in vivo studies of this interplay are scarce and challenging. We aimed to establish a method to study placental nutrient transfer in humans. Focusing on glucose, we tested a hypothesis that maternal glucose concentrations and uteroplacental arterio-venous difference (reflecting maternal supply determines the fetal venous-arterial glucose difference (reflecting fetal consumption.Cross-sectional in vivo study of 40 healthy women with uncomplicated term pregnancies undergoing planned caesarean section. Glucose and insulin were measured in plasma from maternal and fetal sides of the placenta, at the incoming (radial artery and umbilical vein and outgoing vessels (uterine vein and umbilical artery.There were significant mean (SD uteroplacental arterio-venous 0.29 (0.23 mmol/L and fetal venous-arterial 0.38 (0.31 mmol/L glucose differences. The transplacental maternal-fetal glucose gradient was 1.22 (0.42 mmol/L. The maternal arterial glucose concentration was correlated to the fetal venous glucose concentration (r = 0.86, p<0.001, but not to the fetal venous-arterial glucose difference. The uteroplacental arterio-venous glucose difference was neither correlated to the level of glucose in the umbilical vein, nor fetal venous-arterial glucose difference. The maternal-fetal gradient was correlated to fetal venous-arterial glucose difference (r = 0.8, p<0.001 and the glucose concentration in the umbilical artery (r = -0.45, p = 0.004. Glucose and insulin concentrations were correlated in the mother (r = 0.52, p = 0.001, but not significantly in the fetus. We found no significant correlation between maternal and fetal insulin values.We did not find a relation between indicators of maternal glucose supply and the fetal venous-arterial glucose difference. Our findings indicate that the maternal-fetal glucose gradient is significantly

  4. 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

    Placental malaria is a serious problem in sub-Saharan Africa. Young women are particular susceptible to contracting this form of malaria during their first or second pregnancy despite previously acquired immunity from past infections. Placental malaria is caused by Plasmodium falciparum parasites...... 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...... of malaria. In an effort to better understand this infection, chondroitin sulfate was isolated from the cotyledon part of the placenta, which should be accessible for parasite adhesion, as well as two non-accessible parts of the placenta to serve as controls. The placental chondroitin sulfate structures...

  5. Chromosomal Mosaicism in Human Feto-Placental Development: Implications for Prenatal Diagnosis

    Directory of Open Access Journals (Sweden)

    Francesca Romana Grati

    2014-07-01

    Full Text Available Chromosomal mosaicism is one of the primary interpretative issues in prenatal diagnosis. In this review, the mechanisms underlying feto-placental chromosomal mosaicism are presented. Based on the substantial retrospective diagnostic experience with chorionic villi samples (CVS of a prenatal diagnosis laboratory the following items are discussed: (i The frequency of the different types of mosaicism (confined placental, CPM, and true fetal mosaicisms, TFM; (ii The risk of fetal confirmation after the detection of a mosaic in CVS stratified by chromosome abnormality and placental tissue involvement; (iii The frequency of uniparental disomy for imprinted chromosomes associated with CPM; (iv The incidence of false-positive and false-negative results in CVS samples analyzed by only (semi-direct preparation or long term culture; and (v The implications of the presence of a feto-placental mosaicism for microarray analysis of CVS and non-invasive prenatal screening (NIPS.

  6. Pharmacology and placental transfer of a human alphav integrin monoclonal antibody in rabbits.

    Science.gov (United States)

    Martin, Pauline L; Zhou, Zhao; Van den Bulck, Kathleen; Kwok, Deborah; Powers, Gordon; Jiao, Qun; Schantz, Allen; Treacy, George

    2010-04-01

    Intetumumab is a human IgG1 anti-alphav-integrin monoclonal antibody that inhibits angiogenesis. Integrin binding and angiogenesis are important in reproduction including fertilization, implantation, and embryofetal development. These studies were designed to determine the pharmacological relevance of the rabbit for the evaluation of potential effects on embryofetal development and to evaluate the placental transfer of intetumumab in rabbits. In vitro pharmacology studies evaluated the binding of intetumumab to rabbit cells and the inhibition of vessel sprouting from rabbit aorta. For the evaluation of placental transfer, pregnant rabbits (8/group) were injected intravenously with intetumumab 50 or 100 mg/kg every 2 days from Gestation Day (GD)7 to GD19. Maternal sera, fetal homogenates/sera, and amniotic fluid were collected at necropsy on GD19 or GD28 for evaluation of intetumumab concentrations. Clinical condition of the dams was monitored and fetuses were screened for abnormalities. Intetumumab (5-40 microg/mL) inhibited aortic cell adhesion to vitronectin and vessel sprouting from rabbit aortic rings. Immunohistochemical staining of rabbit tissues demonstrated binding of intetumumab to placenta. Administration of intetumumab to pregnant rabbits was well tolerated by the dams and the fetuses did not show major abnormalities. Fetal exposure to intetumumab relative to maternal exposure was rabbit is a pharmacologically relevant species for evaluation of potential developmental effects of intetumumab. Intetumumab crosses the rabbit placenta during the fetal period (GD 19-28). 2010 Wiley-Liss, Inc.

  7. 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. Copyright © 2011 John Wiley & Sons, Ltd.

  8. Effects of human placental extract on brain monoamines and monoamine oxidase activity in rats.

    Science.gov (United States)

    Banerjee, K K; Bishayee, A; Chatterjee, M

    1995-05-01

    Human placental extract, an agent clinically used world-wide in a number of physiological anomalies, has been claimed to be effective in children of slow learners. Since the monoaminergic neurotransmitter systems in the brain play an important role in the processes of learning and memory, we examined the effects of human placental extract on the levels of norepinephrine, dopamine and serotonine in rat brain as an attempt to evaluate the possible underlying biochemical mechanism of action of the extract. We also determined the changes of brain monoamine oxidase (MAO) activity following placental extract treatment. The results showed that subchronic (5, 10, 15 or 20) administration of placental extract (2-4 ml/kg/day) had the effect of increasing all the monoamines and decreasing the MAO activity which could be the possible mode of action of the extract in slow learners.

  9. Proteomic analysis on the alteration of protein expression in the placental villous tissue of early pregnancy loss.

    Science.gov (United States)

    Liu, Ai-Xia; Jin, Fan; Zhang, Wu-Wen; Zhou, Tian-Hua; Zhou, Cai-Yun; Yao, Wei-Miao; Qian, Yu-Li; Huang, He-Feng

    2006-09-01

    Early pregnancy loss is the most common complication of human reproduction. Given the complexities of early development, it is likely that many mechanisms are involved. Knowledge of differences in protein expression in parallel profiling is essential to understand the comprehensive pathophysiological mechanism underlying early pregnancy loss. To identify proteins with different expression profiles related to early pregnancy loss, we applied a proteomic approach and performed two-dimensional gel electrophoresis (2-DE) on six placental villous tissues from patients with early pregnancy loss and six from normal pregnant women, followed by comparison of the silver-stained 2-DE profiles. It was found that 13 proteins were downregulated and 5 proteins were upregulated significantly (P ionization time-of-flight mass spectrometry. Anomalies of these proteins, including three principal antioxidant enzymes (copper/zinc-superoxide dismutase, peroxiredoxin 3, and thioredoxin-like 1 protein), S100 calcium binding protein, galectin-1, chorionic somatomammotropin hormone 1, transthyretin, fas inhibitory molecule, eukaryotic translation elongation factor, RNA-binding protein, ubiquitin-conjugating enzyme E2N, and proteasome beta-subunit, indicate widespread failure in cell regulations and processes such as antioxidative defense, differentiation, cell proliferation, metabolism, apoptosis, transcription, and proteolysis in early pregnancy loss. This study has identified several proteins that are associated with placentation and early development, shedding a new insight into the proteins that may be potentially involved in the pathophysiological mechanisms underlying early pregnancy loss.

  10. Sexually Dimorphic Impact of Chromium Accumulation on Human Placental Oxidative Stress and Apoptosis.

    Science.gov (United States)

    Banu, Sakhila K; Stanley, Jone A; Taylor, Robert J; Sivakumar, Kirthiram K; Arosh, Joe A; Zeng, Lixia; Pennathur, Subramaniam; Padmanabhan, Vasantha

    2017-10-23

    Environmental contamination with CrVI is a growing problem both in the U.S and developing countries. CrVI is widely used in numerous industries. Environmental exposure to hexavalent chromium (CrVI) adversely affects pregnancy outcomes and subsequent health of two generations, resulting in higher pregnancy loss, spontaneous abortion and low birth rate. Pregnant women exposed to CrVI through occupational settings experience increased risk of spontaneous abortion, stillbirth, preterm birth, and neonatal death. Children of the CrVI exposed women experience respiratory problems, perinatal jaundice, and increased birth defects. Since placental dysfunction may have a role in such adverse pregnancy outcome, we tested the hypothesis that environmental Cr exposure in pregnant women results in Cr accumulation in the human placenta, which could increase placental oxidative stress by disrupting antioxidant machinery and inducing apoptosis . Studies using frozen, deidentified human term placenta samples indicated that: (i) Cr accumulates in human term placenta tissues and (ii) increase in Cr accumulation is positively correlated with oxidative stress and apoptotic markers, and altered antioxidants levels. Interestingly, there was a sexual dimorphism in the correlation between Cr accumulation and oxidative stress, and expression of apoptotic and antioxidant markers. Mechanistic in vitro studies using human trophoblast cells BeWo confirmed the detrimental effects of Cr in altering antioxidant genes. For the first time, the current study provides evidence in support of a positive correlation between Cr accumulation in the human placenta and accelerated oxidative stress, with a gender bias towards the male sex. © The Author 2017. Published by Oxford University Press on behalf of the Society of Toxicology. All rights reserved. For permissions, please email: journals.permissions@oup.com.

  11. MicroRNAs in Human Placental Development and Pregnancy Complications

    Directory of Open Access Journals (Sweden)

    Chun Peng

    2013-03-01

    Full Text Available MicroRNAs (miRNAs are small non-coding RNAs, which function as critical posttranscriptional regulators of gene expression by promoting mRNA degradation and translational inhibition. Placenta expresses many ubiquitous as well as specific miRNAs. These miRNAs regulate trophoblast cell differentiation, proliferation, apoptosis, invasion/migration, and angiogenesis, suggesting that miRNAs play important roles during placental development. Aberrant miRNAs expression has been linked to pregnancy complications, such as preeclampsia. Recent research of placental miRNAs focuses on identifying placental miRNA species, examining differential expression of miRNAs between placentas from normal and compromised pregnancies, and uncovering the function of miRNAs in the placenta. More studies are required to further understand the functional significance of miRNAs in placental development and to explore the possibility of using miRNAs as biomarkers and therapeutic targets for pregnancy-related disorders. In this paper, we reviewed the current knowledge about the expression and function of miRNAs in placental development, and propose future directions for miRNA studies.

  12. Comparative placental transfer, localization, and effects of radionuclides in experimental animal and human pregnancies

    Energy Technology Data Exchange (ETDEWEB)

    Sikov, M.R.; Meznarich, H.K.; Traub, R.J.

    1991-11-01

    Estimating radiation doses to the human embryo/fetus from radionuclides and predicting effects requires extrapolation of data from studies of laboratory species, with scaling for species-specific developmental stage and gestational time relationships and maturities at birth. Combinations of fetal-to-maternal ratios of concentrations, patterns of deposition, transfer kinetics, and compartmental and physiologic models are used to predict radioactivity levels and radiation doses to the conceptus. There is agreement between values expressing fractional transfer across the placenta ({theta}) with tabulated values for fractional absorption (f{sub 1}) from gastrointestinal (GI) tract or lung for most substances commonly involved in metabolic processes. A tendency toward disagreement for some other materials is thought to involve explanations based on their physicochemistry, toxicity, or the influence of target tissue development on placental transfer kinetics.

  13. Placental economies

    DEFF Research Database (Denmark)

    Lee, Jieun

    2016-01-01

    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...

  14. In vitro studies of ferric carboxymaltose on placental permeability using the dual perfusion model of human placenta.

    Science.gov (United States)

    Malek, Antoine

    2010-01-01

    An in vitro perfusion model of human placenta was used to study the transplacental passage of iron applied in the form of the drug compound ferric carboxymaltose (FCM) which had been radio-labelled with 59Fe. In four placental perfusion experiments, two simulated circuits for the maternal and fetal sides of the placenta were set up with two experimental phases each lasting 3 h. FCM was added to the maternal circuit at the beginning of each phase to a final iron concentration of 11 mM, which is at least 10 times higher than the maximal predicted level in blood after an administration of 200 mg iron as FCM. The effects of adding transferrin at a physiological concentration of 1.67 mg/ ml were also tested. The concentration profiles of 59Fe showed a 10% decrease within the first 30 min of perfusion on the maternal side. Thereafter the radioactivity levels remained unchanged. The addition of transferrin had no effect on the tissue uptake of 59Fe-FCM. No transferred iron radioactivity could be detected in the fetal circuit. Despite a loss of approximately 10% of the radio-labelled iron observed on the maternal side, only 0.5-2% of the radioactivity was detected in the placental tissue after perfusion. No free iron could be detected at the end of perfusion on the maternal side using ultrafiltration or acid precipitation methods. In addition, the production of transferrin receptor remained unchanged, with similar concentrations in placental tissue before and after perfusion. No effects of FCM on placental viability were observed in terms of energy metabolism (glucose consumption and lactate production), hormone release or placental permeability (assessed by the transfer rates of creatinine and antipyrine). However, two additional observations were made: firstly, a significant reduction in the rate of cell death compared to control conditions was observed in the presence of FCM; secondly, the integrity of the fetal capillary system was improved on the fetal side of the

  15. Assessing drug transport across the human placental barrier: from in vivo and in vitro measurements to the ex vivo perfusion method and in silico techniques.

    Science.gov (United States)

    Giaginis, Constantinos; Tsantili-Kakoulidou, Anna; Theocharis, Stamatios

    2011-05-01

    Assessing drug transport across the human placental barrier is of vital importance in order to guarantee drug safety during pregnancy. However, due to ethical reasons, in vivo fetal development risk assessment studies related to maternal drugs and chemicals exposure remain extremely limited. To overcome any ethical issues, several in vitro models applying primary trophoblastic cells, immortal cell lines and tissue explants of placental origin have recently been advanced. Alternatively, ex vivo human placental perfusion seems to be a more representative and highly informative method, which offers better insights into the different drug transporters, xenobiotic metabolism and tissue binding. Recently, in silico techniques have further been advanced as complementary tools to validate experimental placental transfer data, offering an attractive alternative for high throughput screening of potential fetotoxicity at the early stages of drug design. The present review scrutinizes, from a critical point of view, the current trends and perspectives in the emerging topic of drug transport across the human placental barrier. The special characteristics of the recently developed biopharmaceuticals on the transplacental transfer process are also discussed.

  16. Laeverin/aminopeptidase Q induces trophoblast invasion during human early placentation.

    Science.gov (United States)

    Horie, Akihito; Fujiwara, Hiroshi; Sato, Yukiyasu; Suginami, Koh; Matsumoto, Hisanori; Maruyama, Masato; Konishi, Ikuo; Hattori, Akira

    2012-05-01

    In primate placenta, extravillous trophoblast (EVT) invades maternal tissue in temporally- and spatially-regulated fashions. We previously identified a novel placenta-specific cell-surface aminopeptidase, laeverin/aminopeptidase Q, which is expressed on EVT-lineage cells in the fetal membrane. Laeverin possesses a peptide-binding site that is evolutionally unique to primates, suggesting possible involvement of laeverin in a primate-specific phenomenon during placentation. Thus, this study was designed to elucidate the molecular characteristics and physiological roles of laeverin in human EVT. Placental tissues of various developmental stages were subjected to immunostaining and western blotting. Effects of siRNA and a soluble form of recombinant laeverin on EVT cells isolated from primary villous explant cultures were examined using Matrigel invasion assays and cell proliferation assays. Laeverin was specifically immunolocalized to HLA-G-positive EVT in placentas from early and term pregnancy. In primary villous explant cultures, laeverin expression was induced on the cell surface of the outgrowing EVT. In western blotting, laeverin protein was detected as two distinct bands at 130 and 160 kDa along with a broad band ranging from 200 to 270 kDa. De-glycosylation treatment showed that these native laeverin isotypes are N-linked glycoproteins sharing a common 115-kDa core protein. In invasion assays, the reduction of laeverin expression by siRNA suppressed migration of the isolated EVT, while the soluble form of recombinant laeverin enhanced its migration. Laeverin is a specific cell-surface marker for human EVT and plays a regulatory role in EVT migration.

  17. Secreted phosphoprotein 1 expression in endometrium and placental tissues of hyperprolific large white and meishan gilts.

    Science.gov (United States)

    Hernandez, Silvia C; Hogg, Charis O; Billon, Yvon; Sanchez, Marie-Pierre; Bidanel, Jean-Pierre; Haley, Christopher S; Archibald, Alan L; Ashworth, Cheryl J

    2013-05-01

    Increased litter size and within-litter uniformity in birth weight would improve pig reproductive efficiency. This study compared the location and gene and protein expression of secreted phosphoprotein 1 in placental and uterine tissues supplying a normally sized and the smallest fetus carried by hyperprolific Large White and Meishan gilts on Days 41-42 of pregnancy. Immunohistochemistry and in situ hybridization showed that the protein and gene encoding secreted phosphoprotein 1 were located in the glandular and luminal epithelium of the endometrium and in the placenta. Secreted phosphoprotein 1 protein levels were higher in glandular epithelium, luminal epithelium, and placenta from Meishan gilts compared to corresponding tissues from hyperprolific Large White gilts. Reverse transcription quantitative PCR demonstrated secreted phosphoprotein 1 mRNA levels were higher in endometrium, but not placenta, from Meishan compared to hyperprolific Large White gilts. In hyperprolific Large White gilts, secreted phosphoprotein 1 protein levels were higher in glandular epithelium and placenta surrounding small fetuses than corresponding tissues supplying normal-sized fetuses. Similarly, in Meishan gilts, secreted phosphoprotein 1 protein levels were higher in luminal epithelium surrounding small compared to normal-sized fetuses. Within hyperprolific Large White, but not Meishan, gilts secreted phosphoprotein 1 mRNA was higher in endometrium surrounding the normal-sized fetus than the control fetus. The contradictory relationship between fetal size and secreted phosphoprotein 1 protein and mRNA in the hyperprolific Large White is intriguing and may reflect breed differences in posttranslational modification. The striking breed differences in secreted phospoprotein 1 expression suggest that SPP1 may be associated with placental efficiency.

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

    Directory of Open Access Journals (Sweden)

    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.

  19. Zika Virus RNA Replication and Persistence in Brain and Placental Tissue

    Science.gov (United States)

    Rabeneck, Demi B.; Martines, Roosecelis B.; Reagan-Steiner, Sarah; Ermias, Yokabed; Estetter, Lindsey B.C.; Suzuki, Tadaki; Ritter, Jana; Keating, M. Kelly; Hale, Gillian; Gary, Joy; Muehlenbachs, Atis; Lambert, Amy; Lanciotti, Robert; Oduyebo, Titilope; Meaney-Delman, Dana; Bolaños, Fernando; Saad, Edgar Alberto Parra; Shieh, Wun-Ju; Zaki, Sherif R.

    2017-01-01

    Zika virus is causally linked with congenital microcephaly and may be associated with pregnancy loss. However, the mechanisms of Zika virus intrauterine transmission and replication and its tropism and persistence in tissues are poorly understood. We tested tissues from 52 case-patients: 8 infants with microcephaly who died and 44 women suspected of being infected with Zika virus during pregnancy. By reverse transcription PCR, tissues from 32 (62%) case-patients (brains from 8 infants with microcephaly and placental/fetal tissues from 24 women) were positive for Zika virus. In situ hybridization localized replicative Zika virus RNA in brains of 7 infants and in placentas of 9 women who had pregnancy losses during the first or second trimester. These findings demonstrate that Zika virus replicates and persists in fetal brains and placentas, providing direct evidence of its association with microcephaly. Tissue-based reverse transcription PCR extends the time frame of Zika virus detection in congenital and pregnancy-associated infections. PMID:27959260

  20. A proposed study on the transplacental transport of parabens in the human placental perfusion model

    DEFF Research Database (Denmark)

    Mathiesen, Line; Zuri, Giuseppina; Andersen, Maria H

    2013-01-01

    Human exposure to parabens as a preservative used in personal care products is of increasing concern, as there is evidence from in vivo and in vitro studies of hormone disruption in association with exposure to parabens. Transport across the placenta could be critical for risk assessment, but the......Human exposure to parabens as a preservative used in personal care products is of increasing concern, as there is evidence from in vivo and in vitro studies of hormone disruption in association with exposure to parabens. Transport across the placenta could be critical for risk assessment......, but the available data are sparse. The aim is to develop a method for estimating fetal exposure, via the placenta, to the most commonly-used parabens, by using a human placental perfusion model. The use of human tissue is vital for determining human fetal exposure, because animal studies are of little relevance......, since the placenta exhibits significant interspecies variation. An HPLC model is currently being established to simultaneously quantify four different parabens, namely, methylparaben, ethylparaben, propylparaben and butylparaben, and their main metabolite, p-hydroxybenzoic acid. With this model, we aim...

  1. An international network (PlaNet) to evaluate a human placental testing platform for chemicals safety testing in pregnancy

    DEFF Research Database (Denmark)

    Brownbill, Paul; Chernyavsky, Igor; Bottalico, Barbara

    2016-01-01

    in pregnancy and how ex vivo and in vitro human placental models might be advanced to reproducible human placental test systems (HPTSs), refining a weight of evidence to the guidance given around compound risk assessment during pregnancy. The placental pharmacokinetics of xenobiotic transfer, dysregulated...... placental function in pregnancy-related pathologies and influx/efflux transporter polymorphisms are a few caveats that could be addressed by HPTSs, not the specific focus of current mammalian reproductive toxicology systems. An international consortium, “PlaNet”, will bridge academia, industry...

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

    Directory of Open Access Journals (Sweden)

    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

  3. Mammalian Placentation

    DEFF Research Database (Denmark)

    Carter, Anthony Michael; Mess, A. M.

    2014-01-01

    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......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...... 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...

  4. Aberrant upregulation of miR-21 in placental tissues of macrosomia.

    Science.gov (United States)

    Jiang, H; Wu, W; Zhang, M; Li, J; Peng, Y; Miao, T-T; Zhu, H; Xu, G

    2014-09-01

    With China's rapid economic growth in the past 3 decades, an increase in rate of macrosomia has been reported in China. Fetal growth is a result of multiple factors including genetic potential for growth, maternal nutrition, maternal metabolism, endocrine factors and placental perfusion and function. However, the detailed mechanism of how macrosomia happened remains poorly known. Recent studies showed that the expression of a number of microRNAs (miRNAs) in placentas is involved in fetal growth. We hypothesized that aberrant expression of microRNA-21 (miR-21) and microRNA-16 (miR-16) in placenta is associated with macrosomia. Using quantitative real time PCR, we analyzed the expression level of miR-21 and miR-16 in terminal placentas of macrosomia pregnancies (n=35) and normal controls (n=35). Potential target genes of miRNA were predicted using TargetScan, miRanda and PicTar. Target genes were mapped to KEGG pathways using KEGG Mapper with an in-house Perl script with KEGG Gene IDs. MiR-21 showed significant up-regulation in macrosomia (P=0.037). After controlling the potential confounders, multivariable logistic regression analysis suggested the risk of macrosomia increased, multivariable adjusted ORs of macrosomia for those in the highest tertile was 3.931 (95%CI: 1.049-14.736) compared with those in the lowest tertile in terms of miR-21 level. The target genes of miR-21 were involved in eight possible signaling pathways. They were pathways in P53 signaling pathway, MAPK signaling pathway, HIF-1 signaling pathway, TGF-beta signaling pathway and PI3K-Akt signaling pathway (Pmacrosomia. Our results indicate that the expression level of miR-21 in placental tissue may be involved in the development of macrosomia.

  5. Urinary estrogen excretion and concentration of serum human placental lactogen in pregnancies following legally induced abortion

    DEFF Research Database (Denmark)

    Obel, E B; Madsen, Mette

    1980-01-01

    concentration of hPL in serum were no lower in this group than in women without previous induced abortion. Neither was the frequency of a low 24-hour excretion of estrogens in urine or low concentration of hPL in serum (values less than mean - 1.96 s) found to be increased. This study could not demonstrate......Feto-placental function was assessed by 24-hour excretion of estrogen in urine and by the concentration of human Placental Lactogen (hPL) in serum in pregnant women whose previous pregnancy was terminated by legally induced abortion. The mean 24-hour excretion of estrogens in urine and the mean...... an increased frequency of dysfunction of the feto-placental unit during the last part of pregnancy in women with previous legally induced abortion. These findings indicate that legal abortion does not seem to increase the frequency of retarded intrauterine growth in a subsequent pregnancy....

  6. Urinary estrogen excretion and concentration of serum human placental lactogen in pregnancies following legally induced abortion.

    Science.gov (United States)

    Obel, E B; Madsen, M

    1980-01-01

    Feto-placental function was assessed by 24-hour excretion of estrogen in urine and by the concentration of human Placental Lactogen (hPL) in serum in pregnant women whose previous pregnancy was terminated by legally induced abortion. The mean 24-hour excretion of estrogens in urine and the mean concentration of hPL in serum were no lower in this group than in women without previous induced abortion. Neither was the frequency of a low 24-hour excretion of estrogens in urine or low concentration of hPL in serum (values less than mean - 1.96 s) found to be increased. This study could not demonstrate an increased frequency of dysfunction of the feto-placental unit during the last part of pregnancy in women with previous legally induced abortion. These findings indicate that legal abortion does not seem to increase the frequency of retarded intrauterine growth in a subsequent pregnancy.

  7. Zika virus damages the human placental barrier and presents marked fetal neurotropism

    Directory of Open Access Journals (Sweden)

    Lucia de Noronha

    2016-01-01

    Full Text Available An unusually high incidence of microcephaly in newborns has recently been observed in Brazil. There is a temporal association between the increase in cases of microcephaly and the Zika virus (ZIKV epidemic. Viral RNA has been detected in amniotic fluid samples, placental tissues and newborn and fetal brain tissues. However, much remains to be determined concerning the association between ZIKV infection and fetal malformations. In this study, we provide evidence of the transplacental transmission of ZIKV through the detection of viral proteins and viral RNA in placental tissue samples from expectant mothers infected at different stages of gestation. We observed chronic placentitis (TORCH type with viral protein detection by immunohistochemistry in Hofbauer cells and some histiocytes in the intervillous spaces. We also demonstrated the neurotropism of the virus via the detection of viral proteins in glial cells and in some endothelial cells and the observation of scattered foci of microcalcifications in the brain tissues. Lesions were mainly located in the white matter. ZIKV RNA was also detected in these tissues by real-time-polymerase chain reaction. We believe that these findings will contribute to the body of knowledge of the mechanisms of ZIKV transmission, interactions between the virus and host cells and viral tropism.

  8. Maternal celiac disease autoantibodies bind directly to syncytiotrophoblast and inhibit placental tissue transglutaminase activity

    Directory of Open Access Journals (Sweden)

    Robinson Nicola J

    2009-02-01

    Full Text Available Abstract Background Celiac disease (CD occurs in as many as 1 in 80 pregnant women and is associated with poor pregnancy outcome, but it is not known if this is an effect on maternal nutrient absorption or, alternatively, if the placenta is an autoimmune target. The major autoantigen, tissue transglutaminase (tTG, has previously been shown to be present in the maternal-facing syncytiotrophoblast plasma membrane of the placenta. Methods ELISA was used to demonstrate the presence of antibodies to tissue transglutaminase in a panel of CD sera. Immunohistochemistry was used to evaluate the binding of IgA autoantibodies from CD serum to term placenta. In addition, novel direct binding and activity assays were developed to mimic the in vivo exposure of the villous placenta to maternal autoantibody. Results and Discussion CD IgA autoantibodies located to the syncytial surface of the placenta significantly more than IgA antibodies in control sera (P Conclusion These data indicate that direct immune effects in untreated CD women may compromise placental function.

  9. Modelling nutrient transfer based on 3D imaging of the human placental microstructure.

    Science.gov (United States)

    Perazzolo, S; Lewis, R M; Sengers, B G

    2016-08-01

    Impaired transfer of nutrients from mother to fetus can affect pregnancy outcomes. The placenta has a complex microstructure, including the maternal intervillous space and fetal capillaries. Previous computational models of placental transfer either assumed a simplified idealized local geometry or were based on 2D imaging. In this study, we present a novel 3D computational model to assess the placental transfer of nutrients at the microscale in interaction with the maternal flow environment. A stack of confocal microscopy images of the placental terminal villi was collected and reconstructed. The 3D simulation framework was tested for the transport of oxygen. Preliminary results identified local stagnant zones, as well as areas of high nutrient transfer into the fetal capillaries in the most exposed branches of the villi as a result of better perfusion, combined with a smaller thickness of the tissue barrier. Overall, the current model may serve as a tool for assessing pregnancy conditions affected by inefficient nutrient transfer due to altered microscale placental morphology.

  10. Cadmium chronic administration to lactating ewes. Reproductive performance, cadmium tissue accumulation and placental transfer

    Energy Technology Data Exchange (ETDEWEB)

    Floris, B.; Bomboi, G.; Sechi, P.; Marongiu, M. L. [Sassari Univ., Sassari (Italy). Dipt. di Biologia Animale; Pirino, S. [Sassari Univ., Sassari (Italy). Ist. di Patologia Generale, Anatomia Patologica e Clinica Ostetrico-chirurgica Veterinaria

    2000-12-01

    20 lactating ewes were allotted to two groups: 10 subjects received orally 100 mg/day of CdCl{sub 2} for 108 consecutive days, and the remaining 10 acted as control. Reproductive performance in ewes and cadmium tissue accumulation, both in ewes and their lambs, were investigated. The results showed that in ewes: 1) the regular cadmium intestinal intake negatively influences all reproductive parameters; 2) cadmium is particularly accumulated in kidney and liver, bur also in mammary gland, although at distinctly lower level; 3) chronic administration does not increase cadmium placental transfer in lactating pregnant subjects. [Italian] 20 pecore in lattazione sono state suddivise in 2 gruppi: 10 soggetti ricevettero per os 100 mg/giorno di CdCl{sub 2} per 108 giorni consecutivi, e i restanti 10 funsero da controllo. Sono stati studiati i parametri riproduttivi delle pecore e l'accumulo di cadmio nei tessuti, sia delle pecore che dei loro agnelli. I risultati hanno mostrato che negli ovini: 1) il regolare assorbimento intestinale di cadmio influenza negativamente tutti i parametri riproduttivi; 2) il cadmio viene accumulato principalmente nei reni e nel fegato, ma anche dalla ghiandola mammaria, sebbene in misura nettamente inferiore; 3) la somministrazione cronica di cadmio nei soggetti gravidi non incrementa il suo passaggio transplacentare.

  11. Intermedin/adrenomedullin 2 is associated with implantation and placentation via trophoblast invasion in human pregnancy.

    Science.gov (United States)

    Havemann, Dara; Balakrishnan, Meena; Borahay, Mostafa; Theiler, Regan; Jennings, Kristofer; Endsley, Janice; Phelps, John; Hankins, Gary D V; Yallampalli, Chandra; Chauhan, Madhu

    2013-02-01

    Intermedin (IMD) is a novel peptide expressed in trophoblast cells in human placenta and enhances the invasion, migration, and human leukocyte antigen class I, G (HLA-G) expression in first-trimester HTR-8SV/neo cells. We recently reported that infusion of IMD antagonist in pregnant rats is detrimental to pregnancy outcome, resulting in impaired fetoplacental growth and deformed placental vasculature. This study was undertaken to assess expression of IMD and its involvement in human implantation and early placentation and assess whether its expression is altered in spontaneous abortion. We demonstrate for the first time that IMD is present in day 5 embryonic secretome; villous and decidual expression of IMD is higher at 6-8 weeks after a decline as gestation advances toward the second trimester; first-trimester spontaneous abortion is associated with a lower expression of IMD in serum, villi, and decidua; IMD stimulates the invasive capacity of first-trimester primary Extravillous cytotrophoblast cells; and IMD decreases elevated levels of tumor suppressor Kangia-1 in decidual explants from first-trimester spontaneous abortion. In conclusion, this study is the first to demonstrate a potential involvement of IMD in human embryo implantation and placental development via regulation of trophoblast invasion at the maternal-fetal interface and suggests a physiological role for this novel peptide in establishment of human pregnancy.

  12. Placental transfer of the polybrominated diphenyl ethers BDE-47, BDE-99 and BDE-209 in a human placenta perfusion system: an experimental study

    Directory of Open Access Journals (Sweden)

    Frederiksen Marie

    2010-07-01

    Full Text Available Abstract Background Polybrominated diphenyl ethers (PBDEs have been widely used as flame retardants in consumer products. PBDEs may affect thyroid hormone homeostasis, which can result in irreversible damage of cognitive performance, motor skills and altered behaviour. Thus, in utero exposure is of very high concern due to critical windows in fetal development. Methods A human ex vivo placenta perfusion system was used to study the kinetics and extent of the placental transfer of BDE-47, BDE-99 and BDE-209 during four-hour perfusions. The PBDEs were added to the maternal circulation and monitored in the maternal and fetal compartments. In addition, the perfused cotyledon, the surrounding placental tissue as well as pre-perfusion placental tissue and umbilical cord plasma were also analysed. The PBDE analysis included Soxhlet extraction, clean-up by adsorption chromatography and GC-MS analysis. Results and Discussion Placental transfer of BDE-47 was faster and more extensive than for BDE-99. The fetal-maternal ratios (FM-ratio after four hours of perfusion were 0.47 and 0.25 for BDE-47 and BDE-99, respectively, while the indicative permeability coefficient (IPC measured after 60 minutes of perfusion was 0.26 h-1 and 0.10 h-1, respectively. The transport of BDE-209 seemed to be limited. These differences between the congeners may be related to the degree of bromination. Significant accumulation was observed for all congeners in the perfused cotyledon as well as in the surrounding placental tissue. Conclusion The transport of BDE-47 and BDE-99 indicates in utero exposure to these congeners. Although the transport of BDE-209 was limited, however, possible metabolic debromination may lead to products which are both more toxic and transportable. Our study demonstrates fetal exposure to PBDEs, which should be included in risk assessment of PBDE exposure of women of child-bearing age.

  13. Modeling oxygen transport in human placental terminal villi.

    Science.gov (United States)

    Gill, J S; Salafia, C M; Grebenkov, D; Vvedensky, D D

    2011-12-21

    Oxygen transport from maternal blood to fetal blood is a primary function of the placenta. Quantifying the effectiveness of this exchange remains key in identifying healthy placentas because of the great variability in capillary number, caliber and position within the villus-even in placentas deemed clinically "normal". By considering villous membrane to capillary membrane transport, stationary oxygen diffusion can be numerically solved in terminal villi represented by digital photomicrographs. We aim to provide a method to determine whether and if so to what extent diffusional screening may operate in placental villi. Segmented digital photomicrographs of terminal villi from the Pregnancy, Infection and Nutrition study in North Carolina 2002 are used as a geometric basis for solving the stationary diffusion equation. Constant maternal villous oxygen concentration and perfect fetal capillary membrane absorption are assumed. System efficiency is defined as the ratio of oxygen flux into a villus and the sum of the capillary areas contained within. Diffusion screening is quantified by comparing numerical and theoretical maximum oxygen fluxes. A strong link between various measures of villous oxygen transport efficiency and the number of capillaries within a villus is established. The strength of diffusional screening is also related to the number of capillaries within a villus. Our measures of diffusional efficiency are shown to decrease as a function of the number of capillaries per villus. This low efficiency, high capillary number relationship supports our hypothesis that diffusional screening is present in this system. Oxygen transport per capillary is reduced when multiple capillaries compete for diffusing oxygen. A complete picture of oxygen fluxes, capillary and villus areas is obtainable and presents an opportunity for future work. Copyright © 2011 Elsevier Ltd. All rights reserved.

  14. Expressional regulation of genes linked to immunity & programmed development in human early placental villi

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    M A Khan

    2014-01-01

    Full Text Available Background & objectives: During 6 to 8 wk of gestation, human placental villi show a complex pattern of morphogenesis. There is however, no large scale gene expression study exploring the temporal pattern of the developmental molecular networks in placental villi during the early weeks of gestation. We evaluated the transcriptome profiling of humn placental villus samples obtained from fertile women with voluntarily terminated normal pregnancies between 6-8 wk of gestation. Methods: Transcriptomic profiles of individual human placental villous samples from 25 women with normal pregnancies during 6 to 8 wk of gestation were examined using human whole genome expression arrays. Quantitative RT-PCR validation of copy numbers of transcripts for selected 15 genes and exploratory analysis of the microarray data revealed a high degree of quality assurance supportive of further clustering and differential analyses. Immunoblot and immunohistochemical analysis of selected five candidate proteins (CAGE1, CD9, SLC6A2, TANK and VEGFC based on transcript profiles were done to assess the pattern of down stream informational flow. Results: A large number (~9K of genes with known functions were expressed in the experimental samples. The clustering analysis identified three major expression clusters with gestational age, and four co-expressional clusters. Differential analysis identified a highly discrete regulatory process involving only about 160 genes. Immunochemical analysis of selected candidate proteins based on transcript profiles revealed generally synchronous expression in human early placental villi. Interpretation & conclusions: Several signaling pathways linked to immunity (COL1, JAK2, JAK3, IL12, IL13, IL15, IL27, STAT3 and STAT5 were downregulated, while genes of the enriched category of antiviral immunity (ATF/AP1, IL10R and OAS were clearly over-expressed. Transcriptional integration supportive of programmed development was observed in first

  15. 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. Copyright © 2013 Elsevier Ltd. All rights reserved.

  16. Infectious Achilles Tendinitis After Local Injection of Human Placental Extracts: A Case Report.

    Science.gov (United States)

    Kim, Yoon-Chung; Ahn, Jae Hoon; Kim, Man-Soo

    2015-01-01

    Local injections of corticosteroids or human placental extracts are sometimes used for the treatment of resistant tendinitis or fasciitis. We report a case of infectious Achilles tendinitis complicated by calcaneal osteomyelitis after injection of human placental extracts for the Achilles tendinitis. She was treated with excision of the infected bone and tendon, followed by V-Y lengthening of the proximal portion of the Achilles tendon in a single stage. At 2 years postoperative, she remained symptom free without any signs of recurrence, and the follow-up magnetic resonance imaging scan demonstrated a well-maintained Achilles tendon with normal signal intensity. Copyright © 2015 American College of Foot and Ankle Surgeons. Published by Elsevier Inc. All rights reserved.

  17. 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

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

    Directory of Open Access Journals (Sweden)

    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.

  19. An international network (PlaNet) to evaluate a human placental testing platform for chemicals safety testing in pregnancy.

    Science.gov (United States)

    Brownbill, Paul; Chernyavsky, Igor; Bottalico, Barbara; Desoye, Gernot; Hansson, Stefan; Kenna, Gerry; Knudsen, Lisbeth E; Markert, Udo R; Powles-Glover, Nicola; Schneider, Henning; Leach, Lopa

    2016-09-01

    The human placenta is a critical life-support system that nourishes and protects a rapidly growing fetus; a unique organ, species specific in structure and function. We consider the pressing challenge of providing additional advice on the safety of prescription medicines and environmental exposures in pregnancy and how ex vivo and in vitro human placental models might be advanced to reproducible human placental test systems (HPTSs), refining a weight of evidence to the guidance given around compound risk assessment during pregnancy. The placental pharmacokinetics of xenobiotic transfer, dysregulated placental function in pregnancy-related pathologies and influx/efflux transporter polymorphisms are a few caveats that could be addressed by HPTSs, not the specific focus of current mammalian reproductive toxicology systems. An international consortium, "PlaNet", will bridge academia, industry and regulators to consider screen ability and standardisation issues surrounding these models, with proven reproducibility for introduction into industrial and clinical practice. Copyright © 2016 Elsevier Inc. All rights reserved.

  20. Comparative systems biology of human and mouse as a tool to guide the modeling of human placental pathology.

    Science.gov (United States)

    Cox, Brian; Kotlyar, Max; Evangelou, Andreas I; Ignatchenko, Vladimir; Ignatchenko, Alex; Whiteley, Kathie; Jurisica, Igor; Adamson, S Lee; Rossant, Janet; Kislinger, Thomas

    2009-01-01

    Placental abnormalities are associated with two of the most common and serious complications of human pregnancy, maternal preeclampsia (PE) and fetal intrauterine growth restriction (IUGR), each disorder affecting approximately 5% of all pregnancies. An important question for the use of the mouse as a model for studying human disease is the degree of functional conservation of genetic control pathways from human to mouse. The human and mouse placenta show structural similarities, but there have been no systematic attempts to assess their molecular similarities or differences. We collected protein and mRNA expression data through shot-gun proteomics and microarray expression analysis of the highly vascular exchange region, microdissected from the human and mouse near-term placenta. Over 7000 ortholog genes were detected with 70% co-expressed in both species. Close to 90% agreement was found between our human proteomic results and 1649 genes assayed by immunohistochemistry for expression in the human placenta in the Human Protein Atlas. Interestingly, over 80% of genes known to cause placental phenotypes in mouse are co-expressed in human. Several of these phenotype-associated proteins form a tight protein-protein interaction network involving 15 known and 34 novel candidate proteins also likely important in placental structure and/or function. The entire data are available as a web-accessible database to guide the informed development of mouse models to study human disease.

  1. High temperature requirement A1 and fibronectin: two possible players in placental tissue remodelling

    Directory of Open Access Journals (Sweden)

    G. Tossetta

    2016-11-01

    Full Text Available High temperature requirement A1 (HtrA1 is a secreted protease involved in placental development. Fibronectin (FN is involved in important process such as wound healing, cell adhesion and spreading, growth, migration, and differentiation. The purpose of this study was to analyse the expression patterns of HtrA1 in relationship to FN and to the key growth zones of placenta such as mesenchymal villi as well as cell islands and cell columns. We demonstrated that FN and HtrA1 are localized in the placental key growth zones suggesting a pivotal role in maintaining the balance among the molecules involved in the placental development and differentiation.

  2. Three-dimensional digital reconstruction of human placental villus architecture in normal and complicated pregnancies.

    Science.gov (United States)

    McCarthy, R; Orsi, N M; Treanor, D; Moran, O; Vernooij, M; Magee, D R; Roberts, N; Stahlschmidt, J; Simpson, N A B

    2016-02-01

    This study aimed to examine the use of digital technology in the three-dimensional reconstruction of human placentas. Placentas obtained at term elective caesarean section were sampled, formalin-fixed and embedded in paraffin. Two hundred 5 μm consecutive sections were cut from each specimen and the resultant slides stained with haematoxylin and eosin. Slides were then scanned and the digitised images reconstructed using customised software. Three-dimensional reconstructions were successfully achieved in placentas from normal pregnancies and those complicated by pre-eclampsia, growth restriction, and gestational diabetes. Marked morphological differences were readily identifiable, most clearly in the stem villus architecture. This method is an emerging research tool for examining placental histoarchitecture at high resolution and gaining clinically relevant insight into the placental pathology allied to pregnancy complications such as PET, IUGR and GD. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

  3. [Human brown adipose tissue].

    Science.gov (United States)

    Virtanen, Kirsi A; Nuutila, Pirjo

    2015-01-01

    Adult humans have heat-producing and energy-consuming brown adipose tissue in the clavicular region of the neck. There are two types of brown adipose cells, the so-called classic and beige adipose cells. Brown adipose cells produce heat by means of uncoupler protein 1 (UCP1) from fatty acids and sugar. By applying positron emission tomography (PET) measuring the utilization of sugar, the metabolism of brown fat has been shown to multiply in the cold, presumably influencing energy consumption. Active brown fat is most likely present in young adults, persons of normal weight and women, least likely in obese persons.

  4. Effects of the interleukin-6 (IL-6) polymorphism on toxic metal and trace element levels in placental tissues

    Energy Technology Data Exchange (ETDEWEB)

    Kayaalti, Zeliha, E-mail: kayaalti@medicine.ankara.edu.tr [Ankara University, Institute of Forensic Sciences, Dikimevi, 06590, Ankara (Turkey); Tekin, Deniz; Aliyev, Vugar [Ankara University, Institute of Forensic Sciences, Dikimevi, 06590, Ankara (Turkey); Yalcin, Serap [Ahi Evran University, Kirsehir (Turkey); Kurtay, Guelay [Ankara University, Faculty of Medicine, Department of Obstetrics and Gynecology, Dikimevi, 06590, Ankara (Turkey); Soeylemezoglu, Tuelin [Ankara University, Institute of Forensic Sciences, Dikimevi, 06590, Ankara (Turkey)

    2011-11-01

    The placenta is a crucial organ of fetal origin that functions in providing nutrients to the fetus from the mother. During pregnancy, the need for essential micronutrients, such as Fe and Zn, increases due to the requirements of the growing fetus. Maternal Fe deficiency induces an increase in Cu levels and can also affect cytokine levels in the placenta. On the other hand, Cu deficiency, although not as common, can also have destructive effects on the fetus. Interleukin-6 (IL-6) is a pleiotropic cytokine with a wide range of biological activities, including such as immune responses, acute-phase reactions, and inflammation. The placenta produces a significant amount of IL-6 during pregnancy. The effects of the IL-6 -174 G/C single nucleotide polymorphism (SNP) on IL-6 gene transcription and on plasma cytokine levels were assessed in the present study. We investigated the association between the IL-6 -174 G/C polymorphism and trace element/toxic metal levels in placental tissues. For the purposes of this study, 95 healthy volunteers were evaluated. Presence of the IL-6 polymorphism was determined using the standard polymerase chain reaction (PCR)-restriction fragment length polymorphism (RFLP) technique, and metal levels were analyzed by atomic absorption spectrometry (AAS). Based on our data, there were no significant associations between the IL-6 -174 G/C polymorphism and Pb, Cd, Fe, or Zn levels in the placental tissues (p > 0.05), but a statistically significant association was detected between the polymorphism and Cu levels (p = 0.016). We determined that the mean Cu levels in the placental tissues from individuals with GG, GC and CC genotypes were 5.62 {+-} 1.98, 6.22 {+-} 3.22 and 8.00 {+-} 1.32 ppm, respectively, whereas the overall mean Cu level from the placental tissues was 5.98 {+-} 2.51 ppm. - Highlights: {yields} We studied between the association of IL-6 polymorphism and metal levels in the placenta tissues. {yields} It was the first report evaluating

  5. Maternal drug abuse and human term placental xenobiotic and steroid metabolizing enzymes in vitro.

    Science.gov (United States)

    Paakki, P; Stockmann, H; Kantola, M; Wagner, P; Lauper, U; Huch, R; Elovaara, E; Kirkinen, P; Pasanen, M

    2000-01-01

    We evaluated the impact of maternal drug abuse at term on human placental cytochrome P450 (CYP)-mediated (Phase I) xenobiotic and steroid-metabolizing activities [aromatase, 7-ethoxyresorufin O-deethylase (EROD), 7-ethoxycoumarin O-deethylase (ECOD), pyrene 1-hydroxylase (P1OH), and testosterone hydroxylase], and androstenedione-forming isomerase, NADPH quinone oxidoreductase (Phase II), UDP-glucuronosyltransferase (UGT), and glutathione S-transferase (GST) activities in vitro. Overall, the formation of androstenedione, P1OH, and testosterone hydroxylase was statistically significant between control and drug-abusing subjects; we observed no significant differences in any other of the phase I and II activities. In placentas from drug-abusing mothers, we found significant correlations between ECOD and P1OH activities (p abuse drugs but did smoke cigarettes), the P1OH activity correlated with ECOD, EROD (p abusing mothers and the significant correlation between P1OH and ECOD activities, but not with aromatase or EROD activities) indicate that maternal drug abuse results in an additive effect in enhancing placental xenobiotic metabolizing enzymes when the mother also smokes cigarettes; this may be due to enhancing a "silent" CYP form, or a new placental CYP form may be activated. The change in the steroid metabolism profile in vitro suggests that maternal drug abuse may alter normal hormonal homeostasis during pregnancy. PMID:10656854

  6. Hypoxic treatment of human dual placental perfusion induces a preeclampsia-like inflammatory response.

    Science.gov (United States)

    Jain, Arjun; Schneider, Henning; Aliyev, Eldar; Soydemir, Fatimah; Baumann, Marc; Surbek, Daniel; Hediger, Matthias; Brownbill, Paul; Albrecht, Christiane

    2014-08-01

    Preeclampsia is a human pregnancy-specific disorder characterized by a placental pro-inflammatory response in combination with an imbalance of angiogenic factors and clinical symptoms, including hypertension and proteinuria. Insufficient uteroplacental oxygenation in preeclampsia due to impaired trophoblast invasion during placentation is believed to be responsible for many of the molecular events leading to the clinical manifestations of this disease. We investigated the use of hypoxic treatment of the dual placental perfusion system as a model for preeclampsia. A modified perfusion technique allowed us to achieve a mean soluble oxygen tension within the intervillous space (IVS) of 5-7% for normoxia and preeclampsia). We assayed for the levels of different inflammatory cytokines, oxidative stress markers, as well as other factors, such as endothelin (ET)-1 that are known to be implicated as part of the inflammatory response in preeclampsia. Our results show a significant increase under hypoxia in the levels of different inflammatory cytokines, including IL-6 (P=0.002), IL-8 (Ppreeclampsia. This would therefore provide a powerful tool for studying and further delineating the molecular mechanisms involved in the underlying pathophysiology of preeclampsia.

  7. Human placental lipid induces mitogenesis and melanogenesis in ...

    Indian Academy of Sciences (India)

    A hydroalcoholic extract of fresh term human placenta was found to be mitogenic as well as melanogenic on B16F10 mouse melanoma in an in vitro culture. The extract, a reservoir of a large number of bioactive molecules, was resolved to get the lipid fraction. Its activity was evaluated on B16F10 mouse melanoma by ...

  8. Human placental lipid induces mitogenesis and melanogenesis in ...

    Indian Academy of Sciences (India)

    Unknown

    cascade of stress activated protein kinase (Coroneos et al. 1996). Human placenta is an enriched reservoir of .... as compared to the control (100%) (figure 2A). However, at concentrations higher than 10 µg/ml, ..... phosphate phosphatase: A key regulator of sphingolipid metabolism and stress response; Proc. Natl. Acad.

  9. 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.

  10. Placental expression of CD100, CD72 and CD45 is dysregulated in human miscarriage.

    Science.gov (United States)

    Lorenzi, Teresa; Turi, Angelo; Lorenzi, Maria; Paolinelli, Francesca; Mancioli, Francesca; La Sala, Lucia; Morroni, Manrico; Ciarmela, Pasquapina; Mantovani, Angelo; Tranquilli, Andrea Luigi; Castellucci, Mario; Marzioni, Daniela

    2012-01-01

    The etiology of miscarriage is often multifactorial. One major cause, immunological rejection of the fetus, has not been clearly elucidated. Our aim was to establish whether the semaphorin CD100, its natural receptor CD72, and the glycoprotein CD45, implicated in immune mechanisms, are involved in pregnancy loss by examining their placental expression with real-time PCR, immunohistochemistry and western blotting techniques. Placenta tissue from 72 Caucasian women undergoing surgical uterine evacuation due to early spontaneous pregnancy loss between the 8(th) and 12(th) week of gestation was divided into four groups based on miscarriage number. Gestational age-matched placentas from 18 healthy women without a history of miscarriage undergoing voluntary pregnancy termination were the control group. Placenta from 6 Caesarean deliveries performed at 38-40 weeks of gestation was also studied. CD100, CD72 and CD45 were expressed in placenta and exhibited different mRNA and protein levels in normal pregnancy and miscarriage. In particular, protein levels were highly dysregulated around 10 weeks of gestation in first and second miscarriage placentas. The CD100 soluble form was produced and immediately shed from placental tissue in all samples. Fetal CD100, CD72 and CD45 seem to play a role in miscarriage. The present data support the involvement of the fetal immune system in pregnancy maintenance as well as failure.

  11. Placental Expression of CD100, CD72 and CD45 Is Dysregulated in Human Miscarriage

    Science.gov (United States)

    Lorenzi, Maria; Paolinelli, Francesca; Mancioli, Francesca; La Sala, Lucia; Morroni, Manrico; Ciarmela, Pasquapina; Mantovani, Angelo; Tranquilli, Andrea Luigi; Castellucci, Mario; Marzioni, Daniela

    2012-01-01

    Context and Objective The etiology of miscarriage is often multifactorial. One major cause, immunological rejection of the fetus, has not been clearly elucidated. Our aim was to establish whether the semaphorin CD100, its natural receptor CD72, and the glycoprotein CD45, implicated in immune mechanisms, are involved in pregnancy loss by examining their placental expression with real-time PCR, immunohistochemistry and western blotting techniques. Patients Placenta tissue from 72 Caucasian women undergoing surgical uterine evacuation due to early spontaneous pregnancy loss between the 8th and 12th week of gestation was divided into four groups based on miscarriage number. Gestational age-matched placentas from 18 healthy women without a history of miscarriage undergoing voluntary pregnancy termination were the control group. Placenta from 6 Caesarean deliveries performed at 38–40 weeks of gestation was also studied. Results CD100, CD72 and CD45 were expressed in placenta and exhibited different mRNA and protein levels in normal pregnancy and miscarriage. In particular, protein levels were highly dysregulated around 10 weeks of gestation in first and second miscarriage placentas. The CD100 soluble form was produced and immediately shed from placental tissue in all samples. Conclusions Fetal CD100, CD72 and CD45 seem to play a role in miscarriage. The present data support the involvement of the fetal immune system in pregnancy maintenance as well as failure. PMID:22606231

  12. Placental expression of CD100, CD72 and CD45 is dysregulated in human miscarriage.

    Directory of Open Access Journals (Sweden)

    Teresa Lorenzi

    Full Text Available CONTEXT AND OBJECTIVE: The etiology of miscarriage is often multifactorial. One major cause, immunological rejection of the fetus, has not been clearly elucidated. Our aim was to establish whether the semaphorin CD100, its natural receptor CD72, and the glycoprotein CD45, implicated in immune mechanisms, are involved in pregnancy loss by examining their placental expression with real-time PCR, immunohistochemistry and western blotting techniques. PATIENTS: Placenta tissue from 72 Caucasian women undergoing surgical uterine evacuation due to early spontaneous pregnancy loss between the 8(th and 12(th week of gestation was divided into four groups based on miscarriage number. Gestational age-matched placentas from 18 healthy women without a history of miscarriage undergoing voluntary pregnancy termination were the control group. Placenta from 6 Caesarean deliveries performed at 38-40 weeks of gestation was also studied. RESULTS: CD100, CD72 and CD45 were expressed in placenta and exhibited different mRNA and protein levels in normal pregnancy and miscarriage. In particular, protein levels were highly dysregulated around 10 weeks of gestation in first and second miscarriage placentas. The CD100 soluble form was produced and immediately shed from placental tissue in all samples. CONCLUSIONS: Fetal CD100, CD72 and CD45 seem to play a role in miscarriage. The present data support the involvement of the fetal immune system in pregnancy maintenance as well as failure.

  13. The presence of morphine as heroin metabolites in placental tissue and fetus: Case report

    Directory of Open Access Journals (Sweden)

    Nikolić Slobodan

    2014-01-01

    Full Text Available Introduction. Females who have developed addiction to heroin also abuse it during pregnancy. Heroin can be detected in the fetal blood-flow already an hour after maternal i.v. injection. Heroin metabolites enter the fetal blood-flow through the placental barrier by passive transport. Case Outline. We present a 27-year-old female in the 5th month of pregnancy that had a miscarriage. Chemo-toxicological analysis (gas chromatography with mass spectrometry - GC/MS, showed the presence of morphine in the fetal liver (31.92 ng/g, placenta (27.94 ng/g and meconium (136.33 ng/g. The analysis did not show the presence of 6-monoacetylmorphine. Conclusion. In all cases when the autopsy of fetus or newborn is performed, with mother suspected as i.v. heroin abuser, chemotoxicological placental analysis, placenta and meconium should be also done. [Projekat Ministarstva nauke Republike Srbije, br. 45005

  14. Bidirectional placental transfer of Bisphenol A and its main metabolite, Bisphenol A-Glucuronide, in the isolated perfused human placenta.

    Science.gov (United States)

    Corbel, T; Gayrard, V; Puel, S; Lacroix, M Z; Berrebi, A; Gil, S; Viguié, C; Toutain, P-L; Picard-Hagen, N

    2014-08-01

    The widespread human exposure to Bisphenol A (BPA), an endocrine disruptor interfering with developmental processes, raises the question of the risk for human health of BPA fetal exposure. In humans, highly variable BPA concentrations have been reported in the feto-placental compartment. However the human fetal exposure to BPA still remains unclear. The aim of the study was to characterize placental exchanges of BPA and its main metabolite, Bisphenol A-Glucuronide (BPA-G) using the non-recirculating dual human placental perfusion. This high placental bidirectional permeability to the lipid soluble BPA strongly suggests a transport by passive diffusion in both materno-to-fetal and feto-to-maternal direction, leading to a calculated ratio between fetal and maternal free BPA concentrations of about 1. In contrast, BPA-G has limited placental permeability, particularly in the materno-to-fetal direction. Thus the fetal exposure to BPA conjugates could be explained mainly by its limited capacity to extrude BPA-G. Copyright © 2014 Elsevier Inc. All rights reserved.

  15. Recurrent secondary postpartum hemorrhages due to placental site vessel subinvolution and local uterine tissue coagulopathy.

    Science.gov (United States)

    Zubor, Pavol; Kajo, Karol; Dokus, Karol; Krivus, Stefan; Straka, Lubomir; Bodova, Kristina Biskupska; Danko, Jan

    2014-02-21

    Postpartum hemorrhage (PPH) represents a serious problem for women and obstetricians. Because of its association with hemorrhagic shock and predisposition to disseminated coagulopathy, it is a leading cause of maternal deaths worldwide. Furthermore, the jeopardy of PPH is rising with the secondary form of PPH occurring between 24 hours and 6 weeks postpartum, when women are already discharged home. The causes of this pathology are severe inflammation (endometritis), inherited coagulation disorders, consumptive coagulopathy, and retained products of conceptions. Others are of rare occurrence, such as vessel subinvolution (VSI) of the placental implantation site, uterine artery pseudoaneurysm, or trauma. We present a rare form of recurrent secondary postpartum hemorrhage in a woman after uncomplicated cesarean delivery, with review of the literature linked to the management of this situation originating in the rare local VSI in the placental implantation site, defective decidual homeostasis, and coagulopathy confined to the uterus. The placental site VSI is one of the rare causes of secondary PPH, and this situation is frequently underdiagnosed by clinicians. The histological confirmation of dilated "clustered"-shaped myometrial arteries partially occluded by thrombi of variable "age" together with the presence of endovascular extravillous trophoblasts confirms the diagnosis.

  16. Human placental growth hormone: a potential new biomarker in gestational trophoblastic disease.

    Science.gov (United States)

    Hübener, Christoph; Bidlingmaier, Martin; Wu, Zida; Diebold, Joachim; Delius, Maria; Friese, Klaus; Strasburger, Christian J; Hasbargen, Uwe

    2015-02-01

    Gestational trophoblastic disease (GTD) involves a spectrum of abnormal proliferations arising from the placental villous trophoblast. Although the incidence is low, a biomarker with short serum half-life would be a major clinical advance to monitor surgical and medical treatment reducing the socioeconomic burden of multiple control visits as well as patient's anxiety. Placental growth hormone (hGH-V) plays an important role in the regulation of normal placental growth and has shown angiogenic effects. We aimed to determine by immunohistochemistry (IHC) whether hGH-V is expressed in GTD and whether it can be detected in the patient's blood for potential monitoring of surgical or medical treatment procedures. Tissue and sera were collected from women undergoing treatment for GTD in a tertiary care university hospital. We evaluated partial and complete hydatidiform moles, invasive moles and choriocarcinoma, n=16. Trophoblast specimens were examined by a newly developed IHC set-up for hGH-V in addition to gross morphologic and histopathological examination. Serum samples were analyzed by a highly sensitive hGH-V specific immunoassay. hGH-V was localized in all entities of GTD to the syncytiotrophoblast by immunohistochemistry. Serum hGH-V was detected for the first time in GTD and was present in a high percentage of all analyzed entities. hGH-V can be detected in all entities of GTD by IHC as well as by serum analysis and may therefore serve as a novel biomarker for the disease. Its clinical utility in diagnosis of GTD and monitoring surgical or medical treatment needs to be determined in further studies. Copyright © 2014 Elsevier Inc. All rights reserved.

  17. Comparison of tissue prolidase enzyme activity and serum oxidative stress level between pregnant women with placental abruption and those with a healthy pregnancy.

    Science.gov (United States)

    Incebiyik, Adnan; Vural, Mehmet; Camuzcuoglu, Aysun; Camuzcuoglu, Hakan; Hilali, Nese Gul; Taskin, Abdullah; Aydin, Halef; Aksoy, Nurten

    2015-04-01

    Although placental abruption is an acute condition, it is thought that the underlying pathology is chronic vasculopathy. Collagen is one of the important components of vascular structure, and there is a correlation between collagen turnover and prolidase enzyme activity (PEA). Thus, our aim was to assess whether there is a difference in serum oxidative stress level and PEA between pregnant women with placental abruption and those with a healthy pregnancy. The study group consisted of 36 pregnant women who underwent caesarean section with a diagnosis of placental abruption, while the control group comprised 36 pregnant women who underwent caesarean section due to obstetric reasons. Venous blood samples were drawn from all patients before caesarean section. In addition, tissue samples were obtained during caesarean section to evaluate tissue PEA. No significant differences in demographic characteristics were detected between groups (p > 0.05). Oxidative stress parameters, such as total oxidant status and oxidative stress index, were found to be significantly higher in the study group (p stress parameters (r = 0.332, p = 0.004). Our results indicated that elevated tissue PEA and serum oxidative stress levels are closely related to placental abruption. Thus, we think that increased collagen turnover may have a significant role in the aetiopathogenesis of placental abruption.

  18. Polyclonal antibodies directed against human placental Fcgamma receptor. Characterization of the antibodies and their interaction with the receptor.

    Science.gov (United States)

    Mikulska, J; Lisowski, J

    1987-01-01

    Antibodies to the putative Fc gamma receptor (Fc gamma R) of human placenta were raised by immunization of rabbits with the receptor purified form syncytiotrophoblast plasma membranes of human placenta. The rabbit antibodies were of IgG class and their F(ab')2 fragment interacted with Fc receptors in solubilized form and membrane-bound, as well. Immunological reactivity of the antibodies with Fc gamma R was demonstrated using immunodiffusion, solid-phase immunoassay, and ELISA. Studies on interaction of the antibodies with the isolated placental Fc gamma R showed that antigenic determinants of the receptor were different from the IgG-binding site. Rabbit anti-human placental Fc gamma R crossreacted, to various extent, with Fc gamma R-positive human cell lines showing antigenic relatedness of the placental receptor with Fc gamma R on other cell types. The antibodies showed only a weak crossreactivity with guinea pig peritoneal macrophage Fc gamma R. SDS-PAGE analysis of immunoprecipitates obtained by treatment of detergent lysates of 3H-labeled human placental trophoblasts membranes with the rabbit antibodies or with human IgG showed the presence of the some components which were observed in the case of the isolated, purified placental Fc gamma R: Mr of 123,000 and 52,000-56,000 under nonreducing conditions, and Mr of 64,000-67,000, 52,000-56,000, and 26,000-29,000, under reducing conditions. The polypeptide chains of the purified human placental receptor resolved in SDS-PAGE and transferred on nitrocellulose strips were able to interact both with the rabbit anti-placental receptor IgG F(ab')2 fragments and with human IgG. This gives an evidence that human placental Fc gamma R polypeptide chains Mr of approx. 64,000, 54,000, and 28,000 contain antigenic determinants of the receptor and binding sites for the Fc region of IgG, as well.

  19. Bisphenol A differentially activates protein kinase C isoforms in murine placental tissue

    Energy Technology Data Exchange (ETDEWEB)

    Tan, Wenjuan; Huang, Hui; Wang, Yanfei [Biochemistry Programme, School of Life Sciences, Faculty of Science, The Chinese University of Hong Kong, Shatin, N.T. (Hong Kong); Wong, Tsz Yan [Food and Nutritional Sciences Programme, School of Life Sciences, Faculty of Science, The Chinese University of Hong Kong, Shatin, N.T. (Hong Kong); Wang, C.C. [Department of Obstetrics and Gynecology, Faculty of Medicine, The Chinese University of Hong Kong, Shatin, N.T. (Hong Kong); Leung, Lai K., E-mail: laikleung@cuhk.edu.hk [Biochemistry Programme, School of Life Sciences, Faculty of Science, The Chinese University of Hong Kong, Shatin, N.T. (Hong Kong); Food and Nutritional Sciences Programme, School of Life Sciences, Faculty of Science, The Chinese University of Hong Kong, Shatin, N.T. (Hong Kong)

    2013-06-01

    Bisphenol A is utilized to make polycarbonate plastics and is an environmental pollutant. Recent research has indicated that it is an endocrine disruptor and may interfere with reproductive processes. Our lab has previously shown that bisphenol A could regulate corticotrophin releasing hormone and aromatase in cultured placental cells. In the present study, the effect of bisphenol A on these two genes in the placenta was investigated in mice. Pregnant ICR mice were gavaged with bisphenol A at 2, 20 and 200 mg/kg body weight/day from E13 to E16 and were euthanized at E17. Compared to the control mice, increased plasma estrogen and corticotrophin releasing hormone were observed in bisphenol A-treated mice. Messenger RNA quantification indicated that placental crh but not cyp19 was induced in mice treated with bisphenol A. Tracking the related signaling pathway, we found that protein kinase C ζ/λ and δ were activated in the placentas of bisphenol A-treated mice. As the gene promoter of crh contains CRE and the half site of ERE, either phospho-PKC or estrogen could stimulate the gene transactivation. These results indicate that bisphenol A might increase plasma concentrations of estradiol, testosterone, corticotrophin releasing hormone and placental phospho-PKC ζ/λ and δ in mice. Ultimately, the incidence of premature birth in these mice could increase. - Highlights: • The pollutant bisphenol A differentially activated PKC isoforms in the placenta. • CRE-binding activity in the nuclear protein of placenta was increased. • Bisphenol A induces CRH mRNA expression in mice.

  20. Evaluation of Placental and Fetal Tissue Specimens for Zika Virus Infection - 50 States and District of Columbia, January-December, 2016.

    Science.gov (United States)

    Reagan-Steiner, Sarah; Simeone, Regina; Simon, Elizabeth; Bhatnagar, Julu; Oduyebo, Titilope; Free, Rebecca; Denison, Amy M; Rabeneck, Demi B; Ellington, Sascha; Petersen, Emily; Gary, Joy; Hale, Gillian; Keating, M Kelly; Martines, Roosecelis B; Muehlenbachs, Atis; Ritter, Jana; Lee, Ellen; Davidson, Alexander; Conners, Erin; Scotland, Sarah; Sandhu, Kayleigh; Bingham, Andrea; Kassens, Elizabeth; Smith, Lou; St George, Kirsten; Ahmad, Nina; Tanner, Mary; Beavers, Suzanne; Miers, Brooke; VanMaldeghem, Kelley; Khan, Sumaiya; Rabe, Ingrid; Gould, Carolyn; Meaney-Delman, Dana; Honein, Margaret A; Shieh, Wun-Ju; Jamieson, Denise J; Fischer, Marc; Zaki, Sherif R

    2017-06-23

    Zika virus infection during pregnancy can cause congenital microcephaly and brain abnormalities (1), and detection of Zika virus RNA in clinical and tissue specimens can provide definitive laboratory evidence of recent Zika virus infection. Whereas duration of viremia is typically short, prolonged detection of Zika virus RNA in placental, fetal, and neonatal brain tissue has been reported and can provide key diagnostic information by confirming recent Zika virus infection (2). In accordance with recent guidance (3,4), CDC provides Zika virus testing of placental and fetal tissues in clinical situations where this information could add diagnostic value. This report describes the evaluation of formalin-fixed paraffin-embedded (FFPE) tissue specimens tested for Zika virus infection in 2016 and the contribution of this testing to the public health response. Among 546 live births with possible maternal Zika virus exposure, for which placental tissues were submitted by the 50 states and District of Columbia (DC), 60 (11%) were positive by Zika virus reverse transcription-polymerase chain reaction (RT-PCR). Among 81 pregnancy losses for which placental and/or fetal tissues were submitted, 18 (22%) were positive by Zika virus RT-PCR. Zika virus RT-PCR was positive on placental tissues from 38/363 (10%) live births with maternal serologic evidence of recent unspecified flavivirus infection and from 9/86 (10%) with negative maternal Zika virus immunoglobulin M (IgM) where possible maternal exposure occurred >12 weeks before serum collection. These results demonstrate that Zika virus RT-PCR testing of tissue specimens can provide a confirmed diagnosis of recent maternal Zika virus infection.

  1. Type III Interferons Produced by Human Placental Trophoblasts Confer Protection against Zika Virus Infection.

    Science.gov (United States)

    Bayer, Avraham; Lennemann, Nicholas J; Ouyang, Yingshi; Bramley, John C; Morosky, Stefanie; Marques, Ernesto Torres De Azeved; Cherry, Sara; Sadovsky, Yoel; Coyne, Carolyn B

    2016-05-11

    During mammalian pregnancy, the placenta acts as a barrier between the maternal and fetal compartments. The recently observed association between Zika virus (ZIKV) infection during human pregnancy and fetal microcephaly and other anomalies suggests that ZIKV may bypass the placenta to reach the fetus. This led us to investigate ZIKV infection of primary human trophoblasts (PHTs), which are the barrier cells of the placenta. We discovered that PHT cells from full-term placentas are refractory to ZIKV infection. In addition, medium from uninfected PHT cells protects non-placental cells from ZIKV infection. PHT cells constitutively release the type III interferon (IFN) IFNλ1, which functions in both a paracrine and autocrine manner to protect trophoblast and non-trophoblast cells from ZIKV infection. Our data suggest that for ZIKV to access the fetal compartment, it must evade restriction by trophoblast-derived IFNλ1 and other trophoblast-specific antiviral factors and/or use alternative strategies to cross the placental barrier. Copyright © 2016 Elsevier Inc. All rights reserved.

  2. Evolution of invasive placentation with special reference to non-human primates

    DEFF Research Database (Denmark)

    Carter, Anthony Michael; Pijnenborg, Robert

    2011-01-01

    It is now possible to view human placentation in an evolutionary context because advances in molecular phylogenetics provide a reliable scenario for the evolution of mammals. Perhaps the most striking finding is the uniqueness of human placenta. The lower primates have non-invasive placentae...... and even tarsiers and New World monkeys show restricted trophoblast invasion. Moreover, a truly villous placenta occurs only in Old World monkeys and great apes. The two latter groups of haplorhine primates show varying degrees of trophoblast-uterine interaction, including differences in the extent...... of decidualization, formation and disintegration of a cytotrophoblastic shell, degree of interstitial trophoblast invasion and depth of trophoblast invasion into spiral arteries. Recently, the occurrence of human-like deep invasion was confirmed in gorillas and chimpanzees. As the still enigmatic disease of pre...

  3. Oral bacteria in placental tissues: increased molecular detection in pregnant periodontitis patients.

    Science.gov (United States)

    Blanc, V; O'Valle, F; Pozo, E; Puertas, A; León, R; Mesa, F

    2015-10-01

    The objective of this study was to identify the DNA of oral bacteria in placental samples from women with and without periodontitis who had or had not had preterm births and/or low birthweight (PB/LBW) neonates. Data were gathered from 57 puerperal women in relation to socio-demographic, gynaecological, and periodontal variables and to placental histomorphology. Fifty-seven biopsies, 28 from mothers with periodontitis, were taken aseptically from preterm placentas (n = 36) and from full-term placentas (n = 21). Total DNA was extracted, and the presence of 15 oral bacteria was assessed using Nested-PCR. The placentas from women with periodontitis showed a higher prevalence of periodontopathogens compared to those from women without periodontitis (P = 0.009). Samples showed low prevalences of Actinomyces israelii, Parvimonas micra and Tannerella forsythia. An association was found between Eikenella corrodens in placenta and periodontitis (P = 0.002). The most ubiquitous bacterium, Fusobacterium nucleatum, was more prevalent in mothers with periodontitis and PB/LBW (P = 0.033). Porphyromonas gingivalis, Treponema denticola, Prevotella intermedia and Aggregatibacter actinomycetemcomitans were not detected. These results, along with previous findings, show that oral bacteria may be normally present in the placenta, however, the levels of certain oral pathogens in the placenta would highly depend on the mother's periodontal state. © 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  4. [Effect of hydrogen peroxide on human leukocyte antigen-G expression in placental trophoblasts in pre-eclampsia].

    Science.gov (United States)

    Zhou, Xue; Sun, Li-zhou; Yin, Yin

    2010-05-01

    To explore the effect of hydrogen peroxide (H2O2) on the expression of human leukocyte antigen-G (HLA-G) in placental trophoblasts in pregnant women with pre-eclampsia. Forty pregnant women, delivered through cesarean section in the Department of Obstetrics of and Gynecology, the First Affiliated Hospital of Nanjing Medical University from October 2008 to October 2009, were enrolled, including 20 women with pre-eclampsia and 20 healthy gravidas (control group). Colorimetry and western blot were applied, respectively, to determine the level of H2O2 and the expression of HLA-G protein in placental tissues and the correlation between them were analyzed. After 24 hours of seeding, JEG-3 cells (the HLA-G positive cell line of choriocarcinoma) were divided into two groups: intervention group (exposure to 175 micromol/L H2O2) and control group (without H2O2). Immunofluorescence and western blot were used to investigate the expression of HLA-G protein in JEG-3 cells at 24 hours and 48 hours after incubation. (1) The level of H2O2 in placenta in the pre-eclampsia group was significantly higher than that in control group [(105+/-13) nmolxmg(-1)xprot(-1) vs (62+/-18) nmol.mg(-1)xprot(-1), PHLA-G protein in placenta of the pre-eclampsia group was reduced by 88% compared with that of the control (0.20+/-0.08 vs 1.67+/-0.65, PHLA-G level and H2O2 expression in the placenta in both groups (r=-0.895, P=0.000). (4) Compared with the control group, the expression of HLA-G protein in JEG-3 cells, after 24 hours and 48 hours exposure to H2O2, reduced by 39% and 80%, respectively, (3.21+/-0.33 vs 1.95+/-0.25 and 0.65+/-0.08, PHLA-G in JEG-E cells in the intervention group at 48 hours compared to the control group (PHLA-G expression in the placental trophoblasts in pre-eclampsia which may be involved in the pathogenesis of pre-eclampsia.

  5. Maternal hemochromatosis gene H63D single-nucleotide polymorphism and lead levels of placental tissue, maternal and umbilical cord blood

    Energy Technology Data Exchange (ETDEWEB)

    Kayaalti, Zeliha, E-mail: kayaalti@ankara.edu.tr [Ankara University, Institute of Forensic Sciences, Ankara (Turkey); Kaya-Akyüzlü, Dilek [Ankara University, Institute of Forensic Sciences, Ankara (Turkey); Söylemez, Esma [Ankara University, Institute of Forensic Sciences, Ankara (Turkey); Middle Black Sea Passage Generation of Agricultural Research Station Director, Tokat (Turkey); Söylemezoğlu, Tülin [Ankara University, Institute of Forensic Sciences, Ankara (Turkey)

    2015-07-15

    Human hemochromatosis protein (HFE), a major histocompatibility complex class I-like integral membrane protein, participates in the down regulation of intestinal iron absorption by binding to transferrin receptor (TR). HFE competes with transferrin-bound iron for the TR and thus reduces uptake of iron into cells. On the other hand, a lack of HFE increases the intestinal absorption of iron similarly to iron deficiency associated with increasing in absorption and deposition of lead. During pregnancy, placenta cannot prevent transfer lead to the fetus; even low-level lead poisoning causes neurodevelopmental toxicity in children. The aim of this study was to determine the association between the maternal HFE H63D single-nucleotide polymorphism and lead levels in placental tissue, maternal blood and umbilical cord bloods. The study population comprised 93 mother–placenta pairs. Venous blood from mother was collected to investigate lead levels and HFE polymorphism that was detected by standard PCR–RFLP technique. Cord bloods and placentas were collected for lead levels which were analyzed by dual atomic absorption spectrometer system. The HFE H63D genotype frequencies of mothers were found as 75.3% homozygote typical (HH), 23.6% heterozygote (HD) and 1.1% homozygote atypical (DD). Our study results showed that the placental tissue, umbilical cord and maternal blood lead levels of mothers with HD+DD genotypes were significantly higher than those with HH genotype (p<0.05). The present study indicated for the first time that mothers with H63D gene variants have higher lead levels of their newborn's placentas and umbilical cord bloods. - Highlights: • Mothers with H63D gene variants have higher lead levels of their newborn's umbilical cord blood. • Unborn child of women with HD+DD genotypes may be at increased risk of internal exposure to lead. • Maternal HFE status may have an effect on increased placenta, maternal and cord blood lead levels.

  6. Preliminary interlaboratory comparison of the ex vivo dual human placental perfusion system

    DEFF Research Database (Denmark)

    Myllynen, Päivi; Mathiesen, Line; Weimer, Marc

    2010-01-01

    As a part of EU-project ReProTect, a comparison of the dual re-circulating human placental perfusion system was carried out, by two independent research groups. The detailed placental transfer data of model compounds [antipyrine, benzo(a)pyrene, PhIP (2-amino-1-methyl-6-phenylimidazo(4,5-b......)pyridine) and IQ (2-amino-3-methylimidazo(4,5-f)quinoline] has been/will be published separately. For this project, a comparative re-analysis was done, by curve fitting the data and calculating two endpoints: AUC(120), defined as the area under the curve between time 0 and time 120min and as t(0.5), defined...... as the time when the fetal to maternal concentration ratio is expected to be 0.5. The transport of the compounds from maternal to fetal circulation across the perfused placenta could be ranked in the order of antipyrine>IQ>PhIP in terms of both t(0.5) and AUC(120) by both partners. For benzo...

  7. Valproic acid transfer across human placental cotyledon during dual perfusion in vitro.

    Science.gov (United States)

    Semczuk-Sikora, Anna; Czuczwar, Stanislaw; Semczuk, Andrzej; Kwasniewska, Anna; Semczuk, Marian

    2010-01-01

    Valproic acid (VPA ) is a well-known antiepileptic drug with a significant teratogenic effect when administered during pregnancy. To investigate the transplacental transport of VPA, we used an in vitro experiment of dual perfusion of a human placental cotyledon. Eighteen normal placentas at term were investigated; ten were treated with a therapeutic dose of VPA (initial level at maternal circulation 75 microgram/ml), while the remaining eight were supplied with toxic VPA doses (initial level at maternal circulation 225 microgram/ml). VPA concentrations in fetal compartment were lower than those in the maternal compartment at all timepoints with both doses applied. The maternal and foetal VPA concentrations were stable at 60 min and 120 min for the therapeutic dose of VPA (transfer percentages from the maternal to the fetal circulation were 22.7 +- 9.1 percent and 22.7 +- 7.1 percent, respectively). Interestingly, a significant decrease of VPA level in the maternal perfusate was observed after 120 min due to the slightly higher transfer of the drug to the foetal compartment. In conclusion, our data confirmed an easy and rapid transfer of VPA accross the placental barrier. Since the incidence of congenital malformations in infants correlates positively with VPA concentrations in maternal serum, monitoring of VPA should be mandatory due to possible harmful effects on the foetus.

  8. Clinical trial: modulation of human placental multidrug resistance proteins in cholestasis of pregnancy by ursodeoxycholic acid.

    Science.gov (United States)

    Azzaroli, F; Mennone, A; Feletti, V; Simoni, P; Baglivo, E; Montagnani, M; Rizzo, N; Pelusi, G; DE Aloysio, D; Lodato, F; Festi, D; Colecchia, A; Roda, E; Boyer, J L; Mazzella, G

    2007-10-15

    The effects of ursodeoxycholic acid on human placental bile acids and bilirubin transporters in intrahepatic cholestasis of pregnancy are still undefined. To evaluate whether ursodeoxycholic acid affects MRP2, MRP3 and MRP4 expression in the placenta. Forty-three pregnant women were enrolled; fourteen subjects had physiological pregnancies. Intrahepatic cholestasis of pregnancy patients were divided into two groups: (i) 13 received ursodeoxycholic acid (20 mg/kg/day) and (ii) 16 untreated. Total bile acid and bilirubin in serum and cord blood were determined in each subject. Multidrug resistance proteins expression (immunoblot, quantitative real-time PCR) was evaluated in placentas collected at delivery. anova test was used for statistical analysis of data. Ursodeoxycholic acid administration significantly improved maternal serum bile acid and cord blood bilirubin and bile acid levels. MRP2 protein and RNA expression was significantly increased in placentas from treated patients compared to controls (P Ursodeoxycholic acid administration induces placental MRP2 expression, and reduces bilirubin and bile acid levels in cord blood.

  9. Placental exosomes during gestation: liquid biopsies carrying signals for the regulation of human parturition.

    Science.gov (United States)

    Salomon, Carlos; Nuzhat, Zarin; Dixon, Christopher L; Menon, Ramkumar

    2018-01-25

    Parturition is defined as the action or process of giving birth to offspring. Normal term human parturition ensues following the maturation of fetal organ systems typically between 37 and 40 weeks of gestation. Our conventional understanding of how parturition initiation is signaled revolves around feto-maternal immune and endocrine changes occurring in the intrauterine cavity. These changes in turn correlate with the sequence of fetal growth and development. These important physiological changes also result in homeostatic imbalances which result in heightened inflammatory signaling. This disrupts the maintenance of pregnancy, thus leading to labor-related changes. However, the precise mechanisms of the signaling cascades that lead to the initiation of parturition remain unclear, although exosomes may be a mediator of this process. Exosomes are a subtype of extracellular vesicles characterised by their endocytic origin. This involves the trafficking of intraluminal vesicles into multivesicular bodies (MVB) and then exocytosis via the plasmatic membranes. Exosomes are highly stable nanovesicles that are released by a wide range of cells and organs including the human placenta and fetal membranes. Interestingly, exosomes from placental origin have been uncovered in maternal circulation across gestation. In addition, their concentration is higher in pregnancies with complications such as gestational diabetes and preeclampsia. In normal gestation, the concentration of placental exosomes in maternal circulation correlates with placental weight at third trimester. The role of placental exosomes across gestation has not been fully elucidated, although recent studies suggest that placental exosomes are involved in maternal-fetal inmmuno-tolerance, maternal systemic inflammation and nutrient transport. The content of exosomes is of particular importance, encompassing a large range of molecules such as mRNA, miRNAs, DNA, lipids, cell-surface receptors, and protein mediators

  10. Placental apoptosis in recurrent miscarriage

    Directory of Open Access Journals (Sweden)

    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.

  11. Uptake and release of amino acids in the fetal-placental unit in human pregnancies.

    Directory of Open Access Journals (Sweden)

    Maia Blomhoff Holm

    Full Text Available The current concepts of human fetal-placental amino acid exchange and metabolism are mainly based on animal-, in vitro- and ex vivo models. We aimed to determine and assess the paired relationships between concentrations and arteriovenous differences of 19 amino acids on the maternal and fetal sides of the human placenta in a large study sample.This cross-sectional in vivo study included 179 healthy women with uncomplicated term pregnancies. During planned cesarean section, we sampled blood from incoming and outgoing vessels on the maternal (radial artery and uterine vein and fetal (umbilical vein and artery sides of the placenta. Amino acid concentrations were measured by liquid chromatography-tandem mass spectrometry. We calculated paired arteriovenous differences and performed Wilcoxon signed-rank tests and Spearman's correlations.In the umbilical circulation, we observed a positive venoarterial difference (fetal uptake for 14 amino acids and a negative venoarterial difference (fetal release for glutamic acid (p<0.001. In the maternal circulation, we observed a positive arteriovenous difference (uteroplacental uptake for leucine (p = 0.005, isoleucine (p = 0.01, glutamic acid (p<0.001 and arginine (p = 0.04 and a negative arteriovenous difference (uteroplacental release for tyrosine (p = 0.002, glycine (p = 0.01 and glutamine (p = 0.02. The concentrations in the maternal artery and umbilical vein were correlated for all amino acids except tryptophan, but we observed no correlations between the uteroplacental uptake and the fetal uptake or the umbilical vein concentration. Two amino acids showed a correlation between the maternal artery concentration and the fetal uptake.Our human in vivo study expands the current insight into fetal-placental amino acid exchange, and discloses some differences from what has been previously described in animals. Our findings are consistent with the concept that the fetal supply of amino acids in the human is

  12. Differences in collagen ultrastructure of human first trimester decidua basalis and parietalis: implications for trophoblastic invasion of the placental bed.

    Science.gov (United States)

    Sinai Talaulikar, Vikram; Kronenberger, Katrin; Bax, Bridget E; Moss, Raymond; Manyonda, Isaac

    2014-01-01

    The human embryo-maternal interface in the first trimester of pregnancy is an area of extensive tissue remodeling. Because collagen is the most abundant constituent of the extracellular matrix of the placental bed, successful invasion must involve its rapid turnover. We compared the nature and distribution of collagen fibrils in decidua basalis and parietalis. We used a direct-vision hysteroscopic technique to obtain biopsies of the decidua basalis and parietalis from 11 women undergoing pregnancy termination in the first trimester. The biopsies were subjected to light, transmission and scanning electron microscopy, and immunohistochemical studies using mouse monoclonal antibodies against cytokeratin 7 and collagen types I, III and V. Collagen fibrils in the stroma of decidua basalis were significantly thicker when compared to those in decidua parietalis (56.48 ± 1.37 nm vs 45.64 ± 0.85 nm; P collagen fibrils between basalis and parietalis, with thicker and disrupted fibrils within abundant amorphous tissue in basalis, and thinner uniform fibrils in parietalis. These differences may reflect an adaptive response by decidua or a direct consequence of the invading trophoblast cells. © 2013 The Authors. Journal of Obstetrics and Gynaecology Research © 2013 Japan Society of Obstetrics and Gynecology.

  13. Toxic and therapeutic effects of Nifurtimox and Benznidazol on Trypanosoma cruzi ex vivo infection of human placental chorionic villi explants.

    Science.gov (United States)

    Rojo, Gemma; Castillo, Christian; Duaso, Juan; Liempi, Ana; Droguett, Daniel; Galanti, Norbel; Maya, Juan Diego; López-Muñoz, Rodrigo; Kemmerling, Ulrike

    2014-04-01

    Nifurtimox (Nfx) and Benznidazole (Bnz) are the only available drugs in use for the treatment of Chagas disease. These drugs are recommended but not fully validated in evidence-based medicine and reports about the differential toxicity of both drugs are controversial. Here, we evaluated the toxic and therapeutic effects of Nfx and Bnz on human placental chorionic villi explants (HPCVE) during ex vivo infection of Trypanosoma cruzi, performing histopathological, histochemical, immunohistochemical as well as immunofluorescence analysis of the tissue. Additionally, we determined the effect of both drugs on parasite load by real time PCR. Bnz prevents the parasite induced tissue damage in ex vivo infected HPCVE compared to Nfx, which is toxic per se. The presence of T. cruzi antigens and DNA in infected explants suggests that these drugs do not impair parasite invasion into the HPCVE. Additionally, our results confirm reports suggesting that Bnz is less toxic than Nfx and support the need for the development of more effective and better-tolerated drugs. Copyright © 2014 Elsevier B.V. All rights reserved.

  14. Human placentation from nidation to 5 weeks of gestation. Part II: Tools to model the crucial first days

    DEFF Research Database (Denmark)

    James, J L; Carter, Anthony Michael; Chamley, L W

    2012-01-01

    Human pregnancy is unusual with respect to monthly spontaneous decidualisation as well as the degree of placental invasion and interaction with the decidualised endometrial stroma. This review covers in vivo animal models and in vitro cell culture models that have been used to study the earliest...... stages of human implantation and placentation from nidation to 5 weeks of gestation. The field has expanded rapidly in recent years due to the generation of human embryonic stem cell lines and the ability of some scientists to culture human blastocysts. These models have enabled researchers to begin...... to elucidate the interactions involved in human blastocyst apposition, adhesion and implantation. However, we still understand very little about the differentiation processes involved in the formation of the placenta. Continued improvements to current models, including the potential isolation of a human...

  15. Effects of RNA integrity on transcript quantification by total RNA sequencing of clinically collected human placental samples.

    Science.gov (United States)

    Reiman, Mario; Laan, Maris; Rull, Kristiina; Sõber, Siim

    2017-08-01

    RNA degradation is a ubiquitous process that occurs in living and dead cells, as well as during handling and storage of extracted RNA. Reduced RNA quality caused by degradation is an established source of uncertainty for all RNA-based gene expression quantification techniques. RNA sequencing is an increasingly preferred method for transcriptome analyses, and dependence of its results on input RNA integrity is of significant practical importance. This study aimed to characterize the effects of varying input RNA integrity [estimated as RNA integrity number (RIN)] on transcript level estimates and delineate the characteristic differences between transcripts that differ in degradation rate. The study used ribodepleted total RNA sequencing data from a real-life clinically collected set (n = 32) of human solid tissue (placenta) samples. RIN-dependent alterations in gene expression profiles were quantified by using DESeq2 software. Our results indicate that small differences in RNA integrity affect gene expression quantification by introducing a moderate and pervasive bias in expression level estimates that significantly affected 8.1% of studied genes. The rapidly degrading transcript pool was enriched in pseudogenes, short noncoding RNAs, and transcripts with extended 3' untranslated regions. Typical slowly degrading transcripts (median length, 2389 nt) represented protein coding genes with 4-10 exons and high guanine-cytosine content.-Reiman, M., Laan, M., Rull, K., Sõber, S. Effects of RNA integrity on transcript quantification by total RNA sequencing of clinically collected human placental samples. © FASEB.

  16. Spontaneous contractility of human placental vessels in vitro axipetal and isometric recording.

    Science.gov (United States)

    Gonzalez Panizza, V H; Benedetti, W L; Alvarez, H

    1980-01-01

    In vitro contractility of isolated cylindrical segments of chorial arteries and veins from 40 human term placentas was studied. Contractility was recorded by an isometrical and axipetal method. Spontaneous contractility was observed in 75% of the arteries and in 45% of veins. In both types of vessels, contractility was similar and characterized by development of tonic circumferential tension, between 100 and 200 mg/mm. Clonic activity consisting of rhythmic contractions with an average frequency between 0.7 and 0.9/min and an average intensity of 5--40 mg/min was superimposed. Vasoconstrictor drugs (PGF2 alpha, histamine and adrenaline) increase tonic tension without modifying the frequency of clonic activity. It is suggested that spontaneous contractility may be the expression of myogenic excitability related to the regulation of fetal placental blood flow.

  17. In vitro toxicological effects of estrogenic mycotoxins on human placental cells: Structure activity relationships

    Energy Technology Data Exchange (ETDEWEB)

    Prouillac, Caroline, E-mail: c.prouillac@vetagro-sup.fr [Université Lyon, US/C 1233 INRA VetAgroSup, Métabolisme et Toxicologie Comparée des Xénobiotiques, 1 avenue Bourgelat, BP 83, 69280 Marcy l' Etoile (France); Koraichi, Farah; Videmann, Bernadette; Mazallon, Michelle [Université Lyon, US/C 1233 INRA VetAgroSup, Métabolisme et Toxicologie Comparée des Xénobiotiques, 1 avenue Bourgelat, BP 83, 69280 Marcy l' Etoile (France); Rodriguez, Frédéric; Baltas, Michel [Université Paul Sabatier, SPCMIB-UMR5068, Laboratoire de Synthèse et de Physicochimie des Molécules d' Intérêt Biologique, 118 route de Narbonne, 31062 TOULOUSE cedex 9 (France); Lecoeur, Sylvaine [Université Lyon, US/C 1233 INRA VetAgroSup, Métabolisme et Toxicologie Comparée des Xénobiotiques, 1 avenue Bourgelat, BP 83, 69280 Marcy l' Etoile (France)

    2012-03-15

    Zearalenone (ZEN) is a non-steroid estrogen mycotoxin produced by numerous strains of Fusarium which commonly contaminate cereals. After oral administration, ZEN is reduced via intestinal and hepatic metabolism to α- and β-zearalenol (αZEL and βZEL). These reduced metabolites possess estrogenic properties, αZEL showing the highest affinity for ERs. ZEN and reduced metabolites cause hormonal effects in animals, such as abnormalities in the development of the reproductive tract and mammary gland in female offspring, suggesting a fetal exposure to these contaminants. In our previous work, we have suggested the potential impact of ZEN on placental cells considering this organ as a potential target of xenobiotics. In this work, we first compared the in vitro effects of αZEL and βΖΕL on cell differentiation to their parental molecule on human trophoblast (BeWo cells). Secondly, we investigated their molecular mechanisms of action by investigating the expression of main differentiation biomarkers and the implication of nuclear receptor by docking prediction. Conversely to ZEN, reduced metabolites did not induce trophoblast differentiation. They also induced significant changes in ABC transporter expression by potential interaction with nuclear receptors (LXR, PXR, PR) that could modify the transport function of placental cells. Finally, the mechanism of ZEN differentiation induction seemed not to involve nuclear receptor commonly involved in the differentiation process (PPARγ). Our results demonstrated that in spite of structure similarities between ZEN, αZEL and βZEL, toxicological effects and toxicity mechanisms were significantly different for the three molecules. -- Highlights: ► ZEN and metabolites have differential effect on trophoblast differentiation. ► ZEN and metabolites have differential effect on ABC transporter expression. ► ZEN and metabolites effects involved nuclear receptors interaction.

  18. In vitro approaches to evaluate placental drug transport by using differentiating JEG-3 human choriocarcinoma cells.

    Science.gov (United States)

    Ikeda, Kenji; Utoguchi, Naoki; Tsutsui, Hidenobu; Yamaue, Satoko; Homemoto, Manami; Nakao, Erina; Hukunaga, Yumi; Yamasaki, Kyohei; Myotoku, Michiaki; Hirotani, Yoshihiko

    2011-02-01

    Human choriocarcinoma cells have been used as models for studying transcellular drug transport through placental trophoblasts. However, these models allow the transport of low-molecular-weight drugs through intercellular gap junctions. This study aimed at investigating the differentiation patterns of JEG-3 choriocarcinoma cells under different culture conditions and establishing the appropriate model of in vitro syncytiotrophoblast drug transport. Paracellular permeability was estimated by measuring the transepithelial electrical resistance (TEER) across JEG-3 cell layers. The mRNA expression levels of non-expressed in choriocarcinoma clone 1 (NECC1) and breast cancer resistance protein (BCRP), and those of E-cadherin (ECAD) and cadherin-11 (CDH11), which are adherens junction-associated proteins related to fusogenic ability of syncytiotrophoblasts differentiated from cytotrophoblasts, protein expression levels were considered as the differentiation signals. The highest TEER values were obtained in the JEG-3 cells cultured in the Dulbecco's modified Eagle's medium (DMEM)/Ham's F-12 (1:1) mixed medium (CS-C(®) ; Dainippon Sumitomo Pharma Co. Ltd., Osaka, Japan). By comparing the TEER values and the differentiation signals, the authors identified at least five JEG-3 cell-differentiation patterns. The differentiation pattern of JEG-3 cultured in CS-C resembled the syncytiotrophoblast-like differentiation signal characterizations in vivo. In conclusion, the syncytiotrophoblast-like models of differentiating JEG-3 cells cultured in CS-C might be appropriate for evaluating drug transport across the placental trophoblast. © 2010 The Authors. Basic & Clinical Pharmacology & Toxicology © 2010 Nordic Pharmacological Society.

  19. Estimation of placental and lactational transfer and tissue distribution of atrazine and its main metabolites in rodent dams, fetuses, and neonates with physiologically based pharmacokinetic modeling

    Energy Technology Data Exchange (ETDEWEB)

    Lin, Zhoumeng [Department of Physiology and Pharmacology, College of Veterinary Medicine, University of Georgia, Athens, GA 30602 (United States); Interdisciplinary Toxicology Program, University of Georgia, Athens, GA 30602 (United States); Fisher, Jeffrey W. [Division of Biochemical Toxicology, National Center for Toxicological Research, Food and Drug Administration, Jefferson, AR 72079 (United States); Wang, Ran [Center for Environmental Health Sciences, Department of Basic Sciences, College of Veterinary Medicine, Mississippi State University, Mississippi State, MS 39762 (United States); Institute of Food Safety, Jiangsu Academy of Agricultural Sciences, Nanjing 210014 (China); Ross, Matthew K. [Center for Environmental Health Sciences, Department of Basic Sciences, College of Veterinary Medicine, Mississippi State University, Mississippi State, MS 39762 (United States); Filipov, Nikolay M., E-mail: filipov@uga.edu [Department of Physiology and Pharmacology, College of Veterinary Medicine, University of Georgia, Athens, GA 30602 (United States); Interdisciplinary Toxicology Program, University of Georgia, Athens, GA 30602 (United States)

    2013-11-15

    Atrazine (ATR) is a widely used chlorotriazine herbicide, a ubiquitous environmental contaminant, and a potential developmental toxicant. To quantitatively evaluate placental/lactational transfer and fetal/neonatal tissue dosimetry of ATR and its major metabolites, physiologically based pharmacokinetic models were developed for rat dams, fetuses and neonates. These models were calibrated using pharmacokinetic data from rat dams repeatedly exposed (oral gavage; 5 mg/kg) to ATR followed by model evaluation against other available rat data. Model simulations corresponded well to the majority of available experimental data and suggest that: (1) the fetus is exposed to both ATR and its major metabolite didealkylatrazine (DACT) at levels similar to maternal plasma levels, (2) the neonate is exposed mostly to DACT at levels two-thirds lower than maternal plasma or fetal levels, while lactational exposure to ATR is minimal, and (3) gestational carryover of DACT greatly affects its neonatal dosimetry up until mid-lactation. To test the model's cross-species extrapolation capability, a pharmacokinetic study was conducted with pregnant C57BL/6 mice exposed (oral gavage; 5 mg/kg) to ATR from gestational day 12 to 18. By using mouse-specific parameters, the model predictions fitted well with the measured data, including placental ATR/DACT levels. However, fetal concentrations of DACT were overestimated by the model (10-fold). This overestimation suggests that only around 10% of the DACT that reaches the fetus is tissue-bound. These rodent models could be used in fetal/neonatal tissue dosimetry predictions to help design/interpret early life toxicity/pharmacokinetic studies with ATR and as a foundation for scaling to humans. - Highlights: • We developed PBPK models for atrazine in rat dams, fetuses, and neonates. • We conducted pharmacokinetic (PK) study with atrazine in pregnant mice. • Model predictions were in good agreement with experimental rat and mouse PK data

  20. Placental endoplasmic reticulum stress negatively regulates transcription of placental growth factor via ATF4 and ATF6β: implications for the pathophysiology of human pregnancy complications.

    Science.gov (United States)

    Mizuuchi, Masahito; Cindrova-Davies, Tereza; Olovsson, Matts; Charnock-Jones, D Stephen; Burton, Graham J; Yung, Hong Wa

    2016-03-01

    Low maternal circulating concentrations of placental growth factor (PlGF) are one of the hallmarks of human pregnancy complications, including fetal growth restriction (FGR) and early-onset pre-eclampsia (PE). Currently, PlGF is used clinically with other biomarkers to screen for high-risk cases, although the mechanisms underlying its regulation are largely unknown. Placental endoplasmic reticulum (ER) stress has recently been found to be elevated in cases of FGR, and to an even greater extent in early-onset PE complicated with FGR. ER stress activates the unfolded protein response (UPR); attenuation of protein translation and a reduction in cell growth and proliferation play crucial roles in the pathophysiology of these complications of pregnancy. In this study, we further identified that ER stress regulates release of PlGF. We first observed that down-regulation of PlGF protein was associated with nuclear localization of ATF4, ATF6α and ATF6β in the syncytiotrophoblast of placentae from PE patients. Transcript analysis showed a decrease of PlGF mRNA, and an increase from genes encoding those UPR transcription factors in placentae from cases of early-onset PE, but not of late-onset (>34 weeks) PE, compared to term controls. Further investigations indicated a strong correlation between ATF4 and PlGF mRNA levels only (r = - 0.73, p pregnancy complications. © 2015 The Authors. The Journal of Pathology published by John Wiley & Sons Ltd on behalf of Pathological Society of Great Britain and Ireland.

  1. Evaluation of Placental Blood Flow in Patients with Placental Insufficiency

    Directory of Open Access Journals (Sweden)

    Julia E. Dobrokhotova

    2017-03-01

    Full Text Available Background: Placental insufficiency is a major problem of modern obstetrics due to its link to maternal and perinatal morbidity and mortality. Placental microcirculatory disorders play a decisive role in the pathogenesis of this condition. Thus, an evaluation of placental blood flow is of particular importance and crucial for appropriate diagnosis. The aim of this study was to evaluate placental blood flow in patients with placental insufficiency. SMI (superb microvascular imaging was compared to color Doppler for that purpose. Materials and Methods: Primigravida patients (n=91 at 15 to 16 weeks of gestation were enrolled. Inclusion criteria were spontaneous singleton pregnancy, age from 18 to 45 years. All participants were divided into 2 groups: Group 1 – control group (n=27 and Group 2 – threatened miscarriage group (n=64. Transvaginal ultrasound and color Doppler were performed to assess uteroplacental circulation. Placental blood flow was evaluated using a Toshiba Aplio™ 500 machine equipped with an SMI tool. Results: Placental blood flow assessment in patients with normal pregnancy revealed homogenous placental tissue, normal distribution of vessels, and active blood flow; in patients with pregnancy complications, we found inhomogeneous placenta, decreased blood flow, sporadic vessels, and avascular areas. SMI demonstrated several benefits compared to color Doppler imaging. Color Doppler allows us to assess superficial vessels only, whereas SMI provides more comprehensive data on the overall vascularization of the placenta. Conclusion: SMI by Aplio™ 500 (Toshiba may be an effective tool in the assessment of placental blood flow and the diagnosis and prognosis of placental insufficiency.

  2. Calcium-dependant binding proteins associated with human placental syncytiotrophoblast microvillous cytoskeleton.

    Science.gov (United States)

    Webb, P D; Mahadevan, L C

    1987-12-18

    Isolated human placental syncytiotrophoblast microvillous plasma membrane vesicles were extracted with Triton X-100 to yield a detergent-insoluble residue. The residue contained approx. 50% of the total membrane protein and was qualitatively different from untreated trophoblast on SDS-polyacrylamide gel electrophoresis, Western blots and dot-immunobinding assay. Three major proteins, with molecular weights of 68, 36 and 34 kDa, dissociated from this non-ionic detergent-insoluble submembranous cytoskeletal fraction in the presence of calcium chelators. They were immunologically related to human lymphocyte cytoskeletal calcium-binding proteins, and the 36 kDa component reacted with antisera to the phospholipase A2 inhibitor, lipocortin II. Anti-lipocortin I sera did not recognise the 34 kDa protein, but did react with a series of trophoblast cytoskeletal proteins in the 34-37 kDa region. Incubation of epidermal growth factor with isolated trophoblast membrane vesicles stimulated the phosphorylation of a 36 kDa protein on tyrosine residues. Immunoprecipitation studies further showed there was no phosphorylation of the 34 kDa protein, but the 68 kDa protein was a major phosphorylated component of isolated syncytiotrophoblast membranes. p68 was principally phosphorylated on serine with slight tyrosine phosphorylation which showed an apparent increase after epidermal growth factor treatment. These results indicate a family of calcium-dependant binding proteins, some of which are phosphorylated, associated with the submembranous cytoskeleton of syncytiotrophoblast microvilli.

  3. Characterization of human placental alkaline phosphatase by activity and protein assays, capillary electrophoresis and matrix-assisted laser desorption/ionization time-of-flight mass spectrometry

    NARCIS (Netherlands)

    Eriksson, H J; Somsen, G W; Hinrichs, W L; Frijlink, H W; de Jong, G J

    2001-01-01

    Placental alkaline phosphatase (PLAP) that had been isolated from human placenta was further purified using subsequent ion-exchange chromatography (IEC), affinity chromatography (AC) and centrifugal membrane concentration (CMC). During the process, the PLAP samples from the different stages of

  4. L-carnitine is synthesized in the human fetal-placental unit: potential roles in placental and fetal metabolism

    NARCIS (Netherlands)

    Oey, N. A.; van Vlies, N.; Wijburg, F. A.; Wanders, R. J. A.; Attie-Bitach, T.; Vaz, F. M.

    2006-01-01

    Carnitine plays an indispensable role in fatty acid oxidation. Previous studies revealed that fetal carnitine is derived from the mother via transplacental transfer. Recent studies demonstrated the presence and importance of an active fatty acid oxidation system in the human placenta and in the

  5. Differential transcription of exon 1 of the human c-fms gene in placental trophoblasts and monocytes

    Energy Technology Data Exchange (ETDEWEB)

    Visvader, J.; Verma, I.M. (Salk Inst. for Biological Studies, San Diego, CA (USA))

    1989-03-01

    Structural analysis of the 5' end of the human c-fms gene revealed that a large intron of about 25 kilobases separates an upstream noncoding exon (exon 1) from the signal peptide-containing exon (exon 2). Northern (RNA) blot analysis, S1 nuclease mapping, and primer extensions showed that exon 1 is transcribed in placenta but not in cells of the monocytic lineage. This is due to the differential usage or promoters, separated by approximately 25 kilobases, in cell-specific manner. One major c-fms transcript was observed in U-937 cells, whereas multiple initiation sites for transcription appeared to be utilized in placental cells. Nucleotide sequence comparisons showed that the 3' end of the human platelet-derived growth factor receptor gene lies approximately 350 base pairs upstream of the major initiation sites for c-fms transcription in placental trophoblasts.

  6. Differential transcription of exon 1 of the human c-fms gene in placental trophoblasts and monocytes.

    Science.gov (United States)

    Visvader, J; Verma, I M

    1989-01-01

    Structural analysis of the 5' end of the human c-fms gene revealed that a large intron of about 25 kilobases separates an upstream noncoding exon (exon 1) from the signal peptide-containing exon (exon 2). Northern (RNA) blot analysis, S1 nuclease mapping, and primer extensions showed that exon 1 is transcribed in placenta but not in cells of the monocytic lineage. This is due to the differential usage of promoters, separated by approximately 25 kilobases, in a cell-specific manner. One major c-fms transcript was observed in U-937 cells, whereas multiple initiation sites for transcription appeared to be utilized in placental cells. Nucleotide sequence comparisons showed that the 3' end of the human platelet-derived growth factor receptor gene lies approximately 350 base pairs upstream of the major initiation sites for c-fms transcription in placental trophoblasts. Images PMID:2524648

  7. Gas chromatography-mass spectrometric study of 19-oxygenation of the aromatase inhibitor 19-methylandrostenedione with human placental microsomes.

    Science.gov (United States)

    Numazawa, Mitsuteru; Nagaoka, Masao; Handa, Wakako; Yamada, Akane

    2006-06-01

    To gain insight into the catalytic function of aromatase, we studied 19-oxygenation of 19-methyl-substituted derivative of the natural substrate androstenedione (AD), compound 1, with human placental aromatase by use of gas chromatography-mass spectrometry (GC-MS). Incubation of the 19-methyl derivative 1 with human placental microsomes in the presence of NADPH under an aerobic condition did not yield a detectable amount of [19S]19-hydroxy product 2 or its [19R]-isomer 3 when the product was analyzed as the bis-methoxime-trimethylsilyl (TMS) derivative by GC-MS; moreover, the production of estrogen was not detected as the bis-TMS derivative of estradiol (detection limit: about 3 ng and 10 pg per injection for the 19-ol and estradiol, respectively). The results reveal that the 19-methyl steroid 1 does not serve as a substrate of aromatase, although it does serve as a powerful inhibitor of the enzyme.

  8. Heightened pro-inflammatory effect of preeclamptic placental microvesicles on peripheral blood immune cells in humans.

    Science.gov (United States)

    Holder, Beth S; Tower, Clare L; Jones, Carolyn J P; Aplin, John D; Abrahams, Vikki M

    2012-04-01

    Normal pregnancy is associated with the presence of circulating placental microvesicles (MVs). Increased MV shedding and altered immune activation are seen in patients with preeclampsia, suggesting that placental MVs may play a role in the pathophysiology of this disease. Therefore, the aim of this study was to investigate the activation of peripheral blood mononuclear cells (PBMCs) by MVs shed by first-trimester, normal term, and preeclamptic term placenta. First-trimester and preeclamptic term, but not normal term, placental-derived MVs activated PBMCs, as evidenced by elevated IL1B. Significant changes were also seen with several other cytokines and chemokines, and in general when compared to normal term MVs, preeclamptic MVs induced a greater pro-inflammatory response in PBMCs. Pretreatment of PBMCs with first-trimester or normal term placental MVs resulted in a dampened IL1B response to a subsequent lipopolysaccharide (LPS) challenge. In contrast, treatment of PBMCs with preeclamptic term placental MVs exacerbated the LPS response. This was also the case for several other cytokines and chemokines. These studies suggest that placental MVs can modulate basal peripheral immune cell activation and responsiveness to LPS during normal pregnancy, and that in preeclampsia this effect is exacerbated.

  9. Raft partitioning and dynamic behavior of human placental alkaline phosphatase in giant unilamellar vesicles.

    Science.gov (United States)

    Kahya, Nicoletta; Brown, Deborah A; Schwille, Petra

    2005-05-24

    Much attention has recently been drawn to the hypothesis that cellular membranes organize in functionalized platforms called rafts, enriched in sphingolipids and cholesterol. The notion that glycosylphosphatidylinositol (GPI)-anchored proteins are strongly associated with rafts is based on their insolubility in nonionic detergents. However, detergent-based methodologies for identifying raft association are indirect and potentially prone to artifacts. On the other hand, rafts have proven to be difficult to visualize and investigate in living cells. A number of studies have demonstrated that model membranes provide a valuable tool for elucidating some of the raft properties. Here, we present a model membrane system based on domain-forming giant unilamellar vesicles (GUVs), in which the GPI-anchored protein, human placental alkaline phosphatase (PLAP), has been functionally reconstituted. Raft morphology, protein raft partitioning, and dynamic behavior have been characterized by fluorescence confocal microscopy and fluorescence correlation spectroscopy (FCS). Approximately 20-30% of PLAP associate with sphingomyelin-enriched domains. The affinity of PLAP for the liquid-ordered (l(o)) phase is compared to that of a nonraft protein, bacteriorhodopsin. Next, detergent extraction was carried out on PLAP-containing GUVs as a function of temperature, to relate the lipid and protein organization in distinct phases of the GUVs to the composition of detergent resistant membranes (DRMs). Finally, antibody-mediated cross-linking of PLAP induces a shift of its partition coefficient in favor of the l(o) phase.

  10. Regulation of progesterone receptor A and B expression in human preterm, term, and postterm placental villi.

    Science.gov (United States)

    Ziyan, Jiang; Huaibin, Ren; Xiaotian, Ma; Guangtong, She; Xiaoqing, Chen; Zijiang, Dong; Ziyue, Jiang; We, De; Lizhou, Sun

    2010-05-01

    The progesterone receptor (PR)-A/B ratio in the myometrium is reported to be closely related to labor onset. This might represent a potential target for therapeutic interventions for postterm and preterm deliveries, though the mechanisms currently remain unknown. The aim of this study was to investigate the regulation mechanism of PR-A and B expression in human preterm, term, and postterm placental villi. Experimental study. People's Hospital of Jiangsu Province, China. Singleton women of preterm (PRNIL, not in labor, n = 10), term (TNIL, not in labor, n = 10; TIL, in labor, n = 10), and postterm (PONIL, not in labor, n = 10) cesarean deliveries. The PR-A/PR-B mRNA and protein ratios were analyzed using real-time reverse transcription-polymerase chain reaction and western blots in villi from preterm, term, postterm groups. PONIL and PRNIL villi were incubated with prostaglandin F(2alpha) (PG) and indomethacin for 72 hours, respectively, and the PR-A/PR-B mRNA and protein ratios and p38 signaling pathway were explored. The PR-A/PR-B ratio was highest in TIL, followed by PRNIL, PONIL and TNIL. Indomethacin significantly up-regulated PR-B expression, thereby decreasing the PR-A/PR-B ratio (p postterm deliveries.

  11. Expression of human placental lactogen and variant growth hormone genes in placentas.

    Science.gov (United States)

    Martinez-Rodriguez, H G; Guerra-Rodriguez, N E; Iturbe-Cantu, M A; Martinez-Torres, A; Barrera-Saldaña, H A

    1997-01-01

    Previous studies comparing the expression levels of human placental lactogen (hPL) genes have shown varying results, due to, perhaps, the fact that in all of them only one placenta was being analyzed. Here, the expression of hPL and growth hormone variant (hGH-V) genes in fifteen term placentas was comparatively analyzed at the RNA level, using reverse transcription coupled to polymerase chain reaction (RT-PCR). The abundance of the combined RNA transcripts derived from these genes varied from one placenta to another. The authors found that hPL-4 transcripts were more abundant than those of hPL-3 in most samples (ratios from 1:1 to 6:1), transcripts from the putative hPL-1 pseudogene were more abundant at the unprocessed stage while those of the hGH-V gene were mostly processed. Again, the authors of this study observed wide variation from placenta to placenta in the abundance of both of these types of transcripts. The same was observed when a group of six placentas from abortuses and nine from pregnancies complicated by preclampsia, diabetes and hypertension was studied. The authors conclude that the disagreeing results reported in the literature which are not in agreement concerning the expression levels of hPL genes could be explained by normal variations of their expression levels among the different placentas analyzed.

  12. Placental chorangioma

    African Journals Online (AJOL)

    nonimmune fetal hydrops, fetal heart failure, cardiomegaly, intrauterine growth restriction, fetal anemia, thrombocytopenia, and fetal demise. Maternal complications such as preeclampsia, ... Key words: Kano; live birth; placental chorangioma; Pregnancy. Introduction. Placental chorangioma is a rare tumor of the placenta ...

  13. 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

  14. Validated method for the determination of perfluorinated compounds in placental tissue samples based on a simple extraction procedure followed by ultra-high performance liquid chromatography-tandem mass spectrometry analysis.

    Science.gov (United States)

    Martín, J; Rodríguez-Gómez, R; Zafra-Gómez, A; Alonso, E; Vílchez, J L; Navalón, A

    2016-04-01

    Xenobiotic exposure during pregnancy is inevitable. Determination of perfluorinated compounds (PFCs), chemicals described as environmental contaminants by Public Health Authorities due to their persistence, bioaccumulation and toxicity, is a challenge. In the present work, a method based on a simplified sample treatment involving freeze-drying, solvent extraction and dispersive clean-up of the extracts using C18 sorbents followed by an ultra-high performance liquid chromatography-tandem mass spectrometry (UHPLC-MS/MS) analysis was developed and validated for the determination of five perfluorinated carboxylic acids (C4-C8) and perfluorooctane sulfonate (PFOS) in placental tissue samples. The most influential parameters affecting the extraction method and clean-up were optimized using Design of Experiments (DOE). The method was validated using matrix-matched calibration. Found limits of detection (LODs) ranged from 0.03 to 2 ng g(-1) and limits of quantification (LOQs) from 0.08 to 6 ng g(-1), while inter- and intra-day variability was under 14% in all cases. Recovery rates for spiked samples ranged from 94% to 113%. The method was satisfactorily applied for the determination of compounds in human placental tissue samples collected at delivery from 25 randomly selected women. Copyright © 2015 Elsevier B.V. All rights reserved.

  15. Placentation in mammals

    DEFF Research Database (Denmark)

    Carter, A M; Enders, A C

    2016-01-01

    An overview is given of variations in placentation with particular focus on yolk sac, paraplacenta, and other structures important to histotrophic nutrition. The placenta proper varies in general shape, internal structure, and the number of tissues in the interhemal barrier. Yolk sac membranes...

  16. Placental STAT3 signaling is activated in women with polycystic ovary syndrome.

    Science.gov (United States)

    Maliqueo, M; Sundström Poromaa, I; Vanky, E; Fornes, R; Benrick, A; Åkerud, H; Stridsklev, S; Labrie, F; Jansson, T; Stener-Victorin, E

    2015-03-01

    Does polycystic ovary syndrome (PCOS) in women without pregnancy complications affect placental signal transducer and activator of transcription 3 (STAT3) and mechanistic target of rapamycin (mTOR) signaling? Placental STAT3 signaling is activated but mTOR signaling is unaffected in PCOS. Women with PCOS have increased risk of poor pregnancy outcomes (e.g. restricted or accelerated fetal growth), indicating placental dysfunction. Placental STAT3 and mTOR pathways regulate placental function and indirectly affect fetal growth. In a case-control study, placental tissue and maternal blood were collected at delivery from 40 control pregnant women and 38 PCOS women with uncomplicated pregnancy. Women with PCOS were recruited at two medical centers and pregnant controls were recruited at one of these centers. Placental mRNA expression of genes encoding proteins related to steroid action, metabolic pathways and cytokines was analyzed by quantitative RT-PCR. Phosphorylated placental STAT3 (P-STAT3) and mTOR targets was measured by western blot. Levels of sex steroids in serum were determined by mass spectrometry. Placental P-STAT3 (Tyr-705) was increased in women with PCOS (P Becas Chile Programme (Chile) and University of Chile for financial support through a postdoctoral fellowship. There are no competing interests. © The Author 2015. Published by Oxford University Press on behalf of the European Society of Human Reproduction and Embryology. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

  17. 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.

  18. Reactivity of human placental chorionic plate vessels from pregnancies complicated by intrauterine growth restriction (IUGR).

    Science.gov (United States)

    Wareing, Mark; Greenwood, Susan L; Fyfe, Gregor K; Baker, Philip N

    2006-10-01

    A successful pregnancy is dependent on liberal placental perfusion via the maternal and fetal circulations. Doppler waveform analyses of umbilical arteries suggest increased resistance to flow in the fetoplacental circulation of pregnancies complicated by intrauterine growth restriction (IUGR). Neither the site nor the mediators responsible for this altered vascular reactivity are known, to date. In placentas in normal pregnancy, reduced oxygenation promotes contraction of the in vitro-perfused placental cotyledon and modulates agonist-induced contraction of chorionic plate arteries and veins. Placental oxygenation has also been suggested to be reduced in IUGR. We tested the hypothesis that oxygen tension could directly modify placental chorionic plate vessel vasoreactivity in IUGR. Small arteries and veins from the chorionic plate were dissected from biopsies from placentas of pregnancies complicated by IUGR and were studied using parallel wire myography. Vasoconstriction at 20%, 7%, and 2% oxygen was assessed utilizing the thromboxane mimetic U46619. Experiments were also performed in the presence of 4-aminopyridine (4AP), a blocker of voltage-gated potassium channels. Increased oxygenation reduced venous vasoconstriction but did not modify arterial vasoconstriction. 4AP increased basal tone in arteries and veins. We suggest that venoconstriction in response to hypoxia may provide a mechanism for increased fetoplacental vascular resistance associated with IUGR.

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

    Science.gov (United States)

    Baczyk, Dora; Kibschull, Mark; Mellstrom, Britt; Levytska, Khrystyna; Rivas, Marcos; Drewlo, Sascha; Lye, Stephen J; Naranjo, Jose R; Kingdom, John C P

    2013-01-01

    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. 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.

  1. 3D Bioprinting of Vascularized Human Tissues

    OpenAIRE

    Kolesky, David Barry

    2016-01-01

    The ability to manufacture human tissues that replicate the spatial, mechano-chemical, and temporal aspects of biological tissues would enable myriad applications, including drug screening, disease modeling, and tissue repair and regeneration. However, given the complexity of human tissues, this is a daunting challenge. Current biofabrication methods are unable to fully recapitulate the form and function of human tissues, which are composed of multiple cell types, extracellular matrices, and ...

  2. Coumestrol induces mitochondrial dysfunction by stimulating ROS production and calcium ion influx into mitochondria in human placental choriocarcinoma cells.

    Science.gov (United States)

    Lim, Whasun; Yang, Changwon; Jeong, Muhah; Bazer, Fuller W; Song, Gwonhwa

    2017-11-01

    Does coumestrol inhibit proliferation of human placental choriocarcinoma cells? Coumestrol promotes cell death in the choriocarcinoma cells by regulating ERK1/2 MAPK and JNK MAPK signaling pathways and through disruption of Ca2+ and ROS homeostasis. A number of patients who suffer from choriocarcinomas fail to survive due to delayed diagnosis or a recurrent tumor and resistance to traditional chemotherapy using platinum-based agents and methotrexate. To overcome these limitations, it is important to discover novel compounds which have no adverse effects yet can inhibit the expression of a target molecule to develop, as a novel therapeutic for prevention and/or treatment of choriocarcinomas. Effects of coumestrol on human placental choriocarcinoma cell lines, JAR and JEG3, were assessed in diverse assays in a dose- and time-dependent manner. Effects of coumestrol on cell proliferation, apoptosis (annexin V expression, propidium iodide staining, TUNEL and invasion assays), mitochondria-mediated apoptosis, production of reactive oxygen species (ROS), lipid peroxidation, glutathione levels and endoplasmic reticulum (ER) stress proteins in JAR and JEG3 cells were determined. Signal transduction pathways in JAR and JEG3 cells in response to coumestrol were determined by western blot analyses. Results of the present study indicated that coumestrol suppressed proliferation and increased apoptosis in JAR and JEG3 cells by inducing pro-apoptotic proteins, Bax and Bak. In addition, coumestrol increased ROS production, as well as lipid peroxidation and glutathione levels in JAR and JEG3 cells. Moreover, coumestrol-induced depolarization of mitochondrial membrane potential (MMP) and increased cytosolic and mitochondrial Ca2+ levels in JAR and JEG3 cells. Consistent with those results, treatment of JAR and JEG3 cells with a Ca2+ chelator and an inhibitor of IP3 receptor decreased coumestrol-induced depolarization of MMP and increased proliferation in JAR and JEG3 cells. N/A. A

  3. The effect of pH and ion channel modulators on human placental arteries.

    Directory of Open Access Journals (Sweden)

    Tayyba Y Ali

    Full Text Available Chorionic plate arteries (CPA are located at the maternofetal interface where they are able to respond to local metabolic changes. Unlike many other types of vasculature, the placenta lacks nervous control and requires autoregulation for controlling blood flow. The placental circulation, which is of low-resistance, may become hypoxic easily leading to fetal acidosis and fetal distress however the role of the ion channels in these circumstances is not well-understood. Active potassium channel conductances that are subject to local physicochemical modulation may serve as pathways through which such signals are transduced. The aim of this study was to investigate the modulation of CPA by pH and the channels implicated in these responses using wire myography. CPA were isolated from healthy placentae and pre-contracted with U46619 before testing the effects of extracellular pH using 1 M lactic acid over the pH range 7.4-6.4 in the presence of a variety of ion channel modulators. A change from pH 7.4 to 7.2 produced a 29±3% (n = 9 relaxation of CPA which increased to 61±4% at the lowest pH of 6.4. In vessels isolated from placentae of women with pre-eclampsia (n = 6, pH responses were attenuated. L-methionine increased the relaxation to 67±7% (n = 6; p<0.001 at pH 6.4. Similarly the TASK 1/3 blocker zinc chloride (1 mM gave a maximum relaxation of 72±5% (n = 8; p<0.01 which compared with the relaxation produced by the TREK-1 opener riluzole (75±5%; n = 6. Several other modulators induced no significant changes in vascular responses. Our study confirmed expression of several ion channel subtypes in CPA with our results indicating that extracellular pH within the physiological range has an important role in controlling vasodilatation in the human term placenta.

  4. Stem cell collection filter system for human placental/umbilical cord blood processing.

    Science.gov (United States)

    Yasutake, M; Sumita, M; Terashima, S; Tokushima, Y; Nitadori, Y; Takahashi, T A

    2001-02-01

    The hydroxyethyl starch method and the Top & Bottom method have been used worldwide for the volume reduction of human placental/umbilical cord blood (PCB) units. To simplify the preparation of nucleated cell (NC) concentrates, we developed a new filter device--the stem cell collection filter system (SCF SYSTEM)--which can collect mononuclear cells (MNC) at a high recovery rate. The SCF SYSTEM consisted of a filter and two bags. Multilayered polyethylene terephthalate non-wovens, coated with a hydrophilic polymer, were used as filter media. PCB units were filtered by gravity (n = 12). Red blood cells, platelets and plasma were drained into the drain bag, and the NC trapped on the filter media was collected in the recovery bag by reverse washing. Recovered cell fractions were evaluated. The volume of cell concentrate recovered was 27.4 +/- 2.2 ml (mean +/- SD, n = 12). The whole time required for processing was less than 30 min, and handling was very simple. The viability of recovered NC was 97.8 +/- 3.2%. The recovery of lymphocytes, monocytes and granulocytes was 79.5 +/- 16.9%, 79.8 +/- 20.4% and 39.0 +/- 19.5%, respectively. The recovery rate of granulocytes was significantly lower than that of monocytes and lymphocytes (P < or = 0.0001). The recovery rates of CD3+ cells, CD19+ cells and CD56+ cells were almost the same as that of MNC. The recovery rates of CD34+ cells, total colony-forming cells and long-term culture-initiating cells were 81.7 +/- 27.0% (n = 11), 80.8 +/- 27.7% (n = 12) and 75.0 +/- 18.4% (n = 2), respectively. The new filter system was shown to be efficient for PCB processing, encompassing a very simple handling procedure with a good recovery of haematopoietic progenitor cells. Hence, the SCF SYSTEM is potentially useful for the volume reduction of PCB units for cord blood banking.

  5. Disturbed Placental Imprinting in Preeclampsia Leads to Altered Expression of DLX5, a Human-Specific Early Trophoblast Marker.

    Science.gov (United States)

    Zadora, Julianna; Singh, Manvendra; Herse, Florian; Przybyl, Lukasz; Haase, Nadine; Golic, Michaela; Yung, Hong Wa; Huppertz, Berthold; Cartwright, Judith E; Whitley, Guy; Johnsen, Guro M; Levi, Giovanni; Isbruch, Annette; Schulz, Herbert; Luft, Friedrich C; Müller, Dominik N; Staff, Anne Cathrine; Hurst, Laurence D; Dechend, Ralf; Izsvák, Zsuzsanna

    2017-11-07

    Preeclampsia is a complex and common human-specific pregnancy syndrome associated with placental pathology. The human specificity provides both intellectual and methodological challenges, lacking a robust model system. Given the role of imprinted genes in human placentation and the vulnerability of imprinted genes to loss of imprinting changes, there has been extensive speculation, but no robust evidence, that imprinted genes are involved in preeclampsia. Our study aims to investigate whether disturbed imprinting contributes to preeclampsia. We first aimed to confirm that preeclampsia is a disease of the placenta by generating and analyzing genome-wide molecular data on well-characterized patient material. We performed high-throughput transcriptome analyses of multiple placenta samples from healthy controls and patients with preeclampsia. Next, we identified differentially expressed genes in preeclamptic placentas and intersected them with the list of human imprinted genes. We used bioinformatics/statistical analyses to confirm association between imprinting and preeclampsia and to predict biological processes affected in preeclampsia. Validation included epigenetic and cellular assays. In terms of human specificity, we established an in vitro invasion-differentiation trophoblast model. Our comparative phylogenetic analysis involved single-cell transcriptome data of human, macaque, and mouse preimplantation embryogenesis. We found disturbed placental imprinting in preeclampsia and revealed potential candidates, including GATA3 and DLX5 , with poorly explored imprinted status and no prior association with preeclampsia. As a result of loss of imprinting, DLX5 was upregulated in 69% of preeclamptic placentas. Levels of DLX5 correlated with classic preeclampsia markers. DLX5 is expressed in human but not in murine trophoblast. The DLX5 high phenotype resulted in reduced proliferation, increased metabolism, and endoplasmic reticulum stress-response activation in

  6. Human tissue in systems medicine.

    Science.gov (United States)

    Caie, Peter D; Schuur, Klaas; Oniscu, Anca; Mullen, Peter; Reynolds, Paul A; Harrison, David J

    2013-12-01

    Histopathology, the examination of an architecturally artefactual, two-dimensional and static image remains a potent tool allowing diagnosis and empirical expectation of prognosis. Considerable optimism exists that the advent of molecular genetic testing and other biomarker strategies will improve or even replace this ancient technology. A number of biomarkers already add considerable value for prediction of whether a treatment will work. In this short review we argue that a systems medicine approach to pathology will not seek to replace traditional pathology, but rather augment it. Systems approaches need to incorporate quantitative morphological, protein, mRNA and DNA data. A significant challenge for clinical implementation of systems pathology is how to optimize information available from tissue, which is frequently sub-optimal in quality and amount, and yet generate useful predictive models that work. The transition of histopathology to systems pathophysiology and the use of multiscale data sets usher in a new era in diagnosis, prognosis and prediction based on the analysis of human tissue. © 2013 The Authors. FEBS Journal published by John Wiley & Sons Ltd on behalf of FEBS.

  7. Comparative studies of placentation and immunology in non-human primates suggest a scenario for the evolution of deep trophoblast invasion and an explanation for human pregnancy disorders

    DEFF Research Database (Denmark)

    Carter, Anthony Michael

    2011-01-01

    Deep trophoblast invasion in the placental bed has been considered the hallmark of human pregnancy. It occurs by two routes, interstitial and endovascular, and results in transformation of the walls of the spiral arteries as they traverse the decidua and the inner third of the myometrium. Disturb......Deep trophoblast invasion in the placental bed has been considered the hallmark of human pregnancy. It occurs by two routes, interstitial and endovascular, and results in transformation of the walls of the spiral arteries as they traverse the decidua and the inner third of the myometrium....... Disturbances in this process are associated with reproductive disorders such preeclampsia. In contrast, trophoblast invasion in Old World monkeys occurs only by the endovascular route and seldom reaches the myometrium. Recently, it was shown that this pattern is maintained in gibbons, but that the human...... arrangement also occurs in chimpanzee and gorilla. There is an interesting parallel with results from placental immunology regarding the evolution of the major histocompatability complex class I antigen HLA-C and its cognate receptors. HLA-C is not present in Old World monkeys or gibbons. It emerged...

  8. Toxicokinetics of the food-toxin IQ in human placental perfusion is not affected by ABCG2 or xenobiotic metabolism

    DEFF Research Database (Denmark)

    Immonen, E; Kummu, M; Petsalo, A

    2010-01-01

    Metabolizing enzymes and transporters affect toxicokinetics of foreign compounds (e.g. drugs and carcinogens) in human placenta. The heterocyclic amine, 2-amino-3-methylimidazo[4,5-f]quinoline (IQ) is a food-borne carcinogen being metabolically activated by cytochrome P450 (CYP) enzymes, especially...... by CYP1A1/2. IQ is also a substrate for ABCG2 transporter. Placental transfer of (14)C-IQ was evaluated in 4-6 h ex vivo human placental perfusions in Finland and Denmark. In Finland placentas were perfused with (14)C-IQ alone (0.5 muM, n = 6) or in combination with GF120918 (inhibitor of ABCG2, 1 muM, n...... = 6) or Ko143 (specific inhibitor of ABCG2, 2 muM, n = 4) to study the role of ABCG2 inhibition in transfer while in Denmark perfusions were performed with (14)C-IQ alone. Critical parameters (leak from fetal to maternal circulation, pH values, blood gases, glucose consumption, the production of h...

  9. Perfluorinated chemicals: Differential toxicity, inhibition of aromatase activity and alteration of cellular lipids in human placental cells

    Energy Technology Data Exchange (ETDEWEB)

    Gorrochategui, Eva; Pérez-Albaladejo, Elisabet [Department of Environmental Chemistry, IDAEA–CSIC, 08034 Barcelona, Catalonia (Spain); Casas, Josefina [Department of Biomedicinal Chemistry, IQAC–CSIC, 08034 Barcelona, Catalonia (Spain); Lacorte, Sílvia, E-mail: slbqam@cid.csic.es [Department of Environmental Chemistry, IDAEA–CSIC, 08034 Barcelona, Catalonia (Spain); Porte, Cinta, E-mail: cinta.porte@cid.csic.es [Department of Environmental Chemistry, IDAEA–CSIC, 08034 Barcelona, Catalonia (Spain)

    2014-06-01

    The cytotoxicity of eight perfluorinated chemicals (PFCs), namely, perfluorobutanoic acid (PFBA), perfluorohexanoic acid (PFHxA), perfluorooctanoic acid (PFOA), perfluorononanoic acid (PFNA), perfluorododecanoic acid (PFDoA), perfluorobutanesulfonate (PFBS), perfluorohexanesulfonate (PFHxS) and perfluorooctanesulfonate (PFOS) was assessed in the human placental choriocarcinoma cell line JEG-3. Only the long chain PFCs – PFOS, PFDoA, PFNA, PFOA – showed significant cytotoxicity in JEG-3 cells with EC50 values in the range of 107 to 647 μM. The observed cytotoxicity was to some extent related to a higher uptake of the longer chain PFCs by cells (PFDoA > PFOS ≫ PFNA > PFOA > PFHxA). Moreover, this work evidences a high potential of PFOS, PFOA and PFBS to act as aromatase inhibitors in placental cells with IC50s in the range of 57–80 μM, the inhibitory effect of PFBS being particularly important despite the rather low uptake of the compound by cells. Finally, exposure of JEG-3 cells to a mixture of the eight PFCs (0.6 μM each) led to a relative increase (up to 3.4-fold) of several lipid classes, including phosphatidylcholines (PCs), plasmalogen PC and lyso plasmalogen PC, which suggests an interference of PFCs with membrane lipids. Overall, this work highlights the ability of the PFC mixture to alter cellular lipid pattern at concentrations well below those that generate toxicity, and the potential of the short chain PFBS, often considered a safe substitute of PFOS, to significantly inhibit aromatase activity in placental cells. - Highlights: • Eight perfluorinated chemicals of different chain lengths have been selected. • Long chain ones – PFOS, PFDoA, PFNA, PFOA – were cytotoxic in placenta cells. • The uptake of long chain perfluorinated chemicals by cells was comparatively higher. • PFOS, PFOA and the short chain PFBS significantly inhibited aromatase activity. • A mixture of perfluorinated chemicals significantly altered placenta cell

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

    Directory of Open Access Journals (Sweden)

    Alejandra Perez-Sepulveda

    Full Text Available Preeclampsia is a maternal hypertensive disorder with uncertain etiology and a leading cause of maternal and fetal mortality worldwide, causing nearly 40% of premature births delivered before 35 weeks of gestation. The first stage of preeclampsia is characterized by reduction of utero-placental blood flow which is reflected in high blood pressure and proteinuria during the second half of pregnancy. In human placenta androgens derived from the maternal and fetal adrenal glands are converted into estrogens by the enzymatic action of placental aromatase. This implies that alterations in placental steroidogenesis and, subsequently, in the functionality or bioavailability of placental aromatase may be mechanistically involved in the pathophysiology of PE.Serum samples were collected at 32-36 weeks of gestation and placenta biopsies were collected at time of delivery from PE patients (n = 16 and pregnant controls (n = 32. The effect of oxygen tension on placental cells was assessed by incubation JEG-3 cells under 1% and 8% O2 for different time periods, Timed-mated, pregnant New Zealand white rabbits (n = 6 were used to establish an in vivo model of placental ischemia (achieved by ligature of uteroplacental vessels. Aromatase content and estrogens and androgens concentrations were measured.The protein and mRNA content of placental aromatase significantly diminished in placentae obtained from preeclamptic patients compared to controls. Similarly, the circulating concentrations of 17-β-estradiol/testosterone and estrone/androstenedione were reduced in preeclamptic patients vs. controls. These data are consistent with a concomitant decrease in aromatase activity. Aromatase content was reduced in response to low oxygen tension in the choriocarcinoma JEG-3 cell line and in rabbit placentae in response to partial ligation of uterine spiral arteries, suggesting that reduced placental aromatase activity in preeclamptic patients may be associated with chronic

  11. Punicalagin, a polyphenol in pomegranate juice, downregulates p53 and attenuates hypoxia-induced apoptosis in cultured human placental syncytiotrophoblasts.

    Science.gov (United States)

    Chen, Baosheng; Longtine, Mark S; Nelson, D Michael

    2013-11-15

    Oxidative stress is associated with placental dysfunction and suboptimal pregnancy outcomes. Therapeutic interventions to limit placental injury from oxidative stress are lacking. Punicalagin is an ellagitannin and a potent antioxidant in pomegranate juice. We showed that both pomegranate juice and punicalagin decrease oxidative stress and apoptosis in cultured syncytiotrophoblasts. p53 is involved in the oxidative stress-induced apoptosis in trophoblasts. We now test the hypothesis that punicalagin limits trophoblast injury in vitro by regulating the levels of p53. We examined the expression of p53, mouse double minute 2 homolog, p21, hypoxia-inducible factor (HIF) α, and selected members of the B cell lymphoma 2 (BCL2) family of proteins in cultured syncytiotrophoblasts exposed to ≤1% oxygen in the absence or presence of punicalagin. We found that punicalagin attenuated hypoxia-induced apoptosis in syncytiotrophoblasts, as quantified by levels of cleaved poly-ADP ribose polymerase. This protective effect was in part mediated by reduced p53 activity shown by decreased expression of p21, lower HIF1α expression, and limited activity of caspases 9 and 3. There was no change in expression of proteins in the BCL2 family, which are also important in apoptosis. The data support a role for downregulation of p53 in the protection of human trophoblasts by punicalagin.

  12. Microbiota of human breast tissue

    National Research Council Canada - National Science Library

    Urbaniak, Camilla; Cummins, Joanne; Brackstone, Muriel; Macklaim, Jean M; Gloor, Gregory B; Baban, Chwanrow K; Scott, Leslie; O'Hanlon, Deidre M; Burton, Jeremy P; Francis, Kevin P; Tangney, Mark; Reid, Gregor

    2014-01-01

    .... We decided to investigate whether there is a microbiome within the mammary tissue. Using 16S rRNA sequencing and culture, we analyzed breast tissue from 81 women with and without cancer in Canada and Ireland...

  13. Placental Origins of Adverse Pregnancy Outcomes: Potential Molecular Targets- An Executive Workshop Summary of the Eunice Kennedy Shriver National Institute of Child Health and Human Development

    Science.gov (United States)

    Ilekis, John V.; Tsilou, Ekaterini; Fisher, Susan; Abrahams, Vikki M.; Soares, Michael J.; Cross, James C.; Zamudio, Stacy; Illsley, Nicholas P.; Myatt, Leslie; Colvis, Christine; Costantine, Maged M.; Haas, David M.; Sadovsky, Yoel; Weiner, Carl; Rytting, Erik; Bidwell, Gene

    2016-01-01

    Although much progress is being made in understanding the molecular pathways in the placenta involved in the pathophysiology of pregnancy related disorders, a significant gap exists in utilizing this information for developing new drug therapies to improve pregnancy outcome. On March 5–6, 2015, the Eunice Kennedy Shriver National Institute of Child Health and Human Development of the National Institutes of Health sponsored a two day workshop titled Placental Origins of Adverse Pregnancy Outcomes: Potential Molecular Targets to begin to address this gap. Particular emphasis was given in the identification of important molecular pathways that could serve as drug targets and the advantages and disadvantages of targeting these particular pathways. This article is a summary of the proceedings of this workshop. A broad number of topics were covered ranging from basic placental biology to clinical trials. This included research in the basic biology of placentation, such as trophoblast migration and spiral artery remodeling, and trophoblast sensing and response to infectious and non-infectious agents. Research findings in these areas will be critical for formulating developing future treatments and developing therapies for the prevention of a number of pregnancy disorders of placental origin including preeclampsia, fetal growth restriction, and uterine inflammation. Research was also presented summarizing ongoing clinical efforts in the U.S. and in Europe testing novel interventions for preeclampsia and fetal growth restriction, including agents such as oral arginine supplementation, sildenafil, pravastatin, gene therapy using virally-delivered vascular endothelial growth factor, and oxygen supplementation therapy. Strategies were also proposed to improve fetal growth by enhancing nutrient transport to the fetus by modulating their placental transporters, as well as targeting placental mitochondrial dysfunction and oxidative stress to improve placental health. The roles

  14. Placental and serum levels of carotenoids in preeclampsia.

    Science.gov (United States)

    Palan, P R; Mikhail, M S; Romney, S L

    2001-09-01

    We compared placental tissue, maternal serum, and umbilical cord venous blood levels of four dietary carotenoids (alpha-carotene, beta-carotene, lycopene, and canthaxanthin) in normal pregnant women and those with preeclampsia. Levels of alpha-carotene, beta-carotene, lycopene, and canthaxanthin were measured in placental tissue, maternal serum, and umbilical cord venous blood from 22 normal pregnant women and 19 women with preeclampsia. The criteria for recruitment included gestational age of 30-42 weeks, singleton pregnancy, intact membranes, absence of labor contractions, and absence of any other medical complication concurrent with preeclampsia. Carotenoids were measured using high-pressure liquid chromatography. All four carotenoids were detectable in human placental tissue, maternal serum, and umbilical cord venous blood samples. The levels of beta-carotene, lycopene, and canthaxanthin in placentas from preeclamptic women were significantly lower (P =.032, .009, and .013, respectively, by Mann-Whitney test) than those from normal pregnant women. Maternal serum levels of beta-carotene and lycopene were significantly lower (P =.004 and .008, respectively, by Mann-Whitney test) in women with preeclampsia. However, umbilical cord venous blood levels of these carotenoids were not significantly different between the two groups. Lower placental tissue and maternal serum carotenoid levels in women with preeclampsia suggest that oxidative stress or a dietary antioxidant influence might have an effect on the pathophysiology of preeclampsia.

  15. Transcriptome analysis of PPARγ target genes reveals the involvement of lysyl oxidase in human placental cytotrophoblast invasion.

    Science.gov (United States)

    Segond, Nadine; Degrelle, Séverine A; Berndt, Sarah; Clouqueur, Elodie; Rouault, Christine; Saubamea, Bruno; Dessen, Philippe; Fong, Keith S K; Csiszar, Katalin; Badet, Josette; Evain-Brion, Danièle; Fournier, Thierry

    2013-01-01

    Human placental development is characterized by invasion of extravillous cytotrophoblasts (EVCTs) into the uterine wall during the first trimester of pregnancy. Peroxisome proliferator-activated receptor γ (PPARγ) plays a major role in placental development, and activation of PPARγ by its agonists results in inhibition of EVCT invasion in vitro. To identify PPARγ target genes, microarray analysis was performed using GeneChip technology on EVCT primary cultures obtained from first-trimester human placentas. Gene expression was compared in EVCTs treated with the PPARγ agonist rosiglitazone versus control. A total of 139 differentially regulated genes were identified, and changes in the expression of the following 8 genes were confirmed by reverse transcription-quantitative polymerase chain reaction: a disintegrin and metalloproteinase domain12 (ADAM12), connexin 43 (CX43), deleted in liver cancer 1 (DLC1), dipeptidyl peptidase 4 (DPP4), heme oxygenase 1 (HMOX-1), lysyl oxidase (LOX), plasminogen activator inhibitor 1 (PAI-1) and PPARγ. Among the upregulated genes, lysyl oxidase (LOX) was further analyzed. In the LOX family, only LOX, LOXL1 and LOXL2 mRNA expression was significantly upregulated in rosiglitazone-treated EVCTs. RNA and protein expression of the subfamily members LOX, LOXL1 and LOXL2 were analyzed by absolute RT-qPCR and western blotting, and localized by immunohistochemistry and immunofluorescence-confocal microscopy. LOX protein was immunodetected in the EVCT cytoplasm, while LOXL1 was found in the nucleus and nucleolus. No signal was detected for LOXL2 protein. Specific inhibition of LOX activity by β-aminopropionitrile in cell invasion assays led to an increase in EVCT invasiveness. These results suggest that LOX, LOXL1 and LOXL2 are downstream PPARγ targets and that LOX activity is a negative regulator of trophoblastic cell invasion.

  16. Transcriptome analysis of PPARγ target genes reveals the involvement of lysyl oxidase in human placental cytotrophoblast invasion.

    Directory of Open Access Journals (Sweden)

    Nadine Segond

    Full Text Available Human placental development is characterized by invasion of extravillous cytotrophoblasts (EVCTs into the uterine wall during the first trimester of pregnancy. Peroxisome proliferator-activated receptor γ (PPARγ plays a major role in placental development, and activation of PPARγ by its agonists results in inhibition of EVCT invasion in vitro. To identify PPARγ target genes, microarray analysis was performed using GeneChip technology on EVCT primary cultures obtained from first-trimester human placentas. Gene expression was compared in EVCTs treated with the PPARγ agonist rosiglitazone versus control. A total of 139 differentially regulated genes were identified, and changes in the expression of the following 8 genes were confirmed by reverse transcription-quantitative polymerase chain reaction: a disintegrin and metalloproteinase domain12 (ADAM12, connexin 43 (CX43, deleted in liver cancer 1 (DLC1, dipeptidyl peptidase 4 (DPP4, heme oxygenase 1 (HMOX-1, lysyl oxidase (LOX, plasminogen activator inhibitor 1 (PAI-1 and PPARγ. Among the upregulated genes, lysyl oxidase (LOX was further analyzed. In the LOX family, only LOX, LOXL1 and LOXL2 mRNA expression was significantly upregulated in rosiglitazone-treated EVCTs. RNA and protein expression of the subfamily members LOX, LOXL1 and LOXL2 were analyzed by absolute RT-qPCR and western blotting, and localized by immunohistochemistry and immunofluorescence-confocal microscopy. LOX protein was immunodetected in the EVCT cytoplasm, while LOXL1 was found in the nucleus and nucleolus. No signal was detected for LOXL2 protein. Specific inhibition of LOX activity by β-aminopropionitrile in cell invasion assays led to an increase in EVCT invasiveness. These results suggest that LOX, LOXL1 and LOXL2 are downstream PPARγ targets and that LOX activity is a negative regulator of trophoblastic cell invasion.

  17. Cryobanking of human ovarian tissue

    DEFF Research Database (Denmark)

    Macklon, Kirsten Tryde; Ernst, Erik; Andersen, Anders Nyboe

    2014-01-01

    Cryopreservation of ovarian tissue is one way of preserving fertility in young women with a malignant disease or other disorders that require gonadotoxic treatment. The purpose of the study was to explore how many women remained interested in continued cryostorage of their ovarian tissue beyond a...... women with ovarian tissue cryobanked requested continued cryostorage after an initial period of at least 5 years. The main reason for requesting disposal was successful completion of a family.......Cryopreservation of ovarian tissue is one way of preserving fertility in young women with a malignant disease or other disorders that require gonadotoxic treatment. The purpose of the study was to explore how many women remained interested in continued cryostorage of their ovarian tissue beyond...... an initial 5-year period. Between 1999 and 2006, a total of 201 girls and young women had one ovary cryopreserved for fertility preservation in Denmark. One hundred of these met our inclusion criteria, which included a follow-up period of at least 5 years, and were mailed a questionnaire. The response rate...

  18. Effect of human placental extract in the management of biofilm mediated drug resistance - A focus on wound management.

    Science.gov (United States)

    Goswami, Sutapa; Sarkar, Ratul; Saha, Pritam; Maity, Amit; Sarkar, Tridib; Das, Debmalya; Chakraborty, Piyali Datta; Bandyopadhyay, Subhasri; Ghosh, Chandan Kumar; Karmakar, Sanmoy; Sen, Tuhinadri

    2017-10-01

    Management of infectious wounds, particularly chronic wounds and burn injuries, is a matter of global concern. Worldwide estimates reveal that, billions of dollars are being spent annually for the management of such chronic ailments. Evidently, bacterial biofilms pose a greater problem in the effective management of infection in chronic wounds, since most of the currently available antibiotics are unable to act on the microorganisms residing inside the protected environment of the biofilms. Accordingly, in the present study, we have attempted to evaluate the anti-biofilm properties of human placental extract (PLX) and also other virulence factors that are mediated via the quorum sensing (QS) signalling system. PLX is well known for its anti inflammatory action and it has been shown earlier some anti microbial and enzymatic activity also. PLX was found to produce significant inhibition of biofilm formation and also decreased the levels of pyoverdin and pyocyanin. The microscopic analysis (both light microscopy and atomic force microscopy) of biofilms was also used for substantiating the findings from spectrophotometric (crystal violet estimation) and fluorescence analysis (resazurin uptake). PLX pre-treatment decreased the hydrophobicity of gram-positive and gram negative cells, indicating the effect of placental extract on adherence property of planktonic cell, serving as an indicator for its antibiofilm effect on microorganisms. The reduced extracellular DNA (eDNA) content in biofilm matrix following treatment with PLX also indicates the effectiveness of placenta extract on bacterial adherence, which in turn serves as evidence substantiating the antibiofilm effects of the PLX. Furthermore, PLX was also found to be significantly effective in the in vitro wound biofilm model. Thus the present study, the first of its kind with PLX, establishes the therapeutic benefit of the same particularly in infected wounds, opening up newer avenue for further exploration

  19. Grating-based tomography of human tissues

    Science.gov (United States)

    Müller, Bert; Schulz, Georg; Mehlin, Andrea; Herzen, Julia; Lang, Sabrina; Holme, Margaret; Zanette, Irene; Hieber, Simone; Deyhle, Hans; Beckmann, Felix; Pfeiffer, Franz; Weitkamp, Timm

    2012-07-01

    The development of therapies to improve our health requires a detailed knowledge on the anatomy of soft tissues from the human body down to the cellular level. Grating-based phase contrast micro computed tomography using synchrotron radiation provides a sensitivity, which allows visualizing micrometer size anatomical features in soft tissue without applying any contrast agent. We show phase contrast tomography data of human brain, tumor vessels and constricted arteries from the beamline ID 19 (ESRF) and urethral tissue from the beamline W2 (HASYLAB/DESY) with micrometer resolution. Here, we demonstrate that anatomical features can be identified within brain tissue as well known from histology. Using human urethral tissue, the application of two photon energies is compared. Tumor vessels thicker than 20 μm can be perfectly segmented. The morphology of coronary arteries can be better extracted in formalin than after paraffin embedding.

  20. Zika Virus Infects Early- and Midgestation Human Maternal Decidual Tissues, Inducing Distinct Innate Tissue Responses in the Maternal-Fetal Interface.

    Science.gov (United States)

    Weisblum, Yiska; Oiknine-Djian, Esther; Vorontsov, Olesya M; Haimov-Kochman, Ronit; Zakay-Rones, Zichria; Meir, Karen; Shveiky, David; Elgavish, Sharona; Nevo, Yuval; Roseman, Moshe; Bronstein, Michal; Stockheim, David; From, Ido; Eisenberg, Iris; Lewkowicz, Aya A; Yagel, Simcha; Panet, Amos; Wolf, Dana G

    2017-02-15

    Zika virus (ZIKV) has emerged as a cause of congenital brain anomalies and a range of placenta-related abnormalities, highlighting the need to unveil the modes of maternal-fetal transmission. The most likely route of vertical ZIKV transmission is via the placenta. The earliest events of ZIKV transmission in the maternal decidua, representing the maternal uterine aspect of the chimeric placenta, have remained unexplored. Here, we show that ZIKV replicates in first-trimester human maternal-decidual tissues grown ex vivo as three-dimensional (3D) organ cultures. An efficient viral spread in the decidual tissues was demonstrated by the rapid upsurge and continued increase of tissue-associated ZIKV load and titers of infectious cell-free virus progeny, released from the infected tissues. Notably, maternal decidual tissues obtained at midgestation remained similarly susceptible to ZIKV, whereas fetus-derived chorionic villi demonstrated reduced ZIKV replication with increasing gestational age. A genome-wide transcriptome analysis revealed that ZIKV substantially upregulated the decidual tissue innate immune responses. Further comparison of the innate tissue response patterns following parallel infections with ZIKV and human cytomegalovirus (HCMV) revealed that unlike HCMV, ZIKV did not induce immune cell activation or trafficking responses in the maternal-fetal interface but rather upregulated placental apoptosis and cell death molecular functions. The data identify the maternal uterine aspect of the human placenta as a likely site of ZIKV transmission to the fetus and further reveal distinct patterns of innate tissue responses to ZIKV. Our unique experimental model and findings could further serve to study the initial stages of congenital ZIKV transmission and pathogenesis and evaluate the effect of new therapeutic interventions. In view of the rapid spread of the current ZIKV epidemic and the severe manifestations of congenital ZIKV infection, it is crucial to learn

  1. A performance evaluation of a novel human recombinant tissue factor prothrombin time reagent (Revohem™ PT).

    Science.gov (United States)

    Gardiner, C; Kohama, K; Patel, I; Lane, P; Dwyer, S; Machin, S J; Mackie, I J

    2017-10-01

    A new prothrombin time reagent (Revohem™ PT) based on recombinant human tissue factor produced by the silkworm-baculovirus expression system was tested. The aim of this study was to compare the performance of the new PT reagent with two widely used routine PT reagents. All testing was performed on a Sysmex CS-5100 coagulometer. Revohem™ PT was tested for imprecision and stability using normal and abnormal lyophilized commercial control plasmas. Comparability was assessed with two widely used reagents: one containing recombinant human tissue factor (Reagent A) and the other a human placental thromboplastin (Reagent B) using a wide range of normal and abnormal plasmas and analyser-specific ISI values. Excellent between-day imprecision was obtained for Revohem™ PT (CV <1.0%) and acceptable open-vial on-board stability over 7 days. There was good agreement between methods in samples from patients with liver disease and patients receiving warfarin and no significant differences between methods with increasing INR values. Both recombinant reagents suffered less interference from lupus anticoagulant than the placental thromboplastin. Revohem™ PT had similar sensitivity to reagents A and B for FII, V, VII and X deficiency and demonstrated dose responsiveness to dabigatran, apixaban and rivaroxaban with steeper response curves than the comparison reagents. Revohem™ PT showed comparable or improved performance relative to two widely used reagents and is suitable for use in warfarin control, detection of inherited factor II, V, VII and X deficiency and assessment of liver disease coagulopathy. © 2017 John Wiley & Sons Ltd.

  2. NCI’s Cooperative Human Tissue Network

    Science.gov (United States)

    Quality biospecimens are a foundational resource for cancer research. One of NCI’s longest running biospecimen programs is the Cooperative Human Tissue Network, a resource mainly for basic discovery and early translational research.

  3. Melanin content of hamster tissues, human tissues, and various melanomas

    Energy Technology Data Exchange (ETDEWEB)

    Watts, K.P.; Fairchild, R.G.; Slatkin, D.N.; Greenberg, D.; Packer, S.; Atkins, H.L.; Hannon, S.J.

    1981-02-01

    Melanin content (percentage by weight) was determined in both pigmented and nonpigmented tissues of Syrian golden hamsters bearing Greene melanoma. Melanin content was also measured in various other melanoma models (B-16 in C57 mice, Harding-Passey in BALB/c mice, and KHDD in C3H mice) and in nine human melanomas, as well as in selected normal tissues. The purpose was to evaluate the possible efficacy of chlorpromazine, which is known to bind to melanin, as a vehicle for boron transport in neutron capture therapy. Successful therapy would depend upon selective uptake and absolute concentration of borated compounds in tumors; these parameters will in turn depend upon melanin concentration in melanomas and nonpigmented ''background'' tissues. Hamster whole eyes, hamster melanomas, and other well-pigmented animal melanomas were found to contain 0.3 to 0.8% melanin by weight, whereas human melanomas varied from 0.1 to 0.9% (average, 0.35%). Other tissues, with the exception of skin, were lower in content by a factor of greater than or equal to30. Melanin pigment was extracted from tissues, and the melanin content was determined spectrophotometrically. Measurements were found to be sensitive to the presence of other proteins. Previous procedures for isolating and quantifying melanin often neglected the importance of removing proteins and other interfering nonmelanic substances.

  4. The placental transfer of erythromycin in human pregnancies with group B streptococcal infection.

    Science.gov (United States)

    Bulska, Magdalena; Szcześniak, Piotr; Pięta-Dolińska, Agnieszka; Oszukowski, Przemysław; Orszulak-Michalak, Daria

    2015-01-01

    The aim of this study was to investigate the effectiveness of erythromycin in preventing fetal and intrauterine group B streptococcal (GBS) infections. The study evaluated the penetration of erythromycin through the placenta, by comparing umbilical vein and maternal serum erythromycin concentrations. The study subjects were 42 pregnant women, with GBS-positive screening or whose laboratory screening was not available, who delivered between 17th April 2013 and 22nd July 2013. The women were given 600 mg of erythromycin intravenously. After delivery blood was drawn from the mother's antecubital vein and umbilical cord vein. Serum erythromycin concentrations were evaluated using enzyme-linked immunosorbent assay (ELISA) kit. The percentage and correlation between umbilical vein and maternal serum erythromycin concentration were calculated. Based on regression function parameters selected factors: maternal age, maternal body weight, gestational age at delivery related to the umbilical vein serum erythromycin concentration, were investigated. Results: A total of 42 umbilical vein-maternal serum pairs were included in the analysis. The mean umbilical vein-maternal serum erythromycin concentration percentage was 2.64 ± 1.55%. There was a moderate correlation between umbilical vein serum and maternal serum erythromycin concentration. Pregnancy complications and selected variables of mothers in control group had no effect on the serum erythromycin concentration in the umbilical vein. Intravenous application of erythromycin at a dose of 600 mg, allowed to achieve therapeutic concentration in maternal serum. However, when it comes to placental transfer of erythromycin, the lack of therapeutic concentration in umbilical vein serum was observed. The limited transplacental transfer of erythromycin, which was approximately 2.6%, suggests compromised efficacy in the treatment of intrauterine fetal infections. On the other hand, the placenta seems to produce an effective barrier

  5. Interleukin-11 alters placentation and causes preeclampsia features in mice.

    Science.gov (United States)

    Winship, Amy L; Koga, Kaori; Menkhorst, Ellen; Van Sinderen, Michelle; Rainczuk, Katarzyna; Nagai, Miwako; Cuman, Carly; Yap, Joanne; Zhang, Jian-Guo; Simmons, David; Young, Morag J; Dimitriadis, Evdokia

    2015-12-29

    Preeclampsia (PE) is a pregnancy-specific disorder characterized by hypertension and proteinuria after 20 wk gestation. Abnormal extravillous trophoblast (EVT) invasion and remodeling of uterine spiral arterioles is thought to contribute to PE development. Interleukin-11 (IL11) impedes human EVT invasion in vitro and is elevated in PE decidua in women. We demonstrate that IL11 administered to mice causes development of PE features. Immunohistochemistry shows IL11 compromises trophoblast invasion, spiral artery remodeling, and placentation, leading to increased systolic blood pressure (SBP), proteinuria, and intrauterine growth restriction, although nonpregnant mice were unaffected. Real-time PCR array analysis identified pregnancy-associated plasma protein A2 (PAPPA2), associated with PE in women, as an IL11 regulated target. IL11 increased PAPPA2 serum and placental tissue levels in mice. In vitro, IL11 compromised primary human EVT invasion, whereas siRNA knockdown of PAPPA2 alleviated the effect. Genes regulating uterine natural killer (uNK) recruitment and differentiation were down-regulated and uNK cells were reduced after IL11 treatment in mice. IL11 withdrawal in mice at onset of PE features reduced SBP and proteinuria to control levels and alleviated placental labyrinth defects. In women, placental IL11 immunostaining levels increased in PE pregnancies and in serum collected from women before development of early-onset PE, shown by ELISA. These results indicate that elevated IL11 levels result in physiological changes at the maternal-fetal interface, contribute to abnormal placentation, and lead to the development of PE. Targeting placental IL11 may provide a new treatment option for PE.

  6. Placental villous stroma as a model system for myofibroblast differentiation.

    Science.gov (United States)

    Kohnen, G; Kertschanska, S; Demir, R; Kaufmann, P

    1996-06-01

    Different subtypes of myofibroblasts have been described according to their cytoskeletal protein patterns. It is quite likely that these different subtypes represent distinct steps of differentiation. We propose the human placental stem villi as a particularly suitable model to study this differentiation process. During the course of pregnancy, different types of placental villi develop by differentiation of the mesenchymal stroma surrounding the fetal blood vessels. In order to characterise the differentiation of placental stromal cells in the human placenta, the expression patterns of the cytoskeletal proteins vimentin, desmin, alpha- and gamma-smooth muscle actin, pan-actin, smooth muscle myosin, and the monoclonal antibody GB 42, a marker of myofibroblasts, were investigated on placental tissue of different gestational age (7th-40th week of gestation). Proliferation patterns were assessed with the proliferation markers MIB 1 and PCNA. Additionally, dipeptidyl peptidase IV distribution was studied in term placenta and the ultrastructure of placental stromal cells was assessed by electron microscopy. Different subpopulations of extravascular stromal cells were distinguished according to typical co-expression patterns of cytoskeletal proteins. Around the fetal stem vessels in term placental villi they were arranged as concentric layers with increasing stage of differentiation. A variable layer of extravascular stromal cells lying beneath the trophoblast expressed vimentin (V) or vimentin and desmin (VD). They were mitotically active. The next layer co-expressed vimentin, desmin, and alpha-smooth muscle actin (VDA). More centrally towards the fetal vessels, extravascular stromal cells co-expressed vimentin, desmin, alpha- and gamma-smooth muscle actin, and GB 42 (VDAG). Cells close to the fetal vessels additionally co-expressed smooth muscle myosin (VDAGM). Ultrastructurally, V cells resembled typical mesenchymal cells. VD cells corresponded to fibroblasts, while

  7. [BAME-Esterase activity in plasmas from blood of human placental interveillous space and umbilical cord vessels (author's transl)].

    Science.gov (United States)

    Matheus, M; Salles Meirelles, R

    1976-01-01

    The authors studied an enzymatic activity (BAME-esterase) from human plasma, intimately related with the bradykinin release mechanisms. The optimal conditions of evaluation of the different plasmas were determined. Lately, the authors showed the results obtained with plasma from maternal peripheral blood, umbilical vessels blood and human placental intervillous space blood. It was concluded: 1. The study of enzymatic kinetics allows to establish a reaction time of 30 minutes, and the enzymatic concentration contained within 0.5 ml. of plasma, as ideal parameters to determine the enzymatic activities into the different compartments. 2. In the cases studied, considered clinically normals, the enzymatic activity in plasma from the interveillous space, before and after the detachment of the placenta, was greater than in peripheral maternal and umbilical vessels bloods. The activity in umbilical artery plasma was greater than in umbilical vein and practically the same as in maternal plasma. 3. The esterase activity values into the compartments studied in pre-eclamptics, were similar to that found in the cases considered clinically normal.

  8. The anti-aging properties of a human placental hydrolysate combined with dieckol isolated from Ecklonia cava.

    Science.gov (United States)

    Jang, Su Kil; Lee, Do Ik; Kim, Seung Tae; Kim, Gwang Hoon; Park, Da Woon; Park, Jung Youl; Han, Daehee; Choi, Jae Kwon; Lee, Yoon-bok; Han, Nam-Soo; Kim, Yun Bae; Han, Jeongsu; Joo, Seong Soo

    2015-10-05

    In the present study, we aimed to examine the anti-aging properties of human placental hydrolysate (HPE) and dieckol (DE) from Ecklonia cava against free radical scavenging, muscle hypertrophy-related follistatin mRNA expression, amelioration of cognition-related genes and proteins, inhibition of collagenase-regulating genes, and elastinase activity. The anti-aging effects were examined in human fibroblast (CCD986sk), mouse myoblast (C2C12), and neuroblastoma (N2a) cell models, by employing various assays such as 2,2-diphenyl-1-picrylhydrazyl hydrate (DPPH) scavenging, hydroxyl radical-mediated oxidation, quantitative real-time polymerase chain reaction, enzyme activity, and immunocytochemistry observation. Our results show that HPE combined with DE (HPE:DE) strongly scavenged DPPH radicals and protected proteins against degradation by hydroxyl radical attack. HPE:DE effectively inhibited matrix metalloproteinase-1 expression, protein kinase C alpha expression, and elastinase activity. Furthermore, HPE:DE improved the expression of cognition-related genes (choline acetyltransferase and vesicular acetylcholine transporter). These events may proactively contribute to retard the aging processes and the abrupt physiological changes probably induced by mitochondrial dysfunction with aging. Based on these findings, we conclude that the combined treatment of HPE:DE may be useful for anti-aging therapy in which the accumulation of oxidative damage is the main driving force.

  9. Induction of human cytochrome P450 3A enzymes in cultured placental cells by thalidomide and relevance to bioactivation and toxicity.

    Science.gov (United States)

    Murayama, Norie; Kazuki, Yasuhiro; Satoh, Daisuke; Arata, Kazuya; Harada, Tasuku; Shibata, Norio; Guengerich, F Peter; Yamazaki, Hiroshi

    2017-01-01

    Evidence has been presented for auto-induced human cytochrome P450 3A enzyme involvement in the teratogenicity and clinical outcome of thalidomide due to oxidation to 5-hydroxythalidomide and subsequent metabolic activation in livers. In this study, more relevant human placenta preparations and placental BeWo cells showed low but detectable P450 3A4/5 mRNA expression and drug oxidation activities. Human placental microsomal fractions from three subjects showed detectable midazolam 1´- and 4-hydroxylation and thalidomide 5-hydroxylation activities. Human placental BeWo cells, cultured in the recommended media, also indicated detectable midazolam 1´- and 4-hydroxylation and thalidomide 5-hydroxylation activities. To reduce any masking effects by endogenous hormones used in the recommended media, induction of P450 3A4/5 mRNA and oxidation activities were measured in placental BeWo cells cultured with a modified medium containing 5% charcoal-stripped fetal bovine serum. Thalidomide significantly induced P450 3A4/5, 2B6, and pregnane X receptor (PXR) mRNA levels 2 to 3-fold, but rifampicin only enhanced P450 3A5 and PXR mRNA under the modified media conditions. Under these modified conditions, thalidomide also significantly induced midazolam 1´-hydroxylation and thalidomide 5-hydroxylaion activities 3-fold but not bupropion hydroxylation activity. Taken together, activation of thalidomide to 5-hydroxythalidomide with autoinduction of P450 3A enzymes in human placentas, as well as livers, is suggested in vivo.

  10. Placental growth factor reduces blood pressure in a uteroplacental ischemia model of preeclampsia in non-human primates

    Science.gov (United States)

    Makris, Angela; Yeung, Kristen R; Lim, Shirlene M; Sunderland, Neroli; Heffernan, Scott; Thompson, John F; Iliopoulos, Jim; Killingsworth, Murray C; Yong, Jim; Xu, Bei; Ogle, Robert F; Thadhani, Ravi; Karumanchi, S. Ananth; Hennessy, Annemarie

    2016-01-01

    An imbalance in the angiogenesis axis during pregnancy manifests as clinical preeclampsia due to endothelial dysfunction. Circulating sFLT-1 (soluble fms-like tyrosine kinase 1) increases and PlGF (placental growth factor) reduces prior to and during disease. We investigated the clinical and biochemical effects of replenishing the reduced circulating PlGF with recombinant human PlGF (rhPlGF) and thus restoring the angiogenic balance. Hypertensive proteinuria was induced in a non-human primate (Papio hamadryas) by uterine artery ligation at 136 days gestation (of an 182 day pregnancy). Two weeks after uteroplacental ischemia (UPI), rhPlGF (rhPlGF, n=3) or normal saline (control, n=4) was administered by subcutaneous injection (100μg/kg/day) for 5 days. Blood pressure (BP) was monitored by intra-arterial radiotelemetry, sFLT-1 and PlGF by ELISA. UPI resulted in experimental preeclampsia evidenced by increased BP, proteinuria and endotheliosis on renal biopsy and elevated sFLT-1. PlGF significantly reduced after UPI. rhPlGF reduced SBP in the treated group (-5.2mmHg+0.8mmHg;from 132.6+6.6mmHg to 124.1+7.6mmHg) compared to an increase in SBP in controls (6.5mmHg+3mmHg; from 131.3+1.5mmHg to 138.6+1.5mmHg). Proteinuria reduced in the treated group (-72.7±55.7mg/mmol) but increased in the control group. Circulating sFLT-1 was not affected by the administration of PlGF, however a reduction in placental sFLT-1 mRNA expression was demonstrated. There was no significant difference in the weights or lengths of the neonates in the rhPlGF or control group, however, this study was not designed to assess fetal safety or outcomes. Increasing circulating PlGF by the administration of rhPlGF improves clinical parameters in a primate animal model of experimental preeclampsia. PMID:27091894

  11. Clonality evaluation in human tissues

    Directory of Open Access Journals (Sweden)

    Villamizar-Rivera, Nicolás

    2015-07-01

    Full Text Available Malignant proliferations are usually clonal. While most times the biological potential can be established through routine pathologic and clinical examinations, some cases are difficult to classify. Moreover, in some situations there are dominant clones whose analysis is important, such as in autoimmune diseases and immunodeficiency. This paper presents in an understandable way the main techniques for the study of clonality, namely: evaluation of gene rearrangements of antigen receptor, and evaluation of human antigen receptor gene.

  12. CCAAT-enhancer-binding Protein β (C/EBPβ) and Downstream Human Placental Growth Hormone Genes Are Targets for Dysregulation in Pregnancies Complicated by Maternal Obesity*

    Science.gov (United States)

    Vakili, Hana; Jin, Yan; Menticoglou, Savas; Cattini, Peter A.

    2013-01-01

    Human chorionic somatomammotropin (CS) and placental growth hormone variant (GH-V) act as metabolic adaptors in response to maternal insulin resistance, which occurs in “normal” pregnancy. Maternal obesity can exacerbate this “resistance,” suggesting that CS, GH-V, or transcription factors that regulate their production might be targets. The human CS genes, hCS-A and hCS-B, flank the GH-V gene. A significant decrease in pre-term placental CS/GH-V RNA levels was observed in transgenic mice containing the CS/GH-V genes in a model of high fat diet (HFD)-induced maternal obesity. Similarly, a decrease in CS/GH-V RNA levels was detected in term placentas from obese (body mass index (BMI) ≥ 35 kg/m2) versus lean (BMI 20–25 kg/m2) women. A specific decrease in transcription factor CCAAT-enhancer-binding protein β (C/EBPβ) RNA levels was also seen with obesity; C/EBPβ is required for mouse placenta development and is expressed, like CS and GH-V, in syncytiotrophoblasts. Binding of C/EBPβ to the CS gene downstream enhancer regions, which by virtue of their position distally flank the GH-V gene, was reduced in placenta chromatin from mice on a HFD and in obese women; a corresponding decrease in RNA polymerase II associated with CS/GH-V promoters was also observed. Detection of decreased endogenous CS/GH-V RNA levels in human placental tumor cells treated with C/EBPβ siRNA is consistent with a direct effect. These data provide evidence for CS/GH-V dysregulation in acute HFD-induced obesity in mouse pregnancy and chronic obesity in human pregnancy and implicate C/EBPβ, a factor associated with CS regulation and placental development. PMID:23782703

  13. CCAAT-enhancer-binding protein β (C/EBPβ) and downstream human placental growth hormone genes are targets for dysregulation in pregnancies complicated by maternal obesity.

    Science.gov (United States)

    Vakili, Hana; Jin, Yan; Menticoglou, Savas; Cattini, Peter A

    2013-08-02

    Human chorionic somatomammotropin (CS) and placental growth hormone variant (GH-V) act as metabolic adaptors in response to maternal insulin resistance, which occurs in "normal" pregnancy. Maternal obesity can exacerbate this "resistance," suggesting that CS, GH-V, or transcription factors that regulate their production might be targets. The human CS genes, hCS-A and hCS-B, flank the GH-V gene. A significant decrease in pre-term placental CS/GH-V RNA levels was observed in transgenic mice containing the CS/GH-V genes in a model of high fat diet (HFD)-induced maternal obesity. Similarly, a decrease in CS/GH-V RNA levels was detected in term placentas from obese (body mass index (BMI) ≥ 35 kg/m(2)) versus lean (BMI 20-25 kg/m(2)) women. A specific decrease in transcription factor CCAAT-enhancer-binding protein β (C/EBPβ) RNA levels was also seen with obesity; C/EBPβ is required for mouse placenta development and is expressed, like CS and GH-V, in syncytiotrophoblasts. Binding of C/EBPβ to the CS gene downstream enhancer regions, which by virtue of their position distally flank the GH-V gene, was reduced in placenta chromatin from mice on a HFD and in obese women; a corresponding decrease in RNA polymerase II associated with CS/GH-V promoters was also observed. Detection of decreased endogenous CS/GH-V RNA levels in human placental tumor cells treated with C/EBPβ siRNA is consistent with a direct effect. These data provide evidence for CS/GH-V dysregulation in acute HFD-induced obesity in mouse pregnancy and chronic obesity in human pregnancy and implicate C/EBPβ, a factor associated with CS regulation and placental development.

  14. Punicalagin, a polyphenol in pomegranate juice, downregulates p53 and attenuates hypoxia-induced apoptosis in cultured human placental syncytiotrophoblasts

    OpenAIRE

    Chen, Baosheng; Longtine, Mark S.; Nelson, D. Michael

    2013-01-01

    Oxidative stress is associated with placental dysfunction and suboptimal pregnancy outcomes. Therapeutic interventions to limit placental injury from oxidative stress are lacking. Punicalagin is an ellagitannin and a potent antioxidant in pomegranate juice. We showed that both pomegranate juice and punicalagin decrease oxidative stress and apoptosis in cultured syncytiotrophoblasts. p53 is involved in the oxidative stress-induced apoptosis in trophoblasts. We now test the hypothesis that puni...

  15. 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.

  16. Modelling the effect of intervillous flow on solute transfer based on 3D imaging of the human placental microstructure.

    Science.gov (United States)

    Perazzolo, S; Lewis, R M; Sengers, B G

    2017-12-01

    A healthy pregnancy depends on placental transfer from mother to fetus. Placental transfer takes place at the micro scale across the placental villi. Solutes from the maternal blood are taken up by placental villi and enter the fetal capillaries. This study investigated the effect of maternal blood flow on solute uptake at the micro scale. A 3D image based modelling approach of the placental microstructures was undertaken. Solute transport in the intervillous space was modelled explicitly and solute uptake with respect to different maternal blood flow rates was estimated. Fetal capillary flow was not modelled and treated as a perfect sink. For a freely diffusing small solute, the flow of maternal blood through the intervillous space was found to be limiting the transfer. Ignoring the effects of maternal flow resulted in a 2.4 ± 0.4 fold over-prediction of transfer by simple diffusion, in absence of binding. Villous morphology affected the efficiency of solute transfer due to concentration depleted zones. Interestingly, less dense microvilli had lower surface area available for uptake which was compensated by increased flow due to their higher permeability. At super-physiological pressures, maternal flow was not limiting, however the efficiency of uptake decreased. This study suggests that the interplay between maternal flow and villous structure affects the efficiency of placental transfer but predicted that flow rate will be the major determinant of transfer. Copyright © 2017 Elsevier Ltd. All rights reserved.

  17. Hemozoin Differentially Regulates Proinflammatory Cytokine Production in Human Immunodeficiency Virus-Seropositive and -Seronegative Women with Placental Malaria

    Science.gov (United States)

    Moore, Julie M.; Chaisavaneeyakorn, Sujittra; Perkins, Douglas J.; Othoro, Caroline; Otieno, Juliana; Nahlen, Bernard L.; Shi, Ya Ping; Udhayakumar, Venkatachalam

    2004-01-01

    Pregnant women are at an increased risk for malarial infection. Plasmodium falciparum accumulates in the placenta and is associated with dysregulated immune function and poor birth outcomes. Malarial pigment (hemozoin) also accumulates in the placenta and may modulate local immune function. In this study, the impact of hemozoin on cytokine production by intervillous blood mononuclear cells from malaria-infected placentas was investigated. There was a dose-dependent, suppressive effect of hemozoin on production of gamma interferon (IFN-γ), with less of an effect on tumor necrosis factor alpha (TNF-α) and interleukin-10, in human immunodeficiency virus-seronegative (HIV−) women. In contrast, IFN-γ and TNF-α production tended to increase in HIV-seropositive women with increasing hemozoin levels. Production patterns of cytokines, especially IFN-γ in HIV− women, followed different trends as a function of parasite density and hemozoin level. The findings suggest that the influences of hemozoin accumulation and high-density parasitemia on placental cytokine production are not equivalent and may involve different mechanisms, all of which may operate differently in the context of HIV infection. Cytokine production dysregulated by accumulation of hemozoin or high-density parasitemia may induce pathology and impair protective immunity in HIV-infected and -uninfected women. PMID:15557625

  18. Aromatization of 16alpha-hydroxyandrostenedione by human placental microsomes: effect of preincubation with suicide substrates of androstenedione aromatization.

    Science.gov (United States)

    Numazawa, Mitsuteru; Tachibana, Mii; Mutsumi, Ayako; Yoshimura, Akiko; Osawa, Yoshio

    2002-06-01

    Estrogen synthase (aromatase) catalyzes the aromatization of androstenedione (AD) as well as 16alpha-hydroxyandrostenedione (16alpha-OHAD) leading to estrone and estriol, respectively. We found that several steroid analogs including 4-hydroxyandrostenedione (1), 6-oxoandrostenedione (6-oxoAD, 2) and its 19-hydroxy analog (3), 10beta-acetoxyestr-5-ene-7,17-dione (4), androst-5-ene-4,7,17-trione (5), and 17alpha-ethynyl-19-norteststerone (6), which are known suicide inactivators of AD aromatization, are not effective in inactivating 16alpha-OHAD aromatization in a time-dependent manner. The compounds were tested with the use of human placental microsomes and 1beta-tritiated-16alpha-OHAD as the substrate. The results of the tritium water method of 16alpha-OHAD aromatization was confirmed by the gas chromatography-mass spectrometry (GC-MS) method of estriol formation. The 1beta-tritiated-AD was used to measure AD aromatization as a positive control for these experiments. The compounds were tested at concentrations up to 40-fold higher than the K(i)'s determined for inhibition of AD aromatization. These studies suggest that differences exist in the binding site structures responsible for aromatization of 16alpha-OHAD and AD.

  19. Comparative studies of placentation and immunology in non-human primates suggest a scenario for the evolution of deep trophoblast invasion and an explanation for human pregnancy disorders.

    Science.gov (United States)

    Carter, Anthony M

    2011-04-01

    Deep trophoblast invasion in the placental bed has been considered the hallmark of human pregnancy. It occurs by two routes, interstitial and endovascular, and results in transformation of the walls of the spiral arteries as they traverse the decidua and the inner third of the myometrium. Disturbances in this process are associated with reproductive disorders such preeclampsia. In contrast, trophoblast invasion in Old World monkeys occurs only by the endovascular route and seldom reaches the myometrium. Recently, it was shown that this pattern is maintained in gibbons, but that the human arrangement also occurs in chimpanzee and gorilla. There is an interesting parallel with results from placental immunology regarding the evolution of the major histocompatability complex class I antigen HLA-C and its cognate receptors. HLA-C is not present in Old World monkeys or gibbons. It emerged in the orangutan and became polymorphic in the lineage leading to gorilla, bonobo, chimpanzee, and human. Interaction between HLA-C1 and HLA-C2 on the surface of trophoblast and killer immunoglobulin-like receptors (KIRs) expressed by uterine natural killer cells are important regulators of trophoblast invasion. Evolution of this system in great apes may have been one prerequisite for deep trophoblast invasion but seems to have come at a price. The evidence now suggests that certain combinations of maternal genotype for KIRs and fetal genotype for HLA-C imply an increased risk of preeclampsia, fetal growth restriction, and recurrent abortion. The fetal genotype is in part derived from the father providing an explanation for the paternal contribution to reproductive disorders.

  20. The Lin28/Let-7 system in early human embryonic tissue and ectopic pregnancy.

    Directory of Open Access Journals (Sweden)

    Teresa Lozoya

    Full Text Available Our objective was to determine the expression of the elements of the Lin28/Let-7 system, and related microRNAs (miRNAs, in early stages of human placentation and ectopic pregnancy, as a means to assess the potential role of this molecular hub in the pathogenesis of ectopic gestation. Seventeen patients suffering from tubal ectopic pregnancy (cases and forty-three women with normal on-going gestation that desired voluntary termination of pregnancy (VTOP; controls were recruited for the study. Embryonic tissues were subjected to RNA extraction and quantitative PCR analyses for LIN28B, Let-7a, miR-132, miR-145 and mir-323-3p were performed. Our results demonstrate that the expression of LIN28B mRNA was barely detectable in embryonic tissue from early stages of gestation and sharply increased thereafter to plateau between gestational weeks 7-9. In contrast, expression levels of Let-7, mir-132 and mir-145 were high in embryonic tissue from early gestations (≤ 6-weeks and abruptly declined thereafter, especially for Let-7. Opposite trends were detected for mir-323-3p. Embryonic expression of LIN28B mRNA was higher in early stages (≤ 6-weeks of ectopic pregnancy than in normal gestation. In contrast, Let-7a expression was significantly lower in early ectopic pregnancies, while miR-132 and miR-145 levels were not altered. Expression of mir-323-3p was also suppressed in ectopic embryonic tissue. We are the first to document reciprocal changes in the expression profiles of the gene encoding the RNA-binding protein, LIN28B, and the related miRNAs, Let-7a, mir-132 and mir-145, in early stages of human placentation. This finding suggests the potential involvement of LIN28B/Let-7 (deregulated pathways in the pathophysiology of ectopic pregnancy in humans.

  1. The Lin28/Let-7 System in Early Human Embryonic Tissue and Ectopic Pregnancy

    Science.gov (United States)

    Steffani, Liliana; Martínez, Sebastián; Monterde, Mercedes; Ferri, Blanca; Núñez, Maria Jose; AinhoaRomero-Espinós; Zamora, Omar; Gurrea, Marta; Sangiao-Alvarellos, Susana; Vega, Olivia; Simón, Carlos; Pellicer, Antonio; Tena-Sempere, Manuel

    2014-01-01

    Our objective was to determine the expression of the elements of the Lin28/Let-7 system, and related microRNAs (miRNAs), in early stages of human placentation and ectopic pregnancy, as a means to assess the potential role of this molecular hub in the pathogenesis of ectopic gestation. Seventeen patients suffering from tubal ectopic pregnancy (cases) and forty-three women with normal on-going gestation that desired voluntary termination of pregnancy (VTOP; controls) were recruited for the study. Embryonic tissues were subjected to RNA extraction and quantitative PCR analyses for LIN28B, Let-7a, miR-132, miR-145 and mir-323-3p were performed. Our results demonstrate that the expression of LIN28B mRNA was barely detectable in embryonic tissue from early stages of gestation and sharply increased thereafter to plateau between gestational weeks 7–9. In contrast, expression levels of Let-7, mir-132 and mir-145 were high in embryonic tissue from early gestations (≤6-weeks) and abruptly declined thereafter, especially for Let-7. Opposite trends were detected for mir-323-3p. Embryonic expression of LIN28B mRNA was higher in early stages (≤6-weeks) of ectopic pregnancy than in normal gestation. In contrast, Let-7a expression was significantly lower in early ectopic pregnancies, while miR-132 and miR-145 levels were not altered. Expression of mir-323-3p was also suppressed in ectopic embryonic tissue. We are the first to document reciprocal changes in the expression profiles of the gene encoding the RNA-binding protein, LIN28B, and the related miRNAs, Let-7a, mir-132 and mir-145, in early stages of human placentation. This finding suggests the potential involvement of LIN28B/Let-7 (de)regulated pathways in the pathophysiology of ectopic pregnancy in humans. PMID:24498170

  2. Immunohistochemical characterization of human olfactory tissue.

    Science.gov (United States)

    Holbrook, Eric H; Wu, Enming; Curry, William T; Lin, Derrick T; Schwob, James E

    2011-08-01

    The pathophysiology underlying human olfactory disorders is poorly understood because biopsying the olfactory epithelium (OE) can be unrepresentative and extensive immunohistochemical analysis is lacking. Autopsy tissue enriches our grasp of normal and abnormal olfactory immunohistology and guides the sampling of the OE by biopsy. Furthermore, a comparison of the molecular phenotype of olfactory epithelial cells between rodents and humans will improve our ability to correlate human histopathology with olfactory dysfunction. An immunohistochemical analysis of human olfactory tissue using a comprehensive battery of proven antibodies. Human olfactory mucosa obtained from 21 autopsy specimens was analyzed with immunohistochemistry. The position and extent of olfactory mucosa was assayed by staining whole mounts (WMs) with neuronal markers. Sections of the OE were analyzed with an extensive group of antibodies directed against cytoskeletal proteins and transcription factors, as were surgical specimens from an esthesioneuroblastoma. Neuron-rich epithelium is always found inferior to the cribriform plate, even at advanced age, despite the interruptions in the neuroepithelial sheet caused by patchy respiratory metaplasia. The pattern of immunostaining with our antibody panel identifies two distinct types of basal cell progenitors in human OE similar to rodents. The panel also clarifies the complex composition of esthesioneuroblastoma. The extent of human olfactory mucosa at autopsy can easily be delineated as a function of age and neurologic disease. The similarities in human versus rodent OE will enable us to translate knowledge from experimental animals to humans and will extend our understanding of human olfactory pathophysiology. Copyright © 2011 The American Laryngological, Rhinological, and Otological Society, Inc.

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

    Directory of Open Access Journals (Sweden)

    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.

  4. Epidermal Growth Factor-Like Growth Factors Prevent Apoptosis of Alcohol-Exposed Human Placental Cytotrophoblast Cells1

    Science.gov (United States)

    Wolff, Garen S.; Chiang, Po Jen; Smith, Susan M.; Romero, Roberto; Armant, D. Randall

    2007-01-01

    Maternal alcohol abuse during pregnancy can produce an array of birth defects comprising fetal alcohol syndrome. A hallmark of fetal alcohol syndrome is intrauterine growth retardation, which is associated with elevated apoptosis of placental cytotrophoblast cells. Using a human first trimester cytotrophoblast cell line, we examined the relationship between exposure to ethanol and cytotrophoblast survival, as well as the ameliorating effects of epidermal growth factor (EGF)-like growth factors produced by human cytotrophoblast cells. After exposure to 0–100 mM ethanol, cell death was quantified by the TUNEL method, and expression of the nuclear proliferation marker, Ki67, was measured by immunohistochemistry. The mode of cell death was determined by assessing annexin V binding, caspase 3 activation, pyknotic nuclear morphology, reduction of TUNEL by caspase inhibition, and cellular release of lactate dehydrogenase. Ethanol significantly reduced proliferation and increased cell death approximately 2.5-fold through the apoptotic pathway within 1–2 h of exposure to 50 mM alcohol. Exposure to 25–50 mM ethanol significantly increased transforming growth factor alpha (TGFA) and heparin-binding EGF-like growth factor (HBEGF), but not EGF or amphiregulin (AREG). When cytotrophoblasts were exposed concurrently to 100 mM ethanol and 1 nM HBEGF or TGFA, the increase in apoptosis was prevented, while EGF ameliorated at 10 nM and AREG was weakly effective. HBEGF survival-promoting activity required ligation of either of its cognate receptors, HER1 or HER4. These findings reveal the potential for ethanol to rapidly induce cytotrophoblast apoptosis. However, survival factor induction could provide cytotrophoblasts with an endogenous cytoprotective mechanism. PMID:17392498

  5. In vitro dual perfusion of human placental lobules as a flow phantom to investigate the relationship between fetoplacental flow and quantitative 3D power doppler angiography.

    Science.gov (United States)

    Jones, N W; Hutchinson, E S; Brownbill, P; Crocker, I P; Eccles, D; Bugg, G J; Raine-Fenning, N J

    2009-02-01

    Flow phantoms have been used to investigate and quantify three-dimensional power Doppler data but this is the first study to use the in vitro, dual perfused, placental perfusion model. We used this model to investigate and quantify the effect of variation in fetal-side flow rates and attenuation on 3D power Doppler angiography. Perfusion of a placental lobule was commenced within 30 min of delivery and experimentation was successful in 8 of the 18 placenta obtained. Fetal and maternal perfusate was modified Earle's bicarbonate buffer which, following equilibration, was supplemented on the fetal side with whole heparinised cord blood. Imaging was performed with a Voluson-i ultrasound machine. A 'vascular biopsy' the thickness of the placental lobule was defined and signal quantified within using VOCAL (GE Medical Systems, Zipf, Austria). Three vascular indices are generated: vascularisation index (VI) defined as the percentage of power Doppler data within a volume of interest; flow index (FI), the mean signal intensity of the power Doppler information; and vascularisation flow index (VFI), a combination of both factors derived through their multiplication. Attenuation was investigated in this model with the addition of tissue mimic blocks. Our results showed a predictable relationship between flow rates and the vascular indices VI and VFI. However the FI was a less reliable predictor of flow; thus it should be interpreted with caution. The power Doppler signal was markedly affected by attenuation leading to a complete loss of information at a depth of 6 cm in the model used. In conclusion this model can be adapted to provide a phantom to analyse and quantify 3D power Doppler signals and demonstrates that vascular indices within a tissue remain related to volume flow. This model provides further evidence that depth dependent attenuation of signal needs to be accounted for in any in vivo work where the probe is not in direct contact with the tissue of interest.

  6. Viscoelastic Properties of Human Tracheal Tissues.

    Science.gov (United States)

    Safshekan, Farzaneh; Tafazzoli-Shadpour, Mohammad; Abdouss, Majid; Shadmehr, Mohammad B

    2017-01-01

    The physiological performance of trachea is highly dependent on its mechanical behavior, and therefore, the mechanical properties of its components. Mechanical characterization of trachea is key to succeed in new treatments such as tissue engineering, which requires the utilization of scaffolds which are mechanically compatible with the native human trachea. In this study, after isolating human trachea samples from brain-dead cases and proper storage, we assessed the viscoelastic properties of tracheal cartilage, smooth muscle, and connective tissue based on stress relaxation tests (at 5% and 10% strains for cartilage and 20%, 30%, and 40% for smooth muscle and connective tissue). After investigation of viscoelastic linearity, constitutive models including Prony series for linear viscoelasticity and quasi-linear viscoelastic, modified superposition, and Schapery models for nonlinear viscoelasticity were fitted to the experimental data to find the best model for each tissue. We also investigated the effect of age on the viscoelastic behavior of tracheal tissues. Based on the results, all three tissues exhibited a (nonsignificant) decrease in relaxation rate with increasing the strain, indicating viscoelastic nonlinearity which was most evident for cartilage and with the least effect for connective tissue. The three-term Prony model was selected for describing the linear viscoelasticity. Among different models, the modified superposition model was best able to capture the relaxation behavior of the three tracheal components. We observed a general (but not significant) stiffening of tracheal cartilage and connective tissue with aging. No change in the stress relaxation percentage with aging was observed. The results of this study may be useful in the design and fabrication of tracheal tissue engineering scaffolds.

  7. Pregnancy Complications: Placental Abruption

    Science.gov (United States)

    ... belly is harmed from a car accident or physical abuse . If you've had a placental abruption before, ... belly is harmed from a car accident or physical abuse . If you've had a placental abruption before, ...

  8. Gentamicin concentrations in human subcutaneous tissue

    DEFF Research Database (Denmark)

    Lorentzen, Hanne; Kallehave, Finn Lasse; Kolmos, Hans Jørn Jepsen

    1996-01-01

    in human subcutaneous adipose tissue by a microdialysis technique. Seven healthy young volunteers each had four microdialysis probes placed in the fat (subcutaneous) layer of the abdominal skin. After the administration of a 240-mg gentamicin intravenous bolus, consecutive measurements of the drug...

  9. [Human placental mesenchymal stem cells of fetal origin relieves mouse pulmonary fibrosis via downregulating MyD88 and TGF-β signaling pathway].

    Science.gov (United States)

    Tao, Jin; Li, Qinglun; Ma, Xiaowei; Han, Fei; Liu, Xiaoming; Wei, Jun; Zhu, Yongzhao

    2016-10-01

    Objective To investigate the therapeutic effect and mechanism of human placental mesenchymal stem cells of fetal origin (hfPMSCs) cultured in serum-free medium on mouse pulmonary fibrosis induced by bleomycin treatment. Methods Human hfPMSCs were cultured and identified by flow cytometry. Fifteen 6-week-old male SPF C57BL/6J mice were divided into 3 groups: bleomycin treatment group, hfPMSCs transplantation group and negative control group. Pulmonary fibrosis model was induced in the mice of bleomycin treatment group and hfPMSCs transplantation group with bleomycin (1 μg/L, 50 μL) via intratracheal instillation. The mice in negative control group were instilled with PBS (50 μL) through the same manner of the other two groups. Three days post-modelling, 200 μL containing 5×10(5) hfPMSCs were injected into hfPMSCs transplantation group via tail vein. All the mice were sacrificed at day 21 after modeling in batch. Lung tissues were collected for analyzing the pathological changes by HE staining and Masson staining as well as detecting collagen content. The total protein of lung tissues was extracted for observing the expressions of myeloid differentiation factor 88 (MyD88) and transforming growth factor-β (TGF-β); the level of TGF-β in sera was determined by Western blotting. Results The hfPMSCs possessed the morphology of mesenchymal stem cells and expressed the surface markers CD73, CD90 and CD105, but did not express CD14, CD34 and CD45. HE and Masson staining showed that hfPMSCs transplantation significantly reduced the degree of pulmonary fibrosis compared with bleomycin treatment group. The collagen content and the expression levels of MyD88 and TGF-β in bleomycin treatment group were obviously higher than those in hfPMSCs transplantation group and negative control group. Conclusion hfPMSCs possess the capability of alleviating pulmonary fibrosis by down-regulating the expressions of MyD88 and TGF-β.

  10. Combination Effects of (TriAzole Fungicides on Hormone Production and Xenobiotic Metabolism in a Human Placental Cell Line

    Directory of Open Access Journals (Sweden)

    Svenja Rieke

    2014-09-01

    Full Text Available Consumers are exposed to multiple residues of different pesticides via the diet. Therefore, EU legislation for pesticides requires the evaluation of single active substances as well as the consideration of combination effects. Hence the analysis of combined effects of substances in a broad dose range represents a key challenge to current experimental and regulatory toxicology. Here we report evidence for additive effects for (triazole fungicides, a widely used group of antifungal agents, in the human placental cell line Jeg-3. In addition to the triazoles cyproconazole, epoxiconazole, flusilazole and tebuconazole and the azole fungicide prochloraz also pesticides from other chemical classes assumed to act via different modes of action (i.e., the organophosphate chlorpyrifos and the triazinylsulfonylurea herbicide triflusulfuron-methyl were investigated. Endpoints analysed include synthesis of steroid hormone production (progesterone and estradiol and gene expression of steroidogenic and non-steroidogenic cytochrome-P-450 (CYP enzymes. For the triazoles and prochloraz, a dose dependent inhibition of progesterone production was observed and additive effects could be confirmed for several combinations of these substances in vitro. The non-triazoles chlorpyrifos and triflusulfuron-methyl did not affect this endpoint and, in line with this finding, no additivity was observed when these substances were applied in mixtures with prochloraz. While prochloraz slightly increased aromatase expression and estradiol production and triflusulfuron-methyl decreased estradiol production, none of the other substances had effects on the expression levels of steroidogenic CYP-enzymes in Jeg-3 cells. For some triazoles, prochloraz and chlorpyrifos a significant induction of CYP1A1 mRNA expression and potential combination effects for this endpoint were observed. Inhibition of CYP1A1 mRNA induction by the AhR inhibitor CH223191 indicated AhR receptor dependence this

  11. [Distribution of collagen types III and IV in human placental villi].

    Science.gov (United States)

    Nanaev, A K; Rukosuev, V S; Milovanov, A P; Fokin, E I; Shirinskiĭ, V P

    1989-02-01

    Immunofluorescent examination showed more significant accumulation of interstitial collagen type III in the stroma of mature placenta compared with immature one. Localization of membrane collagen type IV was found neither in basal membranes of epithelium and villous vessels of mature term placenta, nor in their stroma. The described patterns of distribution of collagen types III and IV in human placenta villi were proved by immunoelectronmicroscopic method.

  12. Beta adrenergic receptors in human cavernous tissue

    Energy Technology Data Exchange (ETDEWEB)

    Dhabuwala, C.B.; Ramakrishna, C.V.; Anderson, G.F.

    1985-04-01

    Beta adrenergic receptor binding was performed with /sup 125/I iodocyanopindolol on human cavernous tissue membrane fractions from normal tissue and transsexual procedures obtained postoperatively, as well as from postmortem sources. Isotherm binding studies on normal fresh tissues indicated that the receptor density was 9.1 fmoles/mg. with a KD of 23 pM. Tissue stored at room temperature for 4 to 6 hours, then at 4C in saline solution for 19 to 20 hours before freezing showed no significant changes in receptor density or affinity, and provided evidence for the stability of postmortem tissue obtained within the same time period. Beta receptor density of 2 cavernous preparations from transsexual procedures was not significantly different from normal control tissues, and showed that high concentrations of estrogen received by these patients had no effect on beta adrenergic receptor density. Displacement of /sup 125/iodocyanopindolol by 5 beta adrenergic agents demonstrated that 1-propranolol had the greatest affinity followed by ICI 118,551, zinterol, metoprolol and practolol. When the results of these displacement studies were subjected to Scatfit, non- linear regression line analysis, a single binding site was described. Based on the relative potency of the selective beta adrenergic agents it appears that these receptors were of the beta 2 subtype.

  13. Antibodies to Placental Immunoregulatory Ferritin with Transfer of Polyclonal Lymphocytes Arrest MCF-7 Human Breast Cancer Growth in a Nude Mouse Model

    Directory of Open Access Journals (Sweden)

    Marisa Halpern

    2007-06-01

    Full Text Available The recently cloned human gene named “placental immunoregulatory ferritin” (PLIF is a pregnancyrelated immunomodulator. Recombinant PLIF and its bioactive domain C48 are immune-suppressive and induce pronounced IL-10 production by immune cells. PLIF is expressed in the placenta and breast cancer cells. Blocking PLIF in pregnant mice by anti-C48 antibodies inhibited placental and fetal growth and modulated the cytokine network. It has been revealed that anti-C48 treatment inhibited MCF-7 tumor growth in nude mice. However, this significant effect was observed only in those transfused with human peripheral blood mononuclear cells. Blocking PLIF in tumor-engrafted human immune cell transfused mice resulted in massive infiltration of human CD45+ cells (mainly CD8+ T cells, both intratumorally and in the tumor periphery, and a significant number of caspase-3+ cells. In vitro, antiC48 treatment of MCF-7 tumor cells cocultured with human lymphocytes induced a significant increase in interferon-γ secretion. We conclude that blocking PLIF inhibits breast cancer growth, possibly by an effect on the cytokine network in immune cells and on breakdown of immunosuppression.

  14. Placenta Maps: In Utero Placental Health Assessment of the Human Fetus.

    Science.gov (United States)

    Miao, Haichao; Mistelbauer, Gabriel; Karimov, Alexey; Alansary, Amir; Davidson, Alice; Lloyd, David F A; Damodaram, Mellisa; Story, Lisa; Hutter, Jana; Hajnal, Joseph V; Rutherford, Mary; Preim, Bernhard; Kainz, Bernhard; Groller, M Eduard

    2017-06-01

    The human placenta is essential for the supply of the fetus. To monitor the fetal development, imaging data is acquired using (US). Although it is currently the gold-standard in fetal imaging, it might not capture certain abnormalities of the placenta. (MRI) is a safe alternative for the in utero examination while acquiring the fetus data in higher detail. Nevertheless, there is currently no established procedure for assessing the condition of the placenta and consequently the fetal health. Due to maternal respiration and inherent movements of the fetus during examination, a quantitative assessment of the placenta requires fetal motion compensation, precise placenta segmentation and a standardized visualization, which are challenging tasks. Utilizing advanced motion compensation and automatic segmentation methods to extract the highly versatile shape of the placenta, we introduce a novel visualization technique that presents the fetal and maternal side of the placenta in a standardized way. Our approach enables physicians to explore the placenta even in utero. This establishes the basis for a comparative assessment of multiple placentas to analyze possible pathologic arrangements and to support the research and understanding of this vital organ. Additionally, we propose a three-dimensional structure-aware surface slicing technique in order to explore relevant regions inside the placenta. Finally, to survey the applicability of our approach, we consulted clinical experts in prenatal diagnostics and imaging. We received mainly positive feedback, especially the applicability of our technique for research purposes was appreciated.

  15. Proteasome-independent degradation of HIV-1 in naturally non-permissive human placental trophoblast cells

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    Barré-Sinoussi Françoise

    2009-05-01

    Full Text Available Abstract Background The human placenta-derived cell line BeWo has been demonstrated to be restrictive to cell-free HIV-1 infection. BeWo cells are however permissive to infection by VSV-G pseudotyped HIV-1, which enters cells by a receptor-independent mechanism, and to infection by HIV-1 via a cell-to-cell route. Results Here we analysed viral entry in wild type BeWo (CCR5+, CXCR4+ and BeWo-CD4+ (CD4+, CCR5+, CXCR4+ cells. We report that HIV-1 internalisation is not restricted in either cell line. Levels of internalised p24 antigen between VSV-G HIV-1 pseudotypes and R5 or X4 virions were comparable. We next analysed the fate of internalised virions; X4 and R5 HIV-1 virions were less stable over time in BeWo cells than VSV-G HIV-1 pseudotypes. We then investigated the role of the proteasome in restricting cell-free HIV-1 infection in BeWo cells using proteasome inhibitors. We observed an increase in the levels of VSV-G pseudotyped HIV-1 infection in proteasome-inhibitor treated cells, but the infection by R5-Env or X4-Env pseudotyped virions remains restricted. Conclusion Collectively these results suggest that cell-free HIV-1 infection encounters a surface block leading to a non-productive entry route, which either actively targets incoming virions for non-proteasomal degradation, and impedes their release into the cytoplasm, or causes the inactivation of mechanisms essential for viral replication.

  16. Placental transfer of the polybrominated diphenyl ethers BDE-47, BDE-99 and BDE-209 in a human placenta perfusion system: an experimental study

    DEFF Research Database (Denmark)

    Frederiksen, Marie; Vorkamp, Katrin; Mathiesen, Line

    2010-01-01

    BACKGROUND: Polybrominated diphenyl ethers (PBDEs) have been widely used as flame retardants in consumer products. PBDEs may affect thyroid hormone homeostasis, which can result in irreversible damage of cognitive performance, motor skills and altered behaviour. Thus, in utero exposure is of very...... high concern due to critical windows in fetal development. METHODS: A human ex vivo placenta perfusion system was used to study the kinetics and extent of the placental transfer of BDE-47, BDE-99 and BDE-209 during four-hour perfusions. The PBDEs were added to the maternal circulation and monitored...... should be included in risk assessment of PBDE exposure of women of child-bearing age....

  17. 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.

  18. Human leucocyte antigen (HLA) expression of primary trophoblast cells and placental cell lines, determined using single antigen beads to characterize allotype specificities of anti-HLA antibodies.

    Science.gov (United States)

    Apps, Richard; Murphy, Shawn P; Fernando, Raymond; Gardner, Lucy; Ahad, Tashmeeta; Moffett, Ashley

    2009-05-01

    Human trophoblast cells express an unusual repertoire of human leucocyte antigen (HLA) molecules which has been difficult to define. Close homology between and extreme polymorphism at the classical HLA class-I (HLA-I) loci has made it difficult to generate locus-specific monoclonal antibodies (mAbs). The problem of defining an antibody's reactivity against the thousands of existing HLA-I allotypes has often made it impossible to determine the HLA bound by a mAb in biological samples from a normal outbred population. Here we have used commercially available beads coated with individual HLA-I to characterize experimentally the reactivity of nine mAb against 96 common HLA-I allotypes. In conjunction with donor HLA-I genotyping, we could then define the specific HLA molecules bound by these antibodies in normal individuals. We used this approach to analyse the HLA expression of primary trophoblast cells from normal pregnancies; the choriocarcinoma cells JEG-3 and JAR; and the placental cell lines HTR-8/SVneo, Swan-71 and TEV-1. We confirm that primary villous trophoblast cells are HLA null whereas extravillous trophoblast cells express HLA-C, HLA-G and HLA-E, but not HLA-A, HLA-B or HLA-DR molecules in normal pregnancy. Tumour-derived JEG-3 and JAR cells reflect extravillous and villous trophoblast HLA phenotypes, respectively, but the HLA repertoire of the in vitro derived placental cell lines is not representative of either in vivo trophoblast phenotype. This study raises questions regarding the validity of using the placental cell lines that are currently available as model systems for immunological interactions between fetal trophoblast and maternal leucocytes bearing receptors for HLA molecules.

  19. The impact of maternal obesity on iron status, placental transferrin receptor expression and hepcidin expression in human pregnancy.

    Science.gov (United States)

    Garcia-Valdes, L; Campoy, C; Hayes, H; Florido, J; Rusanova, I; Miranda, M T; McArdle, H J

    2015-04-01

    Obesity is associated with decreased iron status, possibly due to a rise in hepcidin, an inflammatory protein known to reduce iron absorption. In animals, we have shown that maternal iron deficiency is minimised in the foetus by increased expression of placental transferrin receptor (pTFR1), resulting in increased iron transfer at the expense of maternal iron stores. This study examines the effect of obesity during pregnancy on maternal and neonatal iron status in human cohorts and whether the placenta can compensate for decreased maternal iron stores by increasing pTFR1 expression. A total of 240 women were included in this study. One hundred and fifty-eight placentas (Normal: 90; Overweight: 37; Obese: 31) were collected at delivery. Maternal iron status was measured by determining serum transferrin receptor (sTFR) and ferritin levels at 24 and 34 weeks and at delivery. Hepcidin in maternal and cord blood was measured by ELISA and pTFR1 in placentas by western blotting and real-time RT-PCR. Low iron stores were more common in obese women. Hepcidin levels (ng ml(-1)) at the end of the pregnancy were higher in obese than normal women (26.03±12.95 vs 18.00±10.77, PMaternal hepcidin levels were correlated with maternal iron status (sTFR r=0.2 P=0.025), but not with neonatal values. mRNA and protein levels of pTFR1 were both inversely related to maternal iron status. For mRNA and all women, sTFR r=0.2 P=0.044. Ferritin mRNA levels correlated only in overweight women r=-0.5 P=0.039 with hepcidin (r=0.1 P=0.349), irrespective of maternal body mass index (BMI). The data support the hypothesis that obese pregnant women have a greater risk of iron deficiency and that hepcidin may be a regulatory factor. Further, we show that the placenta responds to decreased maternal iron status by increasing pTFR1 expression.

  20. Mechanical characterization of human brain tissue.

    Science.gov (United States)

    Budday, S; Sommer, G; Birkl, C; Langkammer, C; Haybaeck, J; Kohnert, J; Bauer, M; Paulsen, F; Steinmann, P; Kuhl, E; Holzapfel, G A

    2017-01-15

    Mechanics are increasingly recognized to play an important role in modulating brain form and function. Computational simulations are a powerful tool to predict the mechanical behavior of the human brain in health and disease. The success of these simulations depends critically on the underlying constitutive model and on the reliable identification of its material parameters. Thus, there is an urgent need to thoroughly characterize the mechanical behavior of brain tissue and to identify mathematical models that capture the tissue response under arbitrary loading conditions. However, most constitutive models have only been calibrated for a single loading mode. Here, we perform a sequence of multiple loading modes on the same human brain specimen - simple shear in two orthogonal directions, compression, and tension - and characterize the loading-mode specific regional and directional behavior. We complement these three individual tests by combined multiaxial compression/tension-shear tests and discuss effects of conditioning and hysteresis. To explore to which extent the macrostructural response is a result of the underlying microstructural architecture, we supplement our biomechanical tests with diffusion tensor imaging and histology. We show that the heterogeneous microstructure leads to a regional but not directional dependence of the mechanical properties. Our experiments confirm that human brain tissue is nonlinear and viscoelastic, with a pronounced compression-tension asymmetry. Using our measurements, we compare the performance of five common constitutive models, neo-Hookean, Mooney-Rivlin, Demiray, Gent, and Ogden, and show that only the isotropic modified one-term Ogden model is capable of representing the hyperelastic behavior under combined shear, compression, and tension loadings: with a shear modulus of 0.4-1.4kPa and a negative nonlinearity parameter it captures the compression-tension asymmetry and the increase in shear stress under superimposed

  1. Human type 2 17beta-hydroxysteroid dehydrogenase mRNA and protein distribution in placental villi at mid and term pregnancy

    Directory of Open Access Journals (Sweden)

    Plante Julie

    2007-07-01

    Full Text Available Abstract Background During human pregnancy, the placental villi produces high amounts of estradiol. This steroid is secreted by the syncytium, which is directly in contact with maternal blood. Estradiol has to cross placental foetal vessels to reach foetal circulation. The enzyme 17beta-hydroxysteroid dehydrogenase type 2 (17beta-HSD2 was detected in placental endothelial cells of foetal vessels inside the villi. This enzyme catalyzes the conversion of estradiol to estrone, and of testosterone to androstenedione. It was proposed that estradiol level into foetal circulation could be regulated by 17beta-HSD2. Methods We obtained placentas from 10 to 26 6/7 weeks of pregnancy from women undergoing voluntary termination of pregnancy, term placentas were collected after normal spontaneous vaginal deliveries. We quantified 17beta-HSD2 mRNA levels in mid-gestation and term human placenta by RT-QPCR. We produced a new anti-17beta-HSD2 antibody to study its spatio-temporal expression by immunohistochemistry. We also compared steroid levels (testosterone, estrone and estradiol and 17beta-HSD2 mRNA and protein levels between term placenta and endometrium. Results High 17beta-HSD2 mRNA and protein levels were found in both mid-gestation and term placentas. However, we showed that 17beta-HSD2 mRNA levels increase by 2.27 fold between mid-gestation and term. This period coincides with a transitional phase in the development of the villous vasculature. In mid-gestation placenta, high levels of 17beta-HSD2 were found in mesenchymal villi and immature intermediate villi, more precisely in endothelial cells of the stromal channel. At term, high levels of 17beta-HSD2 were found in the numerous sinusoidal capillaries of terminal villi. 17beta-HSD2 mRNA and protein levels in term placentas were respectively 25.4 fold and 30 to 60 fold higher than in the endometrium. Steroid levels were also significantly higher in term placenta than in the endometrium. Conclusion

  2. A placental phenotype for intrahepatic cholestasis of pregnancy.

    Science.gov (United States)

    Geenes, V L; Lim, Y-H; Bowman, N; Tailor, H; Dixon, P H; Chambers, J; Brown, L; Wyatt-Ashmead, J; Bhakoo, K; Williamson, C

    2011-12-01

    Intrahepatic cholestasis of pregnancy (ICP) is a pregnancy specific liver disease associated with significant risk of fetal complications. It is hypothesised that the risk of adverse fetal outcomes relates to the toxic effects of bile acids, the levels of which are increased in both maternal and fetal serum. Human and rodent studies have shown that transplacental transfer of bile acids is impaired in ICP. Furthermore, the morphology of placentas from the rodent model of ICP is markedly abnormal, and is associated with increased expression of apoptotic markers and oxidative stress. Using placental tissue from ICP cases and normal pregnancies and cultured placental explant fragments we investigated the histological and molecular effects of cholestasis. We also examined the influence of ursodeoxycholic acid (UDCA) administration on these parameters. Here we report that ICP is associated with several morphological abnormalities of the placenta, including an increase in the number of syncytial knots, and that these can be reproduced in an in vitro (explant) model exposed to the bile acids taurocholic acid and taurochenodoexycholic acid. Furthermore, we demonstrate that ursodeoxycholic acid, a drug commonly used in the management of ICP, has a protective effect on placental tissue both in vivo and in vitro. Copyright © 2011 Elsevier Ltd. All rights reserved.

  3. Placental Adaptations in Growth Restriction

    Science.gov (United States)

    Zhang, Song; Regnault, Timothy R.H.; Barker, Paige L.; Botting, Kimberley J.; McMillen, Isabella C.; McMillan, Christine M.; Roberts, Claire T.; Morrison, Janna L.

    2015-01-01

    The placenta is the primary interface between the fetus and mother and plays an important role in maintaining fetal development and growth by facilitating the transfer of substrates and participating in modulating the maternal immune response to prevent immunological rejection of the conceptus. The major substrates required for fetal growth include oxygen, glucose, amino acids and fatty acids, and their transport processes depend on morphological characteristics of the placenta, such as placental size, morphology, blood flow and vascularity. Other factors including insulin-like growth factors, apoptosis, autophagy and glucocorticoid exposure also affect placental growth and substrate transport capacity. Intrauterine growth restriction (IUGR) is often a consequence of insufficiency, and is associated with a high incidence of perinatal morbidity and mortality, as well as increased risk of cardiovascular and metabolic diseases in later life. Several different experimental methods have been used to induce placental insufficiency and IUGR in animal models and a range of factors that regulate placental growth and substrate transport capacity have been demonstrated. While no model system completely recapitulates human IUGR, these animal models allow us to carefully dissect cellular and molecular mechanisms to improve our understanding and facilitate development of therapeutic interventions. PMID:25580812

  4. Placental Adaptations in Growth Restriction

    Directory of Open Access Journals (Sweden)

    Song Zhang

    2015-01-01

    Full Text Available The placenta is the primary interface between the fetus and mother and plays an important role in maintaining fetal development and growth by facilitating the transfer of substrates and participating in modulating the maternal immune response to prevent immunological rejection of the conceptus. The major substrates required for fetal growth include oxygen, glucose, amino acids and fatty acids, and their transport processes depend on morphological characteristics of the placenta, such as placental size, morphology, blood flow and vascularity. Other factors including insulin-like growth factors, apoptosis, autophagy and glucocorticoid exposure also affect placental growth and substrate transport capacity. Intrauterine growth restriction (IUGR is often a consequence of insufficiency, and is associated with a high incidence of perinatal morbidity and mortality, as well as increased risk of cardiovascular and metabolic diseases in later life. Several different experimental methods have been used to induce placental insufficiency and IUGR in animal models and a range of factors that regulate placental growth and substrate transport capacity have been demonstrated. While no model system completely recapitulates human IUGR, these animal models allow us to carefully dissect cellular and molecular mechanisms to improve our understanding and facilitate development of therapeutic interventions.

  5. PLACENTAL SIZE AND PERINATAL OUTCOMES

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    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.

  6. Tissue-based map of the human proteome

    DEFF Research Database (Denmark)

    Uhlén, Mathias; Fagerberg, Linn; Hallström, Björn M.

    2015-01-01

    Resolving the molecular details of proteome variation in the different tissues and organs of the human body will greatly increase our knowledge of human biology and disease. Here, we present a map of the human tissue proteome based on an integrated omics approach that involves quantitative...... transcriptomics at the tissue and organ level, combined with tissue microarray-based immunohistochemistry, to achieve spatial localization of proteins down to the single-cell level. Our tissue-based analysis detected more than 90% of the putative protein-coding genes. We used this approach to explore the human......, in all major tissues and organs in the human body....

  7. 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

  8. 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...

  9. Domestic sheep show average Coxiella burnetii seropositivity generations after a sheep-associated human Q fever outbreak and lack detectable shedding by placental, vaginal, and fecal routes.

    Science.gov (United States)

    Oliveira, Ryan D; Mousel, Michelle R; Pabilonia, Kristy L; Highland, Margaret A; Taylor, J Bret; Knowles, Donald P; White, Stephen N

    2017-01-01

    Coxiella burnetii is a globally distributed zoonotic bacterial pathogen that causes abortions in ruminant livestock. In humans, an influenza-like illness results with the potential for hospitalization, chronic infection, abortion, and fatal endocarditis. Ruminant livestock, particularly small ruminants, are hypothesized to be the primary transmission source to humans. A recent Netherlands outbreak from 2007-2010 traced to dairy goats resulted in over 4,100 human cases with estimated costs of more than 300 million euros. Smaller human Q fever outbreaks of small ruminant origin have occurred in the United States, and characterizing shedding is important to understand the risk of future outbreaks. In this study, we assessed bacterial shedding and seroprevalence in 100 sheep from an Idaho location associated with a 1984 human Q fever outbreak. We observed 5% seropositivity, which was not significantly different from the national average of 2.7% for the U.S. (P>0.05). Furthermore, C. burnetii was not detected by quantitative PCR from placentas, vaginal swabs, or fecal samples. Specifically, a three-target quantitative PCR of placenta identified 0.0% shedding (exact 95% confidence interval: 0.0%-2.9%). While presence of seropositive individuals demonstrates some historical C. burnetii exposure, the placental sample confidence interval suggests 2016 shedding events were rare or absent. The location maintained the flock with little or no depopulation in 1984 and without C. burnetii vaccination during or since 1984. It is not clear how a zero-shedding rate was achieved in these sheep beyond natural immunity, and more work is required to discover and assess possible factors that may contribute towards achieving zero-shedding status. We provide the first U.S. sheep placental C. burnetii shedding update in over 60 years and demonstrate potential for C. burnetii shedding to reach undetectable levels after an outbreak event even in the absence of targeted interventions, such as

  10. Domestic sheep show average Coxiella burnetii seropositivity generations after a sheep-associated human Q fever outbreak and lack detectable shedding by placental, vaginal, and fecal routes.

    Directory of Open Access Journals (Sweden)

    Ryan D Oliveira

    Full Text Available Coxiella burnetii is a globally distributed zoonotic bacterial pathogen that causes abortions in ruminant livestock. In humans, an influenza-like illness results with the potential for hospitalization, chronic infection, abortion, and fatal endocarditis. Ruminant livestock, particularly small ruminants, are hypothesized to be the primary transmission source to humans. A recent Netherlands outbreak from 2007-2010 traced to dairy goats resulted in over 4,100 human cases with estimated costs of more than 300 million euros. Smaller human Q fever outbreaks of small ruminant origin have occurred in the United States, and characterizing shedding is important to understand the risk of future outbreaks. In this study, we assessed bacterial shedding and seroprevalence in 100 sheep from an Idaho location associated with a 1984 human Q fever outbreak. We observed 5% seropositivity, which was not significantly different from the national average of 2.7% for the U.S. (P>0.05. Furthermore, C. burnetii was not detected by quantitative PCR from placentas, vaginal swabs, or fecal samples. Specifically, a three-target quantitative PCR of placenta identified 0.0% shedding (exact 95% confidence interval: 0.0%-2.9%. While presence of seropositive individuals demonstrates some historical C. burnetii exposure, the placental sample confidence interval suggests 2016 shedding events were rare or absent. The location maintained the flock with little or no depopulation in 1984 and without C. burnetii vaccination during or since 1984. It is not clear how a zero-shedding rate was achieved in these sheep beyond natural immunity, and more work is required to discover and assess possible factors that may contribute towards achieving zero-shedding status. We provide the first U.S. sheep placental C. burnetii shedding update in over 60 years and demonstrate potential for C. burnetii shedding to reach undetectable levels after an outbreak event even in the absence of targeted

  11. Aromatization of androstenedione and 16alpha-hydroxyandrostenedione in human placental microsomes. Kinetic analysis of inhibition by the 19-oxygenated and 3-deoxy analogs.

    Science.gov (United States)

    Numazawa, Mitsuteru; Watari, Yoko; Komatsu, Sachiko; Yamashita, Kouwa; Nagaoka, Masao

    2008-11-01

    Inhibition of aromatase activity in human placental microsomes with androstenedione (AD) (1a) and its 19-oxygenated derivatives 1b and 1c, their 16alpha-hydroxy compounds 2 and 3, and 3-deoxyandrost-4-ene compounds 5 and 6 was studied using [1beta-(3)H]AD as a substrate and compared to that with [1beta-(3)H]16alpha-hydroxyandrostenedione (16-OHAD). AD series of steroids, compounds 1, inhibited competitively [1beta-(3)H]AD aromatization whereas other 16alpha-hydroxy steroids 2, 3, 5, and 6 inhibited AD aromatization in a non-competitive manner. On the other hand, all of 16-OHAD series, compounds 2, blocked the [1beta-(3)H]16-OHAD aromatization in a competitive manner whereas the AD series steroids 1 as well as the 3-deoxy-16alpha-hydroxy-17-one steroids 5 and 3-deoxy-16alpha,17beta-diol steroids 6 inhibited 16-OHAD aromatization non-competitively. 3-carbonyl and 16alpha-hydroxy functions of 16-OHAD play a critical role of selection of the 16-OHAD binding site. The results suggest that the AD derivatives 1 are kinetically aromatized at a different site from the 16-OHAD derivatives 2. Physical and/or chemical environments around the aromatase protein in the microsomal membrane may play a significant role in the expression of the substrate specificity, and the present results do not exclude the idea that the placental microsomes have a single binding site.

  12. Placental Toll-like receptor 3 and Toll-like receptor 7/8 activation contributes to preeclampsia in humans and mice.

    Directory of Open Access Journals (Sweden)

    Piyali Chatterjee

    Full Text Available Preeclampsia (PE is a pregnancy-specific hypertensive syndrome characterized by excessive maternal immune system activation, inflammation, and endothelial dysfunction. Toll-like receptor (TLR 3 activation by double-stranded RNA (dsRNA and TLR7/8 activation by single-stranded RNA (ssRNA expressed by viruses and/or released from necrotic cells initiates a pro-inflammatory immune response; however it is unknown whether viral/endogenous RNA is a key initiating signal that contributes to the development of PE. We hypothesized that TLR3/7/8 activation will be evident in placentas of women with PE, and sufficient to induce PE-like symptoms in mice. Placental immunoreactivity and mRNA levels of TLR3, TLR7, and TLR8 were increased significantly in women with PE compared to normotensive women. Treatment of human trophoblasts with the TLR3 agonist polyinosine-polycytidylic acid (poly I:C, the TLR7-specific agonist imiquimod (R-837, or the TLR7/8 agonist CLO97 significantly increased TLR3/7/8 levels. Treatment of mice with poly I:C, R-837, or CLO97 caused pregnancy-dependent hypertension, endothelial dysfunction, splenomegaly, and placental inflammation. These data demonstrate that RNA-mediated activation of TLR3 and TLR7/8 plays a key role in the development of PE.

  13. Placental hormones and the control of maternal metabolism and fetal growth.

    Science.gov (United States)

    Newbern, Dorothee; Freemark, Michael

    2011-12-01

    To examine the roles of the placental and pituitary hormones in the control of maternal metabolism and fetal growth. In addition to promoting growth of maternal tissues, placental growth hormone (GH-V) induces maternal insulin resistance and thereby facilitates the mobilization of maternal nutrients for fetal growth. Human placental lactogen (hPL) and prolactin increase maternal food intake by induction of central leptin resistance and promote maternal beta-cell expansion and insulin production to defend against the development of gestational diabetes mellitus. The effects of the lactogens are mediated by diverse signaling pathways and are potentiated by glucose. Pathologic conditions of pregnancy are associated with dysregulation of GH-V and hPL gene expression. The somatogenic and lactogenic hormones of the placenta and maternal pituitary gland integrate the metabolic adaptations of pregnancy with the demands of fetal and neonatal development. Dysregulation of placental growth hormone and/or placental lactogen in pathologic conditions of pregnancy may adversely impact fetal growth and postnatal metabolic function.

  14. Detrimental effects of ethanol and its metabolite acetaldehyde, on first trimester human placental cell turnover and function.

    Science.gov (United States)

    Lui, Sylvia; Jones, Rebecca L; Robinson, Nathalie J; Greenwood, Susan L; Aplin, John D; Tower, Clare L

    2014-01-01

    Fetal alcohol spectrum disorder (FASD) describes developmental issues from high maternal alcohol intake, which commonly results in fetal growth restriction and long term morbidity. We aimed to investigate the effect of alcohol and acetaldehyde, on the first trimester placenta, the period essential for normal fetal organogenesis. Normal invasion and establishment of the placenta during this time are essential for sustaining fetal viability to term. We hypothesise that alcohol (ethanol) and acetaldehyde have detrimental effects on cytotrophoblast invasion, turnover and placental function. Taurine is an important amino acid for neuronal and physiological development, and so, its uptake was assayed in cells and placental explants exposed to alcohol or acetaldehyde. First trimester villous explants and BeWo cells were treated with 0, 10, 20, 40 mM ethanol or 0, 10, 20, 40 µM acetaldehyde. The invasive capacity of SGHPL4, a first trimester extravillous cytotrophoblast cell line, was unaffected by ethanol or acetaldehyde (p>0.05; N = 6). The cells in-cycle were estimated using immunostaining for Ki67. Proliferating trophoblast cells treated with ethanol were decreased in both experiments (explants: 40% at 20 mM and 40 mM, pcell line: 5% at 20 mM and 40 mM, pcells in both experiments (explants at 40 µM pcell line at 10 µM and 40 µM; pcell line at 20 µM acetaldehyde demonstrated increased apoptosis (pcells at 10 mM and 40 mM (p<0.05; N = 6), and in placenta at 40 mM (p<0.05; N = 7). Acetaldehyde did not affect taurine transport in either model (P<0.05; N = 6). Interestingly, system A amino acid transport in placental explants was increased at 10 µM and 40 µM acetaldehyde exposure (p<0.05; N = 6). Our results demonstrate that exposure to both genotoxins may contribute to the pathogenesis of FASD by reducing placental growth. Alcohol also reduces the transport of taurine, which is vital for developmental neurogenesis.

  15. Detrimental effects of ethanol and its metabolite acetaldehyde, on first trimester human placental cell turnover and function.

    Directory of Open Access Journals (Sweden)

    Sylvia Lui

    Full Text Available Fetal alcohol spectrum disorder (FASD describes developmental issues from high maternal alcohol intake, which commonly results in fetal growth restriction and long term morbidity. We aimed to investigate the effect of alcohol and acetaldehyde, on the first trimester placenta, the period essential for normal fetal organogenesis. Normal invasion and establishment of the placenta during this time are essential for sustaining fetal viability to term. We hypothesise that alcohol (ethanol and acetaldehyde have detrimental effects on cytotrophoblast invasion, turnover and placental function. Taurine is an important amino acid for neuronal and physiological development, and so, its uptake was assayed in cells and placental explants exposed to alcohol or acetaldehyde. First trimester villous explants and BeWo cells were treated with 0, 10, 20, 40 mM ethanol or 0, 10, 20, 40 µM acetaldehyde. The invasive capacity of SGHPL4, a first trimester extravillous cytotrophoblast cell line, was unaffected by ethanol or acetaldehyde (p>0.05; N = 6. The cells in-cycle were estimated using immunostaining for Ki67. Proliferating trophoblast cells treated with ethanol were decreased in both experiments (explants: 40% at 20 mM and 40 mM, p<0.05, N = 8-9 (cell line: 5% at 20 mM and 40 mM, p<0.05, N = 6. Acetaldehyde also reduced Ki67-positive cells in both experiments (explants at 40 µM p<0.05; N = 6 (cell line at 10 µM and 40 µM; p<0.05; N = 7. Only in the cell line at 20 µM acetaldehyde demonstrated increased apoptosis (p<0.05; N = 6. Alcohol inhibited taurine transport in BeWo cells at 10 mM and 40 mM (p<0.05; N = 6, and in placenta at 40 mM (p<0.05; N = 7. Acetaldehyde did not affect taurine transport in either model (P<0.05; N = 6. Interestingly, system A amino acid transport in placental explants was increased at 10 µM and 40 µM acetaldehyde exposure (p<0.05; N = 6. Our results demonstrate that exposure to both genotoxins may contribute to the pathogenesis of

  16. Conversion of human placental alkaline phosphatase from a high Mr form to a low Mr form during butanol extraction. An investigation of the role of endogenous phosphoinositide-specific phospholipases.

    Science.gov (United States)

    Malik, A S; Low, M G

    1986-12-01

    Alkaline phosphatase in a wide range of tissues has been shown to be anchored in the membrane by a specific interaction with the polar head group of phosphatidylinositol. It has previously been suggested that the production of low Mr alkaline phosphatase during the commonly used butanol extraction procedure may result from the activation of an endogenous phosphoinositide-specific phospholipase C which removes the 1,2-diacylglycerol responsible for membrane anchoring. This conversion process was investigated in greater detail with human placenta used as the source of alkaline phosphatase. Mr and hydrophobicity of the alkaline phosphatase were determined by gel filtration on TSK-250 and partitioning in Triton X-114, respectively. Alkaline phosphatase extracted from human placental particulate fraction with butanol at pH 5.4 or released by incubation with Staphylococcus aureus phosphatidylinositol-specific phospholipase C produced a form of alkaline phosphatase of Mr approx. 170,000 and relatively low hydrophobicity. By contrast, the butanol extract prepared at pH 8.3 was an aggregated form of Mr approx. 600,000 and was relatively hydrophobic. The effect of a variety of inhibitors and activators on the amount of low Mr alkaline phosphatase produced during butanol extraction revealed that it was a Ca2+- and thiol-dependent process. Proteinase inhibitors had no effect. [3H]Phosphatidylinositol hydrolysis by the particulate fraction, unlike low Mr alkaline phosphatase production, was relatively sensitive to heat inactivation, indicating that the phosphoinositide-specific phospholipases C from cytosol and lysosomes were unlikely to be responsible for conversion. A butanol-stimulated activity which removed the [3H]myristic acid from the variant surface glycoprotein ( [3H]mfVSG) of Trypanosoma brucei was detectable in the human placental particulate fraction. Since this activity was acid active, Ca2+- and thiol-dependent and relatively heat stable, it may be the same as

  17. Effects of growth hormone, prolactin, and placental lactogen on insulin content and release, and deoxyribonucleic acid synthesis in cultured pancreatic islets

    DEFF Research Database (Denmark)

    Nielsen, Jens Høiriis

    1982-01-01

    The direct effects of human GH (hGH), ovine pituitary PRL (oPRL), and human chorionic somatomammotropin [placental lactogen (hPL)] on the endocrine pancreas were studied in isolated pancreatic islets maintained in tissue culture. Islets of Langerhans were isolated by collagenase treatment of panc...

  18. Placental pathology and hypospadias.

    Science.gov (United States)

    Chen, Yan; Sun, Luming; Geng, Hongquan; Lei, Xiaoping; Zhang, Jun

    2017-03-01

    Studies have shown that hypospadias is associated with placenta-mediated pregnancy complication (PMPC). The role of placental lesions is still unclear. We aimed to examine the association between hyposadias and placental pathology, and the effect of PMPC. Using data from the US Collaborative Perinatal Project in 1959-1966, we identified 15,780 male subjects (167 hypospadias) for analysis. Detailed placental examinations were conducted following a standard protocol. Subjects were divided into two groups according to whether they had PMPC, including small-for-gestational-age, pre-eclampsia/eclampsia or placental abruption. Logistic regression models were used to explore the association. The prevalence of hypospadias was two times higher in subjects with PMPC than those without. Compared to pregnancies with PMPC but no hypospadias, those with both PMPC and hypospadias had significant higher prevalence of placental lesions, such as low placental weight, vascular lesions, villous lesions, and membranous insertion of cord (adjusted odds ratio (OR) ranging from 2.6 to 5.2) after adjusting for potential confounders. In subjects without PMPC, no significant difference of placental pathology was found between those with or without hypospadias. About one third of hypospadias cases were complicated with PMPC and had a higher risk of placental lesions, suggesting heterogeneity of hypospadias etiology and mechanisms.

  19. 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

  20. The reconstruction and analysis of tissue specific human metabolic networks.

    Science.gov (United States)

    Hao, Tong; Ma, Hong-Wu; Zhao, Xue-Ming; Goryanin, Igor

    2012-02-01

    Human tissues have distinct biological functions. Many proteins/enzymes are known to be expressed only in specific tissues and therefore the metabolic networks in various tissues are different. Though high quality global human metabolic networks and metabolic networks for certain tissues such as liver have already been studied, a systematic study of tissue specific metabolic networks for all main tissues is still missing. In this work, we reconstruct the tissue specific metabolic networks for 15 main tissues in human based on the previously reconstructed Edinburgh Human Metabolic Network (EHMN). The tissue information is firstly obtained for enzymes from Human Protein Reference Database (HPRD) and UniprotKB databases and transfers to reactions through the enzyme-reaction relationships in EHMN. As our knowledge of tissue distribution of proteins is still very limited, we replenish the tissue information of the metabolic network based on network connectivity analysis and thorough examination of the literature. Finally, about 80% of proteins and reactions in EHMN are determined to be in at least one of the 15 tissues. To validate the quality of the tissue specific network, the brain specific metabolic network is taken as an example for functional module analysis and the results reveal that the function of the brain metabolic network is closely related with its function as the centre of the human nervous system. The tissue specific human metabolic networks are available at .

  1. PP128. Placental Caspase-3 gene polymorphisms is associated with preeclampsia.

    Science.gov (United States)

    Hsu, C-D; Polavarapu, S; Parton, L

    2012-07-01

    Increased placental trophoblastic apoptosis (programmed cell death) was previously reported in pregnancies complicated by preeclampsia. Caspase-3 is one of the key executioners of apoptosis. Caspase are expressed in many tissues including human placental trophoblast and other tissues. Variations in the promoter area of the Caspase genes may modulate apoptotic signaling, contributing to an increased risk of preeclampsia To determine if gene polymorphisms of Caspase 3 proteins differ between patient with and without preeclampsia. Forty-three singleton placentas were studied. Twenty-two placentas were with preeclampsia and 21 were normotensive controls. DNA was extracted from placentas using QIAAmp DNA Minikit. Genotyping of Caspase 3 +567 was determined by real-time PCR using the Applied Biosystems Prism 7900 HT SDS machine. Chi-square and Fisher's exact tests were used for statistical analysis. There were no significant differences in maternal age, parity or race between the two groups. Preeclamptic placentas had higher frequency of wild type TT of Caspase-3 SNP (+567) as compared with normotensive controls (59% versus 28.5%). Preeclamptic placentas expressed significantly more genotype of TT of Caspase-3 SNP (+567) than normotensive patients when compared to CC (p=0.02). The alle frequencies of the Caspase SNP (+567) in preeclampstic placentas were 0.77 and 0.23 for T and C, respectively, as compared to 0.52 and 0.48, respectively, in placentas from normotensive pregnancies. Immune intolerance of maternal and placental interaction plays an important role in the pathogenesis of preeclampsia. Increased of placental apoptosis was reported in pregnancy complicated with preeclamsia. Our findings indicate placental Caspase 3 (+567) gene polymorphisms is associated with preeclampsia. Altered placental alle frequencies and caspase-3 SNP (+567) in preeclampsia further suggests preeclampsia is a trophoblastic disorder. Copyright © 2012. Published by Elsevier B.V.

  2. Viscoelastic parameter identification of human brain tissue.

    Science.gov (United States)

    Budday, S; Sommer, G; Holzapfel, G A; Steinmann, P; Kuhl, E

    2017-10-01

    Understanding the constitutive behavior of the human brain is critical to interpret the physical environment during neurodevelopment, neurosurgery, and neurodegeneration. A wide variety of constitutive models has been proposed to characterize the brain at different temporal and spatial scales. Yet, their model parameters are typically calibrated with a single loading mode and fail to predict the behavior under arbitrary loading conditions. Here we used a finite viscoelastic Ogden model with six material parameters-an elastic stiffness, two viscoelastic stiffnesses, a nonlinearity parameter, and two viscous time constants-to model the characteristic nonlinearity, conditioning, hysteresis and tension-compression asymmetry of the human brain. We calibrated the model under shear, shear relaxation, compression, compression relaxation, and tension for four different regions of the human brain, the cortex, basal ganglia, corona radiata, and corpus callosum. Strikingly, unconditioned gray matter with 0.36kPa and white matter with 0.35kPa were equally stiff, whereas conditioned gray matter with 0.52kPa was three times stiffer than white matter with 0.18kPa. While both unconditioned viscous time constants were larger in gray than in white matter, both conditioned constants were smaller. These rheological differences suggest a different porosity between both tissues and explain-at least in part-the ongoing controversy between reported stiffness differences in gray and white matter. Our unconditioned and conditioned parameter sets are readily available for finite element simulations with commercial software packages that feature Ogden type models at finite deformations. As such, our results have direct implications on improving the accuracy of human brain simulations in health and disease. Copyright © 2017 Elsevier Ltd. All rights reserved.

  3. Polarized spectral features of human breast tissues through wavelet ...

    Indian Academy of Sciences (India)

    2015-11-27

    Nov 27, 2015 ... Fluorescence characteristics of human breast tissues are investigated through wavelet transform and principal component analysis (PCA). Wavelet transform of polarized fluorescence spectra of human breast tissues is found to localize spectral features that can reliably differentiate different tissue types.

  4. Dynamic Properties of Human Bronchial Airway Tissues

    CERN Document Server

    Wang, Jau-Yi; Pallai, Prathap; Corrigan, Chris J; Lee, Tak H

    2011-01-01

    Young's Modulus and dynamic force moduli were measured on human bronchial airway tissues by compression. A simple and low-cost system for measuring the tensile-strengh of soft bio-materials has been built for this study. The force-distance measurements were undertaken on the dissected bronchial airway walls, cartilages and mucosa from the surgery-removed lungs donated by lung cancer patients with COPD. Young's modulus is estimated from the initial slope of unloading force-displacement curve and the dynamic force moduli (storage and loss) are measured at low frequency (from 3 to 45 Hz). All the samples were preserved in the PBS solution at room temperature and the measurements were perfomed within 4 hours after surgery. Young's modulus of the human bronchial airway walls are fond ranged between 0.17 and 1.65 MPa, ranged between 0.25 to 1.96 MPa for cartilages, and between 0.02 to 0.28 MPa for mucosa. The storage modulus are found varying 0.10 MPa with frequency while the loss modulus are found increasing from ...

  5. 2010 Great Lakes Human Health Fish Tissue Study Fish Tissue Data Dictionary

    Science.gov (United States)

    The Office of Science and Technology (OST) is providing the fish tissue results from the 2010 Great Lakes Human Health Fish Tissue Study (GLHHFTS). This document includes the “data dictionary” for Mercury, PFC, PBDE and PCBs.

  6. 21 CFR 876.5885 - Tissue culture media for human ex vivo tissue and cell culture processing applications.

    Science.gov (United States)

    2010-04-01

    ... 21 Food and Drugs 8 2010-04-01 2010-04-01 false Tissue culture media for human ex vivo tissue and... DEVICES Therapeutic Devices § 876.5885 Tissue culture media for human ex vivo tissue and cell culture processing applications. (a) Identification. Tissue culture media for human ex vivo tissue and cell culture...

  7. FORUM Human tissue and organ transplant provisions: Chapter 8 of ...

    African Journals Online (AJOL)

    permanent residents; (iii) donations of human bodies and tissue of deceased persons; (iv) consent to donations of human tissue on behalf of deceased persons; (v) allocation and use of human organs of ... It is also an offence to sell or trade.

  8. Placentation in different mammalian species.

    Science.gov (United States)

    Chavatte-Palmer, Pascale; Tarrade, Anne

    2016-06-01

    The placenta is a complex, transient organ associated with viviparity, which is located at the interface of the dam and fetus during pregnancy. It is formed after attachment, or implantation, of the blastocyst on the uterine lining and derives from complex cellular and molecular interactions between uterine and embryonic tissues. In mammals, there are many forms of placentation but this organ has the same function in all species: it is responsible for orchestrating materno-fetal exchanges, together with endocrine and immunological functions. Copyright © 2016 Elsevier Masson SAS. All rights reserved.

  9. Handbook of Human Tissue Sources. A National Resource of Human Tissue Samples

    Science.gov (United States)

    1999-01-01

    supplemental calcium for the prevention of preeclampsia during pregnancy. Five clinical centers, enrolling 4,500 women over a two-year period...Centers for Disease Control and Prevention Institutes 106 National Center for Environmental Health 106 National Center for Infectious Diseases...and Prevention Complementary DNA (deoxyribonucleic acid) xxiv Handbook of Human Tissue Sources CFRBCS CGOP CHR CHTN CJD CLIA CLSS CME CMV

  10. Enoxacin penetration into human prostatic tissue.

    Science.gov (United States)

    Bergeron, M G; Roy, R; Lessard, C; Foucault, P

    1988-01-01

    Concurrent enoxacin concentrations in serum and prostatic tissue were determined in 14 patients. The mean ratios of enoxacin concentration in tissue over concentration in serum were 1.4 +/- 0.2 (standard error of the mean). The levels in serum and prostatic tissue were above the MICs for most urinary pathogens. PMID:3196004

  11. Dielectric characterisation of human tissue samples

    NARCIS (Netherlands)

    Rossum, W.L. van; Nennie, F.; Deiana, D.; Veen, A.J. van der; Monni, S.

    2014-01-01

    The electrical properties of tissues samples are required for investigation and simulation purposes in biomedical applications of EM sensors. While available open literature mostly deals with ex-vivo characterization of isolated tissues, knowledge on dielectric properties of these tissues in their

  12. Gentamicin concentrations in human subcutaneous tissue

    DEFF Research Database (Denmark)

    Lorentzen, Hanne; Kallehave, Finn Lasse; Kolmos, Hans Jørn Jepsen

    1996-01-01

    Wound infections frequently originate from the subcutaneous tissue. The effect of gentamicin in subcutaneous tissue has, however, normally been evaluated from concentrations in blood or wound fluid. The aim of the present study was to investigate the pharmacokinetic properties of gentamicin in hu...... the presence of sufficient concentrations in the adipose tissue to be effective against common bacteria....

  13. Cadmium Concentration in Human Autopsy Tissues.

    Science.gov (United States)

    Lech, Teresa; Sadlik, Józefa K

    2017-10-01

    The concentration of cadmium in human tissues obtained on the basis of autopsies of non-poisoned Polish people (n = 150), aged from 1 to 80 years, examined between 1990 and 2010, is presented. The following values were found in wet digested samples by flame atomic absorption spectrometry (FAAS) (mean ± SD, median, and range, μg/g of wet weight): brain 0.020 ± 0.031, 0.084, 0-0.120 (n = 41); stomach 0.148 ± 0.195, 0.084, 0-1.25 (n = 89); small intestine 0.227 ± 0.231, 0.130, 0-0.830 (n = 39); liver 1.54 ± 1.55, 1.01, 0.015-9.65 (n = 99); kidney 16.0 ± 13.2, 14.0, 0.62-61.3 (n = 91); lung 0.304 ± 0.414, 0.130, 0-1.90 (n = 25); and heart 0.137 ± 0.107, 0.140, 0.017-0.250 (n = 4). Additionally, results (n = 13 people, aged from 2 to 83 years, 63 samples) obtained by inductively coupled plasma optical emission spectrometry (ICP OES) between 2010 and 2015 are given. The obtained data on Cd concentration in the human body can be used to estimate the amounts occurring in "healthy" people and those occurring in cases of chronic or acute poisonings with Cd compounds, which are examined for forensic purposes or to assess environmental exposure levels.

  14. 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

  15. Human papillomavirus infects placental trophoblast and Hofbauer cells, but appears not to play a causal role in miscarriage and preterm labor

    DEFF Research Database (Denmark)

    Ambühl, Lea Maria Margareta; Leonhard, Anne Katrine; Zakhary, Carina Widen

    2017-01-01

    deliveries, 10.9% in spontaneous abortions, and 20.4% in elective abortions. 12 different HPV-types were detected and placental HPV infection was associated to a disease history of cervical cancer. HPV DNA was identified in trophoblast cells, cells of the placental villi mesenchyme including Hofbauer cells...

  16. Transcriptomics resources of human tissues and organs

    DEFF Research Database (Denmark)

    Uhlén, Mathias; Hallström, Björn M.; Lindskog, Cecilia

    2016-01-01

    Quantifying the differential expression of genes in various human organs, tissues, and cell types is vital to understand human physiology and disease. Recently, several large-scale transcriptomics studies have analyzed the expression of protein-coding genes across tissues. These datasets provide...... a framework for defining the molecular constituents of the human body as well as for generating comprehensive lists of proteins expressed across tissues or in a tissue-restricted manner. Here, we review publicly available human transcriptome resources and discuss body-wide data from independent genome...... in all tissues and relatively few in a tissue-restricted manner. Moreover, we discuss the applications of publicly available omics data for building genome-scale metabolic models, used for analyzing cell and tissue functions both in physiological and in disease contexts....

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

    DEFF Research Database (Denmark)

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

    2017-01-01

    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...

  18. 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...

  19. Human Cell and Tissue Establishment Registration Public Query

    Data.gov (United States)

    U.S. Department of Health & Human Services — This application provides Human Cell and Tissue registration information for registered, inactive, and pre-registered firms. Query options are by Establishment Name,...

  20. A SYSTEMATIC REVIEW OF PLACENTAL PATHOLOGY IN MATERNAL DIABETES MELLITUS

    Science.gov (United States)

    Huynh, J.; Dawson, D.; Roberts, D.; Bentley-Lewis, R.

    2014-01-01

    During a pregnancy complicated by diabetes, the human placenta undergoes a number of functional and structural pathologic changes, such as increased placental weight and increased incidence of placental lesions including villous maturational defects and fibrinoid necrosis. The pathologic findings reported have differed among studies, potentially reflecting differences in type of diabetes, study methodology, or glycemic control of study participants. Alternatively, these discrepancies may represent different biologic adaptations to distinct metabolic diseases. In order to clarify these distinctions, we conducted a comprehensive review of English language citations in Pubmed and Embase using the keywords “diabetes”, “placenta”, AND “pathology”. Abstracts were reviewed for relevance then full-text articles were reviewed in order to extract a comprehensive summary of current pathological findings associated with pregestational and gestational diabetes mellitus, as well as an understanding of the impact of glycemic control on placental pathology. Placental abnormalities most consistently associated with maternal diabetes are an increased incidence of villous immaturity, increased measures of angiogenesis, and increased placental weight. The literature suggests that, despite similarities in placental abnormalities, differences in placental pathology may reflect differences in pathophysiology among different types of diabetes. Consequently, standardization of terminology used to define placental lesions is warranted. Moreover, further research is needed to investigate the impact of pathophysiology, glycemic control and clinical factors, such as infant sex, weight and race, on placental structure and function. PMID:25524060

  1. 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

    2016-01-01

    Background Preeclampsia (PE) 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 due to placental abnormalities that contribute to the maternal syndrome. However, the specific factors and signaling pathways leading to impaired placentas and maternal disease development remain elusive. Methods and Results By using two independent animal models of PE—1) genetically-engineered pregnant mice with elevated adenosine exclusively in placentas, and 2) a pathogenic autoantibody-induced PE mouse model—we demonstrated here that chronically elevated placental adenosine was sufficient to induce hallmark features of PE including hypertension, proteinuria, small fetuses, and impaired placental vasculature. Genetic and pharmacologic approaches revealed that elevated placental adenosine coupled with excessive A2B adenosine receptor (ADORA2B) signaling contributed to the development of these features of PE. Mechanistically, we provided both human and mouse evidence that elevated placental CD73 is a key enzyme causing increased placental adenosine, thereby contributing to PE. Conclusions We determined that elevated placental adenosine signaling is a previously unrecognized pathogenic factor for PE. 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 PE, and, thereby highlight novel therapeutic targets. PMID:25538227

  2. A systematic review of placental pathology in maternal diabetes mellitus.

    Science.gov (United States)

    Huynh, J; Dawson, D; Roberts, D; Bentley-Lewis, R

    2015-02-01

    During a pregnancy complicated by diabetes, the human placenta undergoes a number of functional and structural pathologic changes, such as increased placental weight and increased incidence of placental lesions including villous maturational defects and fibrinoid necrosis. The pathologic findings reported have differed among studies, potentially reflecting differences in type of diabetes, study methodology, or glycemic control of study participants. Alternatively, these discrepancies may represent different biologic adaptations to distinct metabolic diseases. We conducted a comprehensive review of English language citations in Pubmed and Embase using the keywords "diabetes", "placenta", AND "pathology". Abstracts were reviewed for relevance then full-text articles were reviewed in order to extract a comprehensive summary of current pathological findings associated with pregestational and gestational diabetes mellitus, as well as an understanding of the impact of glycemic control on placental pathology. Placental abnormalities most consistently associated with maternal diabetes are an increased incidence of villous immaturity, increased measures of angiogenesis, and increased placental weight. The literature suggests that, despite similarities in placental abnormalities, differences in placental pathology may reflect differences in pathophysiology among different types of diabetes. Consequently, standardization of terminology used to define placental lesions is warranted. Moreover, further research is needed to investigate the impact of pathophysiology, glycemic control and clinical factors, such as infant sex, weight and race, on placental structure and function. Copyright © 2014 Elsevier Ltd. All rights reserved.

  3. 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.

  4. Evolution of placental function in mammals

    DEFF Research Database (Denmark)

    Carter, Anthony Michael

    2012-01-01

    gas exchange. They evolved following duplications within the beta-globin gene family with convergent evolution occurring in ruminants and primates. In primates there was also an interesting rearrangement of a cassette of genes in relation to an upstream locus control region. Substrate transfer from...... and placental lactogens from the growth hormone and prolactin genes. There has been a remarkable degree of convergent evolution with placental lactogens emerging separately in the ruminant, rodent, and primate lineages and chorionic gonadotropins evolving separately in equids and higher primates. Finally......, coevolution in the primate lineage of killer immunoglobulin-like receptors and human leukocyte antigens can be linked to the deep invasion of the uterus by trophoblast that is a characteristic feature of human placentation....

  5. Quality assessment of a placental perfusion protocol

    DEFF Research Database (Denmark)

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

    2010-01-01

    Validation of in vitro test systems using the modular approach with steps addressing reliability and relevance is an important aim when developing in vitro tests in e.g. reproductive toxicology. The ex vivo human placental perfusion system may be used for such validation, here presenting the plac......Validation of in vitro test systems using the modular approach with steps addressing reliability and relevance is an important aim when developing in vitro tests in e.g. reproductive toxicology. The ex vivo human placental perfusion system may be used for such validation, here presenting...... 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, p

  6. The use of animal tissues alongside human tissue: Cultural and ethical considerations.

    Science.gov (United States)

    Kaw, Anu; Jones, D Gareth; Zhang, Ming

    2016-01-01

    Teaching and research facilities often use cadaveric material alongside animal tissues, although there appear to be differences in the way we handle, treat, and dispose of human cadaveric material compared to animal tissue. This study sought to analyze cultural and ethical considerations and provides policy recommendations on the use of animal tissues alongside human tissue. The status of human and animal remains and the respect because of human and animal tissues were compared and analyzed from ethical, legal, and cultural perspectives. The use of animal organs and tissues is carried out within the context of understanding human anatomy and function. Consequently, the interests of human donors are to be pre-eminent in any policies that are enunciated, so that if any donors find the presence of animal remains unacceptable, the latter should not be employed. The major differences appear to lie in differences in our perceptions of their respective intrinsic and instrumental values. Animals are considered to have lesser intrinsic value and greater instrumental value than humans. These differences stem from the role played by culture and ethical considerations, and are manifested in the resulting legal frameworks. In light of this discussion, six policy recommendations are proposed, encompassing the nature of consent, respect for animal tissues as well as human remains, and appropriate separation of both sets of tissues in preparation and display. © 2015 Wiley Periodicals, Inc.

  7. Local aromatase activity in human breast tissues.

    Science.gov (United States)

    Thijssen, J H; Daroszewski, J; Milewicz, A; Blankenstein, M A

    1993-03-01

    The presence of oestradiol in malignant breast cells is considered to be an important factor in the promotion of growth of the tumor. Therefore the regulation of the local high intra-tissue oestradiol concentrations, regardless of plasma concentrations, has been investigated. Experimental evidence suggests that in situ biosynthesis of oestrogens is at least partly responsible for the local accumulation of these steroids. In this paper we report further data on measurements in fatty and tumor tissues of local aromatase activities and of concentrations of substrates and products of this enzyme. Data are given on localization of aromatase and on steroid concentrations in tumors and in adipose tissues dissected from different quadrants of breasts with malignant tumors. In adipose tissues small variations in steroid concentrations in fatty tissues were found. No tumor-directed gradients in the adipose tissue-concentrations of the androgens dehydro-epiandrosterone, 5-androstene-3 beta, 17 beta-diol, 4-androstene-3,17-dione and testosterone and of the oestrogens oestradiol, oestrone and their sulfates could be detected. Furthermore no consistent pattern could be recognized in the aromatase activities in the fatty tissues dissected from tumor-bearing and non-affected quadrants of the same breast. No correlations between aromatase activity measured in vitro and product concentrations in vivo were found. Therefore the mechanisms for regulation of the local oestradiol levels in breast tissues remain unknown.

  8. Ceftibuten concentrations in human tonsillar tissue.

    Science.gov (United States)

    Scaglione, F; Pintucci, J P; Demartini, G; Dugnani, S

    1996-12-01

    In a study designed to determine ceftibuten concentrations in tonsillar tissue, subjects scheduled to undergo tonsillectomy were administered 400 mg of ceftibuten in a single oral dose. Between 2 and 24 h after the dose was given, tonsillar tissue samples were taken during surgery and assayed for ceftibuten. Mean concentrations in tonsillar tissue 4.4 h and 24.6 h after the 400 mg dose were 5.3 +/- 2.7 and 0.3 +/- mg/g, respectively. Concurrent mean serum concentrations were 7.42 +/- 1.66 and 0.15 +/- 0.13 mg/ml, respectively. The apparent half-life of drug in the tissue was 5.3 h. The presence of high ceftibuten concentrations in tonsillar tissue suggests that a once-daily regimen may be effective in treating tonsillitis and pharyngitis.

  9. Ethical aspects of banking placental blood for transplantation.

    Science.gov (United States)

    Sugarman, J; Reisner, E G; Kurtzberg, J

    1995-12-13

    Transplantation of blood cells harvested from the umbilical cord immediately after birth has been effective in repopulating the bone marrow. These placental blood transplantations may be safer than conventional bone marrow transplantations and may suspend the need to harvest bone marrow, a process fraught with difficulties. Further understanding and advancement of this emerging technology require developing large banks of placental blood. In this article, we examine some of the ethical issues associated with placental blood banking, including (1) questions about ownership of the tissue, (2) the necessity and nature of obtaining informed consent from parents for harvesting placental blood and the information-gathering process associated with it, (3) obligations to notify parents and children of the results of medical testing for infectious diseases and genetic information, (4) matters of privacy and confidentiality related to such information, and (5) the need for fair and equitable harvesting of and access to placental blood.

  10. [Expression of contractile proteins alpha-actin and myosin of smooth muscle cells and collagen of IV type in human placenta at placental insufficiency in III trimester of pregnancy].

    Science.gov (United States)

    Khozhaĭ, L I; Otellin, V A; Pozharisskiĭ, K M; Pavlova, N G

    2010-01-01

    Changes of expression of contractile proteins (alpha-actin and myosin of smooth muscle cell) and of collagen of IV type in stroma of human placental villi were studied at the diagnosed placental insufficiency (PI) in III trimester of pregnancy. The study revealed pronounced disturbances of expression of contractile proteins and collagen of IV type at PI. It is shown that in perivascular envelopes of vessels of stem and intermediate villi there is present a much greater amount of cells expressing smooth muscle actin and myosin. These cells are arranged by the denser concentric layers and more compactly than in norm and fill the intervascular space inside the villi. The width of perivascular envelopes of vessels is higher, while vascular lumens are lower than in norm. In terminal villi the capillary walls are thickened and the number of pericytes immunopositive against the smooth muscle cell alpha-actin and myosin as well as collagen of IV type is increased. The change of synthesis of the cytoskeletal contractile proteins and collagen of IV type is shown to lead to structural disturbances of villi of different types and of perivascular areas and vessels, which doubtlessly indicates their participation in pathogenesis of placental dysfunction and of disturbance of placental hemodynamics.

  11. The importance of drug transporters in human pluripotent stem cells and in early tissue differentiation.

    Science.gov (United States)

    Apáti, Ágota; Szebényi, Kornélia; Erdei, Zsuzsa; Várady, György; Orbán, Tamás I; Sarkadi, Balázs

    2016-01-01

    Drug transporters are large transmembrane proteins which catalyse the movement of a wide variety of chemicals, including drugs as well as xeno- and endobiotics through cellular membranes. The major groups of these proteins include the ATP-binding cassette transporters which in eukaryotes work as ATP-fuelled drug 'exporters' and the Solute Carrier transporters, with various transport directions and mechanisms. In this review, we discuss the key ATP-binding cassette and Solute Carrier drug transporters which have been reported to contribute to the function and/or protection of undifferentiated human stem cells and during tissue differentiation. We review the various techniques for studying transporter expression and function in stem cells, and the role of drug transporters in foetal and placental tissues is also discussed. We especially focus on the regulation of transporter expression by factors modulating cell differentiation properties and on the function of the transporters in adjustment to environmental challenges. The relatively new and as yet unexplored territory of transporters in stem cell biology may rapidly expand and bring important new information regarding the metabolic and epigenetic regulation of 'stemness' and the early differentiation properties. Drug transporters are clearly important protective and regulatory components in stem cells and differentiation.

  12. Human tissue legislation in South Africa: Focus on stem cell ...

    African Journals Online (AJOL)

    2015-08-04

    Aug 4, 2015 ... under the Human Tissue Act 65 of 1983, which was repealed with the enactment of the final sections of the NHA in 2012.[5]. Chapter 8 of the NHA covers seven areas that are relevant to human tissues. These include: • Blood and blood products. • Assisted reproductive technology. • Cell-based therapy.

  13. Partial relief from the regulatory vacuum involving human tissues ...

    African Journals Online (AJOL)

    Human tissue legislation in South. Africa. Concerning human tissue legislation, the law has traditionally struggled to match the pace of scientific and technological advances.1. In this respect, the National Health Act2 (NHA) assented to by the. President on 18 July 2004 came into force on 2 May 2005. At that time matters ...

  14. Lipolysis in human adipose tissue during exercise

    DEFF Research Database (Denmark)

    Lange, Kai Henrik Wiborg; Lorentsen, Jeanne; Isaksson, Fredrik

    2002-01-01

    Subcutaneous adipose tissue lipolysis was studied in vivo by Fick's arteriovenous (a-v) principle using either calculated (microdialysis) or directly measured (catheterization) adipose tissue venous glycerol concentration. We compared results during steady-state (rest and prolonged continuous...... exercise), as well as during non-steady-state (onset of exercise and early exercise) experimental settings. Fourteen healthy women [age: 74 +/- 1 (SE) yr] were studied at rest and during 60-min continuous bicycling at 60% of peak O(2) uptake. Calculated and measured subcutaneous abdominal adipose tissue...

  15. Placental adaptation: what can we learn from birthweight:placental weight ratio?

    Directory of Open Access Journals (Sweden)

    Christina Elizabeth Hayward

    2016-02-01

    Full Text Available Appropriate fetal growth relies upon adequate placental nutrient transfer. Birthweight:placental weight ratio (BW:PW ratio is often used as a proxy for placental efficiency, defined as the grams of fetus produced per gram placenta. An elevated BW:PW ratio in an appropriately grown fetus (small placenta is assumed to be due to up-regulated placental nutrient transfer capacity i.e. a higher nutrient net flux per gram placenta. In fetal growth restriction (FGR, where a fetus fails to achieve its genetically pre-determined growth potential, placental weight and BW:PW ratio are often reduced which may indicate a placenta that fails to adapt its nutrient transfer capacity to compensate for its small size. This review considers the literature on BW:PW ratio in both large cohort studies of normal pregnancies and those studies offering insight into the relationship between BW:PW ratio and outcome measures including stillbirth, FGR and subsequent postnatal consequences. The core of this review is the question of whether BW:PW ratio is truly indicative of altered placental efficiency, and whether changes in BW:PW ratio reflect those placentas which adapt their nutrient transfer according to their size. We consider this question using data from mice and humans, focusing upon studies that have measured the activity of the well characterized placental system A amino acid transporter, both in uncomplicated pregnancies and in FGR. Evidence suggests that BW:PW ratio is reduced both in FGR and in pregnancies resulting in a small for gestational age (SGA, birthweight <10th centile infant but this effect is more pronounced earlier in gestation (<28 weeks. In mice, there is a clear association between increased BW:PW ratio and increased placental system A activity. Additionally, there is good evidence in wild-type mice that small placentas upregulate placental nutrient transfer to prevent fetal undergrowth. In humans, this association between BW:PW ratio and

  16. The use of functional human tissues in drug development.

    Science.gov (United States)

    Bunton, David

    2010-12-01

    Drug development currently depends on animal models to provide an accurate prediction of human physiology and pathophysiology. However, as is clear from clinical trial failures during phases II and III, such in vivo models do not always predict the effects that a drug can elicit in humans. Tests with human tissues, which are obviously considered to be the closest model of human in vivo function, could fill the gap between animal-based tests and trials in patients. Despite clear advantages, logistical and ethical barriers prevent fresh human tissues from being widely used during drug development. Biopta is aiming to make human tissue testing a regular element of drug development, and works to lower the barriers surrounding the availability of tissue and practicalities of experimental work. 2010 FRAME.

  17. Aromatase reaction of 3-deoxyandrogens: steric mode of the C-19 oxygenation and cleavage of the C10-C19 bond by human placental aromatase.

    Science.gov (United States)

    Numazawa, Mitsuteru; Nagaoka, Masao; Sohtome, Norishige

    2005-08-16

    Aromatase is a cytochrome P-450 enzyme complex that catalyzes the conversion of androst-4-ene-3,17-dione (AD) to estrone and formic acid through three sequential oxygenations of the 19-methyl group. To gain insight into the catalytic function of aromatase as well as the mechanism of the hitherto uncertain third oxygenation step, we focused on the aromatase-catalyzed 19-oxygenation of 3-deoxyandrogens: 3-deoxy-AD (1), which is a very powerful competitive inhibitor but poor substrate of aromatase, and its 5-ene isomer 4, which is a good competitive inhibitor and effective substrate of the enzyme. In incubations of their 19S-(3)H-labeled 19-hydroxy derivatives 2 and 5 and the corresponding 19R-(3)H isomers with human placental microsomes in the presence of NADPH under air, the radioactivity was liberated in both water and formic acid. The productions of (3)H(2)O and (3)HCOOH were blocked by the substrate AD or the inhibitor 4-hydroxy-AD, indicating that these productions are due to a catalytic function of aromatase. A comparison of the (3)H(2)O production from S-(3)H substrates 2 and 5 with that from the corresponding R-(3)H isomers revealed that the 19-pro-R hydrogen atom was stereospecifically (pro-R:pro-S = 100:0) removed in the conversion of 5-ene substrate 5 into the 19-oxo product 6, whereas 75:25 stereoselectivity for the loss of the pro-R and pro-S hydrogen atoms was observed in the oxygenation of the other substrate, 2. The present results reveal that human placental aromatase catalyzes three sequential oxygenations at C-19 of 3-deoxyandrogens 1 and 4 to cause the cleavage of the C(10)-C(19) bond through their 19-hydroxy (2 and 5) and 19-oxo (3 and 6) intermediates, respectively, where there is a difference in the stereochemistry between the two androgens in the second 19-hydroxylation. It is implied that the aromatase-catalyzed 19-oxygenation of 5-ene steroid 4 but not the 4-ene isomer 1 would proceed in the same steric mechanism as that involved in the AD

  18. l-Methionine Placental Uptake

    Science.gov (United States)

    Araújo, João R.; Correia-Branco, Ana; Ramalho, Carla; Gonçalves, Pedro; Pinho, Maria J.; Keating, Elisa

    2013-01-01

    Our aim was to investigate the influence of gestational diabetes mellitus (GDM) and GDM-associated conditions upon the placental uptake of 14C-l-methionine (14C-l-Met). The 14C-l-Met uptake by human trophoblasts (TBs) obtained from normal pregnancies (normal trophoblast [NTB] cells) is mainly system l-type amino acid transporter 1 (LAT1 [L])-mediated, although a small contribution of system y+LAT2 is also present. Comparison of 14C-l-Met uptake by NTB and by human TBs obtained from GDM pregnancies (diabetic trophoblast [DTB] cells) reveals similar kinetics, but a contribution of systems A, LAT2, and b0+ and a greater contribution of system y+LAT1 appears to exist in DTB cells. Short-term exposure to insulin and long-term exposure to high glucose, tumor necrosis factor-α, and leptin decrease 14C-l-Met uptake in a human TB (Bewo) cell line. The effect of leptin was dependent upon phosphoinositide 3-kinase, extracellular-signal-regulated kinase 1/2 (ERK/MEK 1/2), and p38 mitogen-activated protein kinase. In conclusion, GDM does not quantitatively alter 14C-l-Met placental uptake, although it changes the nature of transporters involved in that process. PMID:23653387

  19. Risk factors of placental abruption

    OpenAIRE

    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 co...

  20. 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.

  1. Determinants of human adipose tissue gene expression

    DEFF Research Database (Denmark)

    Viguerie, Nathalie; Montastier, Emilie; Maoret, Jean-José

    2012-01-01

    Weight control diets favorably affect parameters of the metabolic syndrome and delay the onset of diabetic complications. The adaptations occurring in adipose tissue (AT) are likely to have a profound impact on the whole body response as AT is a key target of dietary intervention. Identification ...

  2. French legal framework relating to human tissues and cells.

    Science.gov (United States)

    Pascal, P; Damour, O; Colpart, J J; Braye, F

    2000-03-01

    Thousands of patients receive human tissue grafts every year. Developments in cell and tissue engineering have also increased considerably the number of available products of human origin. France has very strict regulations, in part stimulated by problems of public health and ethics that have emerged in recent years and also in part as a result of a report by the 'Inspection Générale des Affaires Sociales' on the removal and grafting of human tissues in May 1993. These have resulted in two laws on bio-ethics being passed, in July 1994, that are the basis of current legislation and represent the first steps in differentiating between organs and tissues or cells. Henceforth, the French legal framework covering tissues and cells of human origin has been increased to include a large number of legislative texts and regulations. The fundamental ethical principles that are consent, free donation, anonymity, no publicity and respect for public health have become a major ethical imperative that applies to all products originating from the human body including tissue and cells. In addition, specific provisions have been made covering: removal (conditions for removal and system for authorization); conservation, transformation, distribution, packaging, import and export of tissues and cells; and tissue and cell grafts. Finally, penal and administrative sanctions have been foreseen where there is non-compliance with these regulations.

  3. Distribution of a major connective tissue protein, fibronectin, in normal human tissues.

    Science.gov (United States)

    Stenman, S; Vaheri, A

    1978-04-01

    Fibronectin is a major surface-associated glycoprotein of cultured fibroblasts and it is also present in human plasma. Antiserum specific for human fibronectin was used to study the distribution of fibronectin in normal adult human tissues. The protein was detected (a) characteristically in various basement membranes including capillary walls: (b) around individual smooth muscle cells and in the sarcolemma of striated muscle fibers; and (c) in the stroma of lymphatic tissue and as thin fibers in loose connective tissue. The distribution of fibronectin was distinct from that of collagen and elastic fibers, but was very similar to reticulin, as demonstrated by conventional histological staining. The results indicate that fibronectin is a major component of connective tissue matrix. The distribution also indicates that most types of adherent cells abut fibronectin-containing structures. This supports the possible role of fibronectin in cell-cell and cell-matrix interactions in tissues.

  4. Cigarette smoke extract induces placental growth factor release from human bronchial epithelial cells via ROS/MAPK(ERK-1/2/Egr-1 axis

    Directory of Open Access Journals (Sweden)

    Wu D

    2016-12-01

    Full Text Available Dong Wu,1,* Yalian Yuan,1,* Zhixiu Lin,2,* Tianwen Lai,1 Min Chen,1 Wen Li,1 Quanchao Lv,1 Binfan Yuan,1 Dongmin Li,1 Bin Wu1 1Department of Respiratory, Institute of Respiratory Diseases, 2Department of Pharmacy, The Affiliated Hospital of Guangdong Medical University, Zhanjiang, People’s Republic of China *These authors contributed equally to this work Abstract: Etiological evidence demonstrates that there is a significant association between cigarette smoking and chronic airway inflammatory disease. Abnormal expression of placental growth factor (PlGF has been reported in COPD, and its downstream signaling molecules have been reported to contribute to the pathogenesis of airway epithelial cell apoptosis and emphysema. However, the signaling mechanisms underlying cigarette smoke extract (CSE-induced PlGF expression in airway microenvironment remain unclear. Herein, we investigated the effects of reactive oxygen species (ROS-dependent activation of the mitogen-activated protein kinase (MAPK (extracellular signal-regulated kinase1/2 [ERK-1/2]/early growth response-1 (Egr-1 pathway on CSE-induced PlGF upregulation in human bronchial epithelium (HBE. The data obtained with quantitative reverse transcription polymerase chain reaction, Western blot, enzyme-linked immunosorbent assay (ELISA and immunofluorescence staining analyses showed that CSE-induced Egr-1 activation was mainly mediated through production of ROS and activation of the MAPK (ERK-1/2 cascade. The binding of Egr-1 to the PlGF promoter was corroborated by an ELISA-based DNA binding activity assay. These results demonstrate that ROS activation of the MAPK (ERK-1/2/Egr-1 pathway is a main player in the regulatory mechanism for CSE-induced PlGF production and that the use of an antioxidant could partly abolish these effects. Understanding the mechanisms of PlGF upregulation by CSE in the airway microenvironment may provide rational therapeutic interventions for cigarette smoking

  5. Full-length human placental sFlt-1-e15a isoform induces distinct maternal phenotypes of preeclampsia in mice.

    Directory of Open Access Journals (Sweden)

    Gabor Szalai

    Full Text Available Most anti-angiogenic preeclampsia models in rodents utilized the overexpression of a truncated soluble fms-like tyrosine kinase-1 (sFlt-1 not expressed in any species. Other limitations of mouse preeclampsia models included stressful blood pressure measurements and the lack of postpartum monitoring. We aimed to 1 develop a mouse model of preeclampsia by administering the most abundant human placental sFlt-1 isoform (hsFlt-1-e15a in preeclampsia; 2 determine blood pressures in non-stressed conditions; and 3 develop a survival surgery that enables the collection of fetuses and placentas and postpartum (PP monitoring.Pregnancy status of CD-1 mice was evaluated with high-frequency ultrasound on gestational days (GD 6 and 7. Telemetry catheters were implanted in the carotid artery on GD7, and their positions were verified by ultrasound on GD13. Mice were injected through tail-vein with adenoviruses expressing hsFlt-1-e15a (n = 11 or green fluorescent protein (GFP; n = 9 on GD8/GD11. Placentas and pups were delivered by cesarean section on GD18 allowing PP monitoring. Urine samples were collected with cystocentesis on GD6/GD7, GD13, GD18, and PPD8, and albumin/creatinine ratios were determined. GFP and hsFlt-1-e15a expression profiles were determined by qRT-PCR. Aortic ring assays were performed to assess the effect of hsFlt-1-e15a on endothelia.Ultrasound predicted pregnancy on GD7 in 97% of cases. Cesarean section survival rate was 100%. Mean arterial blood pressure was higher in hsFlt-1-e15a-treated than in GFP-treated mice (∆MAP = 13.2 mmHg, p = 0.00107; GD18. Focal glomerular changes were found in hsFlt-1-e15a -treated mice, which had higher urine albumin/creatinine ratios than controls (109.3 ± 51.7 μg/mg vs. 19.3 ± 5.6 μg/mg, p = 4.4 x 10(-2; GD18. Aortic ring assays showed a 46% lesser microvessel outgrowth in hsFlt-1-e15a-treated than in GFP-treated mice (p = 1.2 x 10(-2. Placental and fetal weights did not differ between the groups

  6. Full-length human placental sFlt-1-e15a isoform induces distinct maternal phenotypes of preeclampsia in mice.

    Science.gov (United States)

    Szalai, Gabor; Romero, Roberto; Chaiworapongsa, Tinnakorn; Xu, Yi; Wang, Bing; Ahn, Hyunyoung; Xu, Zhonghui; Chiang, Po Jen; Sundell, Birgitta; Wang, Rona; Jiang, Yang; Plazyo, Olesya; Olive, Mary; Tarca, Adi L; Dong, Zhong; Qureshi, Faisal; Papp, Zoltan; Hassan, Sonia S; Hernandez-Andrade, Edgar; Than, Nandor Gabor

    2015-01-01

    Most anti-angiogenic preeclampsia models in rodents utilized the overexpression of a truncated soluble fms-like tyrosine kinase-1 (sFlt-1) not expressed in any species. Other limitations of mouse preeclampsia models included stressful blood pressure measurements and the lack of postpartum monitoring. We aimed to 1) develop a mouse model of preeclampsia by administering the most abundant human placental sFlt-1 isoform (hsFlt-1-e15a) in preeclampsia; 2) determine blood pressures in non-stressed conditions; and 3) develop a survival surgery that enables the collection of fetuses and placentas and postpartum (PP) monitoring. Pregnancy status of CD-1 mice was evaluated with high-frequency ultrasound on gestational days (GD) 6 and 7. Telemetry catheters were implanted in the carotid artery on GD7, and their positions were verified by ultrasound on GD13. Mice were injected through tail-vein with adenoviruses expressing hsFlt-1-e15a (n = 11) or green fluorescent protein (GFP; n = 9) on GD8/GD11. Placentas and pups were delivered by cesarean section on GD18 allowing PP monitoring. Urine samples were collected with cystocentesis on GD6/GD7, GD13, GD18, and PPD8, and albumin/creatinine ratios were determined. GFP and hsFlt-1-e15a expression profiles were determined by qRT-PCR. Aortic ring assays were performed to assess the effect of hsFlt-1-e15a on endothelia. Ultrasound predicted pregnancy on GD7 in 97% of cases. Cesarean section survival rate was 100%. Mean arterial blood pressure was higher in hsFlt-1-e15a-treated than in GFP-treated mice (∆MAP = 13.2 mmHg, p = 0.00107; GD18). Focal glomerular changes were found in hsFlt-1-e15a -treated mice, which had higher urine albumin/creatinine ratios than controls (109.3 ± 51.7 μg/mg vs. 19.3 ± 5.6 μg/mg, p = 4.4 x 10(-2); GD18). Aortic ring assays showed a 46% lesser microvessel outgrowth in hsFlt-1-e15a-treated than in GFP-treated mice (p = 1.2 x 10(-2)). Placental and fetal weights did not differ between the groups. One

  7. Full-Length Human Placental sFlt-1-e15a Isoform Induces Distinct Maternal Phenotypes of Preeclampsia in Mice

    Science.gov (United States)

    Szalai, Gabor; Romero, Roberto; Chaiworapongsa, Tinnakorn; Xu, Yi; Wang, Bing; Ahn, Hyunyoung; Xu, Zhonghui; Chiang, Po Jen; Sundell, Birgitta; Wang, Rona; Jiang, Yang; Plazyo, Olesya; Olive, Mary; Tarca, Adi L.; Dong, Zhong; Qureshi, Faisal; Papp, Zoltan; Hassan, Sonia S.; Hernandez-Andrade, Edgar; Than, Nandor Gabor

    2015-01-01

    Objective Most anti-angiogenic preeclampsia models in rodents utilized the overexpression of a truncated soluble fms-like tyrosine kinase-1 (sFlt-1) not expressed in any species. Other limitations of mouse preeclampsia models included stressful blood pressure measurements and the lack of postpartum monitoring. We aimed to 1) develop a mouse model of preeclampsia by administering the most abundant human placental sFlt-1 isoform (hsFlt-1-e15a) in preeclampsia; 2) determine blood pressures in non-stressed conditions; and 3) develop a survival surgery that enables the collection of fetuses and placentas and postpartum (PP) monitoring. Methods Pregnancy status of CD-1 mice was evaluated with high-frequency ultrasound on gestational days (GD) 6 and 7. Telemetry catheters were implanted in the carotid artery on GD7, and their positions were verified by ultrasound on GD13. Mice were injected through tail-vein with adenoviruses expressing hsFlt-1-e15a (n = 11) or green fluorescent protein (GFP; n = 9) on GD8/GD11. Placentas and pups were delivered by cesarean section on GD18 allowing PP monitoring. Urine samples were collected with cystocentesis on GD6/GD7, GD13, GD18, and PPD8, and albumin/creatinine ratios were determined. GFP and hsFlt-1-e15a expression profiles were determined by qRT-PCR. Aortic ring assays were performed to assess the effect of hsFlt-1-e15a on endothelia. Results Ultrasound predicted pregnancy on GD7 in 97% of cases. Cesarean section survival rate was 100%. Mean arterial blood pressure was higher in hsFlt-1-e15a-treated than in GFP-treated mice (∆MAP = 13.2 mmHg, p = 0.00107; GD18). Focal glomerular changes were found in hsFlt-1-e15a -treated mice, which had higher urine albumin/creatinine ratios than controls (109.3±51.7μg/mg vs. 19.3±5.6μg/mg, p = 4.4x10-2; GD18). Aortic ring assays showed a 46% lesser microvessel outgrowth in hsFlt-1-e15a-treated than in GFP-treated mice (p = 1.2x10-2). Placental and fetal weights did not differ between the

  8. Construction of retroviral recombinant containing human tissue ...

    African Journals Online (AJOL)

    Correct orientation was verified by restriction endonuclease digestion. Human full length TIMP-2 gene was ligated into a plasmid, which was then transfected into PA317 cell line. G418-resistant individual clones were selected to transfect human SGC-7901 cell line. Cell proliferation, cell electrophoresis, soft agar colony ...

  9. Natural Rubber Nanocomposite with Human-Tissue-Like Mechanical Characteristic

    Science.gov (United States)

    Murniati, Riri; Novita, Nanda; Sutisna; Wibowo, Edy; Iskandar, Ferry; Abdullah, Mikrajuddin

    2017-07-01

    The blends of synthetic rubber and natural rubber with nanosilica were prepared using a blending technique in presence of different filler volume fraction. The effect of filler on morphological and mechanical characteristics was studied. Utilization of human cadaver in means of medical study has been commonly used primarily as tools of medical teaching and training such as surgery. Nonetheless, human cadaver brought inevitable problems. So it is necessary to find a substitute material that can be used to replace cadavers. In orthopaedics, the materials that resemble in mechanical properties to biological tissues are elastomers such as natural rubber (latex) and synthetic rubber (polyurethanes, silicones). This substitution material needs to consider the potential of Indonesia to help the development of the nation. Indonesia is the second largest country producer of natural rubber in the world. This paper aims to contribute to adjusting the mechanical properties of tissue-mimicking materials (TMMs) to the recommended range of biological tissue value and thus allow the development of phantoms with greater stability and similarity to human tissues. Repeatability for the phantom fabrication process was also explored. Characteristics were then compared to the control and mechanical characteristics of different human body part tissue. Nanosilica is the best filler to produce the best nanocomposite similarities with human tissue. We produced composites that approaching the properties of human internal tissues.

  10. Two-way regulation between cells and aligned collagen fibrils: local 3D matrix formation and accelerated neural differentiation of human decidua parietalis placental stem cells.

    Science.gov (United States)

    Li, Wen; Zhu, Bofan; Strakova, Zuzana; Wang, Rong

    2014-08-08

    It has been well established that an aligned matrix provides structural and signaling cues to guide cell polarization and cell fate decision. However, the modulation role of cells in matrix remodeling and the feedforward effect on stem cell differentiation have not been studied extensively. In this study, we report on the concerted changes of human decidua parietalis placental stem cells (hdpPSCs) and the highly ordered collagen fibril matrix in response to cell-matrix interaction. With high-resolution imaging, we found the hdpPSCs interacted with the matrix by deforming the cell shape, harvesting the nearby collagen fibrils, and reorganizing the fibrils around the cell body to transform a 2D matrix to a localized 3D matrix. Such a unique 3D matrix prompted high expression of β-1 integrin around the cell body that mediates and facilitates the stem cell differentiation toward neural cells. The study offers insights into the coordinated, dynamic changes at the cell-matrix interface and elucidates cell modulation of its matrix to establish structural and biochemical cues for effective cell growth and differentiation. Copyright © 2014 Elsevier Inc. All rights reserved.

  11. Kinetic analysis of reversible inhibition of 16alpha-hydroxyandrostenedione aromatization in human placental microsomes by suicide substrates of androstenedione aromatization.

    Science.gov (United States)

    Numazawa, Mitsuteru; Mutsumi, Ayako; Tachibana, Mii; Yoshimura, Akiko

    2003-06-01

    To gain insight into the catalytic function of aromatase and its substrate specificity, we studied reversible inhibition of 16alpha-hydroxyandrostenedione (16alpha-OHAD) aromatization in human placental microsomes by several suicide substrates of androstenedione (AD) aromatization, including 4-hydroxyAD (1), 6-oxoAD (2) and its 19-hydroxy analogue 3, androst-5-ene-4,7,17-trione (4), and 10beta-acetoxyandrost-5-en-7,17-dione (5) that, in contrast, do not cause a suicide inactivation of 16alpha-OHAD aromatization. All inhibitors examined blocked 16alpha-OHAD aromatization in a competitive manner with apparent K(i) values ranging from 0.50 to 980 nM. The relative K(i) values between inhibitors 1-5 obtained in the 16alpha-OHAD aromatization experiments were markedly different from those obtained in the AD aromatization experiments. The results predict that all inhibitors examined bind to the 16alpha-OHAD binding site in a manner that does not cause suicide inactivation of 16alpha-OHAD aromatization. These findings would be useful for understanding the active (binding) site structure as well as the catalytic function of aromatase.

  12. Exposure to a MRI-type high-strength static magnetic field stimulates megakaryocytic/erythroid hematopoiesis in CD34+ cells from human placental and umbilical cord blood.

    Science.gov (United States)

    Monzen, Satoru; Takahashi, Kenji; Toki, Tsutomu; Ito, Etsuro; Sakurai, Tomonori; Miyakoshi, Junji; Kashiwakura, Ikuo

    2009-05-01

    The biological response after exposure to a high-strength static magnetic field (SMF) has recently been widely discussed from the perspective of possible health benefits as well as potential adverse effects. To clarify this issue, CD34+ cells from human placental and umbilical cord blood were exposed under conditions of high-strength SMF in vitro. The high-strength SMF exposure system was comprised of a magnetic field generator with a helium-free superconducting magnet with built-in CO2 incubator. Freshly prepared CD34 cells were exposed to a 5 tesla (T) SMF with the strongest magnetic field gradient (41.7 T/m) or a 10 T SMF without magnetic field gradient for 4 or 16 h. In the harvested cells after exposure to 10 T SMF for 16 h, a significant increase of hematopoietic progenitors in the total burst-forming unit erythroid- and megakaryocytic progenitor cells-derived colony formation was observed, thus producing 1.72- and 1.77-fold higher than the control, respectively. Furthermore, early hematopoiesis-related and cell cycle-related genes were found to be significantly up-regulated by exposure to SMF. These results suggest that the 10 T SMF exposure may change gene expressions and result in the specific enhancement of megakaryocytic/erythroid progenitor (MEP) differentiation from pluripotent hematopoietic stem cells and/or the proliferation of bipotent MEP. Copyright 2009 Wiley-Liss, Inc.

  13. [Metabolism of ornithine in human gingival tissue].

    Science.gov (United States)

    Pinna, G G; Chessa, G; Luglié, P F; Trova, R; Sisini, A

    1989-11-01

    The behavior of two enzymes of the ornithine pathway, leading to the formation of proline and, eventually, of collagen, arginase and ornithine oxo-acid aminotransferase has been investigated in normal and inflamed gingival tissue. Both enzymatic activities show a statistically significant decrease in pathological samples as compared to normal ones. The data on arginase activity may be in agreement with the already documented low level of urea in pathological gingival fluid, while a decrease of the ornithine aminotransferase activity could be linked to the phenomenon of gingival retraction, i.e. the lack of complete regeneration of gingival tissue usually observed in chronically inflamed subjects, that would be reasonably parallel to a decreased proline/collagen synthesis.

  14. Three-Dimensionally Engineered Normal Human Broncho-epithelial Tissue-Like Assemblies: Target Tissues for Human Respiratory Viral Infections

    Science.gov (United States)

    Goodwin, T. J.; McCarthy, M.; Lin, Y-H

    2006-01-01

    In vitro three-dimensional (3D) human broncho-epithelial (HBE) tissue-like assemblies (3D HBE TLAs) from this point forward referred to as TLAs were engineered in Rotating Wall Vessel (RWV) technology to mimic the characteristics of in vivo tissues thus providing a tool to study human respiratory viruses and host cell interactions. The TLAs were bioengineered onto collagen-coated cyclodextran microcarriers using primary human mesenchymal bronchial-tracheal cells (HBTC) as the foundation matrix and an adult human bronchial epithelial immortalized cell line (BEAS-2B) as the overlying component. The resulting TLAs share significant characteristics with in vivo human respiratory epithelium including polarization, tight junctions, desmosomes, and microvilli. The presence of tissue-like differentiation markers including villin, keratins, and specific lung epithelium markers, as well as the production of tissue mucin, further confirm these TLAs differentiated into tissues functionally similar to in vivo tissues. Increasing virus titers for human respiratory syncytial virus (wtRSVA2) and parainfluenza virus type 3 (wtPIV3 JS) and the detection of membrane bound glycoproteins over time confirm productive infections with both viruses. Therefore, TLAs mimic aspects of the human respiratory epithelium and provide a unique capability to study the interactions of respiratory viruses and their primary target tissue independent of the host's immune system.

  15. Three-Dimensionally Engineered Normal Human Lung Tissue-Like Assemblies: Target Tissues for Human Respiratory Viral Infections

    Science.gov (United States)

    Goodwin, Thomas J.; McCarthy, M.; Lin, Y-H.; Deatly, A. M.

    2008-01-01

    In vitro three-dimensional (3D) human lung epithelio-mesenchymal tissue-like assemblies (3D hLEM TLAs) from this point forward referred to as TLAs were engineered in Rotating Wall Vessel (RWV) technology to mimic the characteristics of in vivo tissues thus providing a tool to study human respiratory viruses and host cell interactions. The TLAs were bioengineered onto collagen-coated cyclodextran microcarriers using primary human mesenchymal bronchial-tracheal cells (HBTC) as the foundation matrix and an adult human bronchial epithelial immortalized cell line (BEAS-2B) as the overlying component. The resulting TLAs share significant characteristics with in vivo human respiratory epithelium including polarization, tight junctions, desmosomes, and microvilli. The presence of tissue-like differentiation markers including villin, keratins, and specific lung epithelium markers, as well as the production of tissue mucin, further confirm these TLAs differentiated into tissues functionally similar to in vivo tissues. Increasing virus titers for human respiratory syncytial virus (wtRSVA2) and the detection of membrane bound glycoproteins over time confirm productive infection with the virus. Therefore, we assert TLAs mimic aspects of the human respiratory epithelium and provide a unique capability to study the interactions of respiratory viruses and their primary target tissue independent of the host s immune system.

  16. The nature of placental steroid sulphatase deficiency in man

    NARCIS (Netherlands)

    van der Loos, C. M.; van Breda, A. J.; van den Berg, F. M.; Jöbsis, A. C.

    1983-01-01

    Human placental steroid sulphatase was partially purified from microsome suspensions of control and steroid sulphatase deficient placentae. After polyacrylamidegel electrophoresis, staining for protein and enzymatic activity revealed that steroid sulphatase from control placenta migrates at Rf =

  17. Differential reduction of reactive oxygen species by human tissue ...

    Indian Academy of Sciences (India)

    Swati Paliwal

    2017-06-24

    Jun 24, 2017 ... Clinical trials using human Mesenchymal Stem Cells (MSCs) have shown promising results in the treatment of various diseases. Different tissue sources, such as bone marrow, adipose tissue, dental pulp and umbilical cord, are being routinely used in regenerative medicine. MSCs are known to reduce ...

  18. Differential reduction of reactive oxygen species by human tissue ...

    Indian Academy of Sciences (India)

    Clinical trials using human Mesenchymal Stem Cells (MSCs) have shown promising results in the treatment of variousdiseases. Different tissue sources, such as bone marrow, adipose tissue, dental pulp and umbilical cord, are being routinelyused in regenerative medicine. MSCs are known to reduce increased oxidative ...

  19. 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.

  20. Microwave non-contact imaging of subcutaneous human body tissues

    Science.gov (United States)

    Chernokalov, Alexander; Khripkov, Alexander; Cho, Jaegeol; Druchinin, Sergey

    2015-01-01

    A small-size microwave sensor is developed for non-contact imaging of a human body structure in 2D, enabling fitness and health monitoring using mobile devices. A method for human body tissue structure imaging is developed and experimentally validated. Subcutaneous fat tissue reconstruction depth of up to 70 mm and maximum fat thickness measurement error below 2 mm are demonstrated by measurements with a human body phantom and human subjects. Electrically small antennas are developed for integration of the microwave sensor into a mobile device. Usability of the developed microwave sensor for fitness applications, healthcare, and body weight management is demonstrated. PMID:26609415

  1. Microwave non-contact imaging of subcutaneous human body tissues.

    Science.gov (United States)

    Kletsov, Andrey; Chernokalov, Alexander; Khripkov, Alexander; Cho, Jaegeol; Druchinin, Sergey

    2015-10-01

    A small-size microwave sensor is developed for non-contact imaging of a human body structure in 2D, enabling fitness and health monitoring using mobile devices. A method for human body tissue structure imaging is developed and experimentally validated. Subcutaneous fat tissue reconstruction depth of up to 70 mm and maximum fat thickness measurement error below 2 mm are demonstrated by measurements with a human body phantom and human subjects. Electrically small antennas are developed for integration of the microwave sensor into a mobile device. Usability of the developed microwave sensor for fitness applications, healthcare, and body weight management is demonstrated.

  2. Monocarboxylate Transporter 8 Modulates the Viability and Invasive Capacity of Human Placental Cells and Fetoplacental Growth in Mice

    NARCIS (Netherlands)

    E. Vasilopoulou (Elisavet); L.S. Loubière (Laurence); H. Heuer (Heike); M. Trajkovic-Arsic (Marija); V.M. Darras (Veerle); T.J. Visser (Theo); G.E. Lash (Gendie); G.S. Whitley (Guy); C.J. McCabe (Christopher); J.A. Franklyn (Jayne); M.D. Kilby (Mark); S.Y. Chan (Shiao)

    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,

  3. Cell-specific and dose-dependent effects of PAHs on proliferation, cell cycle, and apoptosis protein expression and hormone secretion by placental cell lines.

    Science.gov (United States)

    Drwal, Eliza; Rak, Agnieszka; Grochowalski, Adam; Milewicz, Tomasz; Gregoraszczuk, Ewa Lucja

    2017-10-05

    In the preset study we measured the concentrations of 16 priority PAHs in maternal blood and placental tissue by using the GC-MS/MS system, and investigated the effects of selected PAHs (naphthalene, anthracene, phenanthrene, pyrene) and mixtures on BeWo and JEG-3 human placental cell line proliferation (Alamar Blue), cytotoxicity (3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyltetrazolium bromide (XTT), lactate dehydrogenase (LDH), acid phosphatase (AP), endocrine activity (progesterone and estradiol secretion) and apoptosis (cyclin A1, cyclin D2, cdk 2, cdk 4, Bcl-xl, Bax, and caspase-3 protein expression). The concentrations of 16 PAHs in maternal blood were higher than in placental tissue. In JEG-3 cells except for naphthalene, all PAHs studied and their mixtures at maternal doses, and only naphthalene at placental doses, increased XTT, while in BeWo cells, placental doses increased XTT and AP activity. A cell-type dependent action: a proapoptotic effect (increased Bax and caspase-3) in BeWo cells and an antiapoptotic effect (decreased Bax and increased cdk2 and cyclin D1) in JEG-3 cells was observed. Naphthalene, pyrene, and phenanthrene exhibited an endocrine-disrupting effect in JEG3 cells but not in BeWo cells. Our results provide evidence of cell specific effects of selected low molecular weight PAHs on proliferation, the cell cycle, proapoptotic protein expression, and hormone secretion. Copyright © 2017 Elsevier B.V. All rights reserved.

  4. Human tissue models in cancer research: looking beyond the mouse

    Directory of Open Access Journals (Sweden)

    Samuel J. Jackson

    2017-08-01

    Full Text Available Mouse models, including patient-derived xenograft mice, are widely used to address questions in cancer research. However, there are documented flaws in these models that can result in the misrepresentation of human tumour biology and limit the suitability of the model for translational research. A coordinated effort to promote the more widespread development and use of ‘non-animal human tissue’ models could provide a clinically relevant platform for many cancer studies, maximising the opportunities presented by human tissue resources such as biobanks. A number of key factors limit the wide adoption of non-animal human tissue models in cancer research, including deficiencies in the infrastructure and the technical tools required to collect, transport, store and maintain human tissue for lab use. Another obstacle is the long-standing cultural reliance on animal models, which can make researchers resistant to change, often because of concerns about historical data compatibility and losing ground in a competitive environment while new approaches are embedded in lab practice. There are a wide range of initiatives that aim to address these issues by facilitating data sharing and promoting collaborations between organisations and researchers who work with human tissue. The importance of coordinating biobanks and introducing quality standards is gaining momentum. There is an exciting opportunity to transform cancer drug discovery by optimising the use of human tissue and reducing the reliance on potentially less predictive animal models.

  5. Mtd Bok takes a swing: proapoptotic Mtd Bok regulates trophoblast cell proliferation during human placental development and in preeclampsia

    National Research Council Canada - National Science Library

    Ray, J E; Garcia, J; Jurisicova, A; Caniggia, I

    2010-01-01

    We have previously reported that matador/Bcl-2 ovarian killer (Mtd/Bok), a proapoptotic member of the Bcl-2 family, regulates human trophoblast apoptosis and that its levels are elevated in severe preeclamptic pregnancy...

  6. Chemical Probes for Visualizing Intact Animal and Human Brain Tissue.

    Science.gov (United States)

    Lai, Hei Ming; Ng, Wai-Lung; Gentleman, Steve M; Wu, Wutian

    2017-06-22

    Newly developed tissue clearing techniques can be used to render intact tissues transparent. When combined with fluorescent labeling technologies and optical sectioning microscopy, this allows visualization of fine structure in three dimensions. Gene-transfection techniques have proved very useful in visualizing cellular structures in animal models, but they are not applicable to human brain tissue. Here, we discuss the characteristics of an ideal chemical fluorescent probe for use in brain and other cleared tissues, and offer a comprehensive overview of currently available chemical probes. We describe their working principles and compare their performance with the goal of simplifying probe selection for neuropathologists and stimulating probe development by chemists. We propose several approaches for the development of innovative chemical labeling methods which, when combined with tissue clearing, have the potential to revolutionize how we study the structure and function of the human brain. Copyright © 2017 Elsevier Ltd. All rights reserved.

  7. A family of hyperelastic models for human brain tissue

    Science.gov (United States)

    Mihai, L. Angela; Budday, Silvia; Holzapfel, Gerhard A.; Kuhl, Ellen; Goriely, Alain

    2017-09-01

    Experiments on brain samples under multiaxial loading have shown that human brain tissue is both extremely soft when compared to other biological tissues and characterized by a peculiar elastic response under combined shear and compression/tension: there is a significant increase in shear stress with increasing axial compression compared to a moderate increase with increasing axial tension. Recent studies have revealed that many widely used constitutive models for soft biological tissues fail to capture this characteristic response. Here, guided by experiments of human brain tissue, we develop a family of modeling approaches that capture the elasticity of brain tissue under varying simple shear superposed on varying axial stretch by exploiting key observations about the behavior of the nonlinear shear modulus, which can be obtained directly from the experimental data.

  8. Human placental IGF-I and IGF-II expression: correlating maternal and infant anthropometric variables and micronutrients at birth in the Pakistani population.

    Science.gov (United States)

    Akram, S K; Akram, M; Bhutta, Z A; Soder, O

    2008-10-01

    To correlate infant birth weight with maternal and infant biometric data, including the expression of placental IGF-I and IGF-II at birth, and levels of serum zinc and ferritin. The data consisted of observations from 89 women from Karachi, Pakistan. Placental and cord blood samples were taken immediately following delivery and were subsequently divided into two groups, small and large for gestational age (SGA and LGA). The mean birth weight was 2.79 kg; the prevalence of SGA being 13.4% ( or =90th percentile). Placental IGF-I and IGF-II mRNA expression was greater in the LGA group (p importance of these growth factors for birth weight outcomes. The higher zinc levels in the LGA group also suggest the importance of this micronutrient in foetal growth. Our results suggest that growth problems have a multifactorial aetiology arising from within the infant rather than due to maternal constraint alone.

  9. First trimester alcohol exposure alters placental perfusion and fetal oxygen availability affecting fetal growth and development in a non-human primate model.

    Science.gov (United States)

    Lo, Jamie O; Schabel, Matthias C; Roberts, Victoria H J; Wang, Xiaojie; Lewandowski, Katherine S; Grant, Kathleen A; Frias, Antonio E; Kroenke, Christopher D

    2017-03-01

    Prenatal alcohol exposure leads to impaired fetal growth, brain development, and stillbirth. Placental impairment likely contributes to these adverse outcomes, but the mechanisms and specific vasoactive effects of alcohol that links altered placental function to impaired fetal development remain areas of active research. Recently, we developed magnetic resonance imaging techniques in nonhuman primates to characterize placental blood oxygenation through measurements of T2* and perfusion using dynamic contrast-enhanced magnetic resonance imaging. The objective of this study was to evaluate the effects of first-trimester alcohol exposure on macaque placental function and to characterize fetal brain development in vivo. Timed-pregnant Rhesus macaques (n=12) were divided into 2 groups: control (n=6) and ethanol exposed (n=6). Animals were trained to self-administer orally either 1.5 g/kg/d of a 4% ethanol solution (equivalent to 6 drinks/d) or an isocaloric control fluid from preconception until gestational day 60 (term is G168). All animals underwent Doppler ultrasound scanning followed by magnetic resonance imaging that consisted of T2* and dynamic contrast-enhanced measurements. Doppler ultrasound scanning was used to measure uterine artery and umbilical vein velocimetry and diameter to calculate uterine artery volume blood flow and placental volume blood flow. After noninvasive imaging, animals underwent cesarean delivery for placenta collection and fetal necropsy at gestational day 110 (n=6) or 135 (n=6). Fetal weight and biparietal diameter were significantly smaller in ethanol-exposed animals compared with control animals at gestational day 110. By Doppler ultrasound scanning, placental volume blood flow was significantly lower (P=.04) at gestational day 110 in ethanol-exposed vs control animals. A significant reduction in placental blood flow was evident by dynamic contrast-enhanced magnetic resonance imaging. As we demonstrated recently, T2* values vary

  10. Global surveillance of DDT and DDE levels in human tissues.

    Science.gov (United States)

    Jaga, Kushik; Dharmani, Chandrabhan

    2003-01-01

    The organochlorine insecticide dichlorodiphenyltrichloroethane (DDT) was initially introduced for control of vector-borne discases It was banned in the United States by the Environmental Protection Agency in 1972 because of potential harmful effects on humans, wildlife and the environment. Since it is a potential human carcinogen, the United Nations Environmental Program (UNEP) has recently restricted the use of DDT in developing countries until alternative methods of vector control are sought. DDT and its metabolite, dichlorodiphenyltrichloroethylene (DDE) are lipid soluble, and bioaccumulate more in human adipose tissue, than breast milk and serum. This article is a review of DDT and DDE levels in human tissues from different countries in the world. Data on p,p'-DDT and p,p'-DDE levels in human adipose tissue, breast milk and serum were selected from more recent literature. It was discovered that countries in Africa, Asia, and Latin America with more recent exposure to DDT and DDE have higher levels in human tissue than in Europe and the United States. The global concern for DDT and DDE is the environmental spread and persistence in the food chain. Hypothetically, there is a potential risk of harmful effects of DDT and DDE to human health. UNEP has cautiously taken action to protect human health, the environment and the earth from further destruction by persistent organic pollutants. Further exposure to DDT should be prevented to achieve this goal.

  11. Genetic effects on gene expression across human tissues

    NARCIS (Netherlands)

    Battle, Alexis; Brown, Christopher D.; Engelhardt, Barbara E.; Montgomery, Stephen B.; Aguet, François; Ardlie, Kristin G.; Cummings, Beryl B.; Gelfand, Ellen T.; Getz, Gad; Hadley, Kane; Handsaker, Robert E.; Huang, Katherine H.; Kashin, Seva; Karczewski, Konrad J.; Lek, Monkol; Li, Xiao; MacArthur, Daniel G.; Nedzel, Jared L.; Nguyen, Duyen T.; Noble, Michael S.; Segrè, Ayellet V.; Trowbridge, Casandra A.; Tukiainen, Taru; Abell, Nathan S.; Balliu, Brunilda; Barshir, Ruth; Basha, Omer; Bogu, Gireesh K.; Brown, Andrew; Castel, Stephane E.; Chen, Lin S.; Chiang, Colby; Conrad, Donald F.; Cox, Nancy J.; Damani, Farhan N.; Davis, Joe R.; Delaneau, Olivier; Dermitzakis, Emmanouil T.; Eskin, Eleazar; Ferreira, Pedro G.; Frésard, Laure; Gamazon, Eric R.; Garrido-Martín, Diego; Gewirtz, Ariel D. H.; Gliner, Genna; Gloudemans, Michael J.; Guigo, Roderic; Hall, Ira M.; Han, Buhm; He, Yuan; Hormozdiari, Farhad; Howald, Cedric; Kyung Im, Hae; Jo, Brian; Yong Kang, Eun; Kim, Yungil; Kim-Hellmuth, Sarah; Lappalainen, Tuuli; Li, Gen; Li, Xin; Liu, Boxiang; Mangul, Serghei; McCarthy, Mark I.; McDowell, Ian C.; Mohammadi, Pejman; Monlong, Jean; Muñoz-Aguirre, Manuel; Ndungu, Anne W.; Nicolae, Dan L.; Nobel, Andrew B.; Oliva, Meritxell; Ongen, Halit; Palowitch, John J.; Panousis, Nikolaos; Papasaikas, Panagiotis; Park, Yoson; Parsana, Princy; Payne, Anthony J.; Peterson, Christine B.; Quan, Jie; Reverter, Ferran; Sabatti, Chiara; Saha, Ashis; Sammeth, Michael; Scott, Alexandra J.; Shabalin, Andrey A.; Sodaei, Reza; Stephens, Matthew; Stranger, Barbara E.; Strober, Benjamin J.; Sul, Jae Hoon; Tsang, Emily K.; Urbut, Sarah; van de Bunt, Martijn; Wang, Gao; Wen, Xiaoquan; Wright, Fred A.; Xi, Hualin S.; Yeger-Lotem, Esti; Zappala, Zachary; Zaugg, Judith B.; Zhou, Yi-Hui; Akey, Joshua M.; Bates, Daniel; Chan, Joanne; Claussnitzer, Melina; Demanelis, Kathryn; Diegel, Morgan; Doherty, Jennifer A.; Feinberg, Andrew P.; Fernando, Marian S.; Halow, Jessica; Hansen, Kasper D.; Haugen, Eric; Hickey, Peter F.; Hou, Lei; Jasmine, Farzana; Jian, Ruiqi; Jiang, Lihua; Johnson, Audra; Kaul, Rajinder; Kellis, Manolis; Kibriya, Muhammad G.; Lee, Kristen; Billy Li, Jin; Li, Qin; Lin, Jessica; Lin, Shin; Linder, Sandra; Linke, Caroline; Liu, Yaping; Maurano, Matthew T.; Molinie, Benoit; Nelson, Jemma; Neri, Fidencio J.; Park, Yongjin; Pierce, Brandon L.; Rinaldi, Nicola J.; Rizzardi, Lindsay F.; Sandstrom, Richard; Skol, Andrew; Smith, Kevin S.; Snyder, Michael P.; Stamatoyannopoulos, John; Tang, Hua; Wang, Li; Wang, Meng; van Wittenberghe, Nicholas; Wu, Fan; Zhang, Rui; Nierras, Concepcion R.; Branton, Philip A.; Carithers, Latarsha J.; Guan, Ping; Moore, Helen M.; Rao, Abhi; Vaught, Jimmie B.; Gould, Sarah E.; Lockart, Nicole C.; Martin, Casey; Struewing, Jeffery P.; Volpi, Simona; Addington, Anjene M.; Koester, Susan E.; Little, A. Roger; Brigham, Lori E.; Hasz, Richard; Hunter, Marcus; Johns, Christopher; Johnson, Mark; Kopen, Gene; Leinweber, William F.; Lonsdale, John T.; McDonald, Alisa; Mestichelli, Bernadette; Myer, Kevin; Roe, Brian; Salvatore, Michael; Shad, Saboor; Thomas, Jeffrey A.; Walters, Gary; Washington, Michael; Wheeler, Joseph; Bridge, Jason; Foster, Barbara A.; Gillard, Bryan M.; Karasik, Ellen; Kumar, Rachna; Miklos, Mark; Moser, Michael T.; Jewell, Scott D.; Montroy, Robert G.; Rohrer, Daniel C.; Valley, Dana R.; Davis, David A.; Mash, Deborah C.; Undale, Anita H.; Smith, Anna M.; Tabor, David E.; Roche, Nancy V.; McLean, Jeffrey A.; Vatanian, Negin; Robinson, Karna L.; Sobin, Leslie; Barcus, Mary E.; Valentino, Kimberly M.; Qi, Liqun; Hunter, Steven; Hariharan, Pushpa; Singh, Shilpi; Um, Ki Sung; Matose, Takunda; Tomaszewski, Maria M.; Barker, Laura K.; Mosavel, Maghboeba; Siminoff, Laura A.; Traino, Heather M.; Flicek, Paul; Juettemann, Thomas; Ruffier, Magali; Sheppard, Dan; Taylor, Kieron; Trevanion, Stephen J.; Zerbino, Daniel R.; Craft, Brian; Goldman, Mary; Haeussler, Maximilian; Kent, W. James; Lee, Christopher M.; Paten, Benedict; Rosenbloom, Kate R.; Vivian, John; Zhu, Jingchun; Brown, Andrew A.; Nguyen, Duyen Y.; Sullivan, Timothy J.; Addington, Anjene; Koester, Susan; Lockhart, Nicole C.; Roe, Bryan; Valley, Dana; He, Amy Z.; Kang, Eun Yong; Quon, Gerald; Ripke, Stephan; Shimko, Tyler C.; Teran, Nicole A.; Zhang, Hailei; Bustamante, Carlos D.; Guigó, Roderic

    2017-01-01

    Characterization of the molecular function of the human genome and its variation across individuals is essential for identifying the cellular mechanisms that underlie human genetic traits and diseases. The Genotype-Tissue Expression (GTEx) project aims to characterize variation in gene expression

  12. Pre-Eclampsia Placental Carbohydrate Metabolism Regulating Enzymes Activity

    OpenAIRE

    Oré, Raquel; Centro de Investigación en Bioquímica y Nutrición, Facultad de Medicina, Universidad Nacional Mayor de San Marcos, Lima, Perú; Suárez, Silvia; Centro de Investigación en Bioquímica y Nutrición, Facultad de Medicina, Universidad Nacional Mayor de San Marcos, Lima, Perú; Arnao, Inés; Centro de Investigación en Bioquímica y Nutrición, Facultad de Medicina, Universidad Nacional Mayor de San Marcos, Lima, Perú

    2014-01-01

    Pre eclampsia is one of the most frecuent pathologies during pregnancy. The placental tissue plays an important role in the development of the pathology. In this report we performed a study of the activities of two regulatory enzymes [ Phosphofructokinase I (E.C. 2.7.1.11) and Glucose 6-P-dehidrogenase (E.C. 1.1.1.49)] of the carbohydrate metabolism in both normal and pre emclampsia placental tissue. It has been found a pronounced decreased in both activities in the pathological tissue. We di...

  13. Regulation of human feto-placental endothelial barrier integrity by vascular endothelial growth factors: competitive interplay between VEGF-A165a, VEGF-A165b, PIGF and VE-cadherin.

    Science.gov (United States)

    Pang, Vincent; Bates, David O; Leach, Lopa

    2017-12-01

    The human placenta nourishes and protects the developing foetus whilst influencing maternal physiology for fetal advantage. It expresses several members of the vascular endothelial growth factor (VEGF) family including the pro-angiogenic/pro-permeability VEGF-A 165 a isoform, the anti-angiogenic VEGF-A 165 b, placental growth factor (PIGF) and their receptors, VEGFR1 and VEGFR2. Alterations in the ratio of these factors during gestation and in complicated pregnancies have been reported; however, the impact of this on feto-placental endothelial barrier integrity is unknown. The present study investigated the interplay of these factors on junctional occupancy of VE-cadherin and macromolecular leakage in human endothelial monolayers and the perfused placental microvascular bed. Whilst VEGF-A 165 a (50 ng/ml) increased endothelial monolayer albumin permeability ( P 0.05) or PlGF ( P >0.05) did not. Moreover, VEGF-A 165 b (100 ng/ml; P 0.05) inhibited VEGF-A 165 a-induced permeability when added singly. PlGF abolished the VEGF-A 165 b-induced reduction in VEGF-A 165 a-mediated permeability ( P >0.05); PlGF was found to compete with VEGF-A 165 b for binding to Flt-1 at equimolar affinity. Junctional occupancy of VE-cadherin matched alterations in permeability. In the perfused microvascular bed, VEGF-A 165 b did not induce microvascular leakage but inhibited and reversed VEGF-A 165 a-induced loss of junctional VE-cadherin and tracer leakage. These results indicate that the anti-angiogenic VEGF-A 165 b isoform does not increase permeability in human placental microvessels or HUVEC primary cells and can interrupt VEGF-A 165 a-induced permeability. Moreover, the interplay of these isoforms with PIGF (and s-flt1) suggests that the ratio of these three factors may be important in determining the placental and endothelial barrier in normal and complicated pregnancies. © 2017 The Author(s).

  14. Assessment of parabens and ultraviolet filters in human placenta tissue by ultrasound-assisted extraction and ultra-high performance liquid chromatography-tandem mass spectrometry.

    Science.gov (United States)

    Vela-Soria, F; Gallardo-Torres, M E; Ballesteros, O; Díaz, C; Pérez, J; Navalón, A; Fernández, M F; Olea, N

    2017-03-03

    Increasing concerns have been raised over recent decades about human exposure to Endocrine Disrupting Chemicals (EDCs), especially about their possible effects on embryo, foetus, newborn, and child. Parabens (PBs) and ultraviolet filters (UV-filters) are prevalent EDCs widely used as additives in cosmetics and personal care products (PCPs). The objective of this study was to determine the presence of four PBs and ten UV-filters in placental tissue samples using a novel analytical method based on ultrasound-assisted extraction (UAE) and ultra-high performance liquid chromatography-tandem mass spectrometry (UHPLC-MS/MS). Multivariate optimization strategies were used to accurately optimize extraction and clean-up parameters. Limits of quantification ranged from 0.15 to 0.5μgkg-1, and inter-day variability (evaluated as relative standard deviation) ranged from 3.6% to 14%. The method was validated using matrix-matched standard calibration followed by a recovery assay with spiked samples. Recovery percents ranged from 94.5% to 112%. The method was satisfactorily applied for the determination of the target compounds in human placental tissue samples collected at delivery from 15 randomly selected women. This new analytical procedure can provide information on foetal exposure to compounds, which has been little studied. Copyright © 2017 Elsevier B.V. All rights reserved.

  15. Immunolocalization of transforming growth factor alpha in normal human tissues

    DEFF Research Database (Denmark)

    Christensen, M E; Poulsen, Steen Seier

    1996-01-01

    anchorage-independent growth of normal cells and was, therefore, considered as an "oncogenic" growth factor. Later, its immunohistochemical presence in normal human cells as well as its biological effects in normal human tissues have been demonstrated. The aim of the present investigation was to elucidate...... the distribution of the growth factor in a broad spectrum of normal human tissues. Indirect immunoenzymatic staining methods were used. The polypeptide was detected with a polyclonal as well as a monoclonal antibody. The polyclonal and monoclonal antibodies demonstrated almost identical immunoreactivity. TGF......-alpha was found to be widely distributed in cells of normal human tissues derived from all three germ layers, most often in differentiated cells. In epithelial cells, three different kinds of staining patterns were observed, either diffuse cytoplasmic, cytoplasmic in the basal parts of the cells, or distinctly...

  16. Maternal obesity and sex-specific differences in placental pathology.

    Science.gov (United States)

    Leon-Garcia, Sandra M; Roeder, Hilary A; Nelson, Katharine K; Liao, Xiaoyan; Pizzo, Donald P; Laurent, Louise C; Parast, Mana M; LaCoursiere, D Yvette

    2016-02-01

    Adverse effects of obesity have been linked to inflammation in various tissues, but studies on placental inflammation and obesity have demonstrated conflicting findings. We sought to investigate the influence of pregravid obesity and fetal sex on placental histopathology while controlling for diabetes and hypertension. Placental histopathology focusing on inflammatory markers of a cohort of normal weight (BMI = 20-24.9) and obese (BMI ≥ 30) patients was characterized. Demographic, obstetric and neonatal variables were assessed. 192 normal and 231 obese women were included. Placental characteristics associated with obesity and fetal sex independent of diabetes and hypertension were placental disc weight >90(th) percentile, decreased placental efficiency, chronic villitis (CV), fetal thrombosis, and normoblastemia. Additionally, female fetuses of obese mothers had higher rates of CV and fetal thrombosis. Increasing BMI increased the risk of normoblastemia and CV. The final grade and extent of CV was significantly associated with obesity and BMI, but not fetal gender. Finally, CV was less common in large-for-gestation placentas. Maternal obesity results in placental overgrowth and fetal hypoxia as manifested by normoblastemia; it is also associated with an increased incidence of CV and fetal thrombosis, both more prevalent in female placentas. We have shown for the first time that the effect of maternal obesity on placental inflammation is independent of diabetes and hypertension, but significantly affected by fetal sex. Our data also point to the intriguing possibility that CV serves to normalize placental size, and potentially fetal growth, in the setting of maternal obesity. Copyright © 2015. Published by Elsevier Ltd.

  17. Human natural killer cell development in secondary lymphoid tissues

    Science.gov (United States)

    Freud, Aharon G.; Yu, Jianhua; Caligiuri, Michael A.

    2014-01-01

    For nearly a decade it has been appreciated that critical steps in human natural killer (NK) cell development likely occur outside of the bone marrow and potentially necessitate distinct microenvironments within extramedullary tissues. The latter include the liver and gravid uterus as well as secondary lymphoid tissues such as tonsils and lymph nodes. For as yet unknown reasons these tissues are naturally enriched with NK cell developmental intermediates (NKDI) that span a maturation continuum starting from an oligopotent CD34+CD45RA+ hematopoietic precursor cell to a cytolytic mature NK cell. Indeed despite the detection of NKDI within the aforementioned tissues, relatively little is known about how, why, and when these tissues may be most suited to support NK cell maturation and how this process fits in with other components of the human immune system. With the discovery of other innate lymphoid subsets whose immunophenotypes overlap with those of NKDI, there is also need to revisit and potentially re-characterize the basic immunophenotypes of the stages of the human NK cell developmental pathway in vivo. In this review, we provide an overview of human NK cell development in secondary lymphoid tissues and discuss the many questions that remain to be answered in this exciting field. PMID:24661538

  18. Ultrastructural Changes in Human Trabecular Meshwork Tissue after Laser Trabeculoplasty

    Directory of Open Access Journals (Sweden)

    Jeffrey R. SooHoo

    2015-01-01

    Full Text Available Purpose. To compare morphologic changes in human trabecular meshwork (TM after selective laser trabeculoplasty (SLT and argon laser trabeculoplasty (ALT. Design. Laboratory evaluation of ex vivo human eye TM after laser trabeculoplasty. Methods. Corneoscleral rims from human cadaver eyes were sectioned and treated with varying powers of either SLT or ALT. Specimens were examined using light microscopy, scanning electron microscopy (SEM, and transmission electron microscopy (TEM. Results. TEM of SLT at all powers resulted in disrupted TM cells with cracked and extracellular pigment granules. SEM of SLT samples treated at high power revealed tissue destruction with scrolling of trabecular beams. SEM of ALT-treated tissue showed increasing destruction with exposure to higher power. The presence or absence of “champagne” bubbles during SLT did not alter the histologic findings. Conclusions. SLT-treated human TM revealed disruption of TM cells with cracked, extracellular pigment granules, particularly at higher treatment powers. Tissue scrolling was noted at very high SLT energy levels. ALT-treated tissue showed significant damage to both the superficial and deeper TM tissues in a dose-dependent fashion. Further studies are needed to guide titration of treatment power to maximize the IOP-lowering effect while minimizing both energy delivered and damage to target tissues.

  19. 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.

  20. Placental site trophoblastic tumor

    Directory of Open Access Journals (Sweden)

    Jean eBouquet De Jolinière

    2014-08-01

    Full Text Available Trophoblastic tumors of placental site (PSTT are rare. They represent a rare form of gestational trophoblastic disease. (GTD. They occur mainly in women who have a history of miscarriage, termination of pregnancy, or even a normal or pathological ongoing pregnancy. The clinical course is unpredictable. This malignancy has different characteristics from other gestational trophoblastic tumors.Following a clinical case that we encountered and treated, we conducted a literary research and review, focusing primarily on prognostic factors and treatment.

  1. Placental Nutrient Transport and Intrauterine Growth Restriction

    Directory of Open Access Journals (Sweden)

    Francesca eGaccioli

    2016-02-01

    Full Text Available Intrauterine growth restriction refers to the inability of the fetus to reach its genetically determined potential size. Fetal growth restriction affects approximately 5–15% of all pregnancies in the United States and Europe. In developing countries the occurrence varies widely between 10 and 55%, impacting about 30 million newborns per year. Besides having high perinatal mortality rates these infants are at greater risk for severe adverse outcomes, such as hypoxic ischemic encephalopathy and cerebral palsy. Moreover, reduced fetal growth has lifelong health consequences, including higher risks of developing metabolic and cardiovascular diseases in adulthood. Numerous reports indicate placental insufficiency as one of the underlying causes leading to altered fetal growth and impaired placental capacity of delivering nutrients to the fetus has been shown to contribute to the etiology of intrauterine growth restriction. Indeed, reduced expression and/or activity of placental nutrient transporters have been demonstrated in several conditions associated with an increased risk of delivering a small or growth restricted infant. This review focuses on human pregnancies and summarizes the changes in placental amino acid, fatty acid, and glucose transport reported in conditions associated with intrauterine growth restriction, such as pre-eclampsia and young maternal age.

  2. Diverse splicing patterns of exonized Alu elements in human tissues.

    Directory of Open Access Journals (Sweden)

    Lan Lin

    2008-10-01

    Full Text Available Exonization of Alu elements is a major mechanism for birth of new exons in primate genomes. Prior analyses of expressed sequence tags show that almost all Alu-derived exons are alternatively spliced, and the vast majority of these exons have low transcript inclusion levels. In this work, we provide genomic and experimental evidence for diverse splicing patterns of exonized Alu elements in human tissues. Using Exon array data of 330 Alu-derived exons in 11 human tissues and detailed RT-PCR analyses of 38 exons, we show that some Alu-derived exons are constitutively spliced in a broad range of human tissues, and some display strong tissue-specific switch in their transcript inclusion levels. Most of such exons are derived from ancient Alu elements in the genome. In SEPN1, mutations of which are linked to a form of congenital muscular dystrophy, the muscle-specific inclusion of an Alu-derived exon may be important for regulating SEPN1 activity in muscle. Realtime qPCR analysis of this SEPN1 exon in macaque and chimpanzee tissues indicates human-specific increase in its transcript inclusion level and muscle specificity after the divergence of humans and chimpanzees. Our results imply that some Alu exonization events may have acquired adaptive benefits during the evolution of primate transcriptomes.

  3. Predicting Tissue-Specific Enhancers in the Human Genome

    Energy Technology Data Exchange (ETDEWEB)

    Pennacchio, Len A.; Loots, Gabriela G.; Nobrega, Marcelo A.; Ovcharenko, Ivan

    2006-07-01

    Determining how transcriptional regulatory signals areencoded in vertebrate genomes is essential for understanding the originsof multi-cellular complexity; yet the genetic code of vertebrate generegulation remains poorly understood. In an attempt to elucidate thiscode, we synergistically combined genome-wide gene expression profiling,vertebrate genome comparisons, and transcription factor binding siteanalysis to define sequence signatures characteristic of candidatetissue-specific enhancers in the human genome. We applied this strategyto microarray-based gene expression profiles from 79 human tissues andidentified 7,187 candidate enhancers that defined their flanking geneexpression, the majority of which were located outside of knownpromoters. We cross-validated this method for its ability to de novopredict tissue-specific gene expression and confirmed its reliability in57 of the 79 available human tissues, with an average precision inenhancer recognition ranging from 32 percent to 63 percent, and asensitivity of 47 percent. We used the sequence signatures identified bythis approach to assign tissue-specific predictions to ~;328,000human-mouse conserved noncoding elements in the human genome. Byoverlapping these genome-wide predictions with a large in vivo dataset ofenhancers validated in transgenic mice, we confirmed our results with a28 percent sensitivity and 50 percent precision. These results indicatethe power of combining complementary genomic datasets as an initialcomputational foray into the global view of tissue-specific generegulation in vertebrates.

  4. Tissue engineering and surgery: from translational studies to human trials

    Directory of Open Access Journals (Sweden)

    Vranckx Jan Jeroen

    2017-06-01

    Full Text Available Tissue engineering was introduced as an innovative and promising field in the mid-1980s. The capacity of cells to migrate and proliferate in growth-inducing medium induced great expectancies on generating custom-shaped bioconstructs for tissue regeneration. Tissue engineering represents a unique multidisciplinary translational forum where the principles of biomaterial engineering, the molecular biology of cells and genes, and the clinical sciences of reconstruction would interact intensively through the combined efforts of scientists, engineers, and clinicians. The anticipated possibilities of cell engineering, matrix development, and growth factor therapies are extensive and would largely expand our clinical reconstructive armamentarium. Application of proangiogenic proteins may stimulate wound repair, restore avascular wound beds, or reverse hypoxia in flaps. Autologous cells procured from biopsies may generate an ‘autologous’ dermal and epidermal laminated cover on extensive burn wounds. Three-dimensional printing may generate ‘custom-made’ preshaped scaffolds – shaped as a nose, an ear, or a mandible – in which these cells can be seeded. The paucity of optimal donor tissues may be solved with off-the-shelf tissues using tissue engineering strategies. However, despite the expectations, the speed of translation of in vitro tissue engineering sciences into clinical reality is very slow due to the intrinsic complexity of human tissues. This review focuses on the transition from translational protocols towards current clinical applications of tissue engineering strategies in surgery.

  5. 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.

  6. The Effects of Vasopressin and Oxytocin on the Fetoplacental Distal Stem Arteriolar Vascular Resistance of the Dual-Perfused, Single, Isolated, Human Placental Cotyledon.

    Science.gov (United States)

    Downing, John W; Baysinger, Curtis L; Johnson, Raymond F; Paschall, Ray L; Shotwell, Matthew S

    2016-09-01

    Vasoactive agents administered to counter maternal hypotension at cesarean delivery may theoretically intensify the hypoxemic fetoplacental vasoconstrictor response and, hence, negatively impact transplacental oxygen delivery to the fetus. Yet, this aspect of their pharmacodynamic profiles is seldom mentioned, let alone investigated. We hypothesized that vasopressin, a potent systemic vasoconstrictor, and oxytocin, a uterotonic agent administered routinely at cesarean delivery, which, in contrast to vasopressin, possesses significant systemic vasodilator properties, would not influence distal stem villous arteriolar resistance. The dual-perfused, single, isolated cotyledon, human placental perfusion model was used to examine the resistance response of the fetoplacental circulation to oxytocin and vasopressin in placentae harvested from healthy women. Twelve of a total of 17 individual experiments were conducted successfully during which either oxytocin (n = 6) or vasopressin (n = 6) was introduced into the fetal reservoir in concentration increments of 10 M. Fetoplacental distal stem villous arteriolar perfusion pressure (FAP) was measured continuously. The fetal circuit concentration of either oxytocin or vasopressin was raised in a stepwise fashion from 10 to 10 M or 10 to 10 M, respectively. Both reservoirs were then purged of drug, after which 1-mL 1.0 mM 5-hydroxytryptamine (2.5 µM), an agent well known to manifestly increase fetoplacental distal stem villous arteriolar resistance, was introduced into the fetal circuit. A significant increase in FAP from baseline in response to exposure to 5-hydroxytryptamine confirmed that the fetoplacental vasoconstrictor response remained reactive. The primary outcome of this study was changes in FAP after incremental dosing of vasopressin and oxytocin. No changes in FAP were observed with either oxytocin or vasopressin regardless of the drug concentration tested. For each drug and concentration, a mean pressure change

  7. Variability in responses observed in human white adipose tissue models.

    Science.gov (United States)

    Abbott, Rosalyn D; Borowsky, Francis E; Alonzo, Carlo A; Zieba, Adam; Georgakoudi, Irene; Kaplan, David L

    2017-09-06

    Obesity is a risk factor for a myriad of diseases including diabetes, cardiovascular dysfunction, cirrhosis, and cancer, and there is a need for new systems to study how excess adipose tissue relates to the onset of disease processes. This study provides proof-of-concept patient-specific tissue models of human white adipose tissue to accommodate the variability in human samples. Our 3D tissue engineering approach established lipolytic responses and changes in insulin-stimulated glucose uptake from small volumes of human lipoaspirate, making this methodology useful for patient specific sample source assessments of treatment strategies, drug responses, disease mechanisms, and other responses that vary between patients. Mature unilocular cells were maintained ex vivo in silk porous scaffolds for up to a month of culture and imaged non-invasively with coherent anti-Stokes Raman scattering. Interestingly, differences in responsiveness between tissues were observed in terms of magnitude of lipolysis, ability to suppress lipolysis, differences in glucose uptake, and lipid droplet size. Body mass index was not a factor in determining tissue responsiveness; rather, it is speculated that other unknown variables in the backgrounds of different patients (ethnicity, athleticism, disease history, lifestyle choices, etc.) likely had a more significant effect on the observed differences. This study reinforces the need to account for the variability in backgrounds and genetics within the human population to determine adipose tissue responsiveness. In the future, this tissue system could be used to inform individualized care strategies-enhancing therapeutic precision, improving patient outcomes, and reducing clinical costs. Copyright © 2017 John Wiley & Sons, Ltd.

  8. Engineered human broncho-epithelial tissue-like assemblies

    Science.gov (United States)

    Goodwin, Thomas J. (Inventor)

    2012-01-01

    Three-dimensional human broncho-epithelial tissue-like assemblies (TLAs) are produced in a rotating wall vessel (RWV) with microcarriers by coculturing mesenchymal bronchial-tracheal cells (BTC) and bronchial epithelium cells (BEC). These TLAs display structural characteristics and express markers of in vivo respiratory epithelia. TLAs are useful for screening compounds active in lung tissues such as antiviral compounds, cystic fibrosis treatments, allergens, and cytotoxic compounds.

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

    Directory of Open Access Journals (Sweden)

    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.

  10. 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...

  11. Advancing biomaterials of human origin for tissue engineering

    Science.gov (United States)

    Chen, Fa-Ming; Liu, Xiaohua

    2015-01-01

    Biomaterials have played an increasingly prominent role in the success of biomedical devices and in the development of tissue engineering, which seeks to unlock the regenerative potential innate to human tissues/organs in a state of deterioration and to restore or reestablish normal bodily function. Advances in our understanding of regenerative biomaterials and their roles in new tissue formation can potentially open a new frontier in the fast-growing field of regenerative medicine. Taking inspiration from the role and multi-component construction of native extracellular matrices (ECMs) for cell accommodation, the synthetic biomaterials produced today routinely incorporate biologically active components to define an artificial in vivo milieu with complex and dynamic interactions that foster and regulate stem cells, similar to the events occurring in a natural cellular microenvironment. The range and degree of biomaterial sophistication have also dramatically increased as more knowledge has accumulated through materials science, matrix biology and tissue engineering. However, achieving clinical translation and commercial success requires regenerative biomaterials to be not only efficacious and safe but also cost-effective and convenient for use and production. Utilizing biomaterials of human origin as building blocks for therapeutic purposes has provided a facilitated approach that closely mimics the critical aspects of natural tissue with regard to its physical and chemical properties for the orchestration of wound healing and tissue regeneration. In addition to directly using tissue transfers and transplants for repair, new applications of human-derived biomaterials are now focusing on the use of naturally occurring biomacromolecules, decellularized ECM scaffolds and autologous preparations rich in growth factors/non-expanded stem cells to either target acceleration/magnification of the body's own repair capacity or use nature's paradigms to create new tissues for

  12. Advancing biomaterials of human origin for tissue engineering.

    Science.gov (United States)

    Chen, Fa-Ming; Liu, Xiaohua

    2016-02-01

    Biomaterials have played an increasingly prominent role in the success of biomedical devices and in the development of tissue engineering, which seeks to unlock the regenerative potential innate to human tissues/organs in a state of deterioration and to restore or reestablish normal bodily function. Advances in our understanding of regenerative biomaterials and their roles in new tissue formation can potentially open a new frontier in the fast-growing field of regenerative medicine. Taking inspiration from the role and multi-component construction of native extracellular matrices (ECMs) for cell accommodation, the synthetic biomaterials produced today routinely incorporate biologically active components to define an artificial in vivo milieu with complex and dynamic interactions that foster and regulate stem cells, similar to the events occurring in a natural cellular microenvironment. The range and degree of biomaterial sophistication have also dramatically increased as more knowledge has accumulated through materials science, matrix biology and tissue engineering. However, achieving clinical translation and commercial success requires regenerative biomaterials to be not only efficacious and safe but also cost-effective and convenient for use and production. Utilizing biomaterials of human origin as building blocks for therapeutic purposes has provided a facilitated approach that closely mimics the critical aspects of natural tissue with regard to its physical and chemical properties for the orchestration of wound healing and tissue regeneration. In addition to directly using tissue transfers and transplants for repair, new applications of human-derived biomaterials are now focusing on the use of naturally occurring biomacromolecules, decellularized ECM scaffolds and autologous preparations rich in growth factors/non-expanded stem cells to either target acceleration/magnification of the body's own repair capacity or use nature's paradigms to create new tissues for

  13. Placental vitamin D metabolism and its associations with circulating vitamin D metabolites in pregnant women.

    Science.gov (United States)

    Park, Heyjun; Wood, Madeleine R; Malysheva, Olga V; Jones, Sara; Mehta, Saurabh; Brannon, Patsy M; Caudill, Marie A

    2017-12-01

    Background: Little is known about placental vitamin D metabolism and its impact on maternal circulating vitamin D concentrations in humans. Objective: This study sought to advance the current understanding of placental vitamin D metabolism and its role in modulating maternal circulating vitamin D metabolites during pregnancy. Design: Nested within a feeding study, 24 healthy pregnant women (26-29 wk of gestation) consumed a single amount of vitamin D (511 IU/d from diet and a cholecalciferol supplement) for 10 wk. Concentrations of placental and blood vitamin D metabolites and placental messenger RNA (mRNA) abundance of vitamin D metabolic pathway components were quantified. In addition, cultured human trophoblasts were incubated with 13 C-cholecalciferol to examine the intracellular generation and secretion of vitamin D metabolites along with the regulation of target genes. Results: In placental tissue, 25-hydroxyvitamin D 3 [25(OH)D 3 ] was strongly correlated ( r = 0.83, P vitamin D metabolic components and circulating vitamin D metabolites [i.e., LDL-related protein 2 ( LRP2 , also known as megalin) with 25(OH)D 3 and the C3 epimer of 25(OH)D 3 [3-epi-25(OH)D 3 ]; cubilin ( CUBN ) with 25(OH)D 3 ; 25-hydroxylase ( CYP2R1 ) with 3-epi-25(OH)D 3 ; 24-hydroxylase ( CYP24A1 ) with 25(OH)D 3 , 3-epi-25(OH)D 3 , and 1,25-dihydroxyvitamin D 3 [1,25(OH) 2 D 3 ]; and 1α-hydroxylase [( CYP27B1 ) with 3-epi-25(OH)D 3 and 1,25(OH) 2 D 3 ]. Notably, in vitro experiments with trophoblasts showed increased production and secretion of 25(OH)D 3 and higher CYP24A1 gene transcript abundance in response to cholecalciferol treatment. Conclusions: The numerous associations of many of the placental biomarkers of vitamin D metabolism with circulating vitamin D metabolites among pregnant women [including a CYP27B1 -associated increase in 1,25(OH) 2 D 3 ] and the evidence of trophoblast production and secretion of vitamin D metabolites, especially 25(OH)D 3 , suggest that the placenta

  14. Presentation of Placental Site Trophoblastic Tumor with Amenorrhea

    Directory of Open Access Journals (Sweden)

    Fariba Behnamfar

    2017-01-01

    Full Text Available Placental site throphoblastic tumor (PSTT is a rare manifestation of gestational trophoblastic neoplasia that may complicate any type of pregnancy. The disease is unique from other type, and is defined by slow growth, low human chorionic gonadotropin (hCG serum levels, the late-onset metastatic potential, and most significantly, insensitivity to chemotherapy. We describe a case of a 31-year-old woman with prolonged amenorrhea and slightly elevated serum beta hCG (βhCG level, referred for termination of abnormal pregnancy. During curettage, necrotic tissue was removed and severs vaginal bleeding was controlled with medical therapy. Histology examination showed neoplastic intermediate trophoblastic cells with invasion to the vessel wall compatible with PSTT. After that, hysterectomy was down and serum βhCG declined to undetectable level 2 weeks after surgery and was followed for 2 years without complication.

  15. Evidence that fetal death is associated with placental aging.

    Science.gov (United States)

    Maiti, Kaushik; Sultana, Zakia; Aitken, Robert J; Morris, Jonathan; Park, Felicity; Andrew, Bronwyn; Riley, Simon C; Smith, Roger

    2017-10-01

    aldehyde oxidase 1 inhibitor raloxifene. Our data are consistent with a role for aldehyde oxidase 1 and G-protein-coupled estrogen receptor 1 in mediating aging of the placenta that may contribute to stillbirth. The placenta is a tractable model of aging in human tissue. Copyright © 2017 Elsevier Inc. All rights reserved.

  16. Role of Exosomes in Placental Homeostasis and Pregnancy Disorders.

    Science.gov (United States)

    Salomon, C; Rice, G E

    2017-01-01

    The human placenta is a unique organ that performs the function of the majority of fetal organs across gestation. How the placenta communicates with maternal tissues to prepare them for pregnancy is not fully understood. Recently, it has been established that placental cells can communicate with maternal tissues to regulate their biological function via extracellular vesicles (EVs). EVs are subclassified into exosomes or microvesicles (MVs) according to their size, cell or tissue of origin, functions, and physical features. Exosomes are a specific type of EVs from an endocytic origin, while MVs are released via budding from the plasma membrane. With regards to pregnancy, the role of EVs has been described in several functions such as immune responses and maternal metabolic adaptation to gestation. Interestingly, EVs of placental origin can be detected in a variety of body fluids including urine and blood, and have been identified in the maternal circulation at as early as 6 weeks of gestation. Moreover, the number of exosomes across gestation is higher in complications of pregnancies such as preeclampsia and gestational diabetes mellitus compared to normal pregnancies. Circulating exosomes contains proteins and RNAs that are representative of the cell of origin, including surface and cytoplasmic protein, messenger RNA, and micro-RNAs. Finally, exosomes are capable of transferring their contents to other cells and regulating the biological function of the target cell. In this review, we will discuss the effect of the maternal microenvironment on secretion and content of placenta-derived EVs, and how this may lead to complications of pregnancies with a special emphasis on exosomes. © 2017 Elsevier Inc. All rights reserved.

  17. Placental growth factor enhances angiogenesis in human intestinal microvascular endothelial cells via PI3K/Akt pathway: Potential implications of inflammation bowel disease

    Energy Technology Data Exchange (ETDEWEB)

    Zhou, Yi, E-mail: mondayzy@126.com; Tu, Chuantao, E-mail: tu.chuantao@zs-hospital.sh.cn; Zhao, Yuan, E-mail: zhao.yuan@zs-hospital.sh.cn; Liu, Hongchun, E-mail: liuhch@aliyun.com; Zhang, Shuncai, E-mail: zhang.shuncai@zs-hospital.sh.cn

    2016-02-19

    Background: Angiogenesis plays a major role in the pathogenesis of inflammatory bowel disease (IBD). Placental growth factor (PlGF) is a specific regulator of pathological angiogenesis and is upregulated in the sera of IBD patients. Therefore, the role of PlGF in IBD angiogenesis was investigated here using HIMECs. Methods: The expression of PlGF and its receptors in human intestinal microvascular endothelial cells (HIMECs) and inflamed mucosa of IBD patients were examined using quantitative PCR and western blot analysis and the role of PlGF in IBD HIMECs was further explored using small interfering RNA (siRNA). The induction of pro-inflammatory cytokine by PlGF in HIMECs was confirmed by ELISA. The capacity of PlGF to induce angiogenesis in HIMECs was tested through proliferation, cell-migration, matrigel tubule-formation assays and its underlying signaling pathway were explored by western blot analysis of ERK1/2 and PI3K/Akt phosphorylation. Results: mRNA and protein expression of PlGF and its receptor NRP-1 were significantly increased in IBD HIMECs. Inflamed mucosa of IBD patients also displayed higher expression of PIGF. The production of IL-6 and TNF-α in culture supernatant of HIMECs treated with exogenous recombinant human PlGF-1 (rhPlGF-1) were increased. Furthermore, rhPlGF-1 significantly induced HIMECs migration and tube formation in a dose-dependent manner and knockdown of endogenous PlGF in IBD HIMECs using siRNA substantially reduced these angiogenesis activities. PlGF induced PI3K/Akt phosphorylation in HIMECs and pretreatment of PlGF-stimulated HIMECs with PI3K inhibitor (LY294002) significantly inhibited the PlGF-induced cell migration and tube formation. Conclusion: Our results demonstrated the pro-inflammatory and angiogenic effects of PlGF on HIMECs in IBD through activation of PI3K/Akt signaling pathway. PlGF/PI3K/Akt signaling may serve as a potential therapeutic target for IBD. - Highlights: • Expression of PlGF and its receptor NRP-1

  18. Transepithelial Transport of PAMAM Dendrimers Across Isolated Human Intestinal Tissue.

    Science.gov (United States)

    Hubbard, Dallin; Enda, Michael; Bond, Tanner; Moghaddam, Seyyed Pouya Hadipour; Conarton, Josh; Scaife, Courtney; Volckmann, Eric; Ghandehari, Hamidreza

    2015-11-02

    Poly(amido amine) (PAMAM) dendrimers have shown transepithelial transport across intestinal epithelial barrier in rats and across Caco-2 cell monolayers. Caco-2 models innately lack mucous barriers, and rat isolated intestinal tissue has been shown to overestimate human permeability. This study is the first report of transport of PAMAM dendrimers across isolated human intestinal epithelium. It was observed that FITC labeled G4-NH2 and G3.5-COOH PAMAM dendrimers at 1 mM concentration do not have a statistically higher permeability compared to free FITC controls in isolated human jejunum and colonic tissues. Mannitol permeability was increased at 10 mM concentrations of G3.5-COOH and G4-NH2 dendrimers. Significant histological changes in human colonic and jejunal tissues were observed at G3.5-COOH and G4-NH2 concentrations of 10 mM implying that dose limiting toxicity may occur at similar concentrations in vivo. The permeability through human isolated intestinal tissue in this study was compared to previous rat and Caco-2 permeability data. This study implicates that PAMAM dendrimer oral drug delivery may be feasible, but it may be limited to highly potent drugs.

  19. Electrospun human keratin matrices as templates for tissue regeneration.

    Science.gov (United States)

    Sow, Wan Ting; Lui, Yuan Siang; Ng, Kee Woei

    2013-04-01

    The aim of this work was to study the feasibility of fabricating human hair keratin matrices through electrospinning and to evaluate the potential of these matrices for tissue regeneration. Keratin was extracted from human hair using Na2S and blended with poly(ethylene oxide) in the weight ratio of 60:1 for electrospinning. Physical morphology and chemical properties of the matrices were characterized using scanning electron microscopy and Fourier transform infrared spectroscopy, respectively. Cell viability and morphology of murine and human fibroblasts cultured on the matrices were evaluated through the Live/Dead(®) assay and scanning electron microscopy. Electrospun keratin matrices were successfully produced without affecting the chemical conformation of keratin. Fibroblasts cultured on keratin matrices showed healthy morphology and penetration into matrices at day 7. Electrospun human hair keratin matrices provide a bioinductive and structural environment for cell growth and are thus attractive as alternative templates for tissue regeneration.

  20. Female reproductive tract and placentation in sucker-footed bats (chiroptera: myzopodidae) endemic to madagascar

    DEFF Research Database (Denmark)

    Carter, A M; Goodman, S M; Enders, A C

    2008-01-01

    The reproductive tract was examined in four non-pregnant and two gravid specimens of Myzopoda. The ovaries had little interstitial tissue. The uterus was bicornuate and the lenticular placental disk was situated mesometrially in one horn. The interhaemal barrier of the placental labyrinth was of ...

  1. Magnetic studies of iron-entities in human tissues

    Energy Technology Data Exchange (ETDEWEB)

    Slawska-Waniewska, A. E-mail: slaws@ifpan.edu.pl; Mosiniewicz-Szablewska, E.; Nedelko, N.; Galazka-Friedman, J.; Friedman, A

    2004-05-01

    Iron-entities in the human liver, brain and blood tissues have been investigated by means of EPR spectroscopy and magnetization measurements over the temperature range 4-300 K. The identification of the most typical forms of iron in the human body (i.e. isolated Fe-ions bonded in hemoglobin and transferrin as well as exchange coupled Fe-ions in nanosized ferritin cores) is presented.

  2. Culture and in vitro hepatogenic differentiation of placenta-derived stem cells, using placental extract as an alternative to serum.

    Science.gov (United States)

    Shin, K S; Lee, H J; Jung, J; Cha, D H; Kim, G J

    2010-10-01

    Translational research using adult stem cells derived from various tissues has been highlighted in cell-based therapy. However, there are many limitations to using conventional culture systems of adult stem cells for clinically applicability, including limited combinations of cytokines and use of nutrients derived from animals. Here, we have investigated the effects of placental extract (PE) for culture of placenta-derived stem cells (PDSCs) as well as their potential for hepatogenic differentiation. Placental extract, extracted using water-soluble methods, was used as a supplement for culture of PDSCs. Cell viability was determined using the MTT assay, and cytokine assay was performed using Luminex assay kit. Gene expression, indocyanine green (ICG) up-take, PAS (Periodic Acid-Schiff) staining and urea production were also analysed. The placental extract contained several types of cytokine and chemokine essential for maintenance and differentiation of stem cells. Expression of stemness markers in PDSCs cultured with PE is no different from that of PDSCs cultured with foetal bovine serum (FBS). After hepatogenic differentiation, expression patterns for hepatocyte-specific markers in PDSCs cultured with PE were consistent and potential for hepatogenic differentiation of PDSCs cultured with PE was similar to that of PDSCs cultured with FBS, as shown by PAS staining and urea production assays. Our findings revealed that placental extract could be used as a new component for culture of adult stem cells, as well as for development of human-based medium, in translational research for regenerative medicine.

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

    Directory of Open Access Journals (Sweden)

    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

  4. Placental Protein 13 (PP13) – A Placental Immunoregulatory Galectin Protecting Pregnancy

    Science.gov (United States)

    Than, Nándor Gábor; Balogh, Andrea; Romero, Roberto; Kárpáti, Éva; Erez, Offer; Szilágyi, András; Kovalszky, Ilona; Sammar, Marei; Gizurarson, Sveinbjorn; Matkó, János; Závodszky, Péter; Papp, Zoltán; Meiri, Hamutal

    2014-01-01

    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 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 concentrations in first trimester maternal sera 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 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 blood pressure

  5. Tissue localization of human trefoil factors 1, 2, and 3

    DEFF Research Database (Denmark)

    Madsen, Jens; Nielsen, Ole; Tornøe, Ida

    2007-01-01

    pattern of the three trefoil factors analyzing mRNA from a panel of 20 human tissues by conventional reverse transcriptase (RT) PCR and, in addition, by real-time PCR. These findings were supported by immunohistochemical analysis of paraffin-embedded human tissues using rabbit polyclonal antibodies raised......Trefoil factors (TTFs) are small, compact proteins coexpressed with mucins in the gastrointestinal tract. Three trefoil factors are known in mammals: TFF1, TFF2, and TFF3. They are implicated to play diverse roles in maintenance and repair of the gastrointestinal channel. We compared the expression...... against these factors. TFF1 showed highest expression in the stomach and colon, whereas TFF2 and TFF3 showed highest expression in stomach and colon, respectively. All three TFFs were found in the ducts of pancreas. Whereas TFF2 was found to be restricted to these two tissues, the structurally more...

  6. Tissue distribution of human acetylcholinesterase and butyrylcholinesterase messenger RNA

    Energy Technology Data Exchange (ETDEWEB)

    Jbilo, O.; Barteles, C.F.; Chatonnet, A.; Toutant, J.P.; Lockridge, O.

    1994-12-31

    Tissue distribution of human acetyicholinesterase and butyryicholinesterase messenger RNA. 1 Cholinesterase inhibitors occur naturally in the calabar bean (eserine), green potatoes (solanine), insect-resistant crab apples, the coca plant (cocaine) and snake venom (fasciculin). There are also synthetic cholinesterase inhibitors, for example man-made insecticides. These inhibitors inactivate acetyicholinesterase and butyrylcholinesterase as well as other targets. From a study of the tissue distribution of acetylcholinesterase and butyrylcholinesterase mRNA by Northern blot analysis, we have found the highest levels of butyrylcholinesterase mRNA in the liver and lungs, tissues known as the principal detoxication sites of the human body. These results indicate that butyrylcholinesterase may be a first line of defense against poisons that are eaten or inhaled.

  7. Infrared absorption of human breast tissues in vitro

    Energy Technology Data Exchange (ETDEWEB)

    Liu Chenglin [Department of Physics, Surface Physics Laboratory (National Key laboratory), Synchrotron Radiation Research Center, Fudan University, Shanghai 200433 (China); Physics Department of Yancheng Teachers' College, Yancheng 224002 (China); Zhang Yuan [Department of Physics, Surface Physics Laboratory (National Key laboratory), Synchrotron Radiation Research Center, Fudan University, Shanghai 200433 (China); Yan Xiaohui [Department of Physics, Surface Physics Laboratory (National Key laboratory), Synchrotron Radiation Research Center, Fudan University, Shanghai 200433 (China); Zhang Xinyi [Department of Physics, Surface Physics Laboratory (National Key laboratory), Synchrotron Radiation Research Center, Fudan University, Shanghai 200433 (China) and Shanghai Research Center of Acupuncture and Meridian, Pudong, Shanghai 201203 (China)]. E-mail: xy-zhang@fudan.edu.cn; Li Chengxiang [National Synchrotron Radiation Laboratory, University of Science and Technology of China, Hefei 230029 (China); Yang Wentao [Cancer Hospital, Medical Center, Fudan University, Shanghai 200032 (China); Shi Daren [Cancer Hospital, Medical Center, Fudan University, Shanghai 200032 (China)

    2006-07-15

    The spectral characteristics of human breast tissues in normal status and during different cancerous stages have been investigated by synchrotron radiation based Fourier transform infrared (SR-FTIR) absorption spectroscopy. Thanks to the excellent synchrotron radiation infrared (IR) source, higher resolving power is achieved in SR-FTIR absorption spectra than in conventional IR absorption measurements. Obvious variations in IR absorption spectrum of breast tissues were found as they change from healthy to diseased, or say in progression to cancer. On the other hand, some specific absorption peaks were found in breast cancer tissues by SR-FTIR spectroscopic methods. These spectral characteristics of breast tissue may help us in early diagnosis of breast cancer.

  8. Comparison of Methods for Analyzing Human Adipose Tissue Macrophage Content

    DEFF Research Database (Denmark)

    Morgan-Bathke, Maria; Harteneck, Debra; Jaeger, Philippa

    2017-01-01

    OBJECTIVE: The relationship between inflammation, obesity, and adverse metabolic conditions is associated with adipose tissue macrophages (ATM). This study compared the measurements of human ATM using flow cytometry, immunohistochemistry (IHC), and real-time polymerase chain reaction (RT-PCR) of ...

  9. Human Bites of the Face with Tissue Losses in Cosmopolitan ...

    African Journals Online (AJOL)

    Dr. Milaki Asuku

    Abstract. A retrospective series of thirty-six cases of human bites to the face with tissue losses requiring reconstruction during a five-year period, January 1999 to December 2003 is presented. The unmarried female in her third decade dominated both as victim and assailant in incidences related to love affairs and love gone ...

  10. Human Bites of the Face with Tissue Losses in Cosmopolitan ...

    African Journals Online (AJOL)

    A retrospective series of thirty-six cases of human bites to the face with tissue losses requiring reconstruction during a five-year period, January 1999 to December 2003 is presented. The unmarried female in her third decade dominated both as victim and assailant in incidences related to love affairs and love gone sour.

  11. Proteome analysis of human colorectal cancer tissue using 2-D ...

    African Journals Online (AJOL)

    Proteome analysis of human colorectal cancer tissue using 2-D DIGE and tandem mass spectrometry for identification of disease-related proteins. ... African Journal of Biotechnology ... The cDNA of the differential protein was transfected into colorectal cancer cells, and the biological behavior of these cells was observed.

  12. Assessment of permeation of lipoproteins in human carotid tissue

    Science.gov (United States)

    Ghosn, Mohamad G.; Syed, Saba H.; Leba, Michael; Morrisett, Joel D.; Tuchin, Valery V.; Larin, Kirill V.

    2010-02-01

    Cardiovascular disease is among the leading causes of death in the United States. Specifically, atherosclerosis is an increasingly devastating contributor to the tally and has been found to be a byproduct of arterial permeability irregularities in regards to lipoprotein penetration. To further explore arterial physiology and molecular transport, the imaging technique of Optical Coherence Tomography (OCT) was employed. With OCT, the permeation of glucose (MW = 180 Da), low density lipoprotein (LDL; MW = 2.1 × 106 Da), and high density lipoprotein (HDL; MW = 2.5 × 105 Da) in human carotid tissue was studied to determine the effect of different molecular characteristics on permeation in atherosclerotic tissues. The permeability rates calculated from the diffusion of the molecular agents into the abnormal carotid tissue samples is compared to those of normal, healthy tissue. The results show that in the abnormal tissue, the permeation of agents correlate to the size constraints. The larger molecules of LDL diffuse the slowest, while the smallest molecules of glucose diffuse the fastest. However, in normal tissue, LDL permeates at a faster rate than the other two agents, implying the existence of a transport mechanism that facilitates the passage of LDL molecules. These results highlight the capability of OCT as a sensitive and specific imaging technique as well as provide significant information to the understanding of atherosclerosis and its effect on tissue properties.

  13. Expression of matrix metalloproteinases in human breast cancer tissues.

    Science.gov (United States)

    Benson, Chellakkan Selvanesan; Babu, Somasundaram Dinesh; Radhakrishna, Selvi; Selvamurugan, Nagarajan; Ravi Sankar, Bhaskaran

    2013-01-01

    Breast cancer is the most common cancer affecting women in the world today. Matrix metalloproteinases (MMPs) are a family of endopeptidases that can degrade extracellular matrix proteins and promote cell invasion and metastasis. MMPs are differentially expressed and their expressions are often associated with a poor prognosis for patients. The aim of this study is to investigate and compare the expression of MMPs in different grades of human breast cancer tissues with normal breast tissues. We collected 39 breast cancer samples (24 grade II and 15 grade III) along with 16 normal breast tissues from outside the tumor margin during cancer removal surgery. The samples were analysed for the expression of all known MMPs using real-time quantitative PCR. The results indicate that mRNA expressions of MMP-1, -9,-11,-15,-24 and -25 were upregulated in breast cancer tissues when compared to normal breast tissues. But, the mRNA expressions of MMP-10 and MMP-19 were downregulated in cancer tissue. In membrane associated MMPs like MMP-15 and MMP-24 we found a grade dependent increase of their mRNA expression. Our studies demonstrate that MMPs are differentially regulated in breast cancer tissues and they might play various roles in tumor invasion, metastasis and angiogenesis. Thus, MMPs are of immense value to be studied as diagnostic markers and drug target.

  14. Profiling RNA editing in human tissues: towards the inosinome Atlas

    Science.gov (United States)

    Picardi, Ernesto; Manzari, Caterina; Mastropasqua, Francesca; Aiello, Italia; D’Erchia, Anna Maria; Pesole, Graziano

    2015-01-01

    Adenine to Inosine RNA editing is a widespread co- and post-transcriptional mechanism mediated by ADAR enzymes acting on double stranded RNA. It has a plethora of biological effects, appears to be particularly pervasive in humans with respect to other mammals, and is implicated in a number of diverse human pathologies. Here we present the first human inosinome atlas comprising 3,041,422 A-to-I events identified in six tissues from three healthy individuals. Matched directional total-RNA-Seq and whole genome sequence datasets were generated and analysed within a dedicated computational framework, also capable of detecting hyper-edited reads. Inosinome profiles are tissue specific and edited gene sets consistently show enrichment of genes involved in neurological disorders and cancer. Overall frequency of editing also varies, but is strongly correlated with ADAR expression levels. The inosinome database is available at: http://srv00.ibbe.cnr.it/editing/. PMID:26449202

  15. Zicam-induced damage to mouse and human nasal tissue.

    Directory of Open Access Journals (Sweden)

    Jae H Lim

    Full Text Available Intranasal medications are used to treat various nasal disorders. However, their effects on olfaction remain unknown. Zicam (zinc gluconate; Matrixx Initiatives, Inc, a homeopathic substance marketed to alleviate cold symptoms, has been implicated in olfactory dysfunction. Here, we investigated Zicam and several common intranasal agents for their effects on olfactory function. Zicam was the only substance that showed significant cytotoxicity in both mouse and human nasal tissue. Specifically, Zicam-treated mice had disrupted sensitivity of olfactory sensory neurons to odorant stimulation and were unable to detect novel odorants in behavioral testing. These findings were long-term as no recovery of function was observed after two months. Finally, human nasal explants treated with Zicam displayed significantly elevated extracellular lactate dehydrogenase levels compared to saline-treated controls, suggesting severe necrosis that was confirmed on histology. Our results demonstrate that Zicam use could irreversibly damage mouse and human nasal tissue and may lead to significant smell dysfunction.

  16. Intrauterine growth restriction and placental angiogenesis

    Directory of Open Access Journals (Sweden)

    Harma Muge

    2010-04-01

    Full Text Available Abstract Background Vascular endothelial growth factor (VEGF, basic-fibroblast growth factor (b-FGF, and endothelial nitric oxide synthase (eNOS are factors that take part in placental angiogenesis. They are highly expressed during embryonic and fetal development, especially in the first trimester. In this study, we aimed to investigate the role of placental angiogenesis in the development of intrauterine growth restriction (IUGR by comparing the levels of expression of VEGF-A, b-FGF, and eNOS in normal-term pregnancy and IUGR placentas. Methods The expression of VEGF-A, b-FGF, and eNOS was studied using the avidin-biotin-peroxidase method in placental tissues diagnosed as normal (n = 55 and IUGR (n = 55. Results were evaluated in a semi-quantitative manner. Results The expression of all the markers was significantly higher (p Conclusion Increased expression of VEGF-A, b-FGF, and eNOS may be the result of inadequate uteroplacental perfusion, supporting the proposal that abnormal angiogenesis plays a role in the pathophysiology of IUGR.

  17. 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.

  18. Slow-freezing versus vitrification for human ovarian tissue cryopreservation.

    Science.gov (United States)

    Klocke, Silke; Bündgen, Nana; Köster, Frank; Eichenlaub-Ritter, Ursula; Griesinger, Georg

    2015-02-01

    Ovarian tissue can be cryopreserved prior to chemotherapy using either the slow-freezing or the vitrification method; however, the data on the equality of the procedures are still conflicting. In this study, a comparison of the cryo-damage of human ovarian tissue induced by either vitrification or slow-freezing was performed. Ovarian tissue from 23 pre-menopausal patients was cryopreserved with either slow-freezing or vitrification. After thawing/warming, the tissue was histologically and immunohistochemically analyzed and cultured in vitro. During tissue culture the estradiol release was assessed. No significant difference was found in the proportion of high-quality follicles after thawing/warming in the slow-freezing and vitrification group, respectively (72.7 versus 66.7 %, p = 0.733). Estradiol secretion by the ovarian tissue was similar between groups during 18 days in vitro culture (area-under-the-curve 5,411 versus 13,102, p = 0.11). Addition of Sphingosine-1-Phosphate or Activin A to the culture medium did not alter estradiol release in both groups. The proportion of Activated Caspase-3 or 'Proliferating-Cell-Nuclear-Antigen' positive follicles at the end of the culture period was similar between slow-freezing and vitrification. Slow-freezing and vitrification result in similar morphological integrity after cryopreservation, a similar estradiol release in culture, and similar rates of follicular proliferation and apoptosis after culture.

  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. 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.

    2011-01-01

    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. PMID:21570381

  1. Comparative Analysis of Human Tissue Interactomes Reveals Factors Leading to Tissue-Specific Manifestation of Hereditary Diseases

    OpenAIRE

    Barshir, Ruth; Shwartz, Omer; Smoly, Ilan Y.; Yeger-Lotem, Esti

    2014-01-01

    An open question in human genetics is what underlies the tissue-specific manifestation of hereditary diseases, which are caused by genomic aberrations that are present in cells across the human body. Here we analyzed this phenomenon for over 300 hereditary diseases by using comparative network analysis. We created an extensive resource of protein expression and interactions in 16 main human tissues, by integrating recent data of gene and protein expression across tissues with data of protein-...

  2. Comparative analysis of human tissue interactomes reveals factors leading to tissue-specific manifestation of hereditary diseases.

    OpenAIRE

    Ruth Barshir; Omer Shwartz; Smoly, Ilan Y.; Esti Yeger-Lotem

    2014-01-01

    An open question in human genetics is what underlies the tissue-specific manifestation of hereditary diseases, which are caused by genomic aberrations that are present in cells across the human body. Here we analyzed this phenomenon for over 300 hereditary diseases by using comparative network analysis. We created an extensive resource of protein expression and interactions in 16 main human tissues, by integrating recent data of gene and protein expression across tissues with data of protein-...

  3. An Introduction to The Royan Human Ovarian Tissue Bank

    Directory of Open Access Journals (Sweden)

    Abtahi Naeimeh Sadat

    2016-07-01

    Full Text Available From December 2000 until 2010, the researchers at Royan Institute conducted a wide range of investigations on ovarian tissue cryopreservation with the intent to provide fertility pres- ervation to cancer patients that were considered to be candidates for these services. In 2010, Royan Institute established the Royan Human Ovarian Tissue Bank as a subgroup of the Embryology Department. Since its inception, approximately 180 patients between the ages of 747 years have undergone consultations. Ovarian samples were cryopreserved from 47 patients (age: 7-35 years diagnosed with cervical adenocarcinoma (n=9; breast carcinoma (n=7, Ewing’s sarcoma (n=7, opposite side ovarian tumor (n=7, endometrial adenocarci- noma (n=4, malignant colon tumors (n=3, as well as Hodgkin’s lymphoma, major thalas- semia and acute lymphoblastic leukemia (n=1-2 patients for each disease. Additionally, two patients requested ovarian tissue transplantation after completion of their treatments.

  4. Notes from the Field: Evidence of Zika Virus Infection in Brain and Placental Tissues from Two Congenitally Infected Newborns and Two Fetal Losses--Brazil, 2015.

    Science.gov (United States)

    Martines, Roosecelis Brasil; Bhatnagar, Julu; Keating, M Kelly; Silva-Flannery, Luciana; Muehlenbachs, Atis; Gary, Joy; Goldsmith, Cynthia; Hale, Gillian; Ritter, Jana; Rollin, Dominique; Shieh, Wun-Ju; Luz, Kleber G; Ramos, Ana Maria de Oliveira; Davi, Helaine Pompeia Freire; Kleber de Oliveria, Wanderson; Lanciotti, Robert; Lambert, Amy; Zaki, Sherif

    2016-02-19

    Zika virus is a mosquito-borne flavivirus that is related to dengue virus and transmitted primarily by Aedes aegypti mosquitoes, with humans acting as the principal amplifying host during outbreaks. Zika virus was first reported in Brazil in May 2015 (1). By February 9, 2016, local transmission of infection had been reported in 26 countries or territories in the Americas.* Infection is usually asymptomatic, and, when symptoms are present, typically results in mild and self-limited illness with symptoms including fever, rash, arthralgia, and conjunctivitis. However, a surge in the number of children born with microcephaly was noted in regions of Brazil with a high prevalence of suspected Zika virus disease cases. More than 4,700 suspected cases of microcephaly were reported from mid-2015 through January 2016, although additional investigations might eventually result in a revised lower number (2). In response, the Brazil Ministry of Health established a task force to further investigate possible connections between the virus and brain anomalies in infants (3).

  5. Autopsy Tissue Program. [Plutonium determination in selected tissues of human cadavers

    Energy Technology Data Exchange (ETDEWEB)

    Fox, T.; Tietjen, G.

    1979-01-01

    The Autopsy Tissue Program was begun in 1960. To date, tissues on 900 or more persons in 7 geographic regions have been collected and analyzed for plutonium content. The tissues generally consist of lung, liver, kidney, lymph, bone, and gonadal tissue for each individual. The original objective of the program was to determine the level of plutonium in human tissues due solely to fall-out from weapons testing. The baseline thus established was to be used to evaluate future changes. From the first, this program was beset with chemical and statistical difficulties. Many factors whose effects were not recognized and not planned for were found later to be important. Privacy and ethical considerations hindered the gathering of adequate data. Since the chemists were looking for amounts of plutonium very close to background, possible contamination was a very real problem. Widely used chemical techniques introduced a host of statistical problems. The difficulties encountered touch on areas common to large data sets, unusual outlier detection methods, minimum detection limits, problems with Aliquot sizes, and time-trends in the data. The conclusions point out areas to which the biologists will have to devote much more careful attention than was believed.

  6. Expression of the endocannabinoid receptors in human fascial tissue

    Directory of Open Access Journals (Sweden)

    C. Fede

    2016-06-01

    Full Text Available Cannabinoid receptors have been localized in the central and peripheral nervous system as well as on cells of the immune system, but recent studies on animal tissue gave evidence for the presence of cannabinoid receptors in different types of tissues. Their presence was supposed also in myofascial tissue, suggesting that the endocannabinoid system may help resolve myofascial trigger points and relieve symptoms of fibromyalgia. However, until now the expression of CB1 (cannabinoid receptor 1 and CB2 (cannabinoid receptor 2 in fasciae has not yet been established. Small samples of fascia were collected from volunteers patients during orthopedic surgery. For each sample were done a cell isolation, immunohistochemical investigation (CB1 and CB2 antibodies and real time RT-PCR to detect the expression of CB1 and CB2. Both cannabinoid receptors are expressed in human fascia and in human fascial fibroblasts culture cells, although to a lesser extent than the control gene. We can assume that the expression of mRNA and protein of CB1 and CB2 receptors in fascial tissue are concentrated into the fibroblasts. This is the first demonstration that the fibroblasts of the muscular fasciae express CB1 and CB2. The presence of these receptors could help to provide a description of cannabinoid receptors distribution and to better explain the role of fasciae as pain generator and the efficacy of some fascial treatments. Indeed the endocannabinoid receptors of fascial fibroblasts can contribute to modulate the fascial fibrosis and inflammation.

  7. Polarized spectral features of human breast tissues through wavelet ...

    Indian Academy of Sciences (India)

    Polarized spectral features of human breast tissues. 0. 5. 10. 15. 20. 25. 0. 10. 20. 30. 40. 50 patient number cancer normal. 1. 2. 3. 4. 5. 0.95. 0.96. 0.97. 0.98. 0.99. 1 levels. Normalized low pass power cancer normal. (a). (b). Figure 1. (a) Standard deviation of percentage fluctuation (of difference of intensities of parallel and ...

  8. Expression of Matrix Metalloproteinases in Human Breast Cancer Tissues

    OpenAIRE

    Benson, Chellakkan Selvanesan; Babu, Somasundaram Dinesh; Radhakrishna, Selvi; Selvamurugan, Nagarajan; Sankar, Bhaskaran Ravi

    2013-01-01

    BACKGROUND: Breast cancer is the most common cancer affecting women in the world today. Matrix metalloproteinases (MMPs) are a family of endopeptidases that can degrade extracellular matrix proteins and promote cell invasion and metastasis. MMPs are differentially expressed and their expressions are often associated with a poor prognosis for patients. OBJECTIVE: The aim of this study is to investigate and compare the expression of MMPs in different grades of human breast cancer tissues with n...

  9. Sympathetic reflex control of blood flow in human peripheral tissues

    DEFF Research Database (Denmark)

    Henriksen, O

    1991-01-01

    sympathetic vasoconstrictor reflexes are blocked. Blood flow has been measure by the local 133Xe-technique. The results indicate the presence of spinal as well as supraspinal sympathetic vasoconstrictor reflexes to human peripheral tissues. Especially is emphasized the presence of a local sympathetic veno......Sympathetic vasoconstrictor reflexes are essential for the maintenance of arterial blood pressure in upright position. It has been generally believed that supraspinal sympathetic vasoconstrictor reflexes elicited by changes in baroreceptor activity play an important role. Recent studies on human...

  10. 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. Copyright © 2015 by The American Association of Immunologists, Inc.

  11. Identification and significance of magnetite in human tissues.

    Science.gov (United States)

    Moatamed, F; Johnson, F B

    1986-07-01

    Magnetite or iron oxide has been identified in humans as well as certain animals and bacteria. With the current popularity of magnetic resonance imaging, the presence of these ferromagnetic particles in the tissues may impose biological significance. So far, identification of magnetite in tissue has been mainly based on magnetometry. Hence, a simple technique for direct identification of the magnetic particles in tissues is described. Lung tissues with abundant iron material and particles were digested in 1N sodium hydroxide solution. After rinsing, the sediments were suspended in 95% alcohol and placed on a glass slide located on a strong magnet. The iron-containing particles from the digestion procedure were aligned in a parallel manner along the north-south poles of the magnet and were confirmed to be magnetite by x-ray diffraction. No such effect was observed with hemosiderin-containing granules from the control liver tissues. The results of this experiment show that the "biological magnetite" is distinctly different from hemosiderin and has characteristic properties when subjected to a magnetic field.

  12. FTIR protein secondary structure analysis of human ascending aortic tissues.

    Science.gov (United States)

    Bonnier, Franck; Rubin, Sylvain; Debelle, Laurent; Ventéo, Lydie; Pluot, Michel; Baehrel, Bernard; Manfait, Michel; Sockalingum, Ganesh D

    2008-08-01

    The advent of moderate dilatations in ascending aortas is often accompanied by structural modifications of the main components of the aortic tissue, elastin and collagen. In this study, we have undertaken an approach based on FTIR microscopy coupled to a curve-fitting procedure to analyze secondary structure modifications in these proteins in human normal and pathological aortic tissues. We found that the outcome of the aortic pathology is strongly influenced by these proteins, which are abundant in the media of the aortic wall, and that the advent of an aortic dilatation is generally accompanied by a decrease of parallel beta-sheet structures. Elastin, essentially composed of beta-sheet structures, seems to be directly related to these changes and therefore indicative of the elastic alteration of the aortic wall. Conventional microscopy and confocal fluorescence microscopy were used to compare FTIR microscopy results with the organization of the elastic fibers present in the tissues. This in-vitro study on 6 patients (three normal and three pathologic), suggests that such a spectroscopic marker, specific to aneurismal tissue characterization, could be important information for surgeons who face the dilemma of moderate aortic tissue dilatation of the ascending aortas.

  13. Isolation of Borna Disease Virus from Human Brain Tissue

    Science.gov (United States)

    Nakamura, Yurie; Takahashi, Hirokazu; Shoya, Yuko; Nakaya, Takaaki; Watanabe, Makiko; Tomonaga, Keizo; Iwahashi, Kazuhiko; Ameno, Kiyoshi; Momiyama, Noriko; Taniyama, Hiroyuka; Sata, Tetsutaro; Kurata, Takeshi; de la Torre, Juan Carlos; Ikuta, Kazuyoshi

    2000-01-01

    Serological and molecular epidemiological studies indicate that Borna disease virus (BDV) can infect humans and is possibly associated with certain neuropsychiatric disorders. We examined brain tissue collected at autopsy from four schizophrenic patients and two healthy controls for the presence of BDV markers in 12 different brain regions. BDV RNA and antigen was detected in four brain regions of a BDV-seropositive schizophrenic patient (P2) with a very recent (2 years) onset of disease. BDV markers exhibited a regionally localized distribution. BDV RNA was found in newborn Mongolian gerbils intracranially inoculated with homogenates from BDV-positive brain regions of P2. Human oligodendroglia (OL) cells inoculated with brain homogenates from BDV-positive gerbils allowed propagation and isolation of BDVHuP2br, a human brain-derived BDV. Virus isolation was also possible by transfection of Vero cells with ribonucleoprotein complexes prepared from BDV-positive human and gerbil brain tissues. BDVHuP2br was genetically closely related to but distinct from previously reported human- and animal-derived BDV sequences. PMID:10775596

  14. Streamlined bioreactor-based production of human cartilage tissues.

    Science.gov (United States)

    Tonnarelli, B; Santoro, R; Adelaide Asnaghi, M; Wendt, D

    2016-05-27

    Engineered tissue grafts have been manufactured using methods based predominantly on traditional labour-intensive manual benchtop techniques. These methods impart significant regulatory and economic challenges, hindering the successful translation of engineered tissue products to the clinic. Alternatively, bioreactor-based production systems have the potential to overcome such limitations. In this work, we present an innovative manufacturing approach to engineer cartilage tissue within a single bioreactor system, starting from freshly isolated human primary chondrocytes, through the generation of cartilaginous tissue grafts. The limited number of primary chondrocytes that can be isolated from a small clinically-sized cartilage biopsy could be seeded and extensively expanded directly within a 3D scaffold in our perfusion bioreactor (5.4 ± 0.9 doublings in 2 weeks), bypassing conventional 2D expansion in flasks. Chondrocytes expanded in 3D scaffolds better maintained a chondrogenic phenotype than chondrocytes expanded on plastic flasks (collagen type II mRNA, 18-fold; Sox-9, 11-fold). After this "3D expansion" phase, bioreactor culture conditions were changed to subsequently support chondrogenic differentiation for two weeks. Engineered tissues based on 3D-expanded chondrocytes were more cartilaginous than tissues generated from chondrocytes previously expanded in flasks. We then demonstrated that this streamlined bioreactor-based process could be adapted to effectively generate up-scaled cartilage grafts in a size with clinical relevance (50 mm diameter). Streamlined and robust tissue engineering processes, as the one described here, may be key for the future manufacturing of grafts for clinical applications, as they facilitate the establishment of compact and closed bioreactor-based production systems, with minimal automation requirements, lower operating costs, and increased compliance to regulatory guidelines.

  15. Regulatory roles of microRNAs in human dental tissues.

    Science.gov (United States)

    Sehic, Amer; Tulek, Amela; Khuu, Cuong; Nirvani, Minou; Sand, Lars Peter; Utheim, Tor Paaske

    2017-01-05

    MicroRNAs (miRNAs) are a class of small, non-coding RNAs that provide an efficient pathway for regulation of gene expression at a post-transcriptional level. Tooth development is regulated by a complex network of cell-cell signaling during all steps of organogenesis. Most of the congenital dental defects in humans are caused by mutations in genes involved in developmental regulatory networks. Whereas the developmental morphological stages of the tooth development already are thoroughly documented, the implicated genetic network is still under investigation. The involvement of miRNAs in the regulation of tooth genetic network was suggested for the first time in 2008. MiRNAs regulate tooth morphogenesis by fine-tuning the signaling networks. Unique groups of miRNAs are expressed in dental epithelium compared with mesenchyme, as well as in molars compared with incisors. The present review focuses on the current state of knowledge on the expression and function of miRNAs in human dental tissues, including teeth and the surrounding structures. Herein, we show that miRNAs exhibit specific roles in human dental tissues and are involved in gingival and periodontal disease, tooth movement and eruption, dental pulp physiology including repair and regeneration, differentiation of dental cells, and enamel mineralization. In light of similarities between the tooth development and other organs originating from the epithelium, further understanding of miRNAs` function in dental tissues may have wide biological relevance. Copyright © 2016 Elsevier B.V. All rights reserved.

  16. Expression cartography of human tissues using self organizing maps.

    Science.gov (United States)

    Wirth, Henry; Löffler, Markus; von Bergen, Martin; Binder, Hans

    2011-07-27

    Parallel high-throughput microarray and sequencing experiments produce vast quantities of multidimensional data which must be arranged and analyzed in a concerted way. One approach to addressing this challenge is the machine learning technique known as self organizing maps (SOMs). SOMs enable a parallel sample- and gene-centered view of genomic data combined with strong visualization and second-level analysis capabilities. The paper aims at bridging the gap between the potency of SOM-machine learning to reduce dimension of high-dimensional data on one hand and practical applications with special emphasis on gene expression analysis on the other hand. The method was applied to generate a SOM characterizing the whole genome expression profiles of 67 healthy human tissues selected from ten tissue categories (adipose, endocrine, homeostasis, digestion, exocrine, epithelium, sexual reproduction, muscle, immune system and nervous tissues). SOM mapping reduces the dimension of expression data from ten of thousands of genes to a few thousand metagenes, each representing a minicluster of co-regulated single genes. Tissue-specific and common properties shared between groups of tissues emerge as a handful of localized spots in the tissue maps collecting groups of co-regulated and co-expressed metagenes. The functional context of the spots was discovered using overrepresentation analysis with respect to pre-defined gene sets of known functional impact. We found that tissue related spots typically contain enriched populations of genes related to specific molecular processes in the respective tissue. Analysis techniques normally used at the gene-level such as two-way hierarchical clustering are better represented and provide better signal-to-noise ratios if applied to the metagenes. Metagene-based clustering analyses aggregate the tissues broadly into three clusters containing nervous, immune system and the remaining tissues. The SOM technique provides a more intuitive and

  17. 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.

  18. Regulation of pregnancy-associated plasma protein A2 (PAPPA2 in a human placental trophoblast cell line (BeWo

    Directory of Open Access Journals (Sweden)

    Christians Julian K

    2011-04-01

    Full Text Available Abstract Background Pregnancy-associated plasma protein A2 (PAPPA2 is an insulin-like growth factor-binding protein (IGFBP protease expressed at high levels in the placenta and upregulated in pregnancies complicated by preeclampsia and HELLP (Hemolytic anemia, Elevated Liver enzymes, and Low Platelet count syndrome. However, it is unclear whether elevated PAPPA2 expression causes abnormal placental development, or whether upregulation compensates for placental pathology. In the present study, we investigate whether PAPPA2 expression is affected by hypoxia, oxidative stress, syncytialization factors or substances known to affect the expression of PAPPA2's paralogue, PAPPA. Methods BeWo cells, a model of placental trophoblasts, were treated with one of the following: hypoxia (2% O2, oxidative stress (20 microM hydrogen peroxide, forskolin (10 microM and 100 microM, TGF-beta (10 and 50 ng/mL, TNF-alpha (100 ng/mL, IL-1beta (100 ng/mL or PGE2 (1 microM. We used quantitative RT-PCR (qRT-PCR to quantify the mRNA levels of PAPPA2, as well as those of PAPPA and ADAM12 since these proteases have similar substrates and are also highly expressed in the placenta. Where we observed significant effects on PAPPA2 mRNA levels, we tested for effects at the protein level using an in-cell Western assay. Results Hypoxia, but not oxidative stress, caused a 47-fold increase in PAPPA2 mRNA expression, while TNF-alpha resulted in a 6-fold increase, and both of these effects were confirmed at the protein level. PGE2 resulted in a 14-fold upregulation of PAPPA2 mRNA but this was not reflected at the protein level. Forskolin, TGF-beta and IL-1beta had no significant effect on PAPPA2 mRNA expression. We observed no effects of any treatment on PAPPA or ADAM12 expression. Conclusion Our study demonstrates that factors previously known to be highly expressed in preeclamptic placentae (PGE2 and TNF-alpha, contribute to the upregulation of PAPPA2. Hypoxia, known to occur in

  19. Maintenance of fetal human pancreatic beta cells in tissue culture.

    Science.gov (United States)

    McEvoy, R C; Thomas, N M; Bowers, C; Ginsberg-Fellner, F

    1986-01-01

    Large quantities of viable human islet tissue (beta cells) are required for transplant and for investigations of the autoimmune basis of Type I diabetes. Fetal pancreas offers a potential advantage over other possible sources of beta cells in that it retains some capacity for growth in vitro. We have cultured a total of 45 human pancreata from fetuses of gestational ages from 18 to 23 weeks. Each pancreas was obtained within minutes after delivery and usually cultured within 30 minutes. Pancreata were dispersed and cultured for up to 32 days. Maintenance and growth of the beta cells was assessed by the content of insulin in extracts of cultured tissue. As has been reported by others, fetal human beta cells survived in vitro for over 4 weeks. In three experiments in which a direct comparison was made, collagenase digestion of the fetal pancreas resulted in a significantly greater loss of insulin content compared to minced tissue cultured without digestion. Storage of three pancreata in medium overnight at 4 degrees C significantly reduced the insulin content of the pancreas compared to pancreata cultured immediately. During culture, the majority of the beta cells (based on insulin content) were found in small, macroscopic clumps attached to the surface of the culture dish, and surrounded by a nearly confluent monolayer of fibroblastoid cells. There was a marked decrease in the insulin content of the tissue during culture, most of it (to less than 25% of the original) occurring over the first 4-6 days of culture.(ABSTRACT TRUNCATED AT 250 WORDS)

  20. PVA matches human liver in needle-tissue interaction.

    Science.gov (United States)

    de Jong, Tonke L; Pluymen, Loes H; van Gerwen, Dennis J; Kleinrensink, Gert-Jan; Dankelman, Jenny; van den Dobbelsteen, John J

    2017-05-01

    Medical phantoms can be used to study needle-tissue interaction and to train medical residents. The purpose of this research is to study the suitability of polyvinyl alcohol (PVA) as a liver tissue mimicking material in terms of needle-tissue interaction. Insertions into ex-vivo human livers were used for reference. Six PVA samples were created by varying the mass percentage of PVA to water (4m% and 7m%) and the number of freeze-thaw cycles (1, 2 and 3 cycles, 16hours of freezing at -19°C, 8hours of thawing). The inner needle of an 18 Gauge trocar needle with triangular tip was inserted 13 times into each of the samples, using an insertion velocity of 5 mm/s. In addition, 39 insertions were performed in two ex-vivo human livers. Axial forces on the needle were captured during insertion and retraction and characterized by friction along the needle shaft, peak forces, and number of peak forces per unit length. The concentration of PVA and the number of freeze-thaw cycles both influenced the mechanical interaction between needle and specimen. Insertions into 4m% PVA phantoms with 2 freeze-thaw cycles were comparable to human liver in terms of estimated friction along the needle shaft and the number of peak forces. Therefore, these phantoms are considered to be suitable liver mimicking materials for image-guided needle interventions. The mechanical properties of PVA hydrogels can be influenced in a controlled manner by varying the concentration of PVA and the number of freeze-thaw cycles, to mimic liver tissue characteristics. Copyright © 2017 Elsevier Ltd. All rights reserved.

  1. Formation of Hyaline Cartilage Tissue by Passaged Human Osteoarthritic Chondrocytes.

    Science.gov (United States)

    Bianchi, Vanessa J; Weber, Joanna F; Waldman, Stephen D; Backstein, David; Kandel, Rita A

    2017-02-01

    When serially passaged in standard monolayer culture to expand cell number, articular chondrocytes lose their phenotype. This results in the formation of fibrocartilage when they are used clinically, thus limiting their use for cartilage repair therapies. Identifying a way to redifferentiate these cells in vitro is critical if they are to be used successfully. Transforming growth factor beta (TGFβ) family members are known to be crucial for regulating differentiation of fetal limb mesenchymal cells and mesenchymal stromal cells to chondrocytes. As passaged chondrocytes acquire a progenitor-like phenotype, the hypothesis of this study was that TGFβ supplementation will stimulate chondrocyte redifferentiation in vitro in serum-free three-dimensional (3D) culture. Human articular chondrocytes were serially passaged twice (P2) in monolayer culture. P2 cells were then placed in high-density (3D) culture on top of membranes (Millipore) and cultured for up to 6 weeks in chemically defined serum-free redifferentiation media (SFRM) in the presence or absence of TGFβ. The tissues were evaluated histologically, biochemically, by immunohistochemical staining, and biomechanically. Passaged human chondrocytes cultured in SFRM supplemented with 10 ng/mL TGFβ3 consistently formed a continuous layer of articular-like cartilage tissue rich in collagen type 2 and aggrecan and lacking collagen type 1 and X in the absence of a scaffold. The tissue developed a superficial zone characterized by expression of lubricin and clusterin with horizontally aligned collagen fibers. This study suggests that passaged human chondrocytes can be used to bioengineer a continuous layer of articular cartilage-like tissue in vitro scaffold free. Further study is required to evaluate their ability to repair cartilage defects in vivo.

  2. 3D Extracellular Matrix from Sectioned Human Tissues

    Science.gov (United States)

    Campbell, Catherine B; Cukierman, Edna; Artym, Vira V

    2014-01-01

    corneal endothelial cell lines produce an ECM mimicking an in vivo subendothelium, and the EHS tumor cell line produces a matrix that can be extracted to produce Matrigel, which simulates basement membrane molecular complexity including laminin, collagen IV and nidogen (Beacham, et al., 2007; Friedl and Brocker, 2000). To simulate a physiological environment even more closely, 3D matrices derived from mouse tissue slices from which cells were extracted have reportedly provided successful ECM replicas for studying in vivo cellular behavior (Cukierman, et al., 2001). Because of the important roles of the extracellular microenvironment on normal and tumor cells, we have developed protocols to produce cell-free (decellularized) 3D matrices from cryostat sections of normal and tumor human tissues. These extracted matrices can be used as a 3D tissue culture environment to analyze effects of various 3D matrices on normal and tumor cell responses and behavior. Using human pancreas and breast tissue samples, we have successfully prepared cell-free 3D ECM models, used them as cell culture substrates for a human breast cancer cell line, MDA-MB-231, and then performed immunofluorescence staining to characterize intracellular structures. A frequently observed difference between normal and tumor tissue-derived ECM environments involves the amount of deposited fibrillar collagen (Provenzano, 2008). Tumor tissues from both breast and pancreas often contain substantially more collagen than normal adjacent tissue, and this protocol preserves this difference in cell-free 3D matrices from these tissues (Vidi, et al., 2013). This 3D culture system we describe using cell-free 3D matrix provides an approach to studying cellular behavior and migratory mechanisms associated with cancer. The basic protocol describes methods for successfully extracting cells and cellular debris from human tissue cryostat sections to obtain a clean, cell-free 3D ECM for plating cell lines (Figure 1). Cellular

  3. Isolation and characterization of membrane-associated placental proteins.

    Science.gov (United States)

    Bohn, H; Winckler, W

    1991-01-01

    Membrane-associated proteins (MPs) of the human term placenta (afterbirth) were obtained by extracting the insoluble part of the tissue with solubilizing agents, after the soluble material had been removed by washing with saline. The insoluble residue was subsequently exhaustively extracted first with the nonionic detergent Triton X-100 and then with 6 M urea. In the Triton extract eleven new different membrane-associated antigens could be detected by immunochemical methods; they were designated as MP2A to MP2L. One of these proteins (MP2C) was found to be immunochemically identical with the already described soluble placental protein PP21 [3]. MP1 another antigen detected in the Triton extract later was identified as heart stable alkaline phosphatase. In the urea extract eight different membrane-associated antigens could be identified by immunochemical methods; they were designated as MP3 to MP10. MP3 later was found to be immunochemically identical with laminin. All these membrane-associated proteins have now been isolated to purity and characterized by their physico-chemical properties. Specific antisera to the new proteins were obtained by immunizing animals with the corresponding purified proteins. They were used to detect and quantitate the new proteins in extracts of placentas and other human tissues by immunochemical methods such as gel diffusion tests. The immunocytochemical localization of the new proteins as well as measurement of their concentrations in body fluids by sensitive radioimmunoassays or enzyme immunoassays are presently under investigation.

  4. Challenges in the Management of Placental Site Trophoblastic Tumor

    African Journals Online (AJOL)

    Mubeen

    Reproductive Health Research Center, Alzahra Hospital Guilan University of Medical Sciences, 1Department of Pathology, Poursina Hospital, ... Beta human chorionic gonadotropin (β-HCG) level was 110 mIU/mL and uterus was diffusely enlarged. Total ... two substances, namely human placental lactogen (HPL) and.

  5. Placental Gas Exchange and the Oxygen Supply to the Fetus

    DEFF Research Database (Denmark)

    Carter, Anthony M

    2015-01-01

    is slowed, although oxygen consumption is unaltered when corrected for fetal mass. Similarly, birth weight is reduced in humans living at high altitude even if the effect is tempered in those with a long highland ancestry. Placental mass changes little during sustained hypoxia in sheep or humans at high...

  6. Human ovarian tissue from cortex surrounding benign cysts: a model to study ovarian tissue cryopreservation.

    Science.gov (United States)

    Schubert, Benoît; Canis, Michel; Darcha, Claude; Artonne, Christine; Pouly, Jean-Luc; Déchelotte, Pierre; Boucher, Daniel; Grizard, Geneviève

    2005-07-01

    The scarcity of human ovarian tissue is a major problem in developing research on ovarian cryopreservation. We were interested in ovarian cortex surrounding benign ovarian cysts harvested during their requisite operations. Ovarian tissue was collected from 25 women (mean age = 27.7 +/- 1.0 SEM) and frozen in serum-free cryoprotective medium. Histological and viability analysis were performed on fresh and frozen-thawed slices of tissue. Dermoid (n = 7), endometriosis (n = 13) and serous (n = 5) cysts were observed. Follicular densities (expressed per mm3) in ovarian cortex surrounding dermoid cysts were higher than in endometriosis and serous cysts for both histological (median of follicular densities: 13.04, 0.31 and 0.89 respectively) and viability analysis (2.93, 0.05 and 0.71 respectively). Freezing-thawing did not result in gross abnormality of follicle population either in number or morphology (80% of follicles preserved a normal pattern). However, a slight decrease of the density of living follicles (expressed per mm2) was reported. Ovarian cortex surrounding ovarian cysts, especially dermoid cysts, could be considered a source of ovarian tissue for future research. In our study, the cryopreservation procedure resulted in high follicular survival assessed by both histological and viability analysis. Nevertheless, further studies of in vivo and in vitro follicular maturation are needed to strengthen this model.

  7. Comparative analysis of human tissue interactomes reveals factors leading to tissue-specific manifestation of hereditary diseases.

    Directory of Open Access Journals (Sweden)

    Ruth Barshir

    2014-06-01

    Full Text Available An open question in human genetics is what underlies the tissue-specific manifestation of hereditary diseases, which are caused by genomic aberrations that are present in cells across the human body. Here we analyzed this phenomenon for over 300 hereditary diseases by using comparative network analysis. We created an extensive resource of protein expression and interactions in 16 main human tissues, by integrating recent data of gene and protein expression across tissues with data of protein-protein interactions (PPIs. The resulting tissue interaction networks (interactomes shared a large fraction of their proteins and PPIs, and only a small fraction of them were tissue-specific. Applying this resource to hereditary diseases, we first show that most of the disease-causing genes are widely expressed across tissues, yet, enigmatically, cause disease phenotypes in few tissues only. Upon testing for factors that could lead to tissue-specific vulnerability, we find that disease-causing genes tend to have elevated transcript levels and increased number of tissue-specific PPIs in their disease tissues compared to unaffected tissues. We demonstrate through several examples that these tissue-specific PPIs can highlight disease mechanisms, and thus, owing to their small number, provide a powerful filter for interrogating disease etiologies. As two thirds of the hereditary diseases are associated with these factors, comparative tissue analysis offers a meaningful and efficient framework for enhancing the understanding of the molecular basis of hereditary diseases.

  8. Comparative analysis of human tissue interactomes reveals factors leading to tissue-specific manifestation of hereditary diseases.

    Science.gov (United States)

    Barshir, Ruth; Shwartz, Omer; Smoly, Ilan Y; Yeger-Lotem, Esti

    2014-06-01

    An open question in human genetics is what underlies the tissue-specific manifestation of hereditary diseases, which are caused by genomic aberrations that are present in cells across the human body. Here we analyzed this phenomenon for over 300 hereditary diseases by using comparative network analysis. We created an extensive resource of protein expression and interactions in 16 main human tissues, by integrating recent data of gene and protein expression across tissues with data of protein-protein interactions (PPIs). The resulting tissue interaction networks (interactomes) shared a large fraction of their proteins and PPIs, and only a small fraction of them were tissue-specific. Applying this resource to hereditary diseases, we first show that most of the disease-causing genes are widely expressed across tissues, yet, enigmatically, cause disease phenotypes in few tissues only. Upon testing for factors that could lead to tissue-specific vulnerability, we find that disease-causing genes tend to have elevated transcript levels and increased number of tissue-specific PPIs in their disease tissues compared to unaffected tissues. We demonstrate through several examples that these tissue-specific PPIs can highlight disease mechanisms, and thus, owing to their small number, provide a powerful filter for interrogating disease etiologies. As two thirds of the hereditary diseases are associated with these factors, comparative tissue analysis offers a meaningful and efficient framework for enhancing the understanding of the molecular basis of hereditary diseases.

  9. Immunolocalization of lymphatic vessels in human fetal knee joint tissues.

    Science.gov (United States)

    Melrose, James; Little, Christopher B

    2010-08-01

    We immunolocalized lymphatic and vascular blood vessels in 12- and 14-week-old human fetal knee joint tissues using a polyclonal antibody to a lymphatic vascular endothelium specific hyaluronan receptor (LYVE-1) and a monoclonal antibody to podoplanin (mAb D2-40). A number of lymphatic vessels were identified in the stratified connective tissues surrounding the cartilaginous knee joint femoral and tibial rudiments. These tissues also contained small vascular vessels with entrapped red blood cells which were imaged using Nomarsky DIC microscopy. Neither vascular nor lymphatic vessels were present in the knee joint cartilaginous rudiments. The menisci in 12-week-old fetal knees were incompletely demarcated from the adjacent tibial and femoral cartilaginous rudiments which was consistent with the ongoing joint cavitation process at the femoral-tibial junction. At 14 weeks of age the menisci were independent structural entities; they contained a major central blood vessel containing red blood cells and numerous communicating vessels at the base of the menisci but no lymphatic vessels. In contrast to the 12-week-old menisci, the 14-week meniscal rudiments contained abundant CD-31 and CD-34 positive but no lymphatic vessels. Isolated 14-week-old meniscal cells also were stained with the CD-31 and CD 34 antibodies; CD-68 +ve cells, also abundant in the 14-week-old menisci, were detectable to a far lesser degree in the 12-week menisci and were totally absent from the femoral and tibial rudiments. The distribution of lymphatic vessels and tissue macrophages in the fetal joint tissues was consistent with their roles in the clearance of metabolic waste and extracellular matrix breakdown products arising from the rapidly remodelling knee joint tissues.

  10. [Studies on human breast cancer tissues with Raman microspectroscopy].

    Science.gov (United States)

    Yu, Ge; Xu, Xiao-xuan; Niu, Yun; Wang, Bin; Song, Zeng-fu; Zhang, Chun-ping

    2004-11-01

    The microscopic Raman spectra from normal and malignant human breast tissues have been measured and investigated. The spectral differences and changes between normal and malignant breast tissue samples mainly involve: (1) the band from the symmetric stretching modes of PO2- group in the DNA shifts from 1082 to 1097 cm(-1) and becomes stronger. The intensity of the symmetric stretching modes of O-P-O at 817 cm(-1) in RNA increases greatly. (2) The bands of Amide I and III at 1657 and 1273 cm(-1) change to 1662 and 1264 cm(-1) respectively with their intensity and band width increasing. The peak of the C-O stretching modes in the amino acids shifts to higher wave number. The tryptophan band at 1368 cm(-1) almost disappears. (3) Fewer characteristic Raman bands from lipids are observed. These spectral changes indicate that nucleic acids increase in contents relatively, while their conformation changes in cancer tissues. The proteins show various conformations and disorder structures with their molecular hydrogen bonds nearly broken. The contents of lipids decrease obviously. This investigation shows that Raman microspectroscopy is useful to biochemical study and vivo diagnosis of human breast cancers.

  11. Analysis of the scattering performance of human retinal tissue layers

    Science.gov (United States)

    Zhu, Dan; Gao, Zhisan; Ye, Haishui; Yuan, Qun

    2017-02-01

    Human retina is different from other ocular tissues, such as cornea, crystalline lens and vitreous because of high scattering performance. As an anisotropic tissue, we cannot neglect its impact on the polarization state of the scattered light. In this paper, Mie scattering and radiative transfer theory are applied to analyze the polarization state of backscattered light from four types of retinal tissues, including neural retina, retinal pigment epithelial (RPE), choroid and sclera. The results show that the most backscattered zones in different depths have almost the same electrical fields of Jones vector, which represents the polarization state of light, whether neural retina layer is under normal incidence or oblique incidence. Very little change occurs in the polarization of backscattered light compared to that of the incident light. Polarization distribution of backward scattered light from neural retina layer doesn't make apparent effects on polarization phase shifting in spectral domain OCT because its thickness is far less than photon mean free path, while other retinal tissues do not meet this rule.

  12. Characterization of human myoblast cultures for tissue engineering.

    Science.gov (United States)

    Stern-Straeter, Jens; Bran, Gregor; Riedel, Frank; Sauter, Alexander; Hörmann, Karl; Goessler, Ulrich Reinhart

    2008-01-01

    Skeletal muscle tissue engineering, a promising specialty, aims at the reconstruction of skeletal muscle loss. In vitro tissue engineering attempts to achieve this goal by creating differentiated, functional muscle tissue through a process in which stem cells are extracted from the patient, e.g. by muscle biopsies, expanded and differentiated in a controlled environment, and subsequently re-implanted. A prerequisite for this undertaking is the ability to cultivate and differentiate human skeletal muscle cell cultures. Evidently, optimal culture conditions must be investigated for later clinical utilization. We therefore analysed the proliferation of human cells in different environments and evaluated the differentiation potential of different culture media. It was shown that human myoblasts have a higher rate of proliferation in the alamarBlue assay when cultured on gelatin-coated culture flasks rather than polystyrene-coated flasks. We also demonstrated that myoblasts treated with a culture medium with a high concentration of growth factors [growth medium (GM)] showed a higher proliferation compared to cultures treated with a culture medium with lower amounts of growth factors [differentiation medium (DM)]. Differentiation of human myoblast cell cultures treated with GM and DM was analysed until day 16 and myogenesis was verified by expression of MyoD, myogenin, alpha-sarcomeric actin and myosin heavy chain by semi-quantitative RT-PCR. Immunohistochemical staining for desmin, Myf-5 and alpha-sarcomeric actin was performed to verify the myogenic phenotype of extracted satellite cells and to prove the maturation of cells. Cultures treated with DM showed positive staining for alpha-sarcomeric actin. Notably, markers of differentiation were also detected in cultures treated with GM, but there was no formation of myotubes. In the enzymatic assay of creatine phosphokinase, cultures treated with DM showed a higher activity, evidencing a higher degree of differentiation

  13. The Lin28/Let-7 System in Early Human Embryonic Tissue and Ectopic Pregnancy

    OpenAIRE

    Lozoya, Teresa; Domínguez, Francisco; Romero-Ruiz, Antonio; Steffani, Liliana; Martínez, Sebastián; Monterde, Mercedes; Ferri, Blanca; Núñez, Maria Jose; AinhoaRomero-Espinós,; Zamora, Omar; Gurrea, Marta; Sangiao-Alvarellos, Susana; Vega, Olivia; Simón, Carlos; Pellicer, Antonio

    2014-01-01

    Our objective was to determine the expression of the elements of the Lin28/Let-7 system, and related microRNAs (miRNAs), in early stages of human placentation and ectopic pregnancy, as a means to assess the potential role of this molecular hub in the pathogenesis of ectopic gestation. Seventeen patients suffering from tubal ectopic pregnancy (cases) and forty-three women with normal on-going gestation that desired voluntary termination of pregnancy (VTOP; controls) were recruited for the stud...

  14. Computational model of soft tissues in the human upper airway.

    Science.gov (United States)

    Pelteret, J-P V; Reddy, B D

    2012-01-01

    This paper presents a three-dimensional finite element model of the tongue and surrounding soft tissues with potential application to the study of sleep apnoea and of linguistics and speech therapy. The anatomical data was obtained from the Visible Human Project, and the underlying histological data was also extracted and incorporated into the model. Hyperelastic constitutive models were used to describe the material behaviour, and material incompressibility was accounted for. An active Hill three-element muscle model was used to represent the muscular tissue of the tongue. The neural stimulus for each muscle group was determined through the use of a genetic algorithm-based neural control model. The fundamental behaviour of the tongue under gravitational and breathing-induced loading is investigated. It is demonstrated that, when a time-dependent loading is applied to the tongue, the neural model is able to control the position of the tongue and produce a physiologically realistic response for the genioglossus.

  15. Mouse DNA contamination in human tissue tested for XMRV.

    Science.gov (United States)

    Robinson, Mark J; Erlwein, Otto W; Kaye, Steve; Weber, Jonathan; Cingoz, Oya; Patel, Anup; Walker, Marjorie M; Kim, Wun-Jae; Uiprasertkul, Mongkol; Coffin, John M; McClure, Myra O

    2010-12-20

    We used a PCR-based approach to study the prevalence of genetic sequences related to a gammaretrovirus, xenotropic murine leukemia virus-related virus, XMRV, in human prostate cancer. This virus has been identified in the US in prostate cancer patients and in those with chronic fatigue syndrome. However, with the exception of two patients in Germany, XMRV has not been identified in prostate cancer tissue in Europe. Most putative associations of new or old human retroviruses with diseases have turned out to be due to contamination. We have looked for XMRV sequences in DNA extracted from formalin-fixed paraffin- embedded prostate tissues. To control for contamination, PCR assays to detect either mouse mitochondrial DNA (mtDNA) or intracisternal A particle (IAP) long terminal repeat DNA were run on all samples, owing to their very high copy number in mouse cells. In general agreement with the US prevalence, XMRV-like sequences were found in 4.8% of prostate cancers. However, these were also positive, as were 21.5% of XMRV-negative cases, for IAP sequences, and many, but not all were positive for mtDNA sequences. These results show that contamination with mouse DNA is widespread and detectable by the highly sensitive IAP assay, but not always with less sensitive assays, such as murine mtDNA PCR. This study highlights the ubiquitous presence of mouse DNA in laboratory specimens and offers a means of rigorous validation for future studies of murine retroviruses in human disease.

  16. Human adipose tissue expresses intrinsic circadian rhythm in insulin sensitivity.

    Science.gov (United States)

    Carrasco-Benso, Maria P; Rivero-Gutierrez, Belen; Lopez-Minguez, Jesus; Anzola, Andrea; Diez-Noguera, Antoni; Madrid, Juan A; Lujan, Juan A; Martínez-Augustin, Olga; Scheer, Frank A J L; Garaulet, Marta

    2016-09-01

    In humans, insulin sensitivity varies according to time of day, with decreased values in the evening and at night. Mechanisms responsible for the diurnal variation in insulin sensitivity are unclear. We investigated whether human adipose tissue (AT) expresses intrinsic circadian rhythms in insulin sensitivity that could contribute to this phenomenon. Subcutaneous and visceral AT biopsies were obtained from extremely obese participants (body mass index, 41.8 ± 6.3 kg/m(2); 46 ± 11 y) during gastric-bypass surgery. To assess the rhythm in insulin signaling, AKT phosphorylation was determined every 4 h over 24 h in vitro in response to different insulin concentrations (0, 1, 10, and 100 nM). Data revealed that subcutaneous AT exhibited robust circadian rhythms in insulin signaling (P circadian rhythms were detected in visceral AT (P = 0.643). Here, we demonstrate the relevance of the time of the day for how sensitive AT is to the effects of insulin. Subcutaneous AT shows an endogenous circadian rhythm in insulin sensitivity that could provide an underlying mechanism for the daily rhythm in systemic insulin sensitivity.-Carrasco-Benso, M. P., Rivero-Gutierrez, B., Lopez-Minguez, J., Anzola, A., Diez-Noguera, A., Madrid, J. A., Lujan, J. A., Martínez-Augustin, O., Scheer, F. A. J. L., Garaulet, M. Human adipose tissue expresses intrinsic circadian rhythm in insulin sensitivity. © FASEB.

  17. Placental thrombomodulin expression in recurrent miscarriage

    Directory of Open Access Journals (Sweden)

    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.

  18. Protective antibodies against placental malaria and poor outcomes during pregnancy, Benin

    DEFF Research Database (Denmark)

    Ndam, Nicaise Tuikue; Denoeud-Ndam, Lise; Doritchamou, Justin

    2015-01-01

    Placental malaria is caused by Plasmodium falciparum-infected erythrocytes that bind to placental tissue. Binding is mediated by VAR2CSA, a parasite antigen coded by the var gene, which interacts with chondroitin sulfate A (CSA). Consequences include maternal anemia and fetal growth retardation....... Antibody-mediated immunity to placental malaria is acquired during successive pregnancies, but the target of VAR2CSA-specific protective antibodies is unclear. We assessed VAR2CSA-specific antibodies in pregnant women and analyzed their relationships with protection against placental infection, preterm...... infection, preterm birth, and low birthweight. These data suggest that antibodies against VAR2CSA N-terminal region mediate immunity to placental malaria and associated outcomes. Our results validate current vaccine development efforts with VAR2CSA N-terminal constructs....

  19. ALTERED EXPRESSION OF SURFACE RECEPTORS AT EA.HY926 ENDOTHELIAL CELL LINE INDUCED WITH PLACENTAL SECRETORY FACTORS

    Directory of Open Access Journals (Sweden)

    O. I. Stepanova

    2012-01-01

    Full Text Available Abstract. Placental cell populations produce a great variety of angiogenic factors and cytokines than control angiogenesis in placenta. Functional regulation of endothelial cells proceeds via modulation of endothelial cell receptors for endogenous angiogenic and apoptotic signals. Endothelial phenotype alteration during normal pregnancy and in cases of preclampsia is not well understood. The goal of this investigation was to evaluate altered expression of angiogenic and cytokine receptors at EA.hy926 endothelial cells under the influence of placental tissue supernatants. Normal placental tissue supernatants from 1st and 3rd trimesters, and pre-eclamptic placental tissue supernatants (3rd trimester stimulated angiogenic and cytokine receptors expression by the cultured endothelial cells, as compared with their background expression. Tissue supernatants from placental samples of 3rd trimester caused a decreased expression of angiogenic and cytokine receptors by endothelial cells, thus reflecting maturation of placental vascular system at these terms. Supernatants from preeclamptic placental tissue induced an increase of CD119 expression, in comparison with normal placental supernatants from the 3rd trimester. This finding suggests that IFNγ may be a factor of endothelial activation in pre-eclampsia. The study was supported by grants ГК №02.740.11.0711, НШ-3594.2010.7., and МД-150.2011.7.

  20. Magnetic Resonance Imaging of Human Tissue-Engineered Adipose Substitutes

    Science.gov (United States)

    Proulx, Maryse; Aubin, Kim; Lagueux, Jean; Audet, Pierre; Auger, Michèle

    2015-01-01

    Adipose tissue (AT) substitutes are being developed to answer the strong demand in reconstructive surgery. To facilitate the validation of their functional performance in vivo, and to avoid resorting to excessive number of animals, it is crucial at this stage to develop biomedical imaging methodologies, enabling the follow-up of reconstructed AT substitutes. Until now, biomedical imaging of AT substitutes has scarcely been reported in the literature. Therefore, the optimal parameters enabling good resolution, appropriate contrast, and graft delineation, as well as blood perfusion validation, must be studied and reported. In this study, human adipose substitutes produced from adipose-derived stem/stromal cells using the self-assembly approach of tissue engineering were implanted into athymic mice. The fate of the reconstructed AT substitutes implanted in vivo was successfully followed by magnetic resonance imaging (MRI), which is the imaging modality of choice for visualizing soft ATs. T1-weighted images allowed clear delineation of the grafts, followed by volume integration. The magnetic resonance (MR) signal of reconstructed AT was studied in vitro by proton nuclear magnetic resonance (1H-NMR). This confirmed the presence of a strong triglyceride peak of short longitudinal proton relaxation time (T1) values (200±53 ms) in reconstructed AT substitutes (total T1=813±76 ms), which establishes a clear signal difference between adjacent muscle, connective tissue, and native fat (total T1 ∼300 ms). Graft volume retention was followed up to 6 weeks after implantation, revealing a gradual resorption rate averaging at 44% of initial substitute's volume. In addition, vascular perfusion measured by dynamic contrast-enhanced-MRI confirmed the graft's vascularization postimplantation (14 and 21 days after grafting). Histological analysis of the grafted tissues revealed the persistence of numerous adipocytes without evidence of cysts or tissue necrosis. This study

  1. Expression of interleukin-17RC protein in normal human tissues

    Directory of Open Access Journals (Sweden)

    Ge Dongxia

    2008-10-01

    Full Text Available Abstract Background Interleukin-17 (IL-17 cytokines and receptors play an important role in many autoimmune and inflammatory diseases. IL-17 receptors IL-17RA and IL-17RC have been found to form a heterodimer for mediating the signals of IL-17A and IL-17F cytokines. While the function and signaling pathway of IL-17RA has been revealed, IL-17RC has not been well characterized. The function and signaling pathway of IL-17RC remain largely unknown. The purpose of the present study was to systematically examine IL-17RC protein expression in 53 human tissues. Results IL-17RC expression in 51 normal human tissues and two benign tumors (i.e., lymphangioma and parathyroid adenoma on the tissue microarrays was determined by immunohistochemical staining, using two polyclonal antibodies against IL-17RC. IL-17RC protein was expressed in many cell types including the myocardial cells, vascular and lymphatic endothelial cells, glandular cells (of the adrenal, parathyroid, pituitary, thyroid, pancreas, parotid salivary, and subepidermal glands, epithelial cells (of the esophagus, stomach, intestine, anus, renal tubule, breast, cervix, Fallopian tube, epididymis, seminal vesicle, prostate, gallbladder, bronchus, lung, and skin, oocytes in the ovary, Sertoli cells in the testis, motor neurons in the spinal cord, autonomic ganglia and nerves in the intestine, skeletal muscle cells, adipocytes, articular chondrocytes, and synovial cells. High levels of IL-17RC protein expression were observed in most vascular and lymphatic endothelium and squamous epithelium. The epithelium of the breast, cervix, Fallopian tube, kidney, bladder and bronchus also expressed high levels of IL-17RC, so did the glandular cells in the adrenal cortex, parotid salivary and subepidermal glands. In contrast, IL-17RC protein was not detectable in the smooth muscle cells, fibroblasts, antral mucosa of the stomach, mucosa of the colon, endometrium of the uterus, neurons of the brain

  2. 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.

  3. Expression and tissue localization of collectin placenta 1 (CL-P1, SRCL) in human tissues

    DEFF Research Database (Denmark)

    Sellman, Lana; Skjødt, Karsten; Nielsen, Ole

    2008-01-01

    Collectin placenta-1 (CL-P1), also known as scavenger receptor with C-type lectin (SRCL), is a type II membrane glycoprotein that shares structural features with both collectins and type A scavenger receptors. CL-P1 was originally cloned from the placenta and found to be associated with endothelial...... proposed that CL-P1 plays a role in the host defense system and in the clearance of glycoproteins from the blood. With the aims of determining the detailed tissue expression of human CL-P1 we expressed CL-P1 recombinantly in both E. coli and CHO cells, and raised monoclonal antibodies against human CL-P1....... Three monoclonal antibodies were characterized and used in immunohistochemical analyses of a panel of cryo- and formalin-fixed sections. We find that CL-P1 mainly associates with cytotrophoblasts and syncytiotrophoblasts of the placenta, alveolar macrophages and to a less degree with macrophage...

  4. Adaptation of human adipose tissue to hypocaloric diet.

    Science.gov (United States)

    Rossmeislová, L; Mališová, L; Kračmerová, J; Štich, V

    2013-05-01

    Hypocaloric diet is a key component of the weight-reducing treatment of obesity and obesity-related disorders. Hypocaloric diets and the associated weight reduction promote improvement of metabolic profile of obese individuals. Among the mechanisms that underlie this beneficial metabolic outcome, the diet-induced modifications of morphological and functional characteristics of human adipose tissue (AT) are believed to have an important role. Prospective studies of hypocaloric weight-reducing dietary intervention demonstrate effects on adipocyte metabolism, namely lipolysis and lipogenesis, and associated changes of the adipocyte size. The endocrine function of AT, which involves cytokine and adipokine production by adipocytes, as well as by cells of stromavascular fraction, is also regulated by dietary intervention. Related inflammatory status of AT is modulated also as a consequence of the changes in recruitment of immune cells, mainly macrophages, in AT. Here, we give an overview of metabolic and endocrine modifications in human AT induced by a variety of hypocaloric diets.

  5. Mechanical stimulation improves tissue-engineered human skeletal muscle

    Science.gov (United States)

    Powell, Courtney A.; Smiley, Beth L.; Mills, John; Vandenburgh, Herman H.

    2002-01-01

    Human bioartificial muscles (HBAMs) are tissue engineered by suspending muscle cells in collagen/MATRIGEL, casting in a silicone mold containing end attachment sites, and allowing the cells to differentiate for 8 to 16 days. The resulting HBAMs are representative of skeletal muscle in that they contain parallel arrays of postmitotic myofibers; however, they differ in many other morphological characteristics. To engineer improved HBAMs, i.e., more in vivo-like, we developed Mechanical Cell Stimulator (MCS) hardware to apply in vivo-like forces directly to the engineered tissue. A sensitive force transducer attached to the HBAM measured real-time, internally generated, as well as externally applied, forces. The muscle cells generated increasing internal forces during formation which were inhibitable with a cytoskeleton depolymerizer. Repetitive stretch/relaxation for 8 days increased the HBAM elasticity two- to threefold, mean myofiber diameter 12%, and myofiber area percent 40%. This system allows engineering of improved skeletal muscle analogs as well as a nondestructive method to determine passive force and viscoelastic properties of the resulting tissue.

  6. The PAXgene(® tissue system preserves phosphoproteins in human tissue specimens and enables comprehensive protein biomarker research.

    Directory of Open Access Journals (Sweden)

    Sibylle Gündisch

    Full Text Available Precise quantitation of protein biomarkers in clinical tissue specimens is a prerequisite for accurate and effective diagnosis, prognosis, and personalized medicine. Although progress is being made, protein analysis from formalin-fixed and paraffin-embedded tissues is still challenging. In previous reports, we showed that the novel formalin-free tissue preservation technology, the PAXgene Tissue System, allows the extraction of intact and immunoreactive proteins from PAXgene-fixed and paraffin-embedded (PFPE tissues. In the current study, we focused on the analysis of phosphoproteins and the applicability of two-dimensional gel electrophoresis (2D-PAGE and enzyme-linked immunosorbent assay (ELISA to the analysis of a variety of malignant and non-malignant human tissues. Using western blot analysis, we found that phosphoproteins are quantitatively preserved in PFPE tissues, and signal intensities are comparable to that in paired, frozen tissues. Furthermore, proteins extracted from PFPE samples are suitable for 2D-PAGE and can be quantified by ELISA specific for denatured proteins. In summary, the PAXgene Tissue System reliably preserves phosphoproteins in human tissue samples, even after prolonged fixation or stabilization times, and is compatible with methods for protein analysis such as 2D-PAGE and ELISA. We conclude that the PAXgene Tissue System has the potential to serve as a versatile tissue fixative for modern pathology.

  7. Human placental growth hormone, insulin-like growth factor I and -II, and insulin requirements during pregnancy in type 1 diabetes

    DEFF Research Database (Denmark)

    Fuglsang, Jens; Lauszus, Finn; Flyvbjerg, Allan

    2003-01-01

    between hPGH and IGF-I in type 1 diabetes mellitus has not been investigated thoroughly. Furthermore, hPGH may be involved in the development of insulin resistance during pregnancy. In this prospective, longitudinal study, 51 type 1 diabetic subjects were followed with repeated blood sampling during...... influence of hPGH on placental weight was found. Serum IGF-I values decreased significantly from the first to the second trimester (P changes in IGF-I followed the increase in hPGH between wk 26-35 (r(s) = 0.53; P ...-II (r(s) = 0.37; P = 0.008). Changes in IGF-I and IGF-II between wk 26-35 also correlated to the birth weight z-score (P

  8. Leptin promotes HLA-G expression on placental trophoblasts via the MEK/Erk and PI3K signaling pathways.

    Science.gov (United States)

    Barrientos, G; Toro, A; Moschansky, P; Cohen, M; Garcia, M G; Rose, M; Maskin, B; Sánchez-Margalet, V; Blois, S M; Varone, C L

    2015-04-01

    The development of the human haemochorial placenta requires complex regulatory mechanisms to protect invasive trophoblast cells from cytotoxic responses elicited by maternal immune cells. Leptin, the adipocyte derived hormone encoded by the Lep gene, is synthesized by placental trophoblasts and exerts pleiotropic effects on the immune system, including the promotion of inflammation and the activation of T cell responses. To address its possible involvement in the modulation of maternal immune responses during pregnancy, we investigated the effect of leptin on the expression of the class Ib histocompatibility antigen HLA-G as one of the chief immunosuppressive strategies used by trophoblast cells. In vitro incubation of the trophoblast derived Swan 71 and JEG-3 cell lines with 25-50 ng/ml recombinant leptin significantly boosted HLA-G mRNA and protein expression, and this effect was abrogated upon pharmacological inhibition of the PI3K-Akt and MEK-Erk signaling pathways. A similar stimulatory effect of leptin was observed in term placental tissue explants, though 10-fold higher doses were required for stimulation. Further, JEG-3 cells treated with a leptin antisense oligodeoxynucleotide displayed decreased HLA-G expression levels, which were partially recovered by addition of stimulating doses of exogenous hormone. Immunofluorescence and qPCR analysis confirmed leptin biosynthesis in placental tissue, further showing that invasive extravillous trophoblast cells were a main source of this hormone during the first trimester of normal pregnancies. Taken together, our results show that leptin acts as an autocrine/paracrine signal promoting HLA-G expression in placental trophoblasts suggesting an important role in the regulation of immune evasion mechanisms at the fetal maternal interface. Copyright © 2015 Elsevier Ltd. All rights reserved.

  9. Distribution of adenosine deaminase complexing protein (ADCP) in human tissues.

    Science.gov (United States)

    Dinjens, W N; ten Kate, J; van der Linden, E P; Wijnen, J T; Khan, P M; Bosman, F T

    1989-12-01

    The normal distribution of adenosine deaminase complexing protein (ADCP) in the human body was investigated quantitatively by ADCP-specific radioimmunoassay (RIA) and qualitatively by immunohistochemistry. In these studies we used a specific rabbit anti-human ADCP antiserum. In all 19 investigated tissues, except erythrocytes, ADCP was found by RIA in the soluble and membrane fractions. From all tissues the membrane fractions contained more ADCP (expressed per mg protein) than the soluble fractions. High membrane ADCP concentrations were found in skin, renal cortex, gastrointestinal tract, and prostate. Immunoperoxidase staining confirmed the predominant membrane-associated localization of the protein. In serous sweat glands, convoluted tubules of renal cortex, bile canaliculi, gastrointestinal tract, lung, pancreas, prostate gland, salivary gland, gallbladder, mammary gland, and uterus, ADCP immunoreactivity was found confined to the luminal membranes of the epithelial cells. These data demonstrate that ADCP is present predominantly in exocrine glands and absorptive epithelia. The localization of ADCP at the secretory or absorptive apex of the cells suggests that the function of ADCP is related to the secretory and/or absorptive process.

  10. Gene expression signatures of human cell and tissue longevity.

    Science.gov (United States)

    Seim, Inge; Ma, Siming; Gladyshev, Vadim N

    2016-01-01

    Different cell types within the body exhibit substantial variation in the average time they live, ranging from days to the lifetime of the organism. The underlying mechanisms governing the diverse lifespan of different cell types are not well understood. To examine gene expression strategies that support the lifespan of different cell types within the human body, we obtained publicly available RNA-seq data sets and interrogated transcriptomes of 21 somatic cell types and tissues with reported cellular turnover, a bona fide estimate of lifespan, ranging from 2 days (monocytes) to a lifetime (neurons). Exceptionally long-lived neurons presented a gene expression profile of reduced protein metabolism, consistent with neuronal survival and similar to expression patterns induced by longevity interventions such as dietary restriction. Across different cell lineages, we identified a gene expression signature of human cell and tissue turnover. In particular, turnover showed a negative correlation with the energetically costly cell cycle and factors supporting genome stability, concomitant risk factors for aging-associated pathologies. In addition, the expression of p53 was negatively correlated with cellular turnover, suggesting that low p53 activity supports the longevity of post-mitotic cells with inherently low risk of developing cancer. Our results demonstrate the utility of comparative approaches in unveiling gene expression differences among cell lineages with diverse cell turnover within the same organism, providing insights into mechanisms that could regulate cell longevity.

  11. Quantification of human body fat tissue percentage by MRI.

    Science.gov (United States)

    Müller, Hans-Peter; Raudies, Florian; Unrath, Alexander; Neumann, Heiko; Ludolph, Albert C; Kassubek, Jan

    2011-01-01

    The MRI-based evaluation of the quantity and regional distribution of adipose tissue is one objective measure in the investigation of obesity. The aim of this article was to report a comprehensive and automatic analytical method for the determination of the volumes of subcutaneous fat tissue (SFT) and visceral fat tissue (VFT) in either the whole human body or selected slices or regions of interest. Using an MRI protocol in an examination position that was convenient for volunteers and patients with severe diseases, 22 healthy subjects were examined. The software platform was able to merge MRI scans of several body regions acquired in separate acquisitions. Through a cascade of image processing steps, SFT and VFT volumes were calculated. Whole-body SFT and VFT distributions, as well as fat distributions of defined body slices, were analysed in detail. Complete three-dimensional datasets were analysed in a reproducible manner with as few operator-dependent interventions as possible. In order to determine the SFT volume, the ARTIS (Adapted Rendering for Tissue Intensity Segmentation) algorithm was introduced. The advantage of the ARTIS algorithm was the delineation of SFT volumes in regions in which standard region grow techniques fail. Using the ARTIS algorithm, an automatic SFT volume detection was feasible. MRI data analysis was able to determine SFT and VFT volume percentages using new analytical strategies. With the techniques described, it was possible to detect changes in SFT and VFT percentages of the whole body and selected regions. The techniques presented in this study are likely to be of use in obesity-related investigations, as well as in the examination of longitudinal changes in weight during various medical conditions. Copyright © 2010 John Wiley & Sons, Ltd.

  12. 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

  13. Alterations in the placental methylome with maternal obesity and evidence for metabolic regulation.

    Science.gov (United States)

    Mitsuya, Kohzoh; Parker, Ashley N; Liu, Lu; Ruan, Jianhua; Vissers, Margreet C M; Myatt, Leslie

    2017-01-01

    The inflammatory and metabolic derangements of obesity in pregnant women generate an adverse intrauterine environment, increase pregnancy complications and adverse fetal outcomes and program the fetus for obesity and metabolic syndrome in later life. We hypothesized that epigenetic modifications in placenta including altered DNA methylation/hydroxymethylation may mediate these effects. Term placental villous tissue was collected following cesarean section from lean (prepregnancy BMIobese (BMI>30) women. Genomic DNA was isolated, methylated and hydroxymethylated DNA immunoprecipitated and hybridized to the NimbleGen 2.1M human DNA methylation array. Intermediate metabolites in placental tissues were measured by HPLC-ESI-MS, ascorbate levels by reverse phase HPLC and gene expression by RT-PCR. Differentially methylated and hydroxymethylated regions occurred across the genome, with a 21% increase in methylated but a 31% decrease in hydroxymethylated regions in obese vs lean groups. Whereas increased methylation and decreased methylation was evident around transcription start sites of multiple genes in the GH/CSH and PSG gene clusters on chromosomes 17 and 19 in other areas there was no relationship. Increased methylation was associated with decreased expression only for some genes in these clusters. Biological pathway analysis revealed the 262 genes which showed reciprocal differential methylation/ hydroxymethylation were enriched for pregnancy, immune response and cell adhesion-linked processes. We found a negative relationship for maternal BMI but a positive relationship for ascorbate with α-ketoglutarate a metabolite that regulates ten eleven translocase (TET) which mediates DNA methylation. We provide evidence for the obese maternal metabolic milieu being linked to an altered DNA methylome that may affect placental gene expression in relation to adverse outcomes.

  14. Xenografted tissue models for the study of human endometrial biology.

    Science.gov (United States)

    Kuokkanen, Satu; Zhu, Liyin; Pollard, Jeffrey W

    The human endometrium undergoes extensive morphological, biochemical and molecular changes under the influence of female sex steroid hormones. Besides the fact that estrogen stimulates endometrial cell proliferation and progesterone inhibits this proliferation and induces differentiation, there is limited knowledge about precise molecular mechanisms underlying human endometrial biology. The importance of paracrine signaling in endometrial physiology explains why in vitro culture of endometrial cells has been challenging. Researchers, therefore, have developed alternative experimental in vivo models for the study of endometrial biology. The objective of this review is to summarize the recent developments and work on these in vivo endometrial research models. The in vivo recombinant tissue models in which wild-type endometrial cells are combined with endometrial cells from a gene-targeted mouse strain followed by xenografting to host mice have been critical in confirming the significance of paracrine signaling between the epithelium and stroma in the growth regulation of the endometrium. Additionally, these studies have uncovered differences between the mouse and human, emphasizing the need for the development of experimental models specifically of the human endometrium. Recently, xenotransplants of human endometrial fragments into the subcutaneous space of host mice and endometrial xenografts of dissociated and recombined epithelial and stromal cells beneath the kidney capsule of immunodeficient host mice have proven to be highly promising tools for in vivo research of endometrial functions. For the first time, the latter approach provides an immense opportunity for the application of genome engineering, such as targeted ablation of endometrial genes for example by using CRISPR/CAS9 system. This research will begin to elucidate the functional role of specific genes in this complex tissue. Another advantage of xenotransplantation and xenograft models of the human

  15. Human treated dentin matrix as a natural scaffold for complete human dentin tissue regeneration.

    Science.gov (United States)

    Li, Rui; Guo, Weihua; Yang, Bo; Guo, Lijuan; Sheng, Lei; Chen, Gang; Li, Ye; Zou, Qing; Xie, Dan; An, Xiaoxue; Chen, Yali; Tian, Weidong

    2011-07-01

    An essential aspect of tooth tissue engineering is the identification of suitable scaffolding materials to support cell growth and tissue regeneration. Treated dentin matrix (TDM) from a rat has recently been shown to be a suitable scaffold for rat dentin regeneration. However, due to species-specific differences, it remains unclear whether a similar fabrication method can be extended to human TDM and human dentin regeneration. Therefore, this present study explored the biological response to a human TDM (hTDM) created using a modified dentin treatment method. Various biological characteristics, including cell proliferation, cell migration, cell viability, and cytotoxity were investigated. To assess the inductive capacity of hTDM, dental follicle cells (DFCs) were combined with hTDM and were implanted in vivo for 8 weeks in a mouse model. The resulting grafts were studied histologically. The results showed hTDM released dentinogenic factors, indicating that hTDM could play a sustained role in odontogenesis. DFC attachment, growth, viability, and cytotoxicity on the surface of hTDM showed a notable improvement over those on calcium phosphate controls. Most importantly, in vivo hTDM induced and supported regeneration of complete dentin tissues, which expressed dentin markers DSP and DMP-1. As cells in and around the regenerated dentin were positive for human mitochondria, implanted DFCs and hTDM were responsible for the regenerated dentin tissues. In conclusion, hTDM is indicated as an ideal biomaterial for human dentin regeneration. Copyright © 2011 Elsevier Ltd. All rights reserved.

  16. Mouse DNA contamination in human tissue tested for XMRV

    Directory of Open Access Journals (Sweden)

    Uiprasertkul Mongkol

    2010-12-01

    Full Text Available Abstract Background We used a PCR-based approach to study the prevalence of genetic sequences related to a gammaretrovirus, xenotropic murine leukemia virus-related virus, XMRV, in human prostate cancer. This virus has been identified in the US in prostate cancer patients and in those with chronic fatigue syndrome. However, with the exception of two patients in Germany, XMRV has not been identified in prostate cancer tissue in Europe. Most putative associations of new or old human retroviruses with diseases have turned out to be due to contamination. We have looked for XMRV sequences in DNA extracted from formalin-fixed paraffin- embedded prostate tissues. To control for contamination, PCR assays to detect either mouse mitochondrial DNA (mtDNA or intracisternal A particle (IAP long terminal repeat DNA were run on all samples, owing to their very high copy number in mouse cells. Results In general agreement with the US prevalence, XMRV-like sequences were found in 4.8% of prostate cancers. However, these were also positive, as were 21.5% of XMRV-negative cases, for IAP sequences, and many, but not all were positive for mtDNA sequences. Conclusions These results show that contamination with mouse DNA is widespread and detectable by the highly sensitive IAP assay, but not always with less sensitive assays, such as murine mtDNA PCR. This study highlights the ubiquitous presence of mouse DNA in laboratory specimens and offers a means of rigorous validation for future studies of murine retroviruses in human disease.

  17. Early studies of placental ultrastructure by electron microscopy

    DEFF Research Database (Denmark)

    Carter, A M; Enders, A C

    2016-01-01

    BACKGROUND: Transmission electron microscopy (TEM) was first applied to study placental ultrastructure in the 1950's. We review those early studies and mention the scientists that employed or encouraged the use of TEM. FINDINGS: Among the pioneers Edward W. Dempsey was a key figure who attracted...... many other scientists to Washington University in St. Louis. Work on human placental ultrastructure was initiated at Cambridge and Kyoto whilst domestic animals were initially studied by Björkman in Stockholm and electron micrographs of bat placenta were published by Wimsatt of Cornell University....... CONCLUSIONS: Prior to the introduction of better fixation techniques, TEM images were of modest technical quality. Nevertheless they gave important insights into placental ultrastructure, particularly the nature of the maternal-fetal interface....

  18. 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.

  19. Loss of Thrombomodulin in Placental Dysfunction in Preeclampsia.

    Science.gov (United States)

    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.

  20. Effect of pregestational diabetes mellitus on first trimester placental characteristics: three-dimensional placental volume and power Doppler indices.

    Science.gov (United States)

    Gonzalez Gonzalez, N L; Gonzalez Davila, E; Castro, A; Padron, E; Plasencia, W

    2014-03-01

    To investigate whether pregestational diabetes mellitus (DM) induces changes in vascular placental development detectable at first trimester. This was a prospective case-control study in 69 women with pregestational DM and 94 controls undergoing first-trimester combined screening for aneuploidies. Maternal characteristics, fetal nuchal translucency thickness, maternal serum pregnancy-associated plasma protein A (PAPP-A) and free β human chorionic gonadotrophin (β-hCG) were evaluated. Three-dimensional ultrasound was used to measure placental volume and three dimensional power Doppler (3D-PD) placental vascular indices including: vascularization index (VI), flow index (FI) and vascularization flow index (VFI). Pregnancy-associated hypertensive complications (PAHC) and perinatal outcomes were analyzed. The total group of diabetic women and the group of diabetic women without PAHC were compared separately with the control group. 3D-PD placental vascular indexes were significantly lower in women with DM than in controls (VI p = 0.007, FI p = 0.003 and VFI p = 0.04). These differences remained on excluding cases with PAHC in the DM group. No differences were found in placental volumes between the DM group and controls. Serum PAPP-A levels were also lower in diabetic women (p effect is independent of the later development of PAHC. Copyright © 2014 Elsevier Ltd. All rights reserved.

  1. Resonance Raman detection of carotenoid antioxidants in living human tissue

    Science.gov (United States)

    Ermakov, Igor V.; Sharifzadeh, M.; Ermakova, Maia; Gellermann, W.

    2011-01-01

    Increasing evidence points to the beneficial effects of carotenoid antioxidants in the human body. Several studies, for example, support the protective role of lutein and zeaxanthin in the prevention of age-related eye diseases. If present in high concentrations in the macular region of the retina, lutein and zeaxanthin provide pigmentation in this most light sensitive retinal spot, and as a result of light filtering and/or antioxidant action, delay the onset of macular degeneration with increasing age. Other carotenoids, such as lycopene and beta-carotene, play an important role as well in the protection of skin from UV and short-wavelength visible radiation. Lutein and lycopene may also have protective function for cardiovascular health, and lycopene may play a role in the prevention of prostate cancer. Motivated by the growing importance of carotenoids in health and disease, and recognizing the lack of any accepted noninvasive technology for the detection of carotenoids in living human tissue, we explore resonance Raman spectroscopy as a novel approach for noninvasive, laser optical carotenoid detection. We review the main results achieved recently with the Raman detection approach. Initially we applied the method to the detection of macular carotenoid pigments, and more recently to the detection of carotenoids in human skin and mucosal tissues. Using skin carotenoid Raman instruments, we measure the carotenoid response from the stratum corneum layer of the palm of the hand for a population of 1375 subjects and develope a portable skin Raman scanner for field studies. These experiments reveal that carotenoids are a good indicator of antioxidant status. They show that people with high oxidative stress, like smokers, and subjects with high sunlight exposure, in general, have reduced skin carotenoid levels, independent of their dietary carotenoid consumption. We find the Raman technique to be precise, specific, sensitive, and well suitable for clinical as well as

  2. The genetic regulation of transcription in human endometrial tissue.

    Science.gov (United States)

    Fung, Jenny N; Girling, Jane E; Lukowski, Samuel W; Sapkota, Yadav; Wallace, Leanne; Holdsworth-Carson, Sarah J; Henders, Anjali K; Healey, Martin; Rogers, Peter A W; Powell, Joseph E; Montgomery, Grant W

    2017-04-01

    Do genetic effects regulate gene expression in human endometrium? This study demonstrated strong genetic effects on endometrial gene expression and some evidence for genetic regulation of gene expression in a menstrual cycle stage-specific manner. Genetic effects on expression levels for many genes are tissue specific. Endometrial gene expression varies across menstrual cycle stages and between individuals, but there are limited data on genetic control of expression in endometrium. We analysed genome-wide genotype and gene expression data to map cis expression quantitative trait loci (eQTL) in endometrium. We recruited 123 women of European ancestry. DNA samples from blood were genotyped on Illumina HumanCoreExome chips. Total RNA was extracted from endometrial tissues. Whole-transcriptome profiles were characterized using Illumina Human HT-12 v4.0 Expression Beadchips. We performed eQTL mapping with ~8 000 000 genotyped and imputed single nucleotide polymorphisms (SNPs) and 12 329 genes. We identified a total of 18 595 cis SNP-probe associations at a study-wide level of significance (P endometrial tissue were rs4902335 for CHURC1 (P = 1.05 × 10-32) and rs147253019 for ZP3 (P = 8.22 × 10-30). We further performed a context-specific eQTL analysis to investigate if genetic effects on gene expression regulation act in a menstrual cycle-specific manner. Interestingly, five cis-eQTLs were identified with a significant stage-by-genotype interaction. The strongest stage interaction was the eQTL for C10ORF33 (PYROXD2) with SNP rs2296438 (P = 2.0 × 10-4), where we observe a 2-fold difference in the average expression levels of heterozygous samples depending on the stage of the menstrual cycle. The summary eQTL results are publicly available to browse or download. A limitation of the present study was the relatively modest sample size. It was not powered to identify trans-eQTLs and larger sample sizes will also be needed to provide better power to detect cis-eQTLs and

  3. Placental Chorangiosis: Increased Risk for Cesarean Section

    Directory of Open Access Journals (Sweden)

    Shariska S. Petersen

    2017-01-01

    Full Text Available We describe a patient with Class C diabetes who presented for nonstress testing at 36 weeks and 4 days of gestation with nonreassuring fetal heart tones (NRFHT and oligohydramnios. Upon delivery, thrombosis of the umbilical cord was grossly noted. Pathological analysis of the placenta revealed chorangiosis, vascular congestion, and 40% occlusion of the umbilical vein. Chorangiosis is a vascular change of the placenta that involves the terminal chorionic villi. It has been proposed to result from longstanding, low-grade hypoxia in the placental tissue and has been associated with such conditions such as diabetes, intrauterine growth restriction (IUGR, and hypertensive conditions in pregnancy. To characterize chorangiosis and its associated obstetric outcomes we identified 61 cases of “chorangiosis” on placental pathology at Henry Ford Hospital from 2010 to 2015. Five of these cases were omitted due to lack of complete records. Among the 56 cases, the cesarean section rate was 51%, indicated in most cases for nonreassuring fetal status. Thus, we suggest that chorangiosis, a marker of chronic hypoxia, is associated with increased rates of cesarean sections for nonreassuring fetal status because of long standing hypoxia coupled with the stress of labor.

  4. Studying placental transfer of highly purified non-dioxin-like PCBs in two models of the placental barrier

    DEFF Research Database (Denmark)

    Correia Carreira, S; Cartwright, L; Mathiesen, L

    2011-01-01

    Currently, toxicology and toxicokinetics of purified non-dioxin-like polychlorinated biphenyls (NDL-PCBs) are poorly characterised. Transplacental kinetics of NDL-PCBs can be studied in a variety of models, but careful validation of each model is crucial. We aimed to develop a standard operating...... procedure for establishing an in vitro model of the human placental barrier. Using this model, we sought to investigate placental transport kinetics of two NDL-PCB congeners. Firstly, we compared the BeWo cell line of the American Type Culture Collection with the BeWo b30 clone and determined parameters...... for monolayer formation. Secondly, we performed placental perfusions to validate the in vitro model. To that end, the transport of radiolabelled PCB52 and 180 was investigated in both models. We were not able to grow the ATCC cell line to confluency, but determined monolayer formation using BeWo b30...

  5. Levels of Macrophage Inflammatory Protein 1α (MIP-1α) and MIP-1β in Intervillous Blood Plasma Samples from Women with Placental Malaria and Human Immunodeficiency Virus Infection

    Science.gov (United States)

    Chaisavaneeyakorn, Sujittra; Moore, Julie M.; Mirel, Lisa; Othoro, Caroline; Otieno, Juliana; Chaiyaroj, Sansanee C.; Shi, Ya Ping; Nahlen, Bernard L.; Lal, Altaf A.; Udhayakumar, Venkatachalam

    2003-01-01

    Macrophage inflammatory protein-1α (MIP-1α) and MIP-1β play an important role in modulating immune responses. To understand their importance in immunity to placental malaria (PM) and in human immunodeficiency virus (HIV)-PM coinfection, we investigated levels of these chemokines in the placental intervillous blood plasma (IVB plasma) and cord blood plasma of HIV-negative PM-negative, HIV-negative PM-positive, HIV-positive PM-negative, and HIV-positive PM-positive women. Compared to HIV-negative PM-negative women, the MIP-1β concentration in IVB plasma was significantly elevated in HIV-negative PM-positive women and HIV-positive PM-positive women, but it was unaltered in HIV-positive PM-negative women. Also, PM-infected women, irrespective of their HIV status, had significantly higher levels of MIP-1β than HIV-positive PM-negative women. The MIP-1α level was not altered in association with either infection. The IVB plasma levels of MIP-1α and MIP-1β positively correlated with the cord blood plasma levels of these chemokines. As with IVB plasma, only cord plasma from PM-infected mothers had significantly elevated levels of MIP-1β compared to PM-negative mothers, irrespective of their HIV infection status. MIP-1β and MIP-1α levels in PM-positive women were positively associated with parasite density and malaria pigment levels. Regardless of HIV serostatus, the IVB MIP-1β level was significantly lower in women with PM-associated anemia. In summary, an elevated level of MIP-1β was associated with PM. HIV infection did not significantly alter these two chemokine levels in IVB plasma. PMID:12853396

  6. MicroRNA expression variability in human cervical tissues.

    Directory of Open Access Journals (Sweden)

    Patrícia M Pereira

    Full Text Available MicroRNAs (miRNAs are short (approximately 22 nt non-coding regulatory RNAs that control gene expression at the post-transcriptional level. Deregulation of miRNA expression has been discovered in a wide variety of tumours and it is now clear that they contribute to cancer development and progression. Cervical cancer is one of the most common cancers in women worldwide and there is a strong need for a non-invasive, fast and efficient method to diagnose the disease. We investigated miRNA expression profiles in cervical cancer using a microarray platform containing probes for mature miRNAs. We have evaluated miRNA expression profiles of a heterogeneous set of cervical tissues from 25 different patients. This set included 19 normal cervical tissues, 4 squamous cell carcinoma, 5 high-grade squamous intraepithelial lesion (HSIL and 9 low-grade squamous intraepithelial lesion (LSIL samples. We observed high variability in miRNA expression especially among normal cervical samples, which prevented us from obtaining a unique miRNA expression signature for this tumour type. However, deregulated miRNAs were identified in malignant and pre-malignant cervical tissues after tackling the high expression variability observed. We were also able to identify putative target genes of relevant candidate miRNAs. Our results show that miRNA expression shows natural variability among human samples, which complicates miRNA data profiling analysis. However, such expression noise can be filtered and does not prevent the identification of deregulated miRNAs that play a role in the malignant transformation of cervical squamous cells. Deregulated miRNAs highlight new candidate gene targets allowing for a better understanding of the molecular mechanism underlying the development of this tumour type.

  7. Placental Histopathologic Changes Associated with Subclinical Malaria Infection and Its Impact on the Fetal Environment

    Science.gov (United States)

    Parekh, Falgunee K.; Davison, Billie B.; Gamboa, Dionicia; Hernandez, Jean; Branch, OraLee H.

    2010-01-01

    Microscopic examination of placental tissue can provide an accurate assessment of malaria infection during pregnancy. In this cross-sectional study of 193 women in Iquitos, Peru, 1.0% and 6.6% had parasites in the peripheral blood as detected by microscopy and polymerase chain reaction, respectively. However, 22% had placental malaria pigment indicating past, subclinical infections. Placental tissues with pigment from 24 cases were matched by gravidity and month of delivery to 24 controls and histopathologically examined. Cases had significantly higher number of monocytes in the intervillous space (44.7 versus 25.5; P = 0.012). Pigmented monocytes in fetal vessels were present in 33.3% of cases. This study demonstrated that subclinical malarial infection occurred frequently in pregnant women and is associated with increased presence of monocytes in the placenta. Pigmented monocytes in fetal vessels suggest parasites can breach the placental barrier and enter the fetal circulation. PMID:21036823

  8. Lactate kinetics in human tissues at rest and during exercise

    DEFF Research Database (Denmark)

    van Hall, Gerrit

    2010-01-01

    Lactate production in skeletal muscle has now been studied for nearly two centuries and still its production and functional role at rest and during exercise is much debated. In the early days skeletal muscle was mainly seen as the site of lactate production during contraction and lactate production...... associated with a lack of muscle oxygenation and fatigue. Later it was recognized that skeletal muscle not only played an important role in lactate production but also in lactate clearance and this led to a renewed interest, not the least from the Copenhagen School in the 1930s, in the metabolic role...... of lactate in skeletal muscle. With the introduction of lactate isotopes muscle lactate kinetics and oxidation could be studied and a simultaneous lactate uptake and release was observed, not only in muscle but also in other tissues. Therefore, this review will discuss in vivo human: (1) skeletal muscle...

  9. Microstructure of mineralized tissues in human primary teeth.

    Science.gov (United States)

    Ruschel, H C; Ligocki, G D; Flaminghi, D L; Fossati, A C M

    2011-01-01

    The aim of this study was to analyze the structural characteristics of the mineralized dental tissues--enamel, dentin and cementum--in primary teeth and to correlate the histological aspects observed in function of the dental type--single-rooted or multi-rooted. Eighteen human primary noncarious teeth were sectioned in facial-lingual (single-rooted) and mesio-distal direction (multi-rooted). One to three samples from each tooth were obtained. The samples were prepared by the ground technique and analyzed under light microscopy at different magnifications. A quantitative and descriptive analysis of the morphology of the mineralized tissues was performed. Spindles, tufts and lamellae were consistently observed mainly in the occlusal surface of the primary molars. The scalloped pattern of the dentinoenamel junction was not always present. The same was seen for zones of interglobular dentin. Dead tracts in dentin and tertiary dentin were observed mainly in single-rooted teeth below areas of dental attrition. Areas of cellular and acellular cementum were observed in the two dental types. Primary teeth have some structural peculiarities and these should be investigated concerning the clinical repercussion.

  10. Magnesium degradation products: effects on tissue and human metabolism.

    Science.gov (United States)

    Seitz, J-M; Eifler, R; Bach, Fr-W; Maier, H J

    2014-10-01

    Owing to their mechanical properties, metallic materials present a promising solution in the field of resorbable implants. The magnesium metabolism in humans differs depending on its introduction. The natural, oral administration of magnesium via, for example, food, essentially leads to an intracellular enrichment of Mg(2+) . In contrast, introducing magnesium-rich substances or implants into the tissue results in a different decomposition behavior. Here, exposing magnesium to artificial body electrolytes resulted in the formation of the following products: magnesium hydroxide, magnesium oxide, and magnesium chloride, as well as calcium and magnesium apatites. Moreover, it can be assumed that Mg(2+) , OH(-) ions, and gaseous hydrogen are also present and result from the reaction for magnesium in an aqueous environment. With the aid of physiological metabolic processes, the organism succeeds in either excreting the above mentioned products or integrating them into the natural metabolic process. Only a burst release of these products is to be considered a problem. A multitude of general tissue effects and responses from the Mg's degradation products is considered within this review, which is not targeting specific implant classes. Furthermore, common alloying elements of magnesium and their hazardous potential in vivo are taken into account. © 2013 Wiley Periodicals, Inc.

  11. 3-D extracellular matrix from sectioned human tissues.

    Science.gov (United States)

    Campbell, Catherine B; Cukierman, Edna; Artym, Vira V

    2014-03-03

    Cell adhesion, migration, and signaling in physiologically normal and pathological processes depend highly on the extracellular matrix that the cell interacts with. A variety of in vitro models of two-dimensional and three-dimensional extracellular matrices have been developed to study multiple aspects of cellular behavior. However, there is a profound need for in vitro models of extracellular matrices to closely mimic both biochemical and physical aspects of a three-dimensional in vivo cellular environment. This unit outlines the preparation of human-tissue-derived, cell-free, three-dimensional extracellular matrices for studying cellular behavior and cell-extracellular matrix interactions ex vivo. These protocols can be used to prepare cell-free matrices from a variety of normal and cancerous tissues. This unit also provides protocols for quality control of acellular matrix preparations, and for immunostaining of cells for specific cellular proteins as well as of extracellular matrices for their components. Copyright © 2014 John Wiley & Sons, Inc.

  12. Photobiomodulation in human muscle tissue: an advantage in sports performance?

    Science.gov (United States)

    Ferraresi, Cleber; Huang, Ying-Ying; Hamblin, Michael R

    2016-12-01

    Photobiomodulation (PBM) describes the use of red or near-infrared (NIR) light to stimulate, heal, and regenerate damaged tissue. Both preconditioning (light delivered to muscles before exercise) and PBM applied after exercise can increase sports performance in athletes. This review covers the effects of PBM on human muscle tissue in clinical trials in volunteers related to sports performance and in athletes. The parameters used were categorized into those with positive effects or no effects on muscle performance and recovery. Randomized controlled trials and case-control studies in both healthy trained and untrained participants, and elite athletes were retrieved from MEDLINE up to 2016. Performance metrics included fatigue, number of repetitions, torque, hypertrophy; measures of muscle damage and recovery such as creatine kinase and delayed onset muscle soreness. Searches retrieved 533 studies, of which 46 were included in the review (n = 1045 participants). Studies used single laser probes, cluster of laser diodes, LED clusters, mixed clusters (lasers and LEDs), and flexible LED arrays. Both red, NIR, and red/NIR mixtures were used. PBM can increase muscle mass gained after training, and decrease inflammation and oxidative stress in muscle biopsies. We raise the question of whether PBM should be permitted in athletic competition by international regulatory authorities. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  13. Phase measurement of light absorption and scatter in human tissue

    Science.gov (United States)

    Chance, B.; Cope, M.; Gratton, E.; Ramanujam, N.; Tromberg, B.

    1998-10-01

    Analog and digital technologies are presented for precise measurement of propagation delay of photons from source and detector placed on portions of the human body. The goal of the apparatus design is to quantify absorption (μa) and scattering (μs') induced by biological pigments and biological structures, respectively. Body tissues are highly scattering with a mean distance between scatterers of less than a mm (at 700-850 nm). Significant absorption is mainly due to 5%-10% of the tissue volume occupied by blood. Measurement of μa and μs' is done by both time and frequency domain equipment. This article focuses upon frequency domain equipment because of its simplicity, reduced noise bandwidth, versatility, and the strong analogy to very high frequency/ultrahigh frequency communication devices, particularly those using phase modulation. Comparisons are made of homodyne and heterodyne systems together with evaluation of single and multiple side band systems, with particular emphasis on methods for multiplexed optical and radio frequencies by frequency encoding or time-sharing technologies. The applications of these phase modulation systems to quantitative brain and muscle blood oximetry, functional activity of the forebrain, and other important problems of medical science, are presented.

  14. The Receptor for the CD200 Tolerance-Signaling Molecule Associated with Successful Pregnancy is Expressed by Early-Stage Breast Cancer Cells in 80% of Patients and by Term Placental Trophoblasts.

    Science.gov (United States)

    Clark, David A; Dhesy-Thind, Sukhbinder; Arredondo, Jorge L; Ellis, Peter M; Ramsay, Jennifer A

    2015-11-01

    The CD200 tolerance-signaling molecule that is expressed by a wide variety of tissues, including placental trophoblast and epithelial tumor cells, lacks an intracytoplasmic tail and must act by binding to CD200 receptors that have a limited expression on lymphomyeloid cells. This binding can inhibit inflammation and NK cells, promote macrophage secretion of indoleamine-2,3 dioxygenase (IDO), and promote generation of Treg cells. Recently, CD200R1 was reported on human first trimester placental villous trophoblast cells. CD200R1 has not been described on malignant tumor cells. As malignant tumor cells exhibit a number of characteristics of trophoblast, is CD200R1 expressed? Affinity-purified rabbit polyclonal antibodies to CD200 and CD200R1 were used to immunostain tissue blocks available from cases in a previous cross-sectional study of Stage 1-IIIA human breast cancer cases and term placental trophoblast. Affinity-purified anti-CD200R1 stained primary breast cancer cells and term placental villous trophoblasts. Tumor cells were also stained by anti-CD200 as in a previous study (correlation P = 0.0042), but CD200R1 and CD200 were not correlated. Presence or absence of strong CD200 expression in the tumor did not correlate with metastasis, and a similar result was obtained with CD200R1. This is the first report of CD200R1 expression by human epithelial tumor cells, and specifically, early-stage human breast cancer cells. It is also the first report of CD200R1 expression by term placental villous trophoblasts. The potential biological significance of CD200R1 expression in non-hematopoietic cells is discussed. © 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  15. Placental histopathological changes associated with Plasmodium vivax infection during pregnancy.

    Directory of Open Access Journals (Sweden)

    Rodrigo M Souza

    Full Text Available Histological evidence of Plasmodium in the placenta is indicative of placental malaria, a condition associated with severe outcomes for mother and child. Histological lesions found in placentas from Plasmodium-exposed women include syncytial knotting, syncytial rupture, thickening of the placental barrier, necrosis of villous tissue and intervillositis. These histological changes have been associated with P. falciparum infections, but little is known about the contribution of P. vivax to such changes. We conducted a cross-sectional study with pregnant women at delivery and assigned them to three groups according to their Plasmodium exposure during pregnancy: no Plasmodium exposure (n = 41, P. vivax exposure (n = 59 or P. falciparum exposure (n = 19. We evaluated their placentas for signs of Plasmodium and placental lesions using ten histological parameters: syncytial knotting, syncytial rupture, placental barrier thickness, villi necrosis, intervillous space area, intervillous leucocytes, intervillous mononucleates, intervillous polymorphonucleates, parasitized erythrocytes and hemozoin. Placentas from P. vivax-exposed women showed little evidence of Plasmodium or hemozoin but still exhibited more lesions than placentas from women not exposed to Plasmodium, especially when infections occurred twice or more during pregnancy. In the Brazilian state of Acre, where diagnosis and primary treatment are readily available and placental lesions occur in the absence of detected placental parasites, relying on the presence of Plasmodium in the placenta to evaluate Plasmodium-induced placental pathology is not feasible. Multivariate logistic analysis revealed that syncytial knotting (odds ratio [OR], 4.21, P = 0.045, placental barrier thickness (OR, 25.59, P = 0.021 and mononuclear cells (OR, 4.02, P = 0.046 were increased in placentas from P. vivax-exposed women when compared to women not exposed to Plasmodium during pregnancy. A

  16. Ultrasensitive detection of oncogenic human papillomavirus in oropharyngeal tissue swabs.

    Science.gov (United States)

    Isaac, Andre; Kostiuk, Morris; Zhang, Han; Lindsay, Cameron; Makki, Fawaz; O'Connell, Daniel A; Harris, Jeffrey R; Cote, David W J; Seikaly, Hadi; Biron, Vincent L

    2017-01-14

    The incidence of oropharyngeal squamous cell carcinoma (OPSCC) caused by oncogenic human papillomavirus (HPV) is rising worldwide. HPV-OPSCC is commonly diagnosed by RT-qPCR of HPV E6 and E7 oncoproteins or by p16 immunohistochemistry (IHC). Droplet digital PCR (ddPCR) has been recently reported as an ultra-sensitive and highly precise method of nucleic acid quantification for biomarker analysis. To validate the use of a minimally invasive assay for detection of oncogenic HPV based on oropharyngeal swabs using ddPCR. Secondary objectives were to compare the accuracy of ddPCR swabs to fresh tissue p16 IHC and RT-qPCR, and to compare the cost of ddPCR with p16 IHC. We prospectively included patients with p16+ oral cavity/oropharyngeal cancer (OC/OPSCC), and two control groups: p16- OC/OPSCC patients, and healthy controls undergoing tonsillectomy. All underwent an oropharyngeal swab with ddPCR for quantitative detection of E6 and E7 mRNA. Surgical specimens had p16 IHC performed. Agreement between ddPCR and p16 IHC was determined for patients with p16 positive and negative OC/OPSCC as well as for healthy control patients. The sensitivity and specificity of ddPCR of oropharyngeal swabs were calculated against p16 IHC for OPSCC. 122 patients were included: 36 patients with p16+OPSCC, 16 patients with p16-OPSCC, 4 patients with p16+OCSCC, 41 patients with p16-OCSCC, and 25 healthy controls. The sensitivity and specificity of ddPCR of oropharyngeal swabs against p16 IHC were 92 and 98% respectively, using 20-50 times less RNA than that required for conventional RT-qPCR. Overall agreement between ddPCR of tissue swabs and p16 of tumor tissue was high at ĸ = 0.826 [0.662-0.989]. Oropharyngeal swabs analyzed by ddPCR is a quantitative, rapid, and effective method for minimally invasive oncogenic HPV detection. This assay represents the most sensitive and accurate mode of HPV detection in OPSCC without a tissue biopsy in the available literature.

  17. 21 CFR 1270.21 - Determination of donor suitability for human tissue intended for transplantation.

    Science.gov (United States)

    2010-04-01

    ... tissue intended for transplantation. 1270.21 Section 1270.21 Food and Drugs FOOD AND DRUG ADMINISTRATION... FOOD AND DRUG ADMINISTRATION HUMAN TISSUE INTENDED FOR TRANSPLANTATION Donor Screening and Testing § 1270.21 Determination of donor suitability for human tissue intended for transplantation. (a) Donor...

  18. 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...

  19. Human epithelial tissue culture study on restorative materials.

    Science.gov (United States)

    Forster, András; Ungvári, Krisztina; Györgyey, Ágnes; Kukovecz, Ákos; Turzó, Kinga; Nagy, Katalin

    2014-01-01

    Health condition of the gingival tissues contacting the surfaces of fixed prostheses is a result of multiple etiologic factors. The aim of the investigation discussed here was to evaluate the attachment and proliferation rate of cultured human epithelial cells on three commonly used restorative materials under in vitro conditions. Morphological and chemical structure of polished lithium-disilicate (IPS e.max Press, Ivoclar Vivadent AG, Germany), yttrium modified zirconium dioxide (5-TEC ICE Zirkon Translucent, Zirkonzahn GmbH Srl, Germany) and cobalt chromium alloy (Remanium star, Dentaurum GmbH & Co. KG, Germany) discs were examined by scanning electron microscopy (SEM), energy dispersive X-ray spectroscopy (EDS) and atomic force microscopy (AFM). Human epithelial cells harvested and cultured from one donor, were applied to investigate cell attachment (24h observation) and proliferation (72h observation) via dimethylthiazol-diphenyl tetrazolium bromide (MTT) and AlamarBlue(®) (AB) assays on control surface (cell-culture plate) and on the restorative materials (n=3×20 specimens/material). SEM and AFM revealed typical morphology and roughness features for the materials. Zirconia presented significantly higher Ra value. EDS confirmed typical elements on the investigated restorative materials: lithium-disilicate (Si, O); Zirconia (Zi, Y, O); CoCr (Co, Cr, W). All surfaces except CoCr exhibited significant cell proliferation according to MTT and AB assays after 72h compared to 24h. Among the restorative materials, CoCr samples showed the highest cell attachment as indicated by MTT assay. AB results showed that attachment and proliferation of human epithelial cells is supported more on lithium-disilicate. Both assays indicated the lowest value for zirconia. The results indicate that the restorative materials examined are equally suitable for subgingival restorations. Lithium-disilicate exhibited the best biocompatibility. The examined materials are indicated for use

  20. The effect of maternal obesity on the expression and functionality of placental P-glycoprotein: Implications in the individualized transplacental digoxin treatment for fetal heart failure.

    Science.gov (United States)

    Wang, Chuan; Li, Huaying; Luo, Chunyan; Li, Yifei; Zhang, Yi; Yun, Ding; Mu, Dezhi; Zhou, Kaiyu; Hua, Yimin

    2015-10-01

    Placental P-glycoprotein (P-gp) plays a significant role in controlling digoxin transplacental rate. Investigations on P-gp regulation in placenta of women with different pregnant pathology are of great significance to the individualized transplacental digoxin treatment for fetal heart failure (FHF). This study aimed to explore the effect of maternal obesity on the expression and functionality of placental P-gp both in human and in mice. Placenta tissues from obese and lean women were collected. Female C57BL mice were fed with either a normal chow diet or a high-fat diet for 12 weeks before mating and throughout pregnancy. Maternal plasma glucose, HDL-C, LDL-C, TC, TGs, insulin, IL-1β, IL-6 and TNF-α concentrations was detected. Placental ABCB1/Abcb1a/Abcb1b/IL-1β/IL-6/TNF-α mRNA and P-gp/IL-1β/IL-6/TNF-α protein expression were determined by real-time quantitative PCR and western-blot, respectively. Maternal plasma and fetal-unit digoxin concentrations were detected by a commercial kit assay. Both ABCB1 gene mRNA and protein expression of obesity group was significantly lower than that of control group in human. The high-fat dietary intervention resulted in an overweight phenotype, a significant increased Lee's index, higher levels of plasma glucose, HDL-C, LDL-C, insulin and TGs, increased peri-renal and peri-reproductive gland adipose tissue weight, and larger size of adipose cell. Compared with control group at the same gestational day (E12.5, E15.5, E17.5), placental Abcb1a mRNA and P-gp expression of obese group were significantly decreased in mice, while digoxin transplacental rates were significantly increased. Higher maternal plasma IL-1β/TNF-α concentrations and placental IL-1β/TNF-α expression were observed in obesity groups in comparison with control group at the same gestational age. Maternal obesity could inhibit placental P-gp expression and its functionality both in human and in mice, which might be resulted from a heightened inflammatory

  1. Physiological Function and Transplantation of Scaffold-Free and Vascularized Human Cardiac Muscle Tissue

    National Research Council Canada - National Science Library

    K. R. Stevens; K. L. Kreutziger; S. K. Dupras; F. S. Korte; M. Regnier; V. Muskheli; M. B. Nourse; K. Bendixen; H. Reinecke; C. E. Murry; William A. Catterall

    2009-01-01

    Success of human myocardial tissue engineering for cardiac repair has been limited by adverse effects of scaffold materials, necrosis at the tissue core, and poor survival after transplantation due to ischemie injury...

  2. Incidental placental choriocarcinoma in a term pregnancy: a case report

    Directory of Open Access Journals (Sweden)

    Chung Christopher

    2008-10-01

    Full Text Available Abstract Introduction Gestational choriocarcinoma occurs in 1 in 40,000 pregnancies. Of all forms of gestational choriocarcinoma, placental choriocarcinoma is the most rare. Maternal choriocarcinoma is usually diagnosed in symptomatic patients with metastases. The incidental finding of a choriocarcinoma confined to the placenta with no evidence of dissemination to the mother, or infant is the least common scenario. Case presentation The patient is an 18 year-old Gravida 1 Para 1 African American female who delivered a viable 3641 g female infant at 39 weeks gestation. Her pregnancy course was complicated by gestational hypertension during the third trimester. Her placenta revealed intraplacental choriocarcinoma. She was then followed closely by the Gynecologic Oncology service with a weekly serum beta human chorionic gonadotropin value. Beta human chorionic gonadotropin values dropped from 3070 mIU/ml to less than 2 mIU/ml two months post partum. No chemotherapy was initiated. Metastasis was ruled out by chest x-ray and whole body computed tomography scan. To date, both mother and baby are well. Conclusion Due to the potential fatal outcome of placental choriocarcinoma, careful evaluation of both mother and infant after the diagnosis is made is important. The incidence of placental choriocarcinoma may actually be higher than expected since it is not routine practice to send placentas for pathological evaluation after a normal spontaneous delivery. The obstetrician, pathologist, and pediatrician should have an increased awareness of placental choriocarcinoma and its manifestations.

  3. Notch signalling in placental development and gestational diseases.

    Science.gov (United States)

    Haider, S; Pollheimer, J; Knöfler, M

    2017-08-01

    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. Copyright © 2017 Elsevier Ltd. All rights reserved.

  4. EFFECTS OF SECRETABLE PLACENTAL FACTORS UPON SECRETION OF CYTOKINES BY THP-1 MONOCYTE-LIKE CELLS

    Directory of Open Access Journals (Sweden)

    Ya. S. Onokhina

    2013-01-01

    Full Text Available Abstract. Мonocytes in feto-placental circulation are exposed to factors secreted by placental tissue. These factors influence monocyte functions in pregnancy. In present study, an in vitro model (monocyte-like THP-1 cells was used for assessing effects of soluble placental factors obtained from women with physiological pregnancies, or preeclampsia cases. The following effects of placental factors were revealed: increased secretion of VEGF by THP-1 cells along with decreased secretion of IL-6, IL-8 and MCP-1 under the influence of placental factors from the I. trimester of pregnancy in comparison with III. trimester. Secretion of IL-6 and MCP-1 by THP-1 cells was increased, and secretion of soluble TNFRII was decreased upon co-cultivation with soluble placental factors from the women with preeclampsia, as compared with placental products from physiological pregnancies.The work is supported by grants ГК № 02.740.11.0711 from Ministry of Education and Science, and НШ-3594.2010.7 grant from the President of Russian Federation.

  5. 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.

  6. Comparison of human dental follicle cells and human periodontal ligament cells for dentin tissue regeneration.

    Science.gov (United States)

    Tian, Ye; Bai, Ding; Guo, Weihua; Li, Jie; Zeng, Jin; Yang, Longqiang; Jiang, Zongting; Feng, Lian; Yu, Mei; Tian, Weidong

    2015-05-01

    To compare the odontogenic potential of human dental follicle cells (DFCs) and periodontal ligament cells (PDLCs). In vitro and in vivo characterization studies of DFCs and PDLCs were performed comparatively. DFCs and PDLCs were subcutaneously implanted into the dorsum of mice for 8 weeks after combined with treated dentin matrix scaffolds respectively. Proteomic analysis identified 32 differentially expressed proteins in DFCs and PDLCs. Examination of the harvested grafts showed PDLCs could form the dentin-like tissues as DFCs did. However, the structure of dentin tissues generated by DFCs was more complete. PDLCs could contribute to regenerate dentin-like tissues in the inductive microenvironment of treated dentin matrix. DFCs presented more remarkable dentinogenic capability than PDLCs did.

  7. Tissue distribution and engraftment of human mesenchymal stem cells immortalized by human telomerase reverse transcriptase gene

    DEFF Research Database (Denmark)

    Bentzon, J F; Stenderup, K; Hansen, F D

    2005-01-01

    Engraftment of mesenchymal stem cells (MSC) in peripheral tissues for replenishing of local stem cell function has been proposed as a therapeutic approach to degenerative diseases. We have previously reported the development of an immortalized human telomerase reverse transcriptase transduced MSC...... line (hMSC-TERT). In the present study, we co-transduced hMSC-TERT with enhanced green fluorescent protein gene, and studied tissue distribution, engraftment, and cell survival after intracardiac and intravenous injections in immunodeficient mice. The pattern of organ distribution suggested...... that infused cells were efficiently arrested in microvasculature during first-pass, but only for a fraction of the infused cells was arrest followed by vascular emigration and tissue engraftment. Few engrafted cells in lungs, heart, and kidney glomeruli remained after 4 weeks. These observations are consistent...

  8. Impact of Statins on Gene Expression in Human Lung Tissues.

    Directory of Open Access Journals (Sweden)

    Jérôme Lane

    Full Text Available Statins are 3-hydroxy-3-methylglutaryl-coenzyme A reductase inhibitors that alter the synthesis of cholesterol. Some studies have shown a significant association of statins with improved respiratory health outcomes of patients with asthma, chronic obstructive pulmonary disease and lung cancer. Here we hypothesize that statins impact gene expression in human lungs and may reveal the pleiotropic effects of statins that are taking place directly in lung tissues. Human lung tissues were obtained from patients who underwent lung resection or transplantation. Gene expression was measured on a custom Affymetrix array in a discovery cohort (n = 408 and two replication sets (n = 341 and 282. Gene expression was evaluated by linear regression between statin users and non-users, adjusting for age, gender, smoking status, and other covariables. The results of each cohort were combined in a meta-analysis and biological pathways were studied using Gene Set Enrichment Analysis. The discovery set included 141 statin users. The lung mRNA expression levels of eighteen and three genes were up-regulated and down-regulated in statin users (FDR < 0.05, respectively. Twelve of the up-regulated genes were replicated in the first replication set, but none in the second (p-value < 0.05. Combining the discovery and replication sets into a meta-analysis improved the significance of the 12 up-regulated genes, which includes genes encoding enzymes and membrane proteins involved in cholesterol biosynthesis. Canonical biological pathways altered by statins in the lung include cholesterol, steroid, and terpenoid backbone biosynthesis. No genes encoding inflammatory, proteases, pro-fibrotic or growth factors were altered by statins, suggesting that the direct effect of statin in the lung do not go beyond its antilipidemic action. Although more studies are needed with specific lung cell types and different classes and doses of statins, the improved health outcomes and survival

  9. 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.

  10. Sexual dimorphism in activation of placental autophagy in obese women with evidence for fetal programming from a placenta-specific mouse model.

    Science.gov (United States)

    Muralimanoharan, Sribalasubashini; Gao, Xiaoli; Weintraub, Susan; Myatt, Leslie; Maloyan, Alina

    2016-05-03

    The incidence of maternal obesity and its co-morbidities (diabetes, cardiovascular disease) continues to increase at an alarming rate, with major public health implications. In utero exposure to maternal obesity has been associated with development of cardiovascular and metabolic diseases in the offspring as a result of developmental programming. The placenta regulates maternal-fetal metabolism and shows significant changes in its function with maternal obesity. Autophagy is a cell-survival process, which is responsible for the degradation of damaged organelles and misfolded proteins. Here we show an activation of autophagosomal formation and autophagosome-lysosome fusion in placentas of males but not females from overweight (OW) and obese (OB) women vs. normal weight (NW) women. However, total autophagic activity in these placentas appeared to be decreased as it showed an increase in SQSTM1/p62 and a decrease in lysosomal biogenesis. A mouse model with a targeted deletion of the essential autophagy gene Atg7 in placental tissue showed significant placental abnormalities comparable to those seen in human placenta with maternal obesity. These included a decrease in expression of mitochondrial genes and antioxidants, and decreased lysosomal biogenesis. Strikingly, the knockout mice were developmentally programmed as they showed an increased sensitivity to high-fat diet-induced obesity, hyperglycemia, hyperinsulinemia, increased adiposity, and cardiac remodeling. In summary, our results indicate a sexual dimorphism in placental autophagy in response to maternal obesity. We also show that autophagy plays an important role in placental function and that inhibition of placental autophagy programs the offspring to obesity, and to metabolic and cardiovascular diseases.

  11. 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.

    2016-01-01

    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. PMID:27125896

  12. Status quo of management of the human tissue banks in Taiwan.

    Science.gov (United States)

    Chou, Ching-Pang; Chou, Szu-Cheng; Chen, Ying-Hua; Chen, Yu-Hsuan; Lee, Ming-Shin

    2017-03-01

    As the technologies associated with transplantation and biological tissue engineering continue to advance, human cells and tissues form an integral part to the practice of regenerative medicine. The patient's use of tissues entails the risk of introducing, transmitting and spreading communicable diseases. To prevent such risk and to ensure that the human organs, tissues and cells remain intact and functional after being handled and processed, the transplanted tissues must be subject to good management standards through all stages of collection, screening, processing, storage and distribution as the safety of the users is of the utmost importance. On February 2009, the government of Taiwan promulgated the Regulations for Administration on Human Organ Bank that requires all human tissues banks to adhere to the Good Tissue Practice for Human Organ, Tissue and Cell in terms of establishment and operation in order to cope with the international management trend and the development and management need of the domestic industry. Six years have passed since the law became effective. This article seeks to introduce the current management mechanism and status quo of management of human tissue banks in Taiwan. We also conducted statistical analysis of the data relating to the tissue banks to identify potential risks and the room for improvement. The study concludes that human tissue banks in Taiwan are on the right track with their management practice, leading to a state of steady development and progress.

  13. Epitope mapping and topographic analysis of VAR2CSA DBL3X involved in P-falciparum placental sequestration

    DEFF Research Database (Denmark)

    Dahlback, Madeleine; Rask, Thomas Salhøj; Andersen, Pernille

    2006-01-01

    Pregnancy-associated malaria is a major health problem, which mainly affects primigravidae living in malaria endemic areas. The syndrome is precipitated by accumulation of infected erythrocytes in placental tissue through an interaction between chondroitin sulphate A on syncytiotrophoblasts...

  14. Investigation of RF transmission properties of human tissues

    Directory of Open Access Journals (Sweden)

    D. Werber

    2006-01-01

    Full Text Available RF transmission properties of human tissues were investigated in the frequency range from 50 MHz to 1 GHz. This work was motivated by the increasing interest in communication links between medically active implants and external interrogator units. We investigated theoretically and experimentally the transmission loss between an implant and an external interrogator unit. We assumed that due to the size of the implant a maximum area of only 1 cm2 is available for the printed circuit antenna. The size of the external interrogator antenna is less restricted. The maximum depth of the implant beneath the surface of the body was assumed to be 10 cm. For the simulations we took the dielectric properties of skin, fat and muscle as published in the literature. For the measurements, an artificial muscle dielectric proposed in the literature was used consisting mainly of a mixture of water, sugar and salt. In simulation and measurements the reactive part of the impedance of the antennas was compensated numerically. In simulations and measurements we obtained a transmission loss between 30 dB around 100 MHz and 65 dB around 900 MHz.

  15. Nattokinase-promoted tissue plasminogen activator release from human cells.

    Science.gov (United States)

    Yatagai, Chieko; Maruyama, Masugi; Kawahara, Tomoko; Sumi, Hiroyuki

    2008-01-01

    When heated to a temperature of 70 degrees C or higher, the strong fibrinolytic activity of nattokinase in a solution was deactivated. Similar results were observed in the case of using Suc-Ala-Ala-Pro-Phe-pNA and H-D-Val-Leu-Lys-pNA, which are synthetic substrates of nattokinase. In the current study, tests were conducted on the indirect fibrinolytic effects of the substances containing nattokinase that had been deactivated through heating at 121 degrees C for 15 min. Bacillus subtilis natto culture solutions made from three types of bacteria strain were heat-treated and deactivated, and it was found that these culture solutions had the ability to generate tissue plasminogen activators (tPA) from vascular endothelial cells and HeLa cells at certain concentration levels. For example, it was found that the addition of heat-treated culture solution of the Naruse strain (undiluted solution) raises the tPA activity of HeLa cells to about 20 times that of the control. Under the same conditions, tPA activity was raised to a level about 5 times higher for human vascular endothelial cells (HUVEC), and to a level about 24 times higher for nattokinase sold on the market. No change in cell count was observed for HeLa cells and HUVEC in the culture solution at these concentrations, and the level of activity was found to vary with concentration. Copyright 2009 S. Karger AG, Basel.

  16. Low Energy Defibrillation in Human Cardiac Tissue: A Simulation Study

    Science.gov (United States)

    Morgan, Stuart W.; Plank, Gernot; Biktasheva, Irina V.; Biktashev, Vadim N.

    2009-02-01

    We aim to assess the effectiveness of feedback controlled resonant drift pacing as a method for low energy defibrillation. Antitachycardia pacing is the only low energy defibrillation approach to have gained clinical significance, but it is still suboptimal. Low energy defibrillation would avoid adverse side effects associated with high voltage shocks and allow the application of ICD therapy where it is not tolerated today. We present results of computer simulations of a bidomain model of cardiac tissue with human atrial ionic kinetics. Re-entry was initiated and low energy shocks were applied with the same period as the re-entry, using feedback to maintain resonance. We demonstrate that such stimulation can move the core of re-entrant patterns, in the direction depending on location of electrodes and a time delay in the feedback. Termination of re-entry is achieved with shock strength one order of magnitude weaker than in conventional single-shock defibrillation. We conclude that resonant drift pacing can terminate re-entry at a fraction of the shock strength currently used for defibrillation and can potentially work where antitachycardia pacing fails, due to the feedback mechanisms. Success depends on a number of details which these numerical simulations have uncovered. \\emph{Keywords} Re-entry; Bidomain model; Resonant drift; ICD; Defibrillation; Antitachycardia pacing; Feedback.

  17. Nonimmune immunoglobulin binding and multiple adhesion characterize Plasmodium falciparum-infected erythrocytes of placental origin

    DEFF Research Database (Denmark)

    Rasti, Niloofar; Namusoke, Fatuma; Chêne, Arnaud

    2006-01-01

    . A P. falciparum erythrocyte membrane protein 1 variant, VAR2CSA, and the placental receptor chondroitin sulfate A (CSA) are currently the focus of PAM research. A role for immunoglobulins (IgG and IgM) from normal human serum and hyaluronic acid as additional receptors in placental sequestration have...

  18. Congenital neuroblastoma with placental involvement

    OpenAIRE

    Kume, Ayako; Morikawa, Teppei; Ogawa, Makiko; Yamashita, Aki; Yamaguchi, Shunichi; Fukayama, Masashi

    2014-01-01

    We describe an extremely rare case of congenital neuroblastoma with placental involvement. A fetus with a left abdominal mass detected during ultrasonography at 23 weeks’ gestation developed hydrops fetalis by 26 weeks’ gestation. The mother developed hypertension at 26 5/7 weeks’ gestation. Based on a clinical diagnosis of pregnancy-induced hypertension, labor was induced at 26 6/7 weeks. However, intrauterine fetal death was diagnosed during delivery. Postmortern examination revealed a soli...

  19. Terahertz pulsed imaging of freshly excised human colonic tissues

    Energy Technology Data Exchange (ETDEWEB)

    Reid, Caroline B; Gibson, Adam P [Department of Medical Physics and Bioengineering, University College London, London, WC1E 6BT (United Kingdom); Fitzgerald, Anthony; Wallace, Vincent P [School of Physics, University of Western Australia, Crawley 6009 (Australia); Reese, George; Tekkis, Paris [Division of Surgery, Chelsea and Westminster Campus, Imperial College London, London (United Kingdom); Goldin, Robert [Centre for Pathology, Imperial College London, St Mary' s Campus, London (United Kingdom); O' Kelly, P S [TeraView Ltd, Platinum Building, St John' s Innovation Park, Cowley Road, Cambridge, CB4 0WS (United Kingdom); Pickwell-MacPherson, Emma, E-mail: c.reid@medphys.ucl.ac.uk [Department of Electronic Engineering, Chinese University of Hong Kong, Shatin, NT (Hong Kong)

    2011-07-21

    We present the results from a feasibility study which measures properties in the terahertz frequency range of excised cancerous, dysplastic and healthy colonic tissues from 30 patients. We compare their absorption and refractive index spectra to identify trends which may enable different tissue types to be distinguished. In addition, we present statistical models based on variations between up to 17 parameters calculated from the reflected time and frequency domain signals of all the measured tissues. These models produce a sensitivity of 82% and a specificity of 77% in distinguishing between healthy and all diseased tissues and a sensitivity of 89% and a specificity of 71% in distinguishing between dysplastic and healthy tissues. The contrast between the tissue types was supported by histological staining studies which showed an increased vascularity in regions of increased terahertz absorption.

  20. Potency testing of mesenchymal stromal cell growth expanded in human platelet lysate from different human tissues.

    Science.gov (United States)

    Fazzina, R; Iudicone, P; Fioravanti, D; Bonanno, G; Totta, P; Zizzari, I G; Pierelli, L

    2016-08-25

    Mesenchymal stromal cells (MSCs) have been largely investigated, in the past decade, as potential therapeutic strategies for various acute and chronic pathological conditions. MSCs isolated from different sources, such as bone marrow (BM), umbilical cord tissue (UCT) and adipose tissue (AT), share many biological features, although they may show some differences on cumulative yield, proliferative ability and differentiation potential. The standardization of MSCs growth and their functional amplification is a mandatory objective of cell therapies. The aim of this study was to evaluate the cumulative yield and the ex vivo amplification potential of MSCs obtained from various sources and different subjects, using defined culture conditions with a standardized platelet lysate (PL) as growth stimulus. MSCs isolated from BM, UCT and AT and expanded in human PL were compared in terms of cumulative yield and growth potential per gram of starting tissue. MSCs morphology, phenotype, differentiation potential, and immunomodulatory properties were also investigated to evaluate their biological characteristics. The use of standardized PL-based culture conditions resulted in a very low variability of MSC growth. Our data showed that AT has the greater capacity to generate MSC per gram of initial tissue, compared to BM and UCT. However, UCT-MSCs replicated faster than AT-MSCs and BM-MSCs, revealing a greater proliferation capacity of this source irrespective of its lower MSC yield. All MSCs exhibited the typical MSC phenotype and the ability to differentiate into all mesodermal lineages, while BM-MSCs showed the most prominent immunosuppressive effect in vitro. The adoption of standardized culture conditions may help researchers and clinicians to reveal particular characteristics and inter-individual variability of MSCs sourced from different tissues. These data will be beneficial to set the standards for tissue collection and MSCs clinical-scale expansion both for cell banking

  1. 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