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Sample records for human placental villi

  1. 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

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

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    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.

  3. 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

  4. Modeling oxygen transport in human placental terminal villi.

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    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.

  5. 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

  6. 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.

  7. [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.

  8. An integrative view on the physiology of human early placental villi.

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    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.

  9. 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.

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

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    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

  11. 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

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    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.

  12. Mechanism of Trypanosoma cruzi Placenta Invasion and Infection: The Use of Human Chorionic Villi Explants

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    Ricardo E. Fretes

    2012-01-01

    Full Text Available Congenital Chagas disease, a neglected tropical disease, endemic in Latin America, is associated with premature labor and miscarriage. During vertical transmission the parasite Trypanosoma cruzi (T. cruzi crosses the placental barrier. However, the exact mechanism of the placental infection remains unclear. We review the congenital transmission of T. cruzi, particularly the role of possible local placental factors that contribute to the vertical transmission of the parasite. Additionally, we analyze the different methods available for studying the congenital transmission of the parasite. In that context, the ex vivo infection with T. cruzi trypomastigotes of human placental chorionic villi constitutes an excellent tool for studying parasite infection strategies as well as possible local antiparasitic mechanisms.

  13. Placental Hypoxia Developed During Preeclampsia Induces Telocytes Apoptosis in Chorionic Villi Affecting The Maternal-Fetus Metabolic Exchange.

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    Bosco, Cleofina Becerra; Díaz, Eugenia Guerra; Gutierrez, Rodrigo Rojas; González, Jaime Montero; Parra-Cordero, Mauro; Rodrigo, Ramón Salinas; Barja, Pilar Yañez

    2016-01-01

    Telocytes (TC) are a new type of stromal cells initially found and studied in digestive and extra- digestive organs. These cells have a small cell body with 2 to 5 thin and extremely long cytoplasmic prolongations named telopodes. In recent years, TC have also been described in placental chorionic villi, located in a strategical position between the smooth muscle cells from fetal vessels and the myofibroblasts in the stromal villi. Unlike other organs, the placenta is not innervated and considering the strategic location of TC is has been postulated that TC function would be related to signal transduction mechanisms involved in the regulation of the fetal vessels blood flow, as well as in the shortening/lengthening of the chorionic villi, providing the necessary rhythmicity to the process of maternal/fetal metabolic exchange. Preeclampsia (PE) is a systemic syndrome that affects 4%-6% of pregnancies worldwide. It is characterized by a placental state of ischemia-hypoxia which triggers an oxidative stress stage with the concomitant production of reactive oxygen species (ROS) leading to an increase in the degree of placental apoptosis. Placental vascular tone is regulated by the vasodilator nitric oxide (NO) and, in PE cases, NO is diverted towards the formation of peroxynitrite, a powerful oxidative agent whose activity leads to an increase of placental apoptosis degree that compromises TC and myofibroblasts, a key feature we would like to emphasize in this work.

  14. The branching pattern of villous capillaries and structural changes of placental terminal villi in type 1 diabetes mellitus

    Czech Academy of Sciences Publication Activity Database

    Jirkovská, M.; Kučera, T.; Kaláb, J.; Jadrníček, M.; Niedobová, V.; Janáček, Jiří; Kubínová, Lucie; Moravcová, M.; Žižka, Z.; Krejčí, V.

    2012-01-01

    Roč. 33, č. 5 (2012), s. 343-351 ISSN 0143-4004 R&D Projects: GA ČR(CZ) GA304/09/0733 Institutional research plan: CEZ:AV0Z50110509 Keywords : angiogenesis * branching * capillaries * collagen * confocal microscopy * desmin * diabetes * placenta * structure * three-dimensional reconstruction * vascular topology * villi * vimentin Subject RIV: EA - Cell Biology Impact factor: 3.117, year: 2012

  15. MORPHOLOGICAL AND MICROMETRICAL CHANGES OF THE PLACENTAL TERMINAL VILLI IN NORMAL AND PREGNANCIES COMPLICATED WITH GESTATIONAL DIABETES MELLITUS

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    Sharmila Bhanu P

    2016-08-01

    Full Text Available AIM & OBJECTIVES Incidence of gestational diabetes mellitus (GDM is escalating in Indian women amounting to 10% of the total pregnancies mainly due to the diet, obesity and sedentary life style. Placenta is a crucial organ of intrauterine life. The functional units of the placenta such as chorionic villi, foetal blood vessels, and the syncytial knots are altered histologically in gestational diabetic condition. The present study is undertaken to observe the morphological and micrometrical changes of the GDM and normal placenta. MATERIAL AND METHODS Total number of 96 placentas, out of which 48 are GDM and 48 from control were procured for the present study. The placentas were collected from our General Hospital, Nellore, AP. Morphology and micrometry of the placentas were studied. RESULTS The shape of placenta was similar in both groups, but the weight in GDM (537.27±131.97 g, diameter (168.2±13.23 mm and thickness (29.9±3.45 mm were significantly (P<0.005 increased when compared to control. The mean number (9.01±2.25 mm3 and diameter (0.08±0.03 mm of the terminal villi and number of foetal blood vessels (21.76±8.52 mm3 were found to be increased in GDM, but the diameter of the blood vessel (0.04±0.02 mm was decreased and highly significant (P<0.001. The syncytial knots and fibrinoid necrosis were also observed in GDM when compared to the normal placenta. CONCLUSION The placentas from GDM were observed with significant morphological and histological changes as compared to controls, which may alter the perinatal outcome resulting in macrosomia, congenital malformations and intrauterine growth retardation.

  16. Animal Models of Human Placentation - A Review

    DEFF Research Database (Denmark)

    Carter, Anthony Michael

    2007-01-01

    This review examines the strengths and weaknesses of animal models of human placentation and pays particular attention to the mouse and non-human primates. Analogies can be drawn between mouse and human in placental cell types and genes controlling placental development. There are, however...... and 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...

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

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    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.

  18. Participation of collagen types I, III, IV, V, and fibronectin in the formation of villi fibrosis in human term placenta.

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    Rukosuev, V S; Nanaev, A K; Milovanov, A P

    1990-01-01

    The indirect immunofluorescence method was used to study the human term placenta in pathological pregnancy for the distribution of collagen types I, III, IV, V, and fibronectin in fibrosis stromatis villi. All collagen types and fibronectin were shown to participate in fibrosis villorum formation. Fibronectin was also detected in the fibrinoid that surrounded villi at stroma. The presence of free cytotrophoblast cells in the fibrinoid was accompanied by a noticeable increase in fibronectin fluorescence. A significant amount of collagen types IV and V and a less amount of collagen types I and III were identified.

  19. [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].

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    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.

  20. 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 ...

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

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    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.

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

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    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.

  3. Heme Oxygenase-1 Attenuates Hypoxia-Induced sFlt-1 and Oxidative Stress in Placental Villi through Its Metabolic Products CO and Bilirubin

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    Eric M. George

    2012-01-01

    Full Text Available One of the most prevalent complications of pregnancy is preeclampsia, a hypertensive disorder which is a leading cause of maternal and perinatal morbidity and premature birth with no effective pharmacological intervention. While the underlying cause is unclear, it is believed that placental ischemia/hypoxia induces the release of factors into the maternal vasculature and lead to widespread maternal endothelial dysfunction. Recently, HO-1 has been shown to downregulate two of these factors, reactive oxygen species and sFlt-1, and we have reported that HO-1 induction attenuates many of the pathological factors of placental ischemia experimentally. Here, we have examined the direct effect of HO-1 and its bioactive metabolites on hypoxia-induced changes in superoxide and sFlt-1 in placental vascular explants and showed that HO-1 and its metabolites attenuate the production of both factors in this system. These findings suggest that the HO-1 pathway may be a promising therapeutic approach for the treatment of preeclampsia.

  4. 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...

  5. 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.

  6. 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.

  7. 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 ...

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

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    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.

  9. 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...

  10. 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.

  11. 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

  12. 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

  13. 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.

  14. 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.

  15. 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.

  16. 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...

  17. 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.

  18. 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.

  19. 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.

  20. 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...

  1. 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.

  2. 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

  3. 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.

  4. 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.

  5. 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.

  6. 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.

  7. Assesment of porcine placental villi remodelling through tunel and PCNA

    OpenAIRE

    Sanchis, Gabriela; González, Silvina Lorena; Fiorimanti, Mariana Rita; Cristofolini, Andrea Lorena; Barbeito, Claudio Gustavo; Merkis, Cecilia

    2015-01-01

    El mantenimiento de la integridad estructural y funcional del tejido placentario involucra un recambio celular altamente regulado que depende de un delicado balance entre proliferación, diferenciación y pérdida celular. Nuestro objetivo fue determinar el porcentaje de células positivas al marcador de proliferación celular (%PCNA), y el índice apoptótico (IAp), a lo largo de la preñez, para evaluar la relación entre los procesos de proliferación y muerte celular. Se trabajó con muestras placen...

  8. 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...

  9. 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...

  10. 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....

  11. 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.

  12. Expression of VEGF receptors VEFGR-1 and VEGFR-2, angiopoietin receptors Tie-1 and Tie-2 in chorionic villi tree during early pregnancy.

    Directory of Open Access Journals (Sweden)

    Ramazan Demir

    2010-02-01

    Full Text Available The aim of this study was to determine the expression of VEGF and its receptors in placentas from normal pregnancies between 22 days p.c. and 48 days p.c. of very early pregnancy. Placental tissues carried out from 19 pregnant women were examined. Immunohistochemical technique, electron microscopy were employed to evaluate the factors expression. In the new developing mesenchymal villi and immature intermediate villi VEGF and its receptors VEGFR-1 and VEGFR-2 immunoreactivity was detected in all the placental components, while in the stem villi and in the chorionic plate with large vessels only in some components. In the mesenchymal villi and immature intermediate villi VEGFR-1 and -2, and angiopoietin receptors Tie-1 and -2 immunoreactivity was dominantly observed in the heamangiogenic cells and cells cords, whereas the matured villi showed immunoreactivity only in other components. The ultrastructural findings were higher in respect to the all of the early pregnancy days. The placental samples from all of pregnancies, showed the VEGF and its receptors in optimal expression levels, whereas the angiopoietin receptors Tie-1 and -2 showed a higher expression levels in respect to other study factors. The receptors protein levels increased from the early days to the advanced days of gestation, but this alteration was not significant. The intensity of the immunolabeling for these proteins were not significant compared to to each other of gestatin days were examined. These findings demonstrated that a dysregulation of the placental expression of the VEGF and its receptors related to the different degrees of the gestational periods. Probably, this event may be related to complete vasculugenesis and angiogenesis in placental villi.

  13. 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.

  14. 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.

  15. 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

  16. 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

  17. 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.

  18. 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

  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. 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.

  2. 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

  3. 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

  4. 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

  5. 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.

  6. 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 ...

  7. 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.

  8. 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.

  9. 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.

  10. 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.

  11. The role of invasive trophoblast in implantation and placentation of primates

    DEFF Research Database (Denmark)

    Carter, Anthony Michael; Enders, Allen C; Pijnenborg, Robert

    2015-01-01

    We here review the evolution of invasive placentation in primates towards the deep penetration of the endometrium and its arteries in hominoids. The strepsirrhine primates (lemurs and lorises) have non-invasive, epitheliochorial placentation, although this is thought to be derived from a more...... invasive type. In haplorhine primates, there is differentiation of trophoblast at the blastocyst stage into syncytial and cellular trophoblast. Implantation involves syncytiotrophoblast that first removes the uterine epithelium then consolidates at the basal lamina before continuing into the stroma...... into the lumen of the spiral arteries. They are responsible for remodelling these vessels to form wide, low-resistance conduits. In human and great apes, there is additional invasion of the endometrium and its vessels by trophoblasts originating from the base of the anchoring villi. Deep trophoblast invasion...

  12. 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.

  13. 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.

  14. 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.

  15. 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...

  16. 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.

  17. 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.

  18. 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...

  19. 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.

  20. 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.

  1. 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.

  2. 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.

  3. 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

  4. 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

  5. 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.

  6. 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...

  7. Modeling Oxygen Transport in the Human Placenta

    Science.gov (United States)

    Serov, Alexander; Filoche, Marcel; Salafia, Carolyn; Grebenkov, Denis

    Efficient functioning of the human placenta is crucial for the favorable pregnancy outcome. We construct a 3D model of oxygen transport in the placenta based on its histological cross-sections. The model accounts for both diffusion and convention of oxygen in the intervillous space and allows one to estimate oxygen uptake of a placentone. We demonstrate the existence of an optimal villi density maximizing the uptake and explain it as a trade-off between the incoming oxygen flow and the absorbing villous surface. Calculations performed for arbitrary shapes of fetal villi show that only two geometrical characteristics - villi density and the effective villi radius - are required to predict fetal oxygen uptake. Two combinations of physiological parameters that determine oxygen uptake are also identified: maximal oxygen inflow of a placentone and the Damköhler number. An automatic image analysis method is developed and applied to 22 healthy placental cross-sections demonstrating that villi density of a healthy human placenta lies within 10% of the optimal value, while overall geometry efficiency is rather low (around 30-40%). In a perspective, the model can constitute the base of a reliable tool of post partum oxygen exchange efficiency assessment in the human placenta. Also affiliated with Department of Chemistry and Biochemistry, UCLA, Los Angeles, CA 90095, USA.

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

    Science.gov (United States)

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

    2017-01-01

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

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

    Directory of Open Access Journals (Sweden)

    Radek Bukowski

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

  10. 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.

  11. 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.

  12. 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.

  13. 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.

  14. DNA Extraction from Chorionic Villi for Prenatal Diagnosis of Foetal ...

    African Journals Online (AJOL)

    BACKGROUND: Extraction of DNA from the chorionic villi is the first major step in the molecular determination of foetal haemoglobin genotype. There are few reports on DNA extraction from the chorionic villi. A desired method should be simple to conduct, reliable and cost effective. OBJECTIVE: The aim of the study was to ...

  15. 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...

  16. Hyaluronate synthesis by synovial villi in organ culture. [Dogs

    Energy Technology Data Exchange (ETDEWEB)

    Myers, S.L.; Christine, T.A.

    1983-06-01

    Individual canine synovial villi were used to establish short-term synovial organ cultures. These villi incorporated /sup 3/H-glucosamine into highly-polymerized /sup 3/H-hyaluronic acid (/sup 3/H-HA), which was the only /sup 3/H-glycosaminoglycan identified in the culture medium. Some /sup 3/H-HA, and larger amounts of other /sup 3/H-glycosaminoglycans, were recovered from cultured tissues. Culture medium /sup 3/H-HA content was proportional to the surface area of cultured villi. Organ cultures of nonvillous synovium were compared with villi; nonvillous cultures synthesized less /sup 3/H-HA per mm2 of their synovial intimal surface than villi. These cultures complement cell culture techniques for in vitro studies of synovial lining cell function.

  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. 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.

  20. 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.

  1. 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

  2. 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

  3. 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.

  4. 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

  5. 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.

  6. 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...

  7. 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...

  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. Villi Pogga ja Tarmo Prikk juhtisid ettevõtted disainiauhinnani

    Index Scriptorium Estoniae

    2007-01-01

    Villi Pogga juhitud Aquator ja Tarmo Priki juhitud Thulema said Saksamaal Essenis toimunud rahvusvahelisel konkursil Design Management Europe eriauhinna. Auhinda annab välja Esseni Disainikeskus koostöös 16 Euroopa disainikeskusega

  10. 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.

  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. 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. 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.

  16. 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.

  17. 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.

  18. Hemoglobin Bart hydrops fetalis: A model for studying vascular changes in placental hypoxia.

    Science.gov (United States)

    Taweevisit, Mana; Thorner, Paul Scott

    2016-08-01

    Placental ischemia can be pre-placental (maternal), placental or post-placental (fetal), with corresponding changes in villous vasculature. Hydrops fetalis (HF) resulting from hemoglobin (Hb) Bart disease can serve as a model for intrauterine hypoxia, and placentas from such cases show a distinctive peripheral villous stromal myofibroblastic hypercellularity (PVSH). We hypothesized that Hb Bart disease, which results in profound fetal hypoxia, would lead to placental hypoxia on a post-placental basis. We assessed villous vasculature using computerized morphometry, comparing placentas in 14 Hb Bart HF cases to 18 non-Hb Bart HF cases. Morphometric parameters were matched as closely as possible to those reported in the literature for comparison purposes. Villous vessels of Hb Bart HF showed significantly increased numbers of vessels (p = 0.001), longer vascular perimeter (p = 0.002), thickening of vascular endothelial layer (p = 0.038) and higher shape coefficient (p = 0.042) indicating a more branching pattern of vessels. In addition, placental villi of Hb Bart HF containing PVSH showed a longer vascular perimeter (p = 0.008) and narrower lumen (p = 0.002), with a higher shape coefficient (p = 0.03), in comparison to villi lacking PVSH. Contrary to expectations, the overall pattern of vascular changes in Hb Bart HF suggested multifactorial hypoxia: pre-placental, on the basis of the marked placentomegaly, compromising blood flow from uterine distention; placental, from hydropic villi causing a generalized diminished intervillous space; and post-placental from the greatly reduced capacity of Hb Bart to extract oxygen from the intervillous space. Standardized vascular morphometry will facilitate comparison between different conditions, for a better understanding of placental hypoxia. Copyright © 2016 Elsevier Ltd. All rights reserved.

  19. Angiotensin II and angiotensin-(1-7 decrease sFlt1 release in normal but not preeclamptic chorionic villi: an in vitro study

    Directory of Open Access Journals (Sweden)

    Moorefield Cheryl

    2010-11-01

    Full Text Available Abstract Background During preeclampsia, placental angiogenesis is impaired. Factors released from the placenta including vascular endothelial growth factor (VEGF, placental growth factor (PLGF, soluble VEGF receptor 1 (sFlt1, and soluble endoglin (sEng are regulatory molecules of placental development and function. While the renin angiotensin system has been shown to regulate angiogenic factors in other research fields, these mechanisms have not been extensively studied during pregnancy. Methods We evaluated the effects of angiotensin II (Ang II and angiotensin-(1-7 [Ang-(1-7] on the release of VEGF, PLGF, sFlt1, and sEng from placental chorionic villi (CV. CV were collected from nulliparous third-trimester normotensive and preeclamptic subjects. CV were incubated for 0, 2, 4, and 16 hours with or without Ang II (1 nM and 1 microM or Ang-(1-7 (1 nM and 1 microM. The release of VEGF, PLGF, sFlt1, sEng, lactate dehydrogenase (LDH, and human placenta lactogen (HPL was measured by ELISA. Results The release of sFlt1, PLGF, sEng from normal and preeclamptic CV increased over time. Release of sFlt1 and sEng was significantly higher from preeclamptic CV. VEGF was below the detectable level of the assay in normal and preeclamptic CV. After 2 hours, sFlt1 release from normal CV was significantly inhibited with Ang II (1 nM and 1 microM and Ang-(1-7 (1 nM and 1 microM. There was a time-dependent increase in HPL indicating that the CV were functioning normally. Conclusions Our study demonstrates a critical inhibitory role of angiotensin peptides on sFlt1 in normal pregnancy. Loss of this regulation in preeclampsia may allow sFlt1 to increase resulting in anti-angiogenesis and end organ damage in the mother.

  20. 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.

  1. 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

  2. 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.

  3. 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.

  4. 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

  5. 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.

  6. 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.

  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. 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...

  9. 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...

  10. 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

  11. Mobiilside uustulnukad võtavad alles hoogu / Villy Paimets

    Index Scriptorium Estoniae

    Paimets, Villy, 1972-

    2004-01-01

    Uued mobiilsideoperaatorid Vertelson Mobiil, CityGSM ja Top Connect valmistuvad turuletulekut ette. Vt. samas: Villy Paimets. Mobiilsideturul tüli majas. OÜ Top Connect konflikti kavandatavate teenuste osutamise pärast läbi Radiolinja võrgu kommenteerivad Radiolinja Eesti juhatuse esimehelt Sami Seppänenilt ja OÜ Top Connect juhatuse liikmelt Vladislav Sobolevilt

  12. 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

  13. 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.

  14. 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.

  15. 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.

  16. 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

  17. 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.

  18. Human cytomegalovirus infection interferes with the maintenance and differentiation of trophoblast progenitor cells of the human placenta.

    Science.gov (United States)

    Tabata, Takako; Petitt, Matthew; Zydek, Martin; Fang-Hoover, June; Larocque, Nicholas; Tsuge, Mitsuru; Gormley, Matthew; Kauvar, Lawrence M; Pereira, Lenore

    2015-05-01

    Human cytomegalovirus (HCMV) is a major cause of birth defects that include severe neurological deficits, hearing and vision loss, and intrauterine growth restriction. Viral infection of the placenta leads to development of avascular villi, edema, and hypoxia associated with symptomatic congenital infection. Studies of primary cytotrophoblasts (CTBs) revealed that HCMV infection impedes terminal stages of differentiation and invasion by various molecular mechanisms. We recently discovered that HCMV arrests earlier stages involving development of human trophoblast progenitor cells (TBPCs), which give rise to the mature cell types of chorionic villi-syncytiotrophoblasts on the surfaces of floating villi and invasive CTBs that remodel the uterine vasculature. Here, we show that viral proteins are present in TBPCs of the chorion in cases of symptomatic congenital infection. In vitro studies revealed that HCMV replicates in continuously self-renewing TBPC lines derived from the chorion and alters expression and subcellular localization of proteins required for cell cycle progression, pluripotency, and early differentiation. In addition, treatment with a human monoclonal antibody to HCMV glycoprotein B rescues differentiation capacity, and thus, TBPCs have potential utility for evaluation of the efficacies of novel antiviral antibodies in protecting and restoring placental development. Our results suggest that HCMV replicates in TBPCs in the chorion in vivo, interfering with the earliest steps in the growth of new villi, contributing to virus transmission and impairing compensatory development. In cases of congenital infection, reduced responsiveness of the placenta to hypoxia limits the transport of substances from maternal blood and contributes to fetal growth restriction. Human cytomegalovirus (HCMV) is a leading cause of birth defects in the United States. Congenital infection can result in permanent neurological defects, mental retardation, hearing loss, visual

  19. 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

  20. The role of invasive trophoblast in implantation and placentation of primates.

    Science.gov (United States)

    Carter, Anthony M; Enders, Allen C; Pijnenborg, Robert

    2015-03-05

    We here review the evolution of invasive placentation in primates towards the deep penetration of the endometrium and its arteries in hominoids. The strepsirrhine primates (lemurs and lorises) have non-invasive, epitheliochorial placentation, although this is thought to be derived from a more invasive type. In haplorhine primates, there is differentiation of trophoblast at the blastocyst stage into syncytial and cellular trophoblast. Implantation involves syncytiotrophoblast that first removes the uterine epithelium then consolidates at the basal lamina before continuing into the stroma. In later stages of pregnancy, especially in Old World monkeys and apes, cytotrophoblast plays a greater role in the invasive process. Columns of trophoblast cells advance to the base of the implantation site where they spread out to form a cytotrophoblastic shell. In addition, cytotrophoblasts advance into the lumen of the spiral arteries. They are responsible for remodelling these vessels to form wide, low-resistance conduits. In human and great apes, there is additional invasion of the endometrium and its vessels by trophoblasts originating from the base of the anchoring villi. Deep trophoblast invasion that extends remodelling of the spiral arteries to segments in the inner myometrium evolved in the common ancestor of gorilla, chimp and human. © 2015 The Author(s) Published by the Royal Society. All rights reserved.

  1. 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.

  2. 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.

  3. 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.

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

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    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

  6. [Immunofluorescence study of the extracellular matrix of the human placenta].

    Science.gov (United States)

    Rukosuev, V S; Fokin, E I; Milovanov, A P

    1989-01-01

    Distribution of collagen types I, III, IV, V and fibronectin in human placental villi has been studied by indirect immunofluorescence. During 9-12 weeks of pregnancy the extracellular matrix of villi represents a network of filaments organized in bundles and aggregates that contain collagen types I and III and finer filaments of collagen types IV and V. Collagen type IV is regularly detected in basal membrane of capillaries and particularly in villous epithelium, collagen type V and fibronectin are occasionally detected there. Marked immunofluorescent reaction on collagen types IV and V and fibronectin, and weak reaction on collagen type III is observed in cellular islets around cytotrophoblasts. In the fetus born in term placental villi have uniform immunofluorescence in thick basal membranes of fetal capillaries and of chorionic epithelium. The immunofluorescent reaction specific for all collagen types is uniform in villous stroma. Distribution of different collagen types and fibronectin, including the unusual localization of membrane collagen type IV, in villous stroma and cellular islets of early and mature placenta is discussed.

  7. Co-localization of P2Y1 receptor and NTPDase1/CD39 within caveolae in human placenta

    Directory of Open Access Journals (Sweden)

    A Kittel

    2009-06-01

    Full Text Available Nucleoside triphosphate diphosphohydrolase-1 (NTPDase1/ CD39 is the dominant ecto-nucleotidase of vascular and placental trophoblastic tissues and appears to modulate the functional expression of type-2 purinergic (P2 Gprotein coupled receptors (GPCRs. Hence, this ectoenzyme could regulate nucleotide-mediated signalling events in placental tissue. This immunohistochemical and immuno-electron microscopic study demonstrates the expression of NTPDase1/CD39, P2Y1 and P2Y2 receptors in different cell types of human placenta. Specifically P2Y1 has an exclusive vascular distribution whereas P2Y2 is localized on trophoblastic villi. Co-localization of P2Y1 and NTPDase1/ CD39 are observed in caveolae, membrane microdomains of endothelial cells. The differential localization of these P2 receptors might indicate their unique roles in the regulation of extracellular nucleotide concentrations in human placental tissues and consequent effects on vascular tone and blood fluidity.

  8. 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

  9. 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.

  10. [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.

  11. 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.

  12. 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.

  13. 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

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

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    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.

  15. 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

  16. 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.

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

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    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...

  18. 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

  19. 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.

  20. 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.

  1. 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.

  2. 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.

  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. [Experiences with transcervical chorionic villi biopsy in 274 studies].

    Science.gov (United States)

    Karkut, G; Becker, R; Starzinski, K; Schulzke, I; Wegner, R D; Weitzel, H K

    1989-08-01

    In the years 1985-1987, 274 transcervical chorionic villi biopsy samples were taken at the Klinikum Steglitz Medical Center of the Free University of Berlin. We have information on the outcome of 264 pregnancies (96.3%). 229 cases (83.6%) yielded diagnostically usable results. Multiple biopsy samples were taken in 59 (21.5%) cases. Abnormal results were found in 14 patients. Pregnancy was terminated in 6 cases (2.2%) for proven chromosomal aberrations. In two others, spontaneous abortion occurred before the intended induced abortion. In 4 cases of mosaics, amniocentesis was performed subsequently in the 16th week of pregnancy; three of those pregnancies were carried to full term, and the children are healthy. In one case, we saw a spontaneous abortion in the 26th week of pregnancy. In two cases, we found balanced translocations. Miscarriage was observed in 16 CVS patients (5.8%). Abortion was febrile in two cases, septic in two others.

  6. Immune tolerance induction using fetal directed placental injection in rodent models: a murine model.

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    Kei Takahashi

    Full Text Available Induction of the immune response is a major problem in replacement therapies for inherited protein deficiencies. Tolerance created in utero can facilitate postnatal treatment. In this study, we aimed to induce immune tolerance towards a foreign protein with early gestational cell transplantation into the chorionic villi under ultrasound guidance in the murine model.Pregnant C57BL/6 (B6 mice on day 10 of gestation were anesthetized and imaged by high resolution ultrasound. Murine embryos and their placenta were positioned to get a clear view in B-mode with power mode of the labyrinth, which is the equivalent of chorionic villi in the human. Bone marrow cells (BMCs from B6-Green Fluorescence Protein (B6GFP transgenic mice were injected into the fetal side of the placenta which includes the labyrinth with glass microcapillary pipettes. Each fetal mouse received 2 x 105 viable GFP-BMCs. After birth, we evaluated the humoral and cell-mediated immune response against GFP.Bone marrow transfer into fetal side of placenta efficiently distributed donor cells to the fetal mice. The survival rate of this procedure was 13.5%(5 out of 37. Successful engraftment of the B6-GFP donor skin grafts was observed in all recipient (5 out of 5 mice 6 weeks after birth. Induction of anti-GFP antibodies was completely inhibited. Cytotoxic immune reactivity of thymic cells against cells harboring GFP was suppressed by ELISPOT assay.In this study, we utilized early gestational placental injection targeting the murine fetus, to transfer donor cells carrying a foreign protein into the fetal circulation. This approach is sufficient to induce both humoral and cell-mediated immune tolerance against the foreign protein.

  7. Immune tolerance induction using fetal directed placental injection in rodent models: a murine model.

    Science.gov (United States)

    Takahashi, Kei; Endo, Masayuki; Miyoshi, Takekazu; Tsuritani, Mitsuhiro; Shimazu, Yukiko; Hosoda, Hiroshi; Saga, Kotaro; Tamai, Katsuto; Flake, Alan W; Yoshimatsu, Jun; Kimura, Tadashi

    2015-01-01

    Induction of the immune response is a major problem in replacement therapies for inherited protein deficiencies. Tolerance created in utero can facilitate postnatal treatment. In this study, we aimed to induce immune tolerance towards a foreign protein with early gestational cell transplantation into the chorionic villi under ultrasound guidance in the murine model. Pregnant C57BL/6 (B6) mice on day 10 of gestation were anesthetized and imaged by high resolution ultrasound. Murine embryos and their placenta were positioned to get a clear view in B-mode with power mode of the labyrinth, which is the equivalent of chorionic villi in the human. Bone marrow cells (BMCs) from B6-Green Fluorescence Protein (B6GFP) transgenic mice were injected into the fetal side of the placenta which includes the labyrinth with glass microcapillary pipettes. Each fetal mouse received 2 x 105 viable GFP-BMCs. After birth, we evaluated the humoral and cell-mediated immune response against GFP. Bone marrow transfer into fetal side of placenta efficiently distributed donor cells to the fetal mice. The survival rate of this procedure was 13.5%(5 out of 37). Successful engraftment of the B6-GFP donor skin grafts was observed in all recipient (5 out of 5) mice 6 weeks after birth. Induction of anti-GFP antibodies was completely inhibited. Cytotoxic immune reactivity of thymic cells against cells harboring GFP was suppressed by ELISPOT assay. In this study, we utilized early gestational placental injection targeting the murine fetus, to transfer donor cells carrying a foreign protein into the fetal circulation. This approach is sufficient to induce both humoral and cell-mediated immune tolerance against the foreign protein.

  8. 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, ...

  9. 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

  10. Relation of placental diagnosis in stillbirth to fetal maceration and gestational age at delivery.

    Science.gov (United States)

    Stanek, Jerzy; Biesiada, Jacek

    2014-07-01

    To study the relation of retention of dead fetus resulting in its maceration and gestational age at delivery to placental diagnosis. Some 75 clinicoplacental phenotypes have been retrospectively analyzed in 520 consecutive stillbirths, 329 macerated and 191 nonmacerated, and at three gestational age interval cohorts (330 second trimester, 102 preterm third trimester, and 88 term). Chi-square and clustering methods (Ward dendrograms and multidimensional scaling) were used for statistical analysis. Maternal diabetes mellitus, induction of labor, fetal growth restriction, various umbilical cord abnormalities, and placental clusters of sclerotic/hemosiderotic chorionic villi were more common in macerated stillbirths, while clinicoplacental signs and symptoms of ascending infection and placental abruption, i.e., retroplacental hematoma, premature rupture of membranes, and acute chorioamnionitis in nonmacerated stillbirths. Placental abnormalities were less common in the second trimester, other than the acute chorioamnionitis. Patterns of chronic hypoxic placental injury were common in preterm third trimester, while signs of in-utero hypoxia (abnormal cardiotocography, meconium, and histological erythroblastosis of fetal blood) in term pregnancy. In addition to classical statistics, the clustering analyses added new information to placental investigation of cause of stillbirth. Macerated third trimester stillbirths have multifactorial etiology more likely than the second trimester stillbirths and the likely stasis-induced fetal thrombotic vasculopathy secondary to occult umbilical cord compromise should be sought in placental investigation in such cases. Nonmacerated stillbirths are associated with ascending infection and placental abruption.

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

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    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.

  12. 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.

  13. 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.

  14. Placental Chorangiosis: Increased Risk for Cesarean Section

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    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.

  15. 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....

  16. 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.

  17. 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.

  18. 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.

  19. Placental vascularization and apoptosis in Type-1 and gestational DM.

    Science.gov (United States)

    Akarsu, Süleyman; Bagirzade, Mahmud; Omeroglu, Suna; Büke, Barıs

    2017-05-01

    The objective of this study is to analyze the alteration in vascularization and apoptosis in the placentas of patients with Type 1 or gestational diabetes mellitus. Placental samples drawn from normal (n = 6), GDM (n = 6), and Type 1 DM (n = 6) pregnancies were rinsed in PBS and fixed in 4% paraformaldehyde. The obtained sections were examined by both light and electron microscopy. Subsequently, immunohistochemical staining was performed to evaluate apoptosis and vascularization with caspase-9 and VEGF antibodies. Capillary structures in various sizes, both in free and in stem villi, were observed to be denser in the GDM group than in the control and Type-1 DM groups, utilizing electron microscopy. Similarly, when compared with Type-1 DM and controls, a decreased amount of microvilli with more irregularity and blunting on the villus surface was detected. GDM group showed increased immunoreactivity in capillaries of stem villi, free villi, and endothelial cells when compared with Type-1 DM and control groups. Regarding the immunohistochemical staining with VEGF, Type-1 DM, and GDM groups showed stronger immunoreactivity than the control group, especially in syncytiotrophoblastic cell nuclei and stromal cell nuclei. However, there was no significant difference between Type-1 DM and GDM groups. Type-1 DM and GDM placentas showed increased villous stromal capillarization, increased immunoreactivity with VEGF and caspase-9, and increased syncytial nodes, which may develop secondary to placental hypoxia-ischemia. However, more participants are needed to confirm these conclusions.

  20. 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

  1. 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.

  2. 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.

  3. 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

  4. 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.

  5. Analytical theory of oxygen transport in the human placenta.

    Science.gov (United States)

    Serov, A S; Salafia, C M; Filoche, M; Grebenkov, D S

    2015-03-07

    We propose an analytical approach to solving the diffusion-convection equations governing oxygen transport in the human placenta. We show that only two geometrical characteristics of a placental cross-section, villi density and the effective villi radius, are needed to predict fetal oxygen uptake. We also identify two combinations of physiological parameters that determine oxygen uptake in a given placenta: (i) the maximal oxygen inflow of a placentone if there were no tissue blocking the flow and (ii) the ratio of transit time of maternal blood through the intervillous space to oxygen extraction time. We derive analytical formulas for fast and simple calculation of oxygen uptake and provide two diagrams of efficiency of oxygen transport in an arbitrary placental cross-section. We finally show that artificial perfusion experiments with no-hemoglobin blood tend to give a two-orders-of-magnitude underestimation of the in vivo oxygen uptake and that the optimal geometry for such setup alters significantly. The theory allows one to adjust the results of artificial placenta perfusion experiments to account for oxygen-hemoglobin dissociation. Combined with image analysis techniques, the presented model can give an easy-to-use tool for prediction of the human placenta efficiency. Copyright © 2014 Elsevier Ltd. All rights reserved.

  6. 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

  7. 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

  8. 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.

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

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    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.

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

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    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.

  11. 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.

  12. 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

  13. Peripheral villous stromal hyperplasia: a distinctive placental lesion in hemoglobin bart hydrops fetalis.

    Science.gov (United States)

    Taweevisit, Mana; Thorner, Paul Scott

    2012-01-01

    In hydrops fetalis (HF) the placenta can be markedly enlarged and the villi show stromal edema, increased Hofbauer cells, and reduced numbers of capillaries. Hemoglobin (Hb) Bart is the most severe form of thalassemia, causing HF due to profound anemia. We report a previously undescribed histologic finding based on a review of Hb Bart HF cases, termed "peripheral villous stromal hypercellularity." This change was noted in 15 of 18 (83%) placentas with Hb Bart HF but not in placentas of 21 cases of HF due to other causes, including 11 cases involving anemia. The hyperplastic stromal cells were determined to be myofibroblastic by immunohistochemistry and electron microscopy, associated with a more complex capillary network in villi than is seen with other causes of HF. The authors hypothesize that this angiogenesis in villi is a response to fetal anemia from Hb Bart. In turn, there is increased villous blood flow, resulting in edematous villous stroma, leading to narrowing of the intervillous space in the placenta. Hyperplasia of myofibroblasts might then be a compensatory change, in that contraction by these cells would reduce the vascular lumina and the size of placental villi, thereby widening the intervillous space to improve capacity for maternal blood circulation. Curiously, this histologic change was restricted to cases of HF caused by Hb Bart. We speculate that in Hb Bart disease, the hypoxia and hydrops develop earlier in gestation, compared to other causes of HF, allowing the time for these adaptive changes to occur in the placenta.

  14. 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.

  15. 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.

  16. EXERCISE EFFECT ON PLACENTAL COMPONENTS: SYSTEMATIC REVIEW AND META-ANALYSIS

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    Walter Krause Neto

    2015-12-01

    Full Text Available Physical exercise has been demonstrated a positive effect on many pregnancy outcomes. Placental components are important for exchanging oxygen and nutrients between mother and fetus. This study aimed to systematic review and meta-analysis whether physical exercise could induce a morphological adjustment on placenta components. We systematically searched PubMed database until October 30th, 2014. We included randomized and non-randomized studies with control group, which aimed to investigate the effect of the physical exercise (water, aerobic and resistance on placental components (placental weight and volume, villous volume and vascular volume, intervillous space and stem villi. Initially, we identified 222 articles, of which 9 articles were used for full text analysis. Finally, four articles were included in the systematic review and meta-analysis. Meta-analysis demonstrated that exercise appeared to affect placental weight (95% CI, 39.73g [4.66-74.80], placental volume (95% CI, 47.11 cm3 [37.99-56.23], intervillous space (95% CI, 16.76 cm3 [12.66-20.68], villous volume (95% CI, 46.01 cm3 [40.21-51.81], villous vascular volume (95% CI, 15.95 cm3 [7.83-24.07] and stem villi (95% CI, 6.00 cm3[4.25-7.75]. Apparently, physical exercise has a positive effect on placental components. However, this conclusion is based on a limited number of studies. Clearly, it stands the necessity of larger samples and better methodology quality.

  17. IL-11 and IL-11Rα immunolocalisation at primate implantation sites supports a role for IL-11 in placentation and fetal development

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    Stoikos C

    2003-04-01

    Full Text Available Abstract Embryo implantation, endometrial stromal cell decidualization and formation of a functional placenta are critical processes in the establishment and maintenance of pregnancy. Interleukin (IL-11 signalling is essential for adequate decidualization in the mouse uterus and IL-11 promotes decidualization in the human. IL-11 action is mediated via binding to the specific IL-11 receptor α (IL-11Rα. The present study examined immunoreactive IL-11 and IL-11Rα in cycling rhesus monkey endometrium, at implantation sites in cynomolgus and rhesus monkeys and in human first trimester decidua and defined distinct spatial and temporal patterns. In cycling rhesus monkey endometrium, IL-11 and IL-11Rα increased in both basalis and functionalis regions during the secretory compared with the proliferative phase, with changing cellular locations in luminal and glandular epithelium and stroma. The patterns were similar overall to those previously described in human endometrium. Differences were seen in immunostaining during implantation in cynomologus and rhesus monkey. In the cynomolgus, very little staining for IL-11 or IL-11Rα was seen in syncytio- and cyto-trophoblast cells in the villi between days 12 and 150 of pregnancy although there was moderate staining in cytotrophoblast in the shell between days 12 and 17 and in subpopulations of cytotrophoblast cells invading the arteries at day 17. By contrast in the rhesus monkey between days 24 and 35 of pregnancy and in human first trimester placenta, cyto- and syncytio-trophoblast in the villi but not cytotrophoblast in the shell were positively stained. The most intense staining for both IL-11 and IL-11Rα was present within the decidua in the maternal component of implantation sites in all three primates but moderate staining was also present in maternal vascular smooth muscle and glands perivascular cells and epithelial plaques. These results are consistent with a role for IL-11 both during

  18. 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.

  19. Oxygen and placental development during the first trimester: implications for the pathophysiology of pre-eclampsia.

    Science.gov (United States)

    Caniggia, I; Winter, J; Lye, S J; Post, M

    2000-01-01

    During early pregnancy, placentation occurs in a relatively hypoxic environment which is essential for appropriate embryonic development. Intervillous blood flow increases at around 10-12 weeks of gestation and results in exposure of the trophoblast to increased oxygen tension (PO2). Prior to this time, low oxygen appears to prevent trophoblast differentiation towards an invasive phenotype. In other mammalian systems, oxygen tension effects are mediated by hypoxia inducible factor-1 (HIF-1). We found that the ontogeny of HIF-1alpha subunit expression during the first trimester of gestation parallels that of transforming growth factor-beta3 (TGFbeta3), an inhibitor of early trophoblast differentiation. Expression of both molecules is high in early pregnancy and falls at around 10 weeks of gestation when placental PO2 levels are believed to increase. Antisense-induced inhibition of HIF-1alpha inhibited the expression of TGFbeta3, and stimulated extravillous trophoblast (EVT) outgrowth and invasion. Of clinical significance we found that TGFbeta3 expression was increased in pre-eclamptic placentae when compared to age-matched controls. Significantly, inhibition of TGFbeta3 by antisense oligonucleotides or antibodies restored the invasive capability to the trophoblast cells in pre-eclamptic explants. We speculate that if oxygen tension fails to increase, or trophoblasts do not detect this increase, HIF-1alpha and TGFbeta3 expression remain high, resulting in shallow trophoblast invasion and predisposing the pregnancy to pre-eclampsia. Effective fetal-maternal interactions during early placentation are critical for a successful pregnancy. Optimal placental perfusion requires the controlled invasion of trophoblast cells deep into the decidua to the spiral arteries. Trophoblast stem cells, also referred to as cytotrophoblast cells, reside in chorionic villi of two types, floating and anchoring villi. Floating villi, which represent the vast majority of chorionic villi

  20. Placental histopathological changes associated with Plasmodium vivax infection during pregnancy.

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    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

  1. Heterogeneous histochemical reaction pattern of the lectin Bandeiraea (Griffonia) simplicifolia with blood vessels of human full-term placenta.

    Science.gov (United States)

    Lang, I; Hahn, T; Dohr, G; Skofitsch, G; Desoye, G

    1994-12-01

    Bandeiraea simplicifolia lectin (BS-I) stains vascular endothelium in various species. In humans, less than 10% of the specimens studied exhibit a reaction with BS-I. In the present histochemical study, the reactivity of BS-I with placental blood vessels and its correlation with the blood group from mother and newborn child was investigated. Acetone-fixed cryosections of representative tissue segments of human full-term placenta and umbilical cord were stained with BS-I. The staining pattern of tissues from patients with different blood groups was identical, although the reaction of BS-I in the placenta was heterogeneous. BS-I did not react with the umbilical cord. Vascular smooth muscle cells at the insertion site of the umbilical cord into the chorionic plate, and endothelium deeper in the chorionic plate, became progressively stained. The endothelial cells and tunica muscularis of smaller arteries and veins in stem villi lost their reactivity in parallel with decreasing vessel size. Arterioles and venules reacted heterogeneously. Capillaries, trophoblastic basement membranes, especially epithelial plates, and sometimes the syncytiotrophoblast were labelled in several terminal villi. The data indicate that 1) the placenta binds BS-I to fetal endothelium independent of the blood group, 2) cell-surface antigens on placental endothelial cells are expressed heterogeneously and 3) cell-surface glycans are constituted in an organ-specific manner on human endothelial cells.

  2. 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...

  3. 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...

  4. 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

  5. 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

  6. 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.

  7. 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.

  8. 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....

  9. 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

  10. 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

  11. Does the maternal age affect the mesenchymal stem cell markers and gene expression in the human placenta? What is the evidence?

    Science.gov (United States)

    Alrefaei, Ghadeer Ibrahim; Al-Karim, Saleh; Ayuob, Nasra Naeim; Ali, Soad Shaker

    2015-08-01

    Although the human placenta is considered medical wastes, it has become a main source of stem cells. Due to their easy isolation, ability to resist immune rejection and ability to differentiate into different types of adult cells, placental stem cells are considered superior to other stem cells. This study aimed to assess the impact of the maternal age on the expression of mesenchymal stem cell (MSC) markers CD105 and CD29 in different areas of a term human placenta and to identify the differential expression of these markers in different placental areas. In this comparative cross sectional study, one hundred term placentas were collected after delivery from healthy mothers divided into five groups according to their age. Placentas were processed to assess both immune- and gene-expression of CD105 and CD29 surface antigen markers. Data of the different studied age groups was compared using the Statistical Package of Social Science (SPSS) software. CD105 and CD29 immunoexpression in decidua basalis, fetal membrane and placental villi showed significant negative correlations with the maternal age. CD105- and CD29-positive MSCs were significantly abundant in the decidua basalis and placental villi. Real-time polymerase chain reaction results were consistent with those of the immunohistochemical study. Labeling the placenta-driven MSCs with the specific area from which the cells were taken as well as the mother's age is advised and could be helpful in controlling the quality of the cell banks as well as the favorable outcome of the therapeutic applications. Copyright © 2015 Elsevier Ltd. All rights reserved.

  12. 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

  13. 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

  14. 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...

  15. 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

  16. 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

  17. 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

  18. 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

  19. 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.

  20. 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.

  1. 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.

  2. 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.

  3. 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

  4. 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 =

  5. 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...

  6. 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,

  7. 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.

  8. Cell proliferation within small intestinal crypts is the principal driving force for cell migration on villi.

    Science.gov (United States)

    Parker, Aimee; Maclaren, Oliver J; Fletcher, Alexander G; Muraro, Daniele; Kreuzaler, Peter A; Byrne, Helen M; Maini, Philip K; Watson, Alastair J M; Pin, Carmen

    2017-02-01

    The functional integrity of the intestinal epithelial barrier relies on tight coordination of cell proliferation and migration, with failure to regulate these processes resulting in disease. It is not known whether cell proliferation is sufficient to drive epithelial cell migration during homoeostatic turnover of the epithelium. Nor is it known precisely how villus cell migration is affected when proliferation is perturbed. Some reports suggest that proliferation and migration may not be related while other studies support a direct relationship. We used established cell-tracking methods based on thymine analog cell labeling and developed tailored mathematical models to quantify cell proliferation and migration under normal conditions and when proliferation is reduced and when it is temporarily halted. We found that epithelial cell migration velocities along the villi are coupled to cell proliferation rates within the crypts in all conditions. Furthermore, halting and resuming proliferation results in the synchronized response of cell migration on the villi. We conclude that cell proliferation within the crypt is the primary force that drives cell migration along the villus. This methodology can be applied to interrogate intestinal epithelial dynamics and characterize situations in which processes involved in cell turnover become uncoupled, including pharmacological treatments and disease models.-Parker, A., Maclaren, O. J., Fletcher, A. G., Muraro, D., Kreuzaler, P. A., Byrne, H. M., Maini, P. K., Watson, A. J. M., Pin, C. Cell proliferation within small intestinal crypts is the principal driving force for cell migration on villi. © The Author(s).

  9. 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...

  10. 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.

  11. 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

  12. Neurorescue effects and stem properties of chorionic villi and amniotic progenitor cells.

    Science.gov (United States)

    Calzarossa, C; Bossolasco, P; Besana, A; Manca, M P; De Grada, L; De Coppi, P; Giardino, D; Silani, V; Cova, L

    2013-03-27

    The capability to integrate into degenerative environment, release neurotrophic cytokines, contrast oxidative stress and an inherent differentiation potential towards siteappropriate phenotypes are considered crucial for the use of stem cells in tissue repair and regeneration. Naïve human chorial villi- (hCVCs) and amniotic fluid- (hAFCs) derived cells, whose properties and potentiality have not been extensively investigated, may represent two novel foetal cell sources for stem cell therapy. We previously described that long-term transplantation of hAFCs in the lateral ventricles of wobbler and healthy mice was feasible and safe. In the present study we examine the in vitro intrinsic stem potential of hCVCs and hAFCs for future therapeutic applications in neurodegenerative disorders. Presence of stem lineages was evaluated assessing the expression pattern of relevant candidate markers by flow cytometry, reverse transcription-polymerase chain reaction (RT-PCR) and immunocytochemistry. Release of cytokines that may potentialy sustain endogenous neurogenesis and/or activate neuroprotective pathways was quantified by enzyme-linked immunosorbent assays (ELISAs). We also performed an in vitro neurorescue assay, wherein a neuroblastoma cell line damaged by 6-hydroxydopamine (6-OHDA) was treated with hCVC/hAFC-derived conditioned medium (CM). Naïve hCVCs/hAFCs show a neurogenic/angiogenic predisposition. Both cell types express several specific neural stem/progenitor markers, such as nestin and connexin 43, and release significant amounts of brain-derived neurotrophic factor, as well as vascular endothelial growth factor. hCVC and hAFC populations comprise several interesting cell lineages, including mesenchymal stem cells (MSCs) and cells with neural-like phenotypes. Moreover, although CMs obtained from both cell cultures actively sustained metabolic activity in a 6-OHDA-induced Parkinson's disease (PD) cell model, only hCVC-derived CMs significantly reduced neurotoxin

  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. Three-dimensional mechanisms of macro-to-micro-scale transport and absorption enhancement by gut villi motions

    Science.gov (United States)

    Wang, Yanxing; Brasseur, James G.

    2017-06-01

    We evaluate the potential for physiological control of intestinal absorption by the generation of "micromixing layers" (MMLs) induced by coordinated motions of mucosal villi coupled with lumen-scale "macro" eddying motions generated by gut motility. To this end, we apply a three-dimensional (3D) multigrid lattice-Boltzmann model of a lid-driven macroscale cavity flow with microscale fingerlike protuberances at the lower surface. Integrated with a previous 2D study of leaflike villi, we generalize to 3D the 2D mechanisms found there to enhance nutrient absorption by controlled villi motility. In three dimensions, increased lateral spacing within villi within groups that move axially with the macroeddy reduces MML strength and absorptive enhancement relative to two dimensions. However, lateral villi motions create helical 3D particle trajectories that enhance absorption rate to the level of axially moving 2D leaflike villi. The 3D enhancements are associated with interesting fundamental adjustments to 2D micro-macro-motility coordination mechanisms and imply a refined potential for physiological or pharmaceutical control of intestinal absorption.

  15. 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.

  16. 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.

  17. 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.

  18. 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.

  19. 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.

  20. 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

  1. 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.

  2. 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...

  3. [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.

  4. 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

  5. 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

  6. 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

  7. Growth and maturation of villi in placentae from well-controlled diabetic women

    DEFF Research Database (Denmark)

    Mayhew, T M; Sørensen, Flemming Brandt; Klebe, J G

    1994-01-01

    Placentae from controls and two groups of diabetic women (one White classes A, B, C and the other classes D, F/R) were collected at 37-42 weeks of gestation. Tissue sections were analysed using stereological methods in order to quantify the growth and maturational status of villi. Birth and place......Placentae from controls and two groups of diabetic women (one White classes A, B, C and the other classes D, F/R) were collected at 37-42 weeks of gestation. Tissue sections were analysed using stereological methods in order to quantify the growth and maturational status of villi. Birth...... with group, mode of delivery and sex of newborn as the principal effects. Mean weights were similar in controls and diabetic groups. Diabetic placentae had a more voluminous fetal capillary bed of greater length, diameter and surface area. In addition, the diffusion distances across fetal plasma (erythrocyte...... on the fetal side of the diabetic placenta. They show that changes can affect the placentae of appropriate-for-age as well as large-for-age babies and provide no evidence that they increase with the severity and duration of diabetes....

  8. Placental Pathology of Zika Virus: Viral Infection of the Placenta Induces Villous Stromal Macrophage (Hofbauer Cell) Proliferation and Hyperplasia.

    Science.gov (United States)

    Rosenberg, Avi Z; Yu, Weiying; Hill, D Ashley; Reyes, Christine A; Schwartz, David A

    2017-01-01

    -The placenta is an important component in understanding the fetal response to intrauterine Zika virus infection, but the pathologic changes in this organ remain largely unknown. Hofbauer cells are fetal-derived macrophages normally present in the chorionic villous stroma. They have been implicated in a variety of physiological and pathologic processes, in particular involving infectious agents. -To characterize the fetal and maternal responses and viral localization in the placenta following Zika virus transmission to an 11 weeks' gestation fetus. The clinical course was notable for prolonged viremia in the mother and extensive neuronal necrosis in the fetus. The fetus was delivered at 21 weeks' gestation after pregnancy termination. -The placenta was evaluated by using immunohistochemistry for inflammatory cells (macrophages/monocytes [Hofbauer cells], B and T lymphocytes) and proliferating cells, and an RNA probe to Zika virus. The fetal brain and the placenta were previously found to be positive for Zika virus RNA by reverse transcription-polymerase chain reaction. -The placenta demonstrated prominently enlarged, hydropic chorionic villi with hyperplasia and focal proliferation of Hofbauer cells. The degree of Hofbauer cell hyperplasia gave an exaggerated immature appearance to the villi. No acute or chronic villitis, villous necrosis, remote necroinflammatory abnormalities, chorioamnionitis, funisitis, or hemorrhages were present. An RNA probe to Zika virus was positive in villous stromal cells, presumably Hofbauer cells. -Zika virus placental infection induces proliferation and prominent hyperplasia of Hofbauer cells in the chorionic villi but does not elicit villous necrosis or a maternal or fetal lymphoplasmacellular or acute inflammatory cell reaction.

  9. 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.

  10. Viral infection, proliferation, and hyperplasia of Hofbauer cells and absence of inflammation characterize the placental pathology of fetuses with congenital Zika virus infection.

    Science.gov (United States)

    Schwartz, David A

    2017-06-01

    Attention is increasingly focused on the potential mechanism(s) for Zika virus infection to be transmitted from an infected mother to her fetus. This communication addresses current evidence for the role of the placenta in vertical transmission of the Zika virus. Placentas from second and third trimester fetuses with confirmed intrauterine Zika virus infection were examined with routine staining to determine the spectrum of pathologic changes. In addition, immunohistochemical staining for macrophages and nuclear proliferation antigens was performed. Viral localization was identified using RNA hybridization. These observations were combined with the recent published results of placental pathology to increase the strength of the pathology data. Results were correlated with published data from experimental studies of Zika virus infection in placental cells and chorionic villous explants. Placentas from fetuses with congenital Zika virus infection are concordant in not having viral-induced placental inflammation. Special stains reveal proliferation and prominent hyperplasia of placental stromal macrophages, termed Hofbauer cells, in the chorionic villi of infected placentas. Zika virus infection is present in Hofbauer cells from second and third trimester placentas. Experimental studies and placentae from infected fetuses reveal that the spectrum of placental cell types infected with the Zika virus is broader during the first trimester than later in gestation. Inflammatory abnormalities of the placenta are not a component of vertical transmission of the Zika virus. The major placental response in second and third trimester transplacental Zika virus infection is proliferation and hyperplasia of Hofbauer cells, which also demonstrate viral infection.

  11. 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.

  12. 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

  13. Reduced placental telomere length during pregnancies complicated by intrauterine growth restriction.

    Directory of Open Access Journals (Sweden)

    Jérôme Toutain

    Full Text Available OBJECTIVES: Recent studies have shown that telomere length was significantly reduced in placentas collected at delivery from pregnancies complicated by intrauterine growth restriction secondary to placental insufficiency. Placental telomere length measurement during ongoing pregnancies complicated by intrauterine growth restriction has never been reported. This was the main objective of our study. METHODS: In our center, late chorionic villus samplings were performed between 18 and 37 weeks of amenorrhea in 24 subjects with severe intrauterine growth restriction (cases and in 28 subjects with other indications for prenatal diagnosis (controls. Placental insufficiency was assessed by histo-pathological examination. Relative measurement of telomere length was carried out prospectively by quantitative Fluorescent In Situ Hybridization using fluorescent Peptide Nucleic Acid probes on interphase nuclei obtained from long-term cultured villi and with an automated epifluorescent microscope. A quantitative Polymerase Chain Reaction technique was performed to confirm the quantitative Fluorescent In Situ Hybridization results. The number of copies of gene loci encoding the RNA template (hTERC and the catalytic subunit (hTERT of the enzyme complex telomerase were also estimated in these placentas by Fluorescent In Situ Hybridization. RESULTS: Mean fluorescence intensity of telomere probes estimated by quantitative Fluorescent In Situ Hybridization was significantly less for cases compared to controls (p<0.001. This result indicated that mean telomere length was significantly reduced in placentas during pregnancies complicated by intrauterine growth restriction. Reduced telomere length was confirmed by the quantitative Polymerase Chain Reaction technique. No copy number variation of the hTERC and hTERT loci was noticed for cases, or for controls. CONCLUSION: This study clearly demonstrates a reduction of placental telomere length in ongoing pregnancies

  14. The Placental Distal Villous Hypoplasia Pattern: Interobserver Agreement and Automated Fractal Dimension as an Objective Metric.

    Science.gov (United States)

    Mukherjee, Anika; Chan, Adrian D C; Keating, Sarah; Redline, Raymond W; Fritsch, Michael K; Machin, Geoffrey A; Cornejo-Palma, Daniel; de Nanassy, Joseph; El-Demellawy, Dina; von Dadelszen, Peter; Benton, Samantha J; Grynspan, David

    2016-01-01

    The distal villous hypoplasia (DVH) pattern is a placental correlate of fetal growth restriction. Because the pattern seems to involve less complexity than do appropriately developed placental villi, we postulated that it may be associated with lower fractal dimension-a mathematical measure of complexity. Our study objectives were to evaluate interobserver agreement related to the DVH pattern among expert pathologists and to determine whether pathologist classification of DVH correlates with fractal dimension. A study set of 30 images of placental parenchyma at ×4 magnification was created by a single pathologist from a digital slide archive. The images were graded for the DVH pattern according to pre-specified definitions and included 10 images graded as "no DVH" (grade  =  0), 10 with mild to moderate DVH (grade  =  1), and 10 with severe DVH (grade  =  2). The images were randomly sorted and shown to a panel of 4 international experts who similarly graded the images for DVH. Weighted kappas were calculated. For each image, fractal dimension was calculated by the Box Counting method. The correlation coefficient between (1) the averaged DVH scores obtained by the 5 pathologists and (2) fractal dimension was calculated. The mean weighted kappa score among the observers was 0.59 (range: 0.42-0.70). The correlation coefficient between fractal dimension and the averaged DVH score was -0.915 (P dimension and represents an objective measure for DVH.

  15. Hypoplastic left heart syndrome is associated with structural and vascular placental abnormalities and leptin dysregulation.

    Science.gov (United States)

    Jones, Helen N; Olbrych, Stephanie K; Smith, Kathleen L; Cnota, James F; Habli, Mounira; Ramos-Gonzales, Osniel; Owens, Kathryn J; Hinton, Andrea C; Polzin, William J; Muglia, Louis J; Hinton, Robert B

    2015-10-01

    Hypoplastic left heart syndrome (HLHS) is a severe cardiovascular malformation (CVM) associated with fetal growth abnormalities. Genetic and environmental factors have been identified that contribute to pathogenesis, but the role of the placenta is unknown. The purpose of this study was to systematically examine the placenta in HLHS with and without growth abnormalities. HLHS term singleton births were identified from a larger cohort when placenta tissue was available. Clinical data were collected from maternal and neonatal medical records, including anthropometrics and placental pathology reports. Placental tissues from cases and controls were analyzed to assess parenchymal morphology, vascular architecture and leptin signaling. HLHS cases (n = 16) and gestational age-matched controls (n = 18) were analyzed. Among cases, the average birth weight was 2993 g, including 31% that were small for gestational age. When compared with controls, gross pathology of HLHS cases demonstrated significantly reduced placental weight and increased fibrin deposition, while micropathology showed increased syncytial nuclear aggregates, decreased terminal villi, reduced vasculature and increased leptin expression in syncytiotrophoblast and endothelial cells. Placentas from pregnancies complicated by fetal HLHS are characterized by abnormal parenchymal morphology, suggesting immature structure may be due to vascular abnormalities. Increased leptin expression may indicate an attempt to compensate for these vascular abnormalities. Further investigation into the regulation of angiogenesis in the fetus and placenta may elucidate the causes of HLHS and associated growth abnormalities in some cases. Copyright © 2015 Elsevier Ltd. All rights reserved.

  16. 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.

  17. Control of human trophoblast function

    Directory of Open Access Journals (Sweden)

    Biondi Carla

    2007-02-01

    Full Text Available Abstract The trophoblast, i.e. the peripheral part of the human conceptus, exerts a crucial role in implantation and placentation. Both processes properly occur as a consequence of an intimate dialogue between fetal and maternal tissues, fulfilled by membrane ligands and receptors, as well as by hormone and local factor release. During blastocyst implantation, generation of distinct trophoblast cell types begins, namely the villous and the extravillous trophoblast, the former of which is devoted to fetal-maternal exchanges and the latter binds the placental body to the uterine wall. Physiological placentation is characterized by the invasion of the uterine spiral arteries by extravillous trophoblast cells arising from anchoring villi. Due to this invasion, the arterial structure is replaced by amorphous fibrinoid material and endovascular trophoblastic cells. This transformation establishes a low-resistance, high-capacity perfusion system from the radial arteries to the intervillous space, in which the villous tree is embedded. The physiology of pregnancy depends upon the orderly progress of structural and functional changes of villous and extravillous trophoblast, whereas a derangement of such processes can lead to different types of complications of varying degrees of gravity, including possible pregnancy loss and maternal life-threatening diseases. In this review we describe the mechanisms which regulate trophoblast differentiation, proliferation, migration and invasiveness, and the alterations in these mechanisms which lead to pathological conditions. Furthermore, based on the growing evidence that proper inflammatory changes and oxidative balance are needed for successful gestation, we explain the mechanisms by which agents able to influence such processes may be useful in the prevention and treatment of pregnancy disorders.

  18. 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.

  19. 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

  20. 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.

  1. 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...

  2. Growth and maturation of villi in placentae from well-controlled diabetic women

    DEFF Research Database (Denmark)

    Mayhew, T M; Sørensen, Flemming Brandt; Klebe, J G

    1994-01-01

    Placentae from controls and two groups of diabetic women (one White classes A, B, C and the other classes D, F/R) were collected at 37-42 weeks of gestation. Tissue sections were analysed using stereological methods in order to quantify the growth and maturational status of villi. Birth...... with group, mode of delivery and sex of newborn as the principal effects. Mean weights were similar in controls and diabetic groups. Diabetic placentae had a more voluminous fetal capillary bed of greater length, diameter and surface area. In addition, the diffusion distances across fetal plasma (erythrocyte...... on the fetal side of the diabetic placenta. They show that changes can affect the placentae of appropriate-for-age as well as large-for-age babies and provide no evidence that they increase with the severity and duration of diabetes....

  3. 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.

  4. 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.

  5. 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

  6. 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

  7. 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....

  8. 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.

  9. 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.

  10. 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.

  11. 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...

  12. 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

  13. Development of a simple, cost-effective, semi-correlative light and electron microscopy method to allow the immunoelectron localisation of non-uniformly distributed placental proteins.

    Science.gov (United States)

    Viall, C A; Holloway, H; Chen, Q; Stone, P R; Chamley, L W

    2014-03-01

    Immunoelectron microscopy is wrought with technical limitations that complicate its use. However, advances in correlative light and electron microscopy have recently lead to improvements in this field. We report the development of a semi-correlative approach to investigate the ultrastructural location of an antiphospholipid antibody within the syncytiotrophoblast. This method offers several advantages over existing methodologies, since it preserves antigenicity, shows good immunolabel penetrability and does not require specialized equipment. The use of a pre-embedding screen has also allowed us to target individual placental villi and overcome sampling limitations of the electron microscope. This simple, cost-effective method is likely to find widespread application in placental research. Copyright © 2014 Elsevier Ltd. All rights reserved.

  14. 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...

  15. 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.

  16. Prenatal depression and stress - risk factors for placental pathology and spontaneous abortion.

    Science.gov (United States)

    Marinescu, Ileana P; Foarfă, Maria Camelia; Pîrlog, Mihail Cristian; Turculeanu, Adriana

    2014-01-01

    Prenatal stress and depression affects 10-25% of pregnant women and is associated with disruption of fetal neurodevelopment, higher rates of placental abnormalities, preeclampsia, spontaneous abortion, or preterm birth. Markers of genetic vulnerability are catechol-O-methyltransferase, monoamine oxidase-A, variation of serotonin transporters, low levels of dopamine-beta-hydroxylase, and brain derived neurotrophic factor Val66Met (BDNF), while hyperactivity of HPA (hypothalamic-pituitary-adrenal) axis and massive release of endogenous cortisol, regulated by metalloproteinase-1, -2, -3 and -9, and are involved both in depressive symptoms and neurodevelopmental abnormalities in fetus. In women with prenatal stress and depression which suffered spontaneous abortion were observed placental abnormalities as regular shape and necrotic villi, decidua with large areas of necrosis, acute inflammation and effusion areas correlated with increase in proinflammatory factors, immune deficit and infections, hyaline type fibrosis, intervilos and deciduous intense hemorrhage, associated with increase of vascular endothelial growth factor. Taking into account the important societal and economic costs becomes important for an interdisciplinary approach, in which pregnancy and its risks are a central point for women mental health.

  17. 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

  18. 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.

  19. 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.

  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. 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

  2. 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...

  3. 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...

  4. Clinical associations with a placental diagnosis of delayed villous maturation: a retrospective study.

    LENUS (Irish Health Repository)

    Higgins, Mary

    2013-02-01

    Delayed villous maturation (DVM) is a spectrum of placental disease characterized by decreased tertiary villus formation, reduced vasculosyncytial membrane formation, and, in its more severe forms, increased large bullous villi. In some series it has been associated with an increased risk of stillbirth in the late third trimester, but overall there are few data on its significance. The aim of this study was to assess perinatal factors associated with, and the clinical significance of, the finding of DVM on placental histology. This was a retrospective study investigating all pregnancies with DVM diagnosed on placental histology in a tertiary level unit between December 2001 and August 2006. Over a 6-year period, 2915 placentas were triaged for histopathological assessment, representing 6.1% of all 48 054 deliveries in this time period. One hundred ninety (6.3%) of these selected cases showed DVM. Fifteen placentas from infants with less than 34 completed weeks of gestation were excluded, leaving 175 for further analysis. When compared with controls matched for gestation and delivering within the same time period (n  =  175), DVM was significantly associated with pregestational diabetes (8% vs 2.8%, P < .05; relative risk 2.8 [95% confidence interval 1.03-7.6]), gestational diabetes (8.6% vs 3.4%, P < 0.05; relative risk 2.5 [95% confidence interval 0.99-6.3]), and prenatal or intrapartum intrauterine death (8.6% vs 0%, P < 0.05). Delayed villous maturation is associated with both gestational and pregestational diabetes mellitus and with perinatal death.

  5. 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...

  6. 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.

  7. IFPA Senior Award Lecture: making sense of pre-eclampsia - two placental causes of preeclampsia?

    Science.gov (United States)

    Redman, C W; Sargent, I L; Staff, A C

    2014-02-01

    Incomplete spiral artery remodelling is the first of two stages of pre-eclampsia, typically of early onset. The second stage comprises dysregulated uteroplacental perfusion and placental oxidative stress. Oxidatively stressed syncytiotrophoblast (STB) over-secretes proteins that perturb maternal angiogenic balance and are considered to be pre-eclampsia biomarkers. We propose that, in addition and more fundamentally, these STB-derived proteins are biomarkers of a cellular (STB) stress response, which typically involves up-regulation of some proteins and down-regulation of others (positive and negative stress proteins respectively). Soluble vascular growth factor receptor-1 (sVEGFR-1) and reduced growth factor (PlGF) then exemplify positive and negative STB stress response proteins in the maternal circulation. Uncomplicated term pregnancy is associated with increasing sVEGFR-1 and decreasing PlGF, which can be interpreted as evidence of increasing STB stress. STB pathology, at or after term (for example focal STB necrosis) demonstrates this stress, with or without pre-eclampsia. We review the evidence that when placental growth reaches its limits at term, terminal villi become over-crowded with diminished intervillous pore size impeding intervillous perfusion with increasing intervillous hypoxia and STB stress. This type of STB stress has no antecedent pathology, so the fetuses are well-grown, as typifies late onset pre-eclampsia, and prediction is less effective than for the early onset syndrome because STB stress is a late event. In summary, abnormal placental perfusion and STB stress contribute to the pathogenesis of early and late onset pre-eclampsia. But the former has an extrinsic cause - poor placentation, whereas the latter has an intrinsic cause, 'microvillous overcrowding', as placental growth reaches its functional limits. This model explains important features of late pre-eclampsia and raises questions of how antecedent medical risk factors such as

  8. Generation of an induced pluripotent stem cell line from chorionic villi of a Turner syndrome spontaneous abortion

    Directory of Open Access Journals (Sweden)

    Shagufta Parveen

    2017-03-01

    Full Text Available A major cause of spontaneous abortions is chromosomal abnormality of foetal cells. We report the generation of an induced pluripotent stem cell line from the fibroblasts isolated from chorionic villi of an early spontaneously aborted foetus with Turner syndrome. The Turner syndrome villus induced pluripotent stem cell line is transgene free, retains the original XO karyotype, expresses pluripotency markers and undergoes trilineage differentiation. This pluripotent stem cell model of Turner syndrome should serve as a tool to study the developmental abnormalities of foetus and placenta that lead to early embryo lethality and profound symptoms like infertility in 45 XO survivors.

  9. The term basal plate of the human placenta as a source of functional extravillous trophoblast cells.

    Science.gov (United States)

    Borbely, Alexandre U; Sandri, Silvana; Fernandes, Isabella R; Prado, Karen M; Cardoso, Elaine C; Correa-Silva, Simone; Albuquerque, Renata; Knöfler, Martin; Beltrão-Braga, Patricia; Campa, Ana; Bevilacqua, Estela

    2014-01-28

    Extravillous trophoblast (EVT) cells are of pivotal importance in human embryo implantation and homeostasis of the maternal fetal interface. Invasion of the endometrium by EVT contributes to placental anchorage, spiral artery remodeling, immunological defense, tolerogenic responses, and several collaborative cross talks involved in establishing and maintaining a successful pregnancy. We report here an improved protocol for the isolation of fully differentiated EVT cells from the basal plate of the human term placenta. The basal plate was carefully dissected from the villous tissue and the amniochorion membrane prior to enzymatic digestion. Term basal EVT cells were isolated using a 30 and 60% Percoll gradient. A panel of markers and characteristics of the isolated cells were used to confirm the specificity and efficiency of the method so that their potential as an investigative tool for placental research could be ascertained. Isolated cells were immunoreactive for cytokeratin-7 (CK-7), placental growth factor, placental alkaline phosphatase, human leukocyte antigen G1 (HLA-G1), and α1 and α5 integrins, similarly to the EVT markers from first trimester placental villi. Around 95% of the isolated cells labeled positively for CK-7 and 82% for HLA-G1. No significant change in viability was observed during 48 h of EVT culture as indicated by propidium iodide incorporation and trypan blue test exclusion. Genes for metalloproteinases MMP-2 and MMP9 (positive regulators of trophoblast invasiveness) were expressed up to 48 h of culturing, as also the gelatinolytic activity of the isolated cells. Transforming growth factor (TGF)-beta, which inhibits proliferation, migration, and invasiveness of first-trimester EVT cells, also reduced invasion of isolated term EVT cells in transwell assays, whereas epidermal growth factor was a positive modulator. Term basal plate may be a viable source of functional EVT cells that is an alternative to villous explant-derived EVT cells and

  10. IFPA Meeting 2010 Workshop Report I: Immunology; ion transport; epigenetics; vascular reactivity; epitheliochorial placentation; proteomics.

    Science.gov (United States)

    Abad, C; Antczak, D F; Carvalho, J; Chamley, L W; Chen, Q; Daher, S; Damiano, A E; Dantzer, V; Díaz, P; Dunk, C E; Daly, E; Escudero, C; Falcón, B; Guillomot, M; Han, Y W; Harris, L K; Huidobro-Toro, J P; Illsley, N; Jammes, H; Jansson, T; Johnson, G A; Kfoury, J R; Marín, R; Murthi, P; Novakovic, B; Myatt, L; Petroff, M G; Pereira, F T V; Pfarrer, C; Redman, C W G; Rice, G; Saffery, R; Tolosa, J M; Vaillancourt, C; Wareing, M; Yuen, R; Lash, G E

    2011-03-01

    Workshops are an important part of the IFPA annual meeting. At IFPA Meeting 2010 there were twelve themed workshops, six of which are summarized in this report. 1. The immunology workshop focused on normal and pathological functions of the maternal immune system in pregnancy. 2. The transport workshop dealt with regulation of ion and water transport across the syncytiotrophoblast of human placenta. 3. The epigenetics workshop covered DNA methylation and its potential role in regulating gene expression in placental development and disease. 4. The vascular reactivity workshop concentrated on methodological approaches used to study placental vascular function. 5. The workshop on epitheliochorial placentation covered current advances from in vivo and in vitro studies of different domestic species. 6. The proteomics workshop focused on a variety of techniques and procedures necessary for proteomic analysis and how they may be implemented for placental research. Copyright © 2011 Elsevier Ltd. All rights reserved.

  11. 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.

  12. Placental iron uptake and its regulation

    NARCIS (Netherlands)

    M. Bierings (Marc)

    1989-01-01

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

  13. Hans Strahl's pioneering studies in comparative placentation

    DEFF Research Database (Denmark)

    Carter, Anthony Michael; Mess, A

    2010-01-01

    Hans Strahl, a contemporary of Duval and Hubrecht, made many important contributions to comparative placentation. Despite this he is not well known and some of his original observations tend to be attributed to later authors. Strahl published a classification of placental types based on their sha...

  14. 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.

  15. 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)

    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 rumina...

  16. Plasmodium vivax adherence to placental glycosaminoglycans.

    Directory of Open Access Journals (Sweden)

    Kesinee Chotivanich

    Full Text Available Plasmodium vivax infections seldom kill directly but do cause indirect mortality by reducing birth weight and causing abortion. Cytoadherence and sequestration in the microvasculature are central to the pathogenesis of severe Plasmodium falciparum malaria, but the contribution of cytoadherence to pathology in other human malarias is less clear.The adherence properties of P. vivax infected red blood cells (PvIRBC were evaluated under static and flow conditions.P. vivax isolates from 33 patients were studied. None adhered to immobilized CD36, ICAM-1, or thrombospondin, putative ligands for P. falciparum vascular cytoadherence, or umbilical vein endothelial cells, but all adhered to immobilized chondroitin sulphate A (CSA and hyaluronic acid (HA, the receptors for adhesion of P. falciparum in the placenta. PvIRBC also adhered to fresh placental cells (N = 5. Pre-incubation with chondroitinase prevented PvIRBC adherence to CSA, and reduced binding to HA, whereas preincubation with hyaluronidase prevented adherence to HA, but did not reduce binding to CSA significantly. Pre-incubation of PvIRBC with soluble CSA and HA reduced binding to the immobilized receptors and prevented placental binding. PvIRBC adhesion was prevented by pre-incubation with trypsin, inhibited by heparin, and reduced by EGTA. Under laminar flow conditions the mean (SD shear stress reducing maximum attachment by 50% was 0.06 (0.02 Pa but, having adhered, the PvIRBC could then resist detachment by stresses up to 5 Pa. At 37 °C adherence began approximately 16 hours after red cell invasion with maximal adherence at 30 hours. At 39 °C adherence began earlier and peaked at 24 hours.Adherence of P. vivax-infected erythrocytes to glycosaminoglycans may contribute to the pathogenesis of vivax malaria and lead to intrauterine growth retardation.

  17. Development of Non-Viral, Trophoblast-Specific Gene Delivery for Placental Therapy.

    Directory of Open Access Journals (Sweden)

    Noura Abd Ellah

    Full Text Available Low birth weight is associated with both short term problems and the fetal programming of adult onset diseases, including an increased risk of obesity, diabetes and cardiovascular disease. Placental insufficiency leading to intrauterine growth restriction (IUGR contributes to the prevalence of diseases with developmental origins. Currently there are no therapies for IUGR or placental insufficiency. To address this and move towards development of an in utero therapy, we employ a nanostructure delivery system complexed with the IGF-1 gene to treat the placenta. IGF-1 is a growth factor critical to achieving appropriate placental and fetal growth. Delivery of genes to a model of human trophoblast and mouse placenta was achieved using a diblock copolymer (pHPMA-b-pDMAEMA complexed to hIGF-1 plasmid DNA under the control of trophoblast-specific promoters (Cyp19a or PLAC1. Transfection efficiency of pEGFP-C1-containing nanocarriers in BeWo cells and non-trophoblast cells was visually assessed via fluorescence microscopy. In vivo transfection and functionality was assessed by direct placental-injection into a mouse model of IUGR. Complexes formed using pHPMA-b-pDMAEMA and CYP19a-923 or PLAC1-modified plasmids induce trophoblast-selective transgene expression in vitro, and placental injection of PLAC1-hIGF-1 produces measurable RNA expression and alleviates IUGR in our mouse model, consequently representing innovative building blocks towards human placental gene therapies.

  18. Placental histopathology of congenital syphilis.

    Science.gov (United States)

    Sheffield, Jeanne S; Sánchez, Pablo J; Wendel, George D; Fong, David W I; Margraf, Linda R; Zeray, Fiker; McIntire, Donald D; Barton Rogers, Beverly

    2002-07-01

    To evaluate the contribution of placental histopathology to the diagnosis of congenital syphilis. From January 1, 1986, through December 31, 1998, all pregnant women presenting to a large, urban Dallas County labor and delivery unit with untreated syphilis at delivery and who had placental evaluation performed were identified. Women were clinically staged, and the infants were evaluated for congenital syphilis using a standard protocol. Each placenta was evaluated by two independent pathologists. Histologic characteristics of the placenta related to congenital syphilis in live-born and stillborn infants were then analyzed. Sixty-seven women met the study criteria: 33 (49%) stillborn and 18 (27%) live-born infants with congenital syphilis, 15 (22%) uninfected live-born infants, and one uninfected stillborn fetus diagnosed by current criteria. There were no differences between the groups with regard to demographic characteristics, prenatal care, or stage of syphilis. Stillborn infants were more likely to deliver preterm (P gestational age, histopathology revealed necrotizing funisitis, villous enlargement, and acute villitis associated with congenital syphilis. Erythroblastosis was more common in stillborn infants with congenital syphilis than all live-born infants (odds ratio 16, 95% confidence interval 1, 370). The addition of histologic evaluation to conventional diagnostic evaluations improved the detection rate for congenital syphilis from 67% to 89% in live-born infants, and 91% to 97% in stillborn infants. Our results show that histopathologic examination of the placenta is a valuable adjunct to the contemporary diagnostic criteria used to diagnose congenital syphilis.

  19. Paternally expressed, imprinted insulin-like growth factor-2 in chorionic villi correlates significantly with birth weight.

    Directory of Open Access Journals (Sweden)

    Charalambos Demetriou

    Full Text Available Fetal growth involves highly complex molecular pathways. IGF2 is a key paternally expressed growth hormone that is critical for in utero growth in mice. Its role in human fetal growth has remained ambiguous, as it has only been studied in term tissues. Conversely the maternally expressed growth suppressor, PHLDA2, has a significant negative correlation between its term placental expression and birth weight.The aim of this study is to address the role in early gestation of expression of IGF1, IGF2, their receptors IGF1R and IGF2R, and PHLDA2 on term birth weight.Real-time quantitative PCR was used to investigate mRNA expression of IGF1, IGF2, IGF1R, IGF2R and PHLDA2 in chorionic villus samples (CVS (n = 260 collected at 11-13 weeks' gestation. Expression was correlated with term birth weight using statistical package R including correction for several confounding factors.Transcript levels of IGF2 and IGF2R revealed a significant positive correlation with birth weight (0.009 and 0.04, respectively. No effect was observed for IGF1, IGF1R or PHLDA2 and birth weight. Critically, small for gestational age (SGA neonates had significantly lower IGF2 levels than appropriate for gestational age neonates (p = 3.6 × 10(-7.Our findings show that IGF2 mRNA levels at 12 weeks gestation could provide a useful predictor of future fetal growth to term, potentially predicting SGA babies. SGA babies are known to be at a higher risk for type 2 diabetes. This research reveals an imprinted, parentally driven rheostat for in utero growth.

  20. Placental transfer of radiopharmaceuticals and dosimetry in pregnancy

    Energy Technology Data Exchange (ETDEWEB)

    Russell, J.R. [Univ. of Maryland, Baltimore, MD (United States); Stabin, M.G.; Sparks, R.B. [Oak Ridge Inst. for Science and Education, TN (United States)

    1999-01-01

    The calculation of radiation dose estimates to the fetus is often important in nuclear medicine. To obtain the best estimates of radiation dose to the fetus, the best biological and physical models should be employed. In this paper, after identification of radiopharmaceuticals often administered to women of childbearing age, the most recent data available on the placental crossover of these radiopharmaceuticals was used (with standard kinetic models describing the maternal distribution and retention and with the best available physical models) to obtain fetal dose estimates for these radiopharmaceuticals were identified as those most commonly administered to women of childbearing years. The literature yielded information on placental crossover of 15 radiopharmaceuticals, from animal or human data. Radiation dose estimates are presented in early pregnancy and at 3-, 6-, and 9-months gestation for these radiopharmaceuticals, as well as for many others used in nuclear medicine (the latter considering only maternal organ contributions to fetal dose). 46 refs., 1 fig., 5 tabs.

  1. Placental Extracellular Vesicles and Feto-Maternal Communication

    Science.gov (United States)

    Tong, M.; Chamley, L.W.

    2015-01-01

    The human placenta is an anatomically unique structure that extrudes a variety of extracellular vesicles into the maternal blood (including syncytial nuclear aggregates, microvesicles, and nanovesicles). Large quantities of extracellular vesicles are produced by the placenta in both healthy and diseased pregnancies. Since their first description more than 120 years ago, placental extracellular vesicles are only now being recognized as important carriers for proteins, lipids, and nucleic acids, which may play a crucial role in feto-maternal communication. Here, we summarize the current literature on the cargos of placental extracellular vesicles and the known effects of such vesicles on maternal cells/systems, especially those of the maternal immune and vascular systems. PMID:25635060

  2. Placental Inflammatory Changes and Bacterial Infection in Premature Neonates with Respiratory Failure

    Directory of Open Access Journals (Sweden)

    S. A. Perepelitsa

    2012-01-01

    Full Text Available Objective: to reveal a relationship of placental inflammatory changes to bacterial infection in premature neonates with respiratory failure. Material and methods. Bronchoalveolar aspirate was bacteriologically studied in 157 premature neonates with respiratory distress syndrome (NRDS; the total and differential leukocyte counts were measured in their peripheral blood. The levels of the cytokines IL-1^3, IL-4, IL-6, and TNF-a were studied in different biological fluids of mothers and their babies; the placentas were also morphologically examined. Results. An analysis of bacterial cultures from the tracheobronchial tree revealed no growth of bacterial microflora in 61.8% of cases, Enterococcus faecalis and Staphylococcus epidermidis were isolated in 6.4 and 8.3% of the infants, respectively; Staphylococcus haemolyticus, Staphylococcus capitis, Enterobacter agglomerans, and hemolytic group A Streptococcus were seen in 1.9% each; moreover, 1.3% of the newborn infants were found to have Bacillus spp., Staphylococcus aureus, Escherichia coli, Acinetobacter spp., and Serratia marcescens. Other microorganisms and a microbial association were encountered in 8.9% of cases. Placental morphological examination revealed different inflammatory changes concurrent with chronic and acute placental insufficiency. The investigation demonstrated that the maternal peripheral plasma levels of IL-1^, IL-4, IL-6, and TNF-a were within the physiological range at the end of the first period of delivery. The amniotic fluid displayed elevated IL-6 and TNF-a concentrations and normal IL-4 and IL-1e levels, suggesting that there was an intrauterine inflammatory process. Conclusion. Premature birth is associated with various placental inflammatory changes, which causes intrauterine stimulation of macrophages in the chorionic villi. Specific immune defense mechanisms that prevent the development of a fetal infectious process, i.e. the maternal infectious process, may induce

  3. Hyperemesis gravidarum and placental dysfunction disorders.

    Science.gov (United States)

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

    2016-11-25

    Evidence about the consequence of hyperemesis gravidarum (HG) on pregnancy outcomes is still inconclusive. In this study, we evaluated if occurrence of hyperemesis gravidarum is associated with placental dysfunction disorders and neonatal outcomes. A prospective cohort study was conducted in a maternal and child health primary care referral center, Budi Kemuliaan Hospital and its branch, in Jakarta, Indonesia. 2252 pregnant women visiting the hospital for regular antenatal care visits from July 2012 until October 2014 were included at their first clinic visit. For women without, with mild and with severe hyperemesis, placental dysfunction disorders (gestational hypertension, preeclampsia (PE), stillbirth, miscarriage), neonatal outcomes (birth weight, small for gestational age (SGA), low birth weight (LBW), Apgar score at 5 min, gestational age at delivery) and placental outcomes (placental weight and placental-weight-to-birth-weight ratio (PW/BW ratio)) were studied. Compared to newborns of women without hyperemesis, newborns of women with severe hyperemesis had a 172 g lower birth weight in adjusted analysis (95%CI -333.26; -10.18; p = 0.04). There were no statistically significant effects on placental dysfunction disorders or other neonatal outcome measures. The results of our study suggest that hyperemesis gravidarum does not seem to induce placental dysfunction disorders, but does, if severe lead to lower birth weight.

  4. Gestational diabetes is associated with changes in placental microbiota and microbiome.

    Science.gov (United States)

    Bassols, Judit; Serino, Matteo; Carreras-Badosa, Gemma; Burcelin, Rémy; Blasco-Baque, Vincent; Lopez-Bermejo, Abel; Fernandez-Real, José-Manuel

    2016-12-01

    The human microbiota is a modulator of the immune system. Variations in the placental microbiota could be related with pregnancy disorders. We profiled the placental microbiota and microbiome in women with gestational diabetes (GDM) and studied its relation to maternal metabolism and placental expression of anti-inflammatory cytokines. Placental microbiota and microbiome and expression of anti-inflammatory cytokines (IL10, TIMP3, ITGAX, and MRC1MR) were analyzed in placentas from women with GDM and from control women. Fasting insulin, glucose, O'Sullivan glucose, lipids, and blood cell counts were assessed at second and third trimester of pregnancy. Bacteria belonging to the Pseudomonadales order and Acinetobacter genus showed lower relative abundance in women with GDM compared to control (P microbiota profile and microbiome is present in GDM. Acinetobacter has been recently shown to induce IL-10 in mice. GDM could constitute a state of placental microbiota-driven altered immunologic tolerance, making placental microbiota a new target for therapy in GDM.

  5. 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.

  6. Evolution of factors affecting placental oxygen transfer

    DEFF Research Database (Denmark)

    Carter, A M

    2009-01-01

    states, are more amenable to analysis. This is exemplified by factors contributing, respectively, to blood oxygen affinity and placental diffusing capacity. Comparative genomics has given fresh insight into the evolution of the beta-globin gene complex. In higher primates, duplication of an embryonic...... that epitheliochorial placentation is a derived state and that the common ancestor of placental mammals probably had a placenta of the endotheliochorial type. Where evolutionary trends are implied for mammals as a whole or within orders such as primates they often accompany a switch in reproductive strategy...

  7. Treatment of Human Placental Choriocarcinoma Cells with Formaldehyde and Benzene Induced Growth and Epithelial Mesenchymal Transition via Induction of an Antioxidant Effect

    Directory of Open Access Journals (Sweden)

    Hae-Miru Lee

    2017-07-01

    Full Text Available Cigarette smoke (CS causes about 480,000 deaths each year worldwide, and it is well-known to have harmful effects on the human body, leading to heart disease, stroke, lung cancer, and cardiovascular problems. In this study, the effects of formaldehyde (FA and benzene (Bz, the main components of CS, on cell proliferation and epithelial mesenchymal transition (EMT of JEG-3 human choriocarcinoma cells were examined to confirm the relationship between CS components and placenta carcinoma. Upon MTT assay, FA (10−8 M to 10−5 M and Bz (10−11 M to 10−8 M increased JEG-3 cell proliferation. Western blot assay revealed that the protein expression of cyclin D1 and E1 increased, while the levels of p21 and p27 were reduced following treatment. In Scratch assay, FA (10−8 M and 10−5 M and Bz (10−11 M and 10−8 M increased migration of JEG-3 cells at 24 h and 48 h compared with that at 0 h. In addition, the expression of the epithelial marker, E-cadherin, was significantly decreased, while the expression of the mesenchymal marker, N-cadherin, was significantly increased by FA (10−8 M and 10−5 M and Bz (10−11 M and 10−8 M. snail and slug transcriptional factors were associated with EMT, which were also up-regulated by FA and Bz, indicating that FA and Bz lead to an increase in the EMT process in JEG-3 choriocarcinoma cells. We further evaluated reactive oxygen species (ROS and activation of antioxidant effect using dichlorofluorescin diacetate (DCFH-DA and Western blot assay. FA and Bz increased the ROS production and an antioxidant related marker, Nrf2, in JEG-3 cells. However, eIF2α levels were reduced by FA and Bz via activation of the antioxidant reaction. Taken together, these results indicated that FA and Bz induce the growth and migration of human choriocarcinoma cells via regulation of the cell cycle and EMT and activation of ROS and antioxidant related markers.

  8. Intravenous xenotransplantation of human placental mesenchymal stem cells to rats: comparative analysis of homing in rat brain in two models of experimental ischemic stroke.

    Science.gov (United States)

    Kholodenko, I V; Yarygin, K N; Gubsky, L V; Konieva, A A; Tairova, R T; Povarova, O V; Kholodenko, R V; Burunova, V V; Yarygin, V N; Skvortsova, V I

    2012-11-01

    Mesenchymal stem cells from human placenta obtained after term natural delivery were cultured and labeled with vital dye Dil of magnetic fluorescing microparticles. The labeled cells were transplanted intravenously to rats with occlusion of the median cerebral artery. Penetration of cells through the brain-blood barrier and their distribution in the brain of experimental animals were studied on serial cryostat sections. Two models of cerebral artery occlusion associated with different traumatic consequences were used. The efficiency of crossing the blood-brain barrier by transplanted cells, the number of mesenchymal cells attaining the ischemic focus and neurogenic zones, and the time of death of transplanted cells largely depended on the degree and nature of injury to the central nervous system, which should be taken into account when planning the experiments for evaluation of the effects of cell therapy on the models of neurological diseases and in clinical studies in the field of regenerative neurology.

  9. Characterization of VAR2CSA-deficient Plasmodium falciparum-infected erythrocytes selected for adhesion to the BeWo placental cell line

    Directory of Open Access Journals (Sweden)

    Brown Graham V

    2008-03-01

    Full Text Available Abstract Background Malaria in pregnancy is characterized by accumulation of infected erythrocytes (IE in the placenta. The key ligand identified as mediating this process is a Plasmodium falciparum erythrocyte membrane protein 1 family member, termed VAR2CSA. VAR2CSA appears to be the main ligand responsible for adhesion to chondroitin sulphate A (CSA. Whether other PfEMP1 molecules can also mediate placental adhesion, independent of CSA binding, is unclear. Methods The parasite line CS2 carrying a disrupted var2csa gene (CS2KO was selected for adhesion to the BeWo choriocarcinoma cell line, which has been proposed as a model for placental malaria. The selected and control IE were tested for adhesion to placental sections and flow cytometry was used to measure recognition of IE by three serum sets from malaria-exposed men and women. Results Wild-type CS2 adhere to BeWo and placental tissue via CSA. CS2KO IE were successfully selected for adhesion to BeWo, and adhered by a CSA-independent mechanism. They bound to immobilized ICAM-1 and CD36. BeWo-selected CS2KO bound at moderate levels to placental sections, but most binding was to placental villi rather than to the syncytiotrophoblast to which IE adherence occurs in vivo. This binding was inhibited by a blocking antibody to CD36 but not to ICAM-1. As expected, sera from malaria-exposed adults recognized CS2 IE in a gender and parity dependent manner. In one serum set, there was a similar but less pronounced pattern of antibody binding to selected CS2KO IE, but this was not seen in two others. One var gene, It4var19, was particularly abundant in the selected line and was detected as full length transcripts in BeWo-selected IE, but not unselected CS2KO. Conclusion This study suggests that IE with characteristics similar to the CS2KO have a limited role in the pathogenesis of placental malaria. VAR2CSA appear to be the major ligand for placental adhesion, and could be the basis for a vaccine

  10. Placental genetic variations in circadian clock-related genes increase the risk of placental abruption

    OpenAIRE

    Chunfang, Qiu; GELAYE, Bizu; Denis, Marie; Tadesse, Mahlet G.; Enquobahrie, Daniel A.; Ananth, Cande V.; Pacora, Percy N; Salazar, Manuel; Sanchez, Sixto E.; Williams, Michelle A

    2016-01-01

    The genetic architecture of placental abruption (PA) remains poorly understood. We examined variations in SNPs of circadian clock-related genes in placenta with PA risk. We also explored placental and maternal genomic contributions to PA risk. Placental genomic DNA samples were isolated from 280 PA cases and 244 controls. Genotyping was performed using the Illumina Cardio-MetaboChip. We examined 116 SNPs in 13 genes known to moderate circadian rhythms. Logistic regression models were fit to e...

  11. Generation of an induced pluripotent stem cell line from chorionic villi of a Turner syndrome spontaneous abortion.

    Science.gov (United States)

    Parveen, Shagufta; Panicker, M M; Gupta, Pawan Kumar

    2017-03-01

    A major cause of spontaneous abortions is chromosomal abnormality of foetal cells. We report the generation of an induced pluripotent stem cell line from the fibroblasts isolated from chorionic villi of an early spontaneously aborted foetus with Turner syndrome. The Turner syndrome villus induced pluripotent stem cell line is transgene free, retains the original XO karyotype, expresses pluripotency markers and undergoes trilineage differentiation. This pluripotent stem cell model of Turner syndrome should serve as a tool to study the developmental abnormalities of foetus and placenta that lead to early embryo lethality and profound symptoms like infertility in 45 XO survivors. Copyright © 2016 The Authors. Published by Elsevier B.V. All rights reserved.

  12. Evolutionary perspectives into placental biology and disease.

    Science.gov (United States)

    Chuong, Edward B; Hannibal, Roberta L; Green, Sherril L; Baker, Julie C

    2013-12-01

    In all mammals including humans, development takes place within the protective environment of the maternal womb. Throughout gestation, nutrients and waste products are continuously exchanged between mother and fetus through the placenta. Despite the clear importance of the placenta to successful pregnancy and the health of both mother and offspring, relatively little is understood about the biology of the placenta and its role in pregnancy-related diseases. Given that pre- and peri-natal diseases involving the placenta affect millions of women and their newborns worldwide, there is an urgent need to understand placenta biology and development. Here, we suggest that the placenta is an organ under unique selective pressures that have driven its rapid diversification throughout mammalian evolution. The high divergence of the placenta complicates the use of non-human animal models and necessitates an evolutionary perspective when studying its biology and role in disease. We suggest that diversifying evolution of the placenta is primarily driven by intraspecies evolutionary conflict between mother and fetus, and that many pregnancy diseases are a consequence of this evolutionary force. Understanding how maternal-fetal conflict shapes both basic placental and reproductive biology - in all species - will provide key insights into diseases of pregnancy.

  13. Evolutionary perspectives into placental biology and disease

    Directory of Open Access Journals (Sweden)

    Edward B. Chuong

    2013-12-01

    Full Text Available In all mammals including humans, development takes place within the protective environment of the maternal womb. Throughout gestation, nutrients and waste products are continuously exchanged between mother and fetus through the placenta. Despite the clear importance of the placenta to successful pregnancy and the health of both mother and offspring, relatively little is understood about the biology of the placenta and its role in pregnancy-related diseases. Given that pre- and peri-natal diseases involving the placenta affect millions of women and their newborns worldwide, there is an urgent need to understand placenta biology and development. Here, we suggest that the placenta is an organ under unique selective pressures that have driven its rapid diversification throughout mammalian evolution. The high divergence of the placenta complicates the use of non-human animal models and necessitates an evolutionary perspective when studying its biology and role in disease. We suggest that diversifying evolution of the placenta is primarily driven by intraspecies evolutionary conflict between mother and fetus, and that many pregnancy diseases are a consequence of this evolutionary force. Understanding how maternal–fetal conflict shapes both basic placental and reproductive biology – in all species – will provide key insights into diseases of pregnancy.

  14. Trypanosoma cruzi (Chagas' disease agent reduces HIV-1 replication in human placenta

    Directory of Open Access Journals (Sweden)

    Cappa Stella

    2008-07-01

    Full Text Available Abstract Background Several factors determine the risk of HIV mother-to-child transmission (MTCT, such as coinfections in placentas from HIV-1 positive mothers with other pathogens. Chagas' disease is one of the most endemic zoonoses in Latin America, caused by the protozoan Trypanosoma cruzi. The purpose of the study was to determine whether T. cruzi modifies HIV infection of the placenta at the tissue or cellular level. Results Simple and double infections were carried out on a placental histoculture system (chorionic villi isolated from term placentas from HIV and Chagas negative mothers and on the choriocarcinoma BeWo cell line. Trypomastigotes of T. cruzi (VD lethal strain, either purified from mouse blood or from Vero cell cultures, 24 h-supernatants of blood and cellular trypomastigotes, and the VSV-G pseudotyped HIV-1 reporter virus were used for the coinfections. Viral transduction was evaluated by quantification of luciferase activity. Coinfection with whole trypomastigotes, either from mouse blood or from cell cultures, decreased viral pseudotype luciferase activity in placental histocultures. Similar results were obtained from BeWo cells. Supernatants of stimulated histocultures were used for the simultaneous determination of 29 cytokines and chemokines with the Luminex technology. In histocultures infected with trypomastigotes, as well as in coinfected tissues, IL-6, IL-8, IP-10 and MCP-1 production was significantly lower than in controls or HIV-1 transducted tissue. A similar decrease was observed in histocultures treated with 24 h-supernatants of blood trypomastigotes, but not in coinfected tissues. Conclusion Our results demonstrated that the presence of an intracellular pathogen, such as T. cruzi, is able to impair HIV-1 transduction in an in vitro system of human placental histoculture. Direct effects of the parasite on cellular structures as well as on cellular/viral proteins essential for HIV-1 replication might influence

  15. 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.

  16. A novel bridge between oxidative stress and immunity: the interaction between hydrogen peroxide and human leukocyte antigen G in placental trophoblasts during preeclampsia.

    Science.gov (United States)

    Zhou, Xue; Zhang, Guo-ying; Wang, Jue; Lu, Shou-lian; Cao, Jun; Sun, Li-zhou

    2012-05-01

    The aim of this study was to investigate a possible association between hydrogen peroxide and human leukocyte antigen G (HLA-G) in preeclampsia. We explored the correlation between HLA-G and hydrogen peroxide in preeclamptic (n = 30) and normotensive (n = 30) placentas, which was confirmed by in vitro experiments. Furthermore, RNA interference was used to explore the influence of HLA-G on the proliferation, apoptosis and invasion of HTR-8/SVneo cells when exposed to hydrogen peroxide. We found an inverse correlation between hydrogen peroxide and HLA-G expression in preeclamptic placentas. High levels of hydrogen peroxide could down-regulate HLA-G expression in HTR-8/SVneo. Compared with HLA-G knockdown HTR-8/SVneo, increased proliferation inhibition, higher apoptosis, and decreased cell invasion were found in the cell expressing HLA-G when exposed to hydrogen peroxide. Our findings highlight that high levels of hydrogen peroxide can down-regulate HLA-G expression in trophoblasts during preeclampsia and trophoblasts expressing HLA-G are vulnerable to oxidative stress. Copyright © 2012 Mosby, Inc. All rights reserved.

  17. Excess LIGHT contributes to placental impairment, increased secretion of vasoactive factors, hypertension, and proteinuria in preeclampsia.

    Science.gov (United States)

    Wang, Wei; Parchim, Nicholas F; Iriyama, Takayuki; Luo, Renna; Zhao, Cheng; Liu, Chen; Irani, Roxanna A; Zhang, Weiru; Ning, Chen; Zhang, Yujin; Blackwell, Sean C; Chen, Lieping; Tao, Lijian; Hicks, M John; Kellems, Rodney E; Xia, Yang

    2014-03-01

    Preeclampsia, a prevalent hypertensive disorder of pregnancy, is believed to be secondary to uteroplacental ischemia. Accumulating evidence indicates that hypoxia-independent mediators, including inflammatory cytokines and growth factors, are associated with preeclampsia, but it is unclear whether these signals directly contribute to placental damage and disease development in vivo. We report that LIGHT, a novel tumor necrosis factor superfamily member, is significantly elevated in the circulation and placentas of preeclamptic women compared with normotensive pregnant women. Injection of LIGHT into pregnant mice induced placental apoptosis, small fetuses, and key features of preeclampsia, hypertension and proteinuria. Mechanistically, using neutralizing antibodies specific for LIGHT receptors, we found that LIGHT receptors herpes virus entry mediator and lymphotoxin β receptor are required for LIGHT-induced placental impairment, small fetuses, and preeclampsia features in pregnant mice. Accordingly, we further revealed that LIGHT functions through these 2 receptors to induce secretion of soluble fms-like tyrosine kinase-1 and endothelin-1, 2 well-accepted pathogenic factors in preeclampsia, and thereby plays an important role in hypertension and proteinuria in pregnant mice. Lastly, we extended our animal findings to human studies and demonstrated that activation of LIGHT receptors resulted in increased apoptosis and elevation of soluble fms-like tyrosine kinase-1 secretion in human placental villous explants. Overall, our human and mouse studies show that LIGHT signaling is a previously unrecognized pathway responsible for placental apoptosis, elevated secretion of vasoactive factors, and subsequent maternal features of preeclampsia, and reveal new therapeutic opportunities for the management of the disease.

  18. Hyperemesis gravidarum and placental dysfunction disorders

    NARCIS (Netherlands)

    Koudijs, Heleen M; Savitri, Ary I; Browne, Joyce L|info:eu-repo/dai/nl/413640671; Amelia, Dwirani; Baharuddin, Mohammad; Grobbee, Diederick E|info:eu-repo/dai/nl/071889256; Uiterwaal, Cuno S P M|info:eu-repo/dai/nl/136603947

    2016-01-01

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

  19. Abnormal umbilical artery Doppler velocimetry and placental ...

    African Journals Online (AJOL)

    stromal fibrosis and calcification). The placental lesions were then compared with DV findings (at delivery) and prospectively with neonatal outcome. Statistical analysis. Statistical software SPSS version 20.0 (IBM Corp., USA) was used for statistical ...

  20. Pregnancy Complications: Placental Accreta, Increta and Percreta

    Science.gov (United States)

    ... If the bleeding is severe, go to the hospital right way. How are these placental conditions diagnosed? These conditions usually are diagnosed using ultrasound . In some cases, your provider may use magnetic resonance imaging (MRI). MRI is a medical test ...

  1. 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

  2. Hemangioblastic foci in human first trimester placenta: Distribution and gestational profile.

    Science.gov (United States)

    Aplin, John D; Whittaker, Hannah; Jana Lim, Yu Ting; Swietlik, Stefanie; Charnock, Jayne; Jones, Carolyn J P

    2015-10-01

    The human placenta is a site of both hematopoiesis and vasculogenesis. There are reports of hemangioblastic foci (HAF) in the first trimester placenta, but little published information about their spatiotemporal incidence. We have used semi-thin sections and whole mount staining techniques on archival early pregnancy hysterectomy material as well as freshly-collected termination tissue. We report a description of the distribution of HAF, their gestational profile, and some characteristics of the constituent cells. We show crypt-shaped HAF are present in villi at different levels from 4 to 11 weeks and in the chorionic plate from 4 to 9 weeks. In the villous placenta, the foci often approach closely at one end to the trophoblast basement membrane. Morphologically they show remarkable similarity to those found in the yolk sac at similar stages. In some crypts, all cells are CD34+, but CD34 and nestin progressively segregate into the endothelial lineage. Brachyury is present in less differentiated cells. The erythroid lineage is dominant, as shown by the widespread expression of CD235a/glycophorin and characteristic erythroid morphologies, indicating various degrees of differentiation. However, CD41 is also present in non-endothelial cells. Initially a discontinuous UEA-1/CD31-positive endothelium forms at the periphery of the foci. These cells appear to become integrated into the developing vasculogenic/angiogenic vessel network. We also demonstrate that, independent of HAF, vasculogenesis occurs near the tips of growing villi during the first trimester. We suggest HAF interface with the developing vascular network, producing communication channels that allow erythrocytes to enter the placental-embryonic circulation. We speculate that the erythroid cells act as oxygen reservoirs during the period before flow of maternal blood through the intervillous space of the placenta, allowing a slow feed of oxygen-rich cells to the developing embryo. Copyright © 2015 Elsevier

  3. Deep trophoblast invasion and spiral artery remodelling in the placental bed of the chimpanzee

    DEFF Research Database (Denmark)

    Pijnenborg, R; Vercruysse, L; Carter, Anthony Michael

    2011-01-01

    Deep trophoblast invasion is usually considered to be a unique feature of human placentation as compared to other primates. Because of the occasional occurrence of preeclampsia in great apes, which in the human is associated with impaired deep invasion, this uniqueness may be questioned...

  4. Placental-Specific Overexpression of sFlt-1 Alters Trophoblast Differentiation and Nutrient Transporter Expression in an IUGR Mouse Model

    NARCIS (Netherlands)

    Kuehnel, Elisabeth; Kleff, Veronika; Stojanovska, Violeta; Kaiser, Stephanie; Waldschuetz, Ralph; Herse, Florian; Plosch, Torsten; Winterhager, Elke; Gellhaus, Alexandra

    Since it is known that placental overexpression of the human anti-angiogenic molecule sFlt-1, the main candidate in the progression of preeclampsia, lead to intrauterine growth restriction (IUGR) in mice by lentiviral transduction of mouse blastocysts, we hypothesize that sFlt-1 influence placental

  5. Novel expression of EGFL7 in placental trophoblast and endothelial cells and its implication in preeclampsia.

    Science.gov (United States)

    Lacko, Lauretta A; Massimiani, Micol; Sones, Jenny L; Hurtado, Romulo; Salvi, Silvia; Ferrazzani, Sergio; Davisson, Robin L; Campagnolo, Luisa; Stuhlmann, Heidi

    2014-08-01

    The mammalian placenta is the site of nutrient and gas exchange between the mother and fetus, and is comprised of two principal cell types, trophoblasts and endothelial cells. Proper placental development requires invasion and differentiation of trophoblast cells, together with coordinated fetal vasculogenesis and maternal vascular remodeling. Disruption in these processes can result in placental pathologies such as preeclampsia (PE), a disease characterized by late gestational hypertension and proteinuria. Epidermal Growth Factor Like Domain 7 (EGFL7) is a largely endothelial-restricted secreted factor that is critical for embryonic vascular development, and functions by modulating the Notch signaling pathway. However, the role of EGFL7 in placental development remains unknown. In this study, we use mouse models and human placentas to begin to understand the role of EGFL7 during normal and pathological placentation. We show that Egfl7 is expressed by the endothelium of both the maternal and fetal vasculature throughout placental development. Importantly, we uncovered a previously unknown site of EGFL7 expression in the trophoblast cell lineage, including the trophectoderm, trophoblast stem cells, and placental trophoblasts. Our results demonstrate significantly reduced Egfl7 expression in human PE placentas, concurrent with a downregulation of Notch target genes. Moreover, using the BPH/5 mouse model of PE, we show that the downregulation of Egfl7 in compromised placentas occurs prior to the onset of characteristic maternal signs of PE. Together, our results implicate Egfl7 as a possible factor in normal placental development and in the etiology of PE. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

  6. The Placental Microbiota Is Altered among Subjects with Gestational Diabetes Mellitus: A Pilot Study.

    Science.gov (United States)

    Zheng, Jia; Xiao, Xinhua; Zhang, Qian; Mao, Lili; Yu, Miao; Xu, Jianping; Wang, Tong

    2017-01-01

    Gestational diabetes mellitus (GDM) has significant implications for the future health of the mother and child. However, the associations between human placental microbiota and GDM are poorly understood. We aimed to profile the placental microbiota of GDM and further define whether or not certain placental microbiota taxon correlates with specific clinical characteristics. Placenta were collected from GDM women and women with normal pregnancies (n = 10, in each group) consecutively recruited at Peking Union Medical College Hospital. The anthropometric parameters of mother and infant, and cord blood hormones, including insulin, leptin and insulin-like growth factor-1 (IGF-1) were measured. Bacterial genomic DNA was isolated using magnetic beads and the human placental microbiota was analyzed using the Illumina MiSeq Sequencing System based on the V3-V4 hypervariable regions of the 16S rRNA gene. It showed there was no statistical difference in the clinical characteristics of mothers and infants, such as BMI at the beginning of pregnancy and gestational weight gain (GWG), birth weight, and cord blood hormones, including insulin, leptin and IGF-1. We found that the placental microbiota is composed of four dominant phyla from Proteobacteria (the most abundant), Bacteroidetes, Actinobacteria and Firmicutes, with the proportion of Proteobacteria increased, and Bacteroidetes and Firmicutes were decreased of women with GDM. Further analyses suggested that bacterial taxonomic composition of placentas from the phylum level down to the bacteria level, differed significantly between women with GDM and non-GDM women with normal pregnancies. Regression analysis showed a cluster of key operational taxonomic units (OTUs), phyla and genera were significantly correlated with GWG during pregnancy of mothers, and cord blood insulin, IGF-1 and leptin concentrations. In conclusion, our novel study showed that a distinct placental microbiota profile is present in GDM, and is associated

  7. The distinct proteome of placental malaria parasites.

    Energy Technology Data Exchange (ETDEWEB)

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

    2007-09-01

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

  8. Ovulation, pregnancy, placentation and husbandry in the African elephant (Loxodonta africana)

    Science.gov (United States)

    Allen, W.R

    2006-01-01

    The African elephant reproduces so efficiently in the wild that overpopulation is now a serious problem in some game parks in Zimbabwe, Botswana and South Africa. The female reaches puberty between 10 and 12 years of age in the wild and, when in captivity, shows oestrous cycles of 14–15 weeks duration. She readily conceives a singleton in the wild yet her uterus has the capacity for twins. She shows a gestation length of 22 months and, in the wild, shows a population density and feed dependent intercalving interval of 4–8 years. The trophoblast erodes the lumenal epithelium of the endometrium and stimulates upgrowths of blood vessel-containing stromal villi, which develop eventually into the broad, tightly folded lamellae of the zonary, endotheliochorial placenta. Significant quantities of leaked maternal erythrocytes and ferric iron are phagocytosed by specialized trophoblast cells in the haemophagous zones at the lateral edges of the placental band. Although the placenta itself is endocrinologically inert, the foetal gonads, which enlarge greatly during the second half of pregnancy can synthesize 5α-dihydryoprogesterone and other 5α pregnane derivatives from cholesterol and pregnenolone. These products may synergize with progestagens secreted by the 2–8 large corpora lutea which are always present in the maternal ovaries throughout gestation to maintain the pregnancy state. PMID:16627297

  9. Deep trophoblast invasion and spiral artery remodelling in the placental bed of the lowland gorilla

    DEFF Research Database (Denmark)

    Pijnenborg, R; Vercruysse, L; Carter, Anthony Michael

    2011-01-01

    In contrast to baboon or rhesus macaque, trophoblast invasion in the human placental bed occurs by the interstitial as well as the endovascular route and reaches as deep as the inner myometrium. We here describe two rare specimens of gorilla placenta. In the light of recent findings in the chimpa......In contrast to baboon or rhesus macaque, trophoblast invasion in the human placental bed occurs by the interstitial as well as the endovascular route and reaches as deep as the inner myometrium. We here describe two rare specimens of gorilla placenta. In the light of recent findings...

  10. Effect of maternal age and growth on placental nutrient transport: potential mechanisms for teenagers' predisposition to small-for-gestational-age birth?

    Science.gov (United States)

    Greenwood, Susan L.; Sibley, Colin P.; Baker, Philip N.; Challis, John R. G.; Jones, Rebecca L.

    2012-01-01

    Teenagers have an increased risk of delivering small-for-gestational-age (SGA) infants. Young maternal age and continued skeletal growth have been implicated as causal factors. In growing adolescent sheep, impaired placental development and nutrient transfer cause reduced birth weight. In human pregnancies, SGA is associated with reduced placental amino acid transport. Maternal growth has no effect on placental morphology or cell turnover, but growing teenagers have higher birth weight:placental weight ratios than nongrowing teenagers. We hypothesized that placental nutrient transporter activity would be affected by maternal age and/or growth status. Placentas from teenagers and adults were collected. Teenagers were defined as growing or nongrowing based on knee height measurements. System A amino acid transporter activity was quantified as sodium-dependent uptake of [14C]methylaminoisobutyric acid into placental fragments. Teenagers had lower placental system A activity than adults (P teenagers, AGA and SGA infants had lower placental system A activity than AGA infants born to adults (P teenagers than in nongrowing teenagers (P teenagers than in adults (P teenagers. There was no difference in transporter protein expression/localization between cohorts. Teenagers have inherently reduced placental transport, which may underlie their susceptibility to delivering SGA infants. Growing teenagers appear to overcome this susceptibility by stimulating the activity, but not expression, of system A transporters. PMID:22028413

  11. Effect of maternal age and growth on placental nutrient transport: potential mechanisms for teenagers' predisposition to small-for-gestational-age birth?

    Science.gov (United States)

    Hayward, Christina E; Greenwood, Susan L; Sibley, Colin P; Baker, Philip N; Challis, John R G; Jones, Rebecca L

    2012-01-15

    Teenagers have an increased risk of delivering small-for-gestational-age (SGA) infants. Young maternal age and continued skeletal growth have been implicated as causal factors. In growing adolescent sheep, impaired placental development and nutrient transfer cause reduced birth weight. In human pregnancies, SGA is associated with reduced placental amino acid transport. Maternal growth has no effect on placental morphology or cell turnover, but growing teenagers have higher birth weight:placental weight ratios than nongrowing teenagers. We hypothesized that placental nutrient transporter activity would be affected by maternal age and/or growth status. Placentas from teenagers and adults were collected. Teenagers were defined as growing or nongrowing based on knee height measurements. System A amino acid transporter activity was quantified as sodium-dependent uptake of [(14)C]methylaminoisobutyric acid into placental fragments. Teenagers had lower placental system A activity than adults (P teenagers, AGA and SGA infants had lower placental system A activity than AGA infants born to adults (P teenagers than in nongrowing teenagers (P teenagers than in adults (P teenagers. There was no difference in transporter protein expression/localization between cohorts. Teenagers have inherently reduced placental transport, which may underlie their susceptibility to delivering SGA infants. Growing teenagers appear to overcome this susceptibility by stimulating the activity, but not expression, of system A transporters.

  12. Peripheral and placental biomarkers in women with placental malaria: a systematic review

    NARCIS (Netherlands)

    Ruizendaal, Esmée; van Leeuwen, Elisabeth; Mens, Petra F.

    2015-01-01

    Placental malaria (PM) causes significant morbidity in mothers and infants. Diagnosis of PM during pregnancy is however problematic due to placental sequestration of parasites. Host biomarkers may therefore be used as a diagnostic method. In this systematic review most studies focused on

  13. Placental amino acid transport and placental leptin resistance in pregnancies complicated by maternal obesity.

    Science.gov (United States)

    Farley, D M; Choi, J; Dudley, D J; Li, C; Jenkins, S L; Myatt, L; Nathanielsz, P W

    2010-08-01

    HYPOTHESIS AND STUDY OBJECTIVES: We hypothesized that maternal obesity is associated with increased placental amino acid transport and hyperleptinemia. Our objectives were to study placental amino acid transport and the effect of leptin on placental amino acid transport in vitro in the setting of maternal obesity. Seven lean, BMI at entry 22.4, and seven obese, BMI at entry 31.5 (p leptin-stimulated placental system A sodium-dependent neutral amino acid transporter (SNAT) activity, placental immunoreactive protein expression of SNAT, leptin and leptin receptor, and maternal and fetal plasma leptin concentrations, with significance set at p leptin receptor (p = 0.01) and SNAT-4 (p leptin in the lean group as compared to the obese group. Maternal weight gain and offspring birth weights were not different between groups. Maternal obesity was accompanied by decreased placental SNAT activity associated with maternal hyperleptinemia and placental leptin resistance in spite of appropriate maternal weight gain and normally grown neonates. These findings suggest altered placental function that may have clinical implications in obese pregnant women.

  14. Human Placental-Derived Stem Cell Transplantation

    Science.gov (United States)

    2017-12-20

    Mucopolysaccharidosis I; Mucopolysaccharidosis VI; Adrenoleukodystrophy; Niemann-Pick Disease; Metachromatic Leukodystrophy; Wolman Disease; Krabbe's Disease; Gaucher's Disease; Fucosidosis; Batten Disease; Severe Aplastic Anemia; Diamond-Blackfan Anemia; Amegakaryocytic Thrombocytopenia; Myelodysplastic Syndrome; Acute Myelogenous Leukemia; Acute Lymphocytic Leukemia

  15. Deoxynivalenol transport across the human placental barrier

    DEFF Research Database (Denmark)

    Nielsen, Jeanette K S; Vikström, Anna C; Turner, Paul

    2011-01-01

    with the ex vivo dual perfusion model. The concentration of DON on the foetal side after 4h was about 21% of that on the maternal side at t=0. These results support the data from the BeWo monolayer model in respect to the transport rate of DON, and are consistent with our hypothesis of foetal exposure to DON...

  16. Placental Nano-vesicles Target to Specific Organs and Modulate Vascular Tone In Vivo.

    Science.gov (United States)

    Tong, Mancy; Stanley, Joanna L; Chen, Q; James, Joanna L; Stone, Peter R; Chamley, Larry W

    2017-11-01

    How do nano-vesicles extruded from normal first trimester human placentae affect maternal vascular function? Placental nano-vesicles affect the ability of systemic mesenteric arteries to undergo endothelium- and nitric oxide- (NO-) dependent vasodilation in vivo in pregnant mice. Dramatic cardiovascular adaptations occur during human pregnancy, including a substantial decrease in total peripheral resistance in the first trimester. The human placenta constantly extrudes extracellular vesicles that can enter the maternal circulation and these vesicles may play an important role in feto-maternal communication. Human placental nano-vesicles were administered into CD1 mice via a tail vein and their localization and vascular effects at 30 min and 24 h post-injection were investigated. Nano-vesicles from normal first trimester human placentae were collected and administered into pregnant (D12.5) or non-pregnant female mice. After either 30 min or 24 h of exposure, all major organs were dissected for imaging (n = 7 at each time point) while uterine and mesenteric arteries were dissected for wire myography (n = 6 at each time point). Additional in vitro studies using HMEC-1 endothelial cells were also conducted to investigate the kinetics of interaction between placental nano-vesicles and endothelial cells. Nano-vesicles from first trimester human placentae localized to the lungs, liver and kidneys 24 h after injection into pregnant mice (n = 7). Exposure of pregnant mice to placental nano-vesicles for 30 min in vivo increased the vasodilatory response of mesenteric arteries to acetylcholine, while exposure for 24 h had the opposite effect (P nano-vesicles did not affect the function of uterine arteries or mesenteric arteries from non-pregnant mice. Placental nano-vesicles rapidly interacted with endothelial cells via a combination of phagocytosis, endocytosis and cell surface binding in vitro. N/A. As it is not ethical to administer labelled placental nano-vesicles to

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

    DEFF Research Database (Denmark)

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

    2010-01-01

    expressed in placental malaria (PM) and specific for chondroitin sulfate A (CSA). In Plasmodium falciparum, these VSA(PM) appear largely synonymous with the P. falciparum erythrocyte membrane protein 1 (PfEMP1) family variant VAR2CSA. As rodent malaria parasites do not possess PfEMP1 homologs......, the usefulness of experimental mouse PM models remains controversial. However, many features of murine and human PM are similar, including involvement of VSAs analogous to PfEMP1. It thus appears that rodent model studies can further the understanding of VSA-dependent malaria pathogenesis and immunity....

  18. Evolution of factors affecting placental oxygen transfer.

    Science.gov (United States)

    Carter, A M

    2009-03-01

    A review is given of the factors determining placental oxygen transfer and the oxygen supply to the fetus. In the case of continuous variables, such as the rate of placental blood flow, it is not possible to trace evolutionary trends. Discontinuous variables, for which we can define character states, are more amenable to analysis. This is exemplified by factors contributing, respectively, to blood oxygen affinity and placental diffusing capacity. Comparative genomics has given fresh insight into the evolution of the beta-globin gene complex. In higher primates, duplication of an embryonic gene yielded HBG-T2, a gene that is expressed in the fetus and confers high oxygen affinity on its haemoglobin. A separate event in ruminants involved duplication of an adult gene, again resulting in a fetally expressed variant (HBB-T3) that conveys high oxygen affinity. In rodents and lagomorphs, where fetal and adult haemoglobin are not different, developmental regulation of 2, 3-diphosphoglycerate ensures the high oxygen affinity of fetal blood. Oxygen diffusing capacity is dependent on diffusion distance, which may vary with the type of interhaemal barrier. It has been shown that epitheliochorial placentation is a derived state and that the common ancestor of placental mammals probably had a placenta of the endotheliochorial type. Where evolutionary trends are implied for mammals as a whole or within orders such as primates they often accompany a switch in reproductive strategy that is manifested in a change of newborn state from poorly developed (altricial) to well developed (precocial).

  19. Ascending placentitis in the mare: A review

    Directory of Open Access Journals (Sweden)

    Cummins C

    2008-05-01

    Full Text Available Abstract Ascending placentitis is a condition that occurs late in pregnancy when bacteria enter the sterile uterus from the lower reproductive tract. It leads to abortion or the birth of premature and weakened foals. Early detection and treatment of this condition is vital for ensuring the production of a viable foal. Mares with ascending placentitis often present in late term pregnancy with signs of premature udder development and premature lactation. There may be a vulvar discharge. Early detection of placental problems is possible using trans-abdominal or trans-rectal ultrasonography. Hormones such as progesterone and relaxin may be measured as indicators of foetal stress and placental failure. Postpartum foetal membranes may be thickened and contain a fibronecrotic exudate. The region most affected is the cervical star. Definitive diagnosis of ascending placentitis is by histopathological examination of the chorioallantoic membrane. Ideal treatment strategies are aimed at curing the infection and prolonging the pregnancy to as close to term as possible and consist of anti-microbials, anti-inflammatories and hormonal support. Swabs are taken from affected mares to determine antibiotic sensitivity and to aid in treatment of foals born from these mares which are at risk of becoming septic. If detected early enough, the chances of producing a viable foal are greatly increased.

  20. Placental vascular dysfunction in diabetic pregnancies: intimations of fetal cardiovascular disease?

    Science.gov (United States)

    Leach, Lopa

    2011-05-01

    In the human placenta, the angioarchitecture of fetal vessels lying in maternal blood is useful for nutrient uptake, but it makes the synthesis, maturation and functioning of placental vessels vulnerable to any alterations in the fetal and maternal environment. This review discusses how the maternal diabetic milieu, and the resultant fetal hyperglycemia and hyperinsulinemia, may act together to produce an altered placental vascular phenotype, which includes increased angiogenesis, altered junctional maturity, increased vascular endothelial-like growth factor (VEGF), altered VEGF and insulin receptor profiles, and upregulation of genes involved in signal transduction, transcription and mitosis in placental endothelial cells. The placental vascular dysfunction does extend to other fetal vascular beds including endothelial cells from umbilical vessels, where there are reports of elevated basal iNOS activity and altered sensitivity to insulin. There is emerging evidence of epigenetic modulation of fetal endothelial genes in diabetes and long-term vascular consequences of this. Thus, placental vascular dysfunction in diabetes may be contributing to and describing disturbances in the fetal vasculature, which may produce an overt pathological response in later life if challenged with additional cardiovascular stresses. © 2011 John Wiley & Sons Ltd.

  1. Short-Term Exposure to Urban Air Pollution and Influences on Placental Vascularization Indexes.

    Science.gov (United States)

    Hettfleisch, Karen; Bernardes, Lisandra Stein; Carvalho, Mariana Azevedo; Pastro, Luciana Duzolina Manfré; Vieira, Sandra Elisabete; Saldiva, Silvia R D M; Saldiva, Paulo; Francisco, Rossana Pulcineli Vieira

    2017-04-01

    It has been widely demonstrated that air pollution can affect human health and that certain pollutant gases lead to adverse obstetric outcomes, such as preeclampsia and fetal growth restriction. We evaluated the influence of individual maternal exposure to air pollution on placental volume and vascularization evaluated in the first trimester of pregnancy. This was a cross-sectional study on low-risk pregnant women living in São Paulo, Brazil. The women carried passive personal NO2 and O3 monitors in the week preceding evaluation. We employed the virtual organ computer-aided analysis (VOCAL) technique using three-dimensional power Doppler ultrasound to evaluate placental volume and placental vascular indexes [vascularization index (VI), flow index (FI), and vascularization flow index (VFI)]. We analyzed the influence of pollutant levels on log-transformed placental vascularization and volume using multiple regression models. We evaluated 229 patients. Increased NO2 levels had a significant negative association with log of VI (p = 0.020 and beta = -0.153) and VFI (p = 0.024 and beta = -0.151). NO2 and O3 had no influence on the log of placental volume or FI. NO2, an estimator of primary air pollutants, was significantly associated with diminished VI and VFI in the first trimester of pregnancy.

  2. Fetal, maternal, and placental sources of serotonin and new implications for developmental programming of the brain.

    Science.gov (United States)

    Bonnin, A; Levitt, P

    2011-12-01

    In addition to its role in neurotransmission, embryonic serotonin (5-HT) has been implicated in the regulation of neurodevelopmental processes. For example, we recently showed that a subset of 5-HT1-receptors expressed in the fetal forebrain mediate a serotonergic modulation of thalamocortical axons response to axon guidance cues, both in vitro and in vivo. This influence of 5-HT signaling on fetal brain wiring raised important questions regarding the source of the ligand during pregnancy. Until recently, it was thought that 5-HT sources impacting brain development arose from maternal transport to the fetus, or from raphe neurons in the brainstem of the fetus. Using genetic mouse models, we uncovered previously unknown differences in 5-HT accumulation between the fore- and hindbrain during early and late fetal stages, through an exogenous source of 5-HT. Using additional genetic strategies, a new technology for studying placental biology ex vivo, and direct manipulation of placental neosynthesis, we investigated the nature of this exogenous source and uncovered a placental 5-HT synthetic pathway from a maternal tryptophan precursor, in both mice and humans. These results implicate a new, direct role for placental metabolic pathways in modulating fetal brain development and suggest an important role for maternal-placental-fetal interactions and 5-HT in the fetal programming of adult mental disorders. Copyright © 2011 IBRO. Published by Elsevier Ltd. All rights reserved.

  3. 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.

  4. [Antenatal diagnosis of placental acretism-percretism].

    Science.gov (United States)

    Haghenbeck-Altamirano, Francisco Javier; Leis-Márquez, Teresa; Ayala-Yáñez, Rodrigo; Juárez-García, Luz del Carmen; García-Moreno, Carla

    2013-05-01

    Placental acretism is an adherencial pathology associated with a high maternal morbidity and mortality rates. Antepartum diagnosis is essential to plan a proper management and reduce serious complications. Risk factors in these patients include prior cesarean sections, uterine scars and placenta previa. Second level ultrasonography may detect placental acretism with high sensitivity and specificity; magnetic resonance imaging may play a complimentary role in the diagnosis of placental acretism when ultrasonographic findings are non-conclusive, specially when determining miometrium invasion in placental acretism (incretism, percretism). This paper reports the case of a patient treated at the ABC Medical Center of Santa Fe, in her second gestation with the diagnosis of an arcuate uterus, previous cesarean section and placenta previa who presented a vaginal bleeding during pregnancy; ultrasound evaluation, in the second trimester, identified a probable placental acretism, in the third trimester, the same technology suggested placenta percreta, complimentary magnetic resonance imaging supported this diagnosis, with probable invasion to bladder, bowel and abdominal wall muscles. Imaging studies were performed at the Hospital Angeles Lomas (Maternal Fetal Clinic). A diagnosis of placenta acreta-percreta, called for a multidisciplinary surgical team, availability of blood products and other resources to face probable complications associated to the obstetrical resolution. Maternal results were optimal since histopathological evaluation reported miometrial incretism, with placental invasion millimeters away from the uterine serosa. Most ultrasonographic studies evaluating the invasion degree of the placenta have small sample sizes, generating a greater degree of false positive or false negative observations. Therefore, we agree with other authors that in all acretism cases (independent of their invasion degree), a multidisciplinary surgical team should be assembled in

  5. Cesarean Delivery for a Life‑threatening Preterm Placental Abruption

    African Journals Online (AJOL)

    Placental abruption is one of the major life‑threatening obstetric conditions. The fetomaternal outcome of a severe placental abruption depends largely on prompt maternal resuscitation and delivery. A case of severe preterm placental abruption with intrauterine fetal death. Following a failed induction of labor with a ...

  6. Immunoinformatics of Placental Malaria Vaccine Development

    DEFF Research Database (Denmark)

    Jessen, Leon Eyrich

    Malaria is an infectious disease caused by a protozoan parasite of the genus Plasmodium, which is transferred by female Anopheles mosquitos. WHO estimates that in 2012 there were 207 million cases of malaria, of which 627,000 were fatal. People living in malaria-endemic areas, gradually acquire...... immunity with multiple infections. Placental malaria (PM) is caused by P. falciparum sequestering in the placenta of pregnant women due to the presence of novel receptors in the placenta. An estimated 200,000 infants die a year as a result of PM. In 2004 the specific protein responsible...... and development in the field of placental malaria vaccine development....

  7. Decreased type III and V collagen expression in chorionic villi of hydatidiform mole.

    Science.gov (United States)

    Iwahashi, M; Muragaki, Y; Ooshima, A; Nakano, R

    2001-07-01

    To investigate the characteristic structure of hydatidiform mole, various types of collagen expression were determined in human villous tissues obtained from normal pregnancies (n = 17) and complete hydatidiform moles (n = 10). Indirect immunofluorescent staining was performed to detect type I, III, and VI collagen with specific monoclonal antibodies. Collagens were also extracted from the villous tissues obtained from normal pregnancy and hydatidiform mole by the salt precipitation method. Immunohistochemical staining for type I, III, and VI collagen revealed weak staining of the villous stroma in hydatidiform mole compared with that in normal pregnancy. Both the ratios of type III to type I collagen and the ratios of type V to type I collagen in the villous tissues were significantly decreased (P collagen might play an important role in determining the pathophysiology and structure of hydatidiform mole.

  8. Downregulation of SPARC expression inhibits the invasion of human trophoblast cells in vitro.

    Directory of Open Access Journals (Sweden)

    Yahong Jiang

    Full Text Available Successful pregnancy depends on the precise regulation of extravilloustrophoblast (EVT invasion into the uterine decidua. SPARC (secreted protein acidic and rich in cysteine is a matricellular glycoprotein that plays critical roles in the pathologies associated with obesity and diabetes, as well as tumorigenesis. The objective of this study was to investigate the role of SPARC in the process of trophoblast invasion which shares many similarities with tumor cell invasion. By Western blot, higher expression of SPARC was observed in mouse brain, ovary and uterus compared to other mouse tissues. Immunohistochemistry analysis revealed a spatio-temporal expression of SPARC in mouse uterus in the periimplantation period. At the implantation site of d8 pregnancy, SPARC mainly accumulated in the secondary decidua zone (SDZ, trophoblast cells and blastocyst. The expression of SPARC was also detected in human placental villi and trophoblast cell lines. In a Matrigel invasion assay, we found SPARC-specific RNA interference significantly reduced the invasion of human extravilloustrophoblast HTR8/SVneo cells. Microarray analysis revealed that SPARC depletion upregulated the expression of interleukin 11 (IL11, KISS1, insulin-like growth factor binding protein 4 (IGFBP4, collagen type I alpha 1 (COLIA1, matrix metallopeptidase 9 (MMP9, and downregulated the expression of the alpha polypeptide of chorionic gonadotropin (CGA, MMP1, gap junction protein alpha 1 (GJA1, et al. The gene array result was further validated by qRT-PCR and Western blot. The present data indicate that SPARC may play an important role in the regulation of normal placentation by promoting the invasion of trophoblast cells into the uterine decidua.

  9. Serum Biochemistry, Organ Weight, Carcass Characteristics, Organoleptic Properties and Villi Morphometry of Nera Black Cocks fed Varying Levels of Moringa oleifera Leaf Meal

    Directory of Open Access Journals (Sweden)

    Taiwo Kayode Ojediran

    2017-11-01

    Full Text Available A total number of sixty-four (28 weeks old matured Nera black cocks were randomly allotted to 4 dietary groups. Diet T1 (control had no Moringa Oleifera leaf meal (MOLM inclusion while diets T2, T3 and T4 contained graded levels of MOLM at 10%, 20% and 30% replacement for soya bean meal (w/w respectively  in a completely randomized design. All the serum biochemistry parameters evaluated differs significantly (P≤0.05 except albumin and cholesterol (P>0.05 among the dietary treatments. The weight of the kidney, heart, pancrease, proventriculus and spleen were influenced by the dietary treatments (P≤0.05. The weights of breast and empty gizzard increased (P≤0.05 linearly with MOLM inclusion while the wings, thigh and drum stick compared (P≤0.05 with those fed the control diet. The villi length and muscle thickness were significantly (P≤0.05 influenced by MOLM inclusion. The MOLM supplemented birds had longer villi than birds in the control group. The result of the this study showed that replacement of soybean meal with MOLM up to 30% inclusion in the diets of Nera black cocks was not detrimental to organ weights, carcass characteristics, sensory attributes and villi morphometrics. However, some serum parameters were adversely affected.

  10. False Negative NIPT Results: Risk Figures for Chromosomes 13, 18 and 21 Based on Chorionic Villi Results in 5967 Cases and Literature Review.

    Directory of Open Access Journals (Sweden)

    Diane Van Opstal

    Full Text Available Non-invasive prenatal testing (NIPT demonstrated a small chance for a false negative result. Since the "fetal" DNA in maternal blood originates from the cytotrophoblast of chorionic villi (CV, some false negative results will have a biological origin. Based on our experience with cytogenetic studies of CV, we tried to estimate this risk. 5967 CV samples of pregnancies at high risk for common aneuplodies were cytogenetically investigated in our centre between January 2000 and December 2011. All cases of fetal trisomy 13, 18 and 21 were retrospectively studied for the presence of a normal karyotype or mosaicism < 30% in short-term cultured (STC- villi. 404 cases of trisomies 13, 18 and 21 were found amongst 5967 samples (6,8%. Of these 404 cases, 14 (3,7% had a normal or low mosaic karyotype in STC-villi and therefore would potentially be missed with NIPT. It involved 2% (5/242 of all trisomy 21 cases and 7.3% (9/123 of all trisomy 18 cases. In 1:426 (14/5967 NIPT samples of patients at high risk for common aneuploidies, a trisomy 18 or 21 will potentially be missed due to the biological phenomenon of absence of the chromosome aberration in the cytotrophoblast.

  11. Simultaneous expression of 70 kilodalton type IV collagenase and type IV collagen alpha 1 (IV) chain genes by cells of early human placenta and gestational endometrium.

    Science.gov (United States)

    Autio-Harmainen, H; Hurskainen, T; Niskasaari, K; Höyhtyä, M; Tryggvason, K

    1992-08-01

    In this study we used in situ hybridization to investigate the expression of the genes 70 kilodalton (kd) collagenase and the alpha 1(IV) collagen chain of type IV collagen in cells of early human placenta and gestational endometrium. The aim was to study the spatial distribution of these gene expressions within a developing tissue which possesses physiologic invasive potential. The results obtained for the 70 kd type IV collagenase mRNA expression were also compared with the immunohistochemical distribution of the corresponding antigen. Expression of mRNAs for these proteins was found in cells of trophoblastic columns, stromal cells of villi and in cells of decidua and endometrial stroma. The only differences between the expressions was the lower level of signals for 70 kd type IV collagenase in fibroblastic stromal cells and endothelial cells of villi and in the pericytic cells of spiral arteries. Otherwise the results for both types of mRNA were comparable. We also studied the immunohistochemical distribution of the 70 kd type IV collagenase using specific monoclonal antibodies against the enzyme. Immunohistochemistry supported well the findings obtained by in situ hybridization. The results indicate that the genes for the 70 kd type IV collagenase and for the alpha 1(IV) collagen chain are simultaneously active in cells of placenta and gestational endometrium and the same cells which produce type IV collagen also can produce the cleaving enzyme, the 70 kd type IV collagenase. The results also show that the cytotrophoblastic cells, which during early pregnancy invade the extracellular matrix and spiral arteries of uterine wall contain significant amount of mRNA for the 70 kd type IV collagenase. This finding supports the concept that the 70 kd type IV collagenase would be important for invasion, and in the case of this study, also for the physiologic invasion of placental cytotrophoblasts.

  12. Characterization of a novel human scavenger receptor cysteine-rich molecule SCART1 expressed by lymphocytes

    DEFF Research Database (Denmark)

    Holm, D.; Fink, D. R.; Steffensen, M. A.

    2013-01-01

    of hSCART1 in the small intestine and colon. An antibody raised against an N-terminal hSCART1 peptide stains a subset of cells in the small intestine, stomach, and gall bladder, and it also stains placental villi. In conclusion, the characterization of hSCART1 at the mRNA and protein level suggests...... that displays synteny to the position of mSCART1 in the murine genome. The primary structure of hSCART1 was established by molecular cloning. The longest cDNA sequence of hSCART1 that was found is 2200bp and encodes a protein composed of a signal peptide, 5 SRCR domains, and an in-frame potential cytoplasmic...... domain. Shorter splice forms have also been isolated. Quantitative real-time PCR analysis on human blood-fractions has shown that hSCART1 is expressed primarily by CD4(+) and CD8(+) T lymphocytes with either αβ or γδ T cell receptors, and real-time PCR on 22 different human tissues showed high expression...

  13. Placental malaria and immunity to infant measles

    NARCIS (Netherlands)

    Owens, S.; Harper, G.; Amuasi, J.; Offei-Larbi, G.; Ordi, J.; Brabin, B. J.

    2006-01-01

    The efficiency of transplacental transfer of measles specific antibody was assessed in relation to placental malaria. Infection at delivery was associated with a 30% decrease in expected cord measles antibody titres. Uninfected women who received anti-malarial drugs during pregnancy transmitted 30%

  14. Placental Mesenchymal Dysplasia: A Case Report

    Directory of Open Access Journals (Sweden)

    Rachna Agarwal

    2012-01-01

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

  15. Abnormal umbilical artery Doppler velocimetry and placental ...

    African Journals Online (AJOL)

    Background. Doppler velocimetry (DV) is widely used to assess the vascular formation of the placenta in fetal growth restriction (FGR) and to estimate the haemodynamic condition of the growth-restricted fetus. Umbilical artery (UA) flow is essentially placental, rather than fetal. Hence, DV provides information about the fetal ...

  16. Placental growth factor and pre-eclampsia

    Science.gov (United States)

    Chau, K; Hennessy, A; Makris, A

    2017-01-01

    Placental growth factor (PlGF) is an increasingly important molecule in the prediction, diagnosis and treatment of pre-eclampsia. It has pro-angiogenic effects on the feto-placental circulation and supports trophoblast growth. Mechanisms by which PlGF expression is regulated continue to be investigated. Low circulating PlGF precedes the manifestation of clinical disease in pre-eclamptic pregnancies and intrauterine growth restriction. This suggests that low PlGF is a marker of abnormal placentation, but it remains uncertain whether this is a cause or consequence. Prediction of pre-eclampsia using PlGF is promising and may assist in the targeting of resources to women at highest risk of adverse pregnancy outcomes. Promisingly, experimental animal models of pre-eclampsia have been successfully treated with supplemental PlGF. Treatment of pre-eclampsia with PlGF is a potential therapeutic option requiring further exploration. This review focuses specifically on the role of PlGF in normal and pathological placental development and in the clinical management of pre-eclampsia. PMID:29115294

  17. Placentation in mammals once grouped as insectivores

    DEFF Research Database (Denmark)

    Carter, Anthony; Enders, Allen

    2009-01-01

    nutrition involving columnar trophoblast cells. These range from areolae in moles through complexly folded hemophagous regions in tenrecs to the trophoblastic annulus in shrews. Of these placental characters, few offer support to current phylogenies. However, the case for placing hedgehogs and gymnures...

  18. Diagnosis of foetal membrane ruptures: Placental alpha ...

    African Journals Online (AJOL)

    Context: Pre‑labour rupture of membranes (PROM) is a common obstetric complication which presents a diagnostic challenge, especially in equivocal cases. Standard methods of diagnosis are limited by high false positives and negatives. This study compared the accuracy of a biomarker placental alpha microglobulin‑1 ...

  19. Placental genetic variations in circadian clock-related genes increase the risk of placental abruption.

    Science.gov (United States)

    Qiu, Chunfang; Gelaye, Bizu; Denis, Marie; Tadesse, Mahlet G; Enquobahrie, Daniel A; Ananth, Cande V; Pacora, Percy N; Salazar, Manuel; Sanchez, Sixto E; Williams, Michelle A

    2016-01-01

    The genetic architecture of placental abruption (PA) remains poorly understood. We examined variations in SNPs of circadian clock-related genes in placenta with PA risk. We also explored placental and maternal genomic contributions to PA risk. Placental genomic DNA samples were isolated from 280 PA cases and 244 controls. Genotyping was performed using the Illumina Cardio-MetaboChip. We examined 116 SNPs in 13 genes known to moderate circadian rhythms. Logistic regression models were fit to estimate odds ratios (ORs). The combined effect of multiple SNPs on PA risk was estimated using a weighted genetic risk score. We examined independent and joint associations of wGRS derived from placental and maternal genomes with PA. Seven SNPs in five genes (ARNTL2, CRY2, DEC1, PER3 and RORA), in the placental genome, were associated with PA risk. Each copy of the minor allele (G) of a SNP in the RORA gene (rs2899663) was associated with a 30% reduced odds of PA (95% CI 0.52-0.95). The odds of PA increased with increasing placental-wGRS (Ptrendcircadian clock-related genes are associated with PA risk; and the association persists after control of genetic variants in the maternal genome.

  20. 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.

  1. Maternal HIV infection and placental malaria reduce transplacental antibody transfer and tetanus antibody levels in newborns in Kenya.

    Science.gov (United States)

    Cumberland, Phillippa; Shulman, Caroline E; Maple, P A Chris; Bulmer, Judith N; Dorman, Edgar K; Kawuondo, Ken; Marsh, Kevin; Cutts, Felicity T

    2007-08-15

    In clinical trials, maternal tetanus toxoid (TT) vaccination is effective in protecting newborns against tetanus infection, but inadequate placental transfer of tetanus antibodies may contribute to lower-than-expected rates of protection in routine practice. We studied the effect of placental malaria and maternal human immunodeficiency virus (HIV) infection on placental transfer of antibodies to tetanus. A total of 704 maternal-cord paired serum samples were tested by ELISA for antibodies to tetanus. The HIV status of all women was determined by an immunoglobulin G antibody-capture particle-adherence test, and placental malaria was determined by placental biopsy. Maternal history of TT vaccination was recorded. Tetanus antibody levels were reduced by 52% (95% confidence interval [CI], 30%-67%) in newborns of HIV-infected women and by 48% (95% CI, 26%-62%) in newborns whose mothers had active-chronic or past placental malaria. Thirty-seven mothers (5.3%) and 55 newborns (7.8%) had tetanus antibody levels tetanus immunization was the strongest predictor of seronegativity and of tetanus antibody levels in maternal and cord serum. Malarial and HIV infections may hinder efforts to eliminate maternal and neonatal tetanus, making implementation of the current policy for mass vaccination of women of childbearing age an urgent priority.

  2. 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

    The risk of unexplained fetal death or stillbirth increases late in pregnancy, suggesting that placental aging is an etiological factor. Aging is associated with oxidative damage to DNA, RNA, and lipids. We hypothesized that placentas at >41 completed weeks of gestation (late-term) would show changes consistent with aging that would also be present in placentas associated with stillbirths. We sought to determine whether placentas from late-term pregnancies and unexplained stillbirth show oxidative damage and other biochemical signs of aging. We also aimed to develop an in vitro term placental explant culture model to test the aging pathways. We collected placentas from women at 37-39 weeks' gestation (early-term and term), late-term, and with unexplained stillbirth. We used immunohistochemistry to compare the 3 groups for: DNA/RNA oxidation (8-hydroxy-deoxyguanosine), lysosomal distribution (lysosome-associated membrane protein 2), lipid oxidation (4-hydroxynonenal), and autophagosome size (microtubule-associated proteins 1A/1B light chain 3B, LC3B). The expression of aldehyde oxidase 1 was measured by real-time polymerase chain reaction. Using a placental explant culture model, we tested the hypothesis that aldehyde oxidase 1 mediates oxidative damage to lipids in the placenta. Placentas from late-term pregnancies show increased aldehyde oxidase 1 expression, oxidation of DNA/RNA and lipid, perinuclear location of lysosomes, and larger autophagosomes compared to placentas from women delivered at 37-39 weeks. Stillbirth-associated placentas showed similar changes in oxidation of DNA/RNA and lipid, lysosomal location, and autophagosome size to placentas from late-term. Placental explants from term deliveries cultured in serum-free medium also showed evidence of oxidation of lipid, perinuclear lysosomes, and larger autophagosomes, changes that were blocked by the G-protein-coupled estrogen receptor 1 agonist G1, while the oxidation of lipid was blocked by the

  3. ATG16L1 governs placental infection risk and preterm birth in mice and women.

    Science.gov (United States)

    Cao, Bin; Macones, Colin; Mysorekar, Indira U

    2016-12-22

    The placenta is a barrier against maternal-fetal transmission of pathogens. Placental infections can cause several adverse pregnancy outcomes, including preterm birth (PTB). Yet, we have limited knowledge regarding the mechanisms the placenta uses to control infections. Here, we show that autophagy, a cellular recycling pathway important for host defense against pathogens, and the autophagy gene Atg16L1 play a key role in placental defense and are negatively associated with PTB in pregnant women. First, we demonstrate that placentas from women who delivered preterm exhibit reduced autophagy activity and are associated with higher infection indicators. Second, we identify the cellular location of the autophagy activity as being in syncytial trophoblasts. Third, we demonstrate that higher levels of autophagy and ATG16L1 in human trophoblasts were associated with increased resistance to infection. Accordingly, loss of autophagy or ATG16L1 impaired trophoblast antibacterial defenses. Fourth, we show that Atg16l1-deficient mice gave birth prematurely upon an inflammatory stimulus and their placentas were significantly less able to withstand infection. Finally, global induction of autophagy in both mouse placentas and human trophoblasts increased infection resistance. Our study has significant implications for understanding the etiology of placental infections and prematurity and developing strategies to mitigate placental infection-induced PTB.

  4. Implementation of a quality system (ISO 9000 series) for placental blood banking.

    Science.gov (United States)

    Sirchia, G; Rebulla, P; Lecchi, L; Mozzi, F; Crepaldi, R; Parravicini, A

    1998-02-01

    Although placental blood has recently become a new source of hematopoietic progenitors for marrow replacement, limited attention has been given to systems suitable to ensure the short-term and long-term quality of placental blood units used for transplantation. In this article, we describe a quality system for placental blood banking developed in accord with ISO 9002 norms at Milano Cord Blood Bank. The quality system is the organizational structure, procedures, processes, and resources needed to implement quality management. ISO 9002 is a model for quality assurance in production, installation, and servicing, which includes a number of clauses providing guidance for the implementation of the quality system. The quality system was started by the bank medical director with step 1: the general quality plan, which included (a) the written description of mission, objectives, technical and organizational policies, and staff organization chart of the placental blood bank, (b) the definition and acquisition of adequate financial, human, and structural resources, (c) the appointment of a quality system head independent from the production laboratory and reporting directly to the medical director. Tasks of the quality system head were (a) to identify the placental blood banking process together with the placental blood bank personnel, (b) to implement a documentation plan finalized at the production and maintenance of (i) the quality manual, which provides a summary on how the bank operates with a quality system in compliance with the ISO 9002 clauses, (ii) the general procedures (or quality system procedures), which provide more detail on selected clauses, including at least those prescribed by the ISO 9002 standard, (iii) the operative procedures (or process procedures), which describe in detail the process of placental blood banking and how technical activities must be performed, (iv) the work instructions, which provide stepwise descriptions of individual activities, (v

  5. Ancestral capture of syncytin-Car1, a fusogenic endogenous retroviral envelope gene involved in placentation and conserved in Carnivora.

    Science.gov (United States)

    Cornelis, Guillaume; Heidmann, Odile; Bernard-Stoecklin, Sibylle; Reynaud, Karine; Véron, Géraldine; Mulot, Baptiste; Dupressoir, Anne; Heidmann, Thierry

    2012-02-14

    Syncytins are envelope protein genes of retroviral origin that have been captured for a function in placentation. Two such genes have already been identified in simians, two distinct, unrelated genes have been identified in Muridae, and a fifth gene has been identified in the rabbit. Here, we searched for similar genes in the Laurasiatheria clade, which diverged from Euarchontoglires--primates, rodents, and lagomorphs--shortly after mammalian radiation (100 Mya). In silico search for envelope protein genes with full-coding capacity within the dog and cat genomes identified several candidate genes, with one common to both species that displayed placenta-specific expression, which was revealed by RT-PCR analysis of a large panel of tissues. This gene belongs to a degenerate endogenous retroviral element, with precise proviral integration at a site common to dog and cat. Cloning of the gene for an ex vivo pseudotype assay showed fusogenicity on both dog and cat cells. In situ hybridization on placenta sections from both species showed specific expression at the level of the invasive fetal villi within the placental junctional zone, where trophoblast cells fuse into a syncytiotrophoblast layer to form the maternofetal interface. Finally, we show that the gene is conserved among a series of 26 Carnivora representatives, with evidence for purifying selection and conservation of fusogenic activity. The gene is not found in the Pholidota order and, therefore, it was captured before Carnivora radiation, between 60 and 85 Mya. This gene is the oldest syncytin gene identified to date, and it is the first in a new major clade of eutherian mammals.

  6. Polychlorinated biphenyls (PCBs) decrease the placental syncytiotrophoblast volume and increase Placental Growth Factor (PlGF) in the placenta of normal pregnancy.

    Science.gov (United States)

    Tsuji, M; Aiko, Y; Kawamoto, T; T Hachisuga; Kooriyama, C; Myoga, M; Tomonaga, C; Matsumura, F; Anan, A; Tanaka, M; Yu, H S; Fujisawa, Y; Suga, R; Shibata, E

    2013-07-01

    Polychlorinated biphenyls (PCBs) are a class of biologically active, highly stable compounds. Exposure risks include consumption of fatty fish, meat, dairy products and human breast milk, as well as environmental and occupational settings. Numerous reports have described PCB-dependent adverse effects on human fetal growth, including increased risk for IUGR, changes in endocrine function and hormone metabolism, and immunosuppressive and neurological deficits. Here we test the prediction that in utero PCB exposure adversely effects placental morphology, potentially leading to placental insufficiency en route to fetal growth restriction. PCB homologs (10) were measured in the maternal and fetal blood of a small cohort of normotensive pregnancies (22) by gas chromatography-mass spectrometry. PCB levels were compared with angiogenesis associated proteins Placental Growth Factor (PlGF) and sFlt-1, determined by ELISA, and the total estimated syncytiotrophoblast (ST) volume. Significant associations between PCB exposure and both PlGF and ST volume were identified. PCB effects on placenta morphology and predicted function are discussed. These results demonstrate that the human placenta, including ST, is a target of PCB toxicity, and that current environmental PCB exposure levels are a risk to reproductive health. Copyright © 2013 Elsevier Ltd. All rights reserved.

  7. Placental mesenchymal dysplasia: chronological observation of placental images during gestation and review of the literature.

    Science.gov (United States)

    Ohira, Satoshi; Ookubo, Nao; Tanaka, Kyoko; Takatsu, Akiko; Kobara, Hisanori; Kikuchi, Norihiko; Ohya, Ayumi; Kanai, Makoto; Shiozawa, Tanri

    2013-01-01

    Placental mesenchymal dysplasia (PMD) is characterized by multiple hypoechoic vesicles which are similar to molar changes in the placenta; however, the process of such morphological changes of PMD during pregnancy has not been fully understood. We performed a review of all PMD cases published in English and identified 49 articles including 110 cases. With regard to the gestational age at which the multicystic pattern was seen, approximately 70% of cases were diagnosed at 13-20 weeks of gestation. Another characteristic feature of PMD is varicose dilation of fetal chorionic vessels. As many as 90% of cases were diagnosed as placenta with dilated fetal chorionic vessels in the third trimester. We also report a case of PMD which was found at 10 weeks of gestation according to ultrasonic molar patterns. Serial observations of the placenta using ultrasound and magnetic resonance imaging revealed that multicystic lesions became smaller after 23 weeks. In contrast, dilated placental vessels on the fetal side became apparent at 38 weeks. The present review highlights that placental vesicular lesions of PMD may precede dilation of fetal chorionic vessels during pregnancy. It also indicates the potential of a gradual reduction in size of PMD's placental vesicular lesions by serial study of placental images. Copyright © 2013 S. Karger AG, Basel.

  8. 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...

  9. Metallothionein expression in placental tissue in Menkes' disease

    DEFF Research Database (Denmark)

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

    1995-01-01

    and children affected by Menkes' disease an additional MT immunostaining appeared in the Hofbauer cells of the chorionic villi. This staining was associated with an increased content of copper as measured by NAA. We conclude that the immunohistochemical demonstration of MT reflects the copper content and may...

  10. Placentation in the Amazonian manatee (Trichechus inunguis)

    DEFF Research Database (Denmark)

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

    2008-01-01

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

  11. Hyperemesis gravidarum and placental dysfunction disorders

    OpenAIRE

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

    2016-01-01

    BACKGROUND: Evidence about the consequence of hyperemesis gravidarum (HG) on pregnancy outcomes is still inconclusive. In this study, we evaluated if occurrence of hyperemesis gravidarum is associated with placental dysfunction disorders and neonatal outcomes. METHODS: A prospective cohort study was conducted in a maternal and child health primary care referral center, Budi Kemuliaan Hospital and its branch, in Jakarta, Indonesia. 2252 pregnant women visiting the hospital for regular antenata...

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

    Science.gov (United States)

    Redman, Christopher W G; Staff, Anne Cathrine

    2015-10-01

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

  13. [Maternal-placental interactions and fetal programming].

    Science.gov (United States)

    Kadyrov, M; Moser, G; Rath, W; Kweider, N; Wruck, C J; Pufe, T; Huppertz, B

    2013-06-01

    Pregnancy-related complications not only represent a risk for maternal and fetal morbidity and mortality, but are also a risk for several diseases later in life. Many epidemiological studies have shown clear associations between an adverse intrauterine environment and an increased risk of diabetes, hypertension, cardiovascular disease, depression, obesity, and other chronic diseases in the adult. Some of these syndromes could be prevented by avoiding adverse stimuli or insults including psychological stress during pregnancy, intake of drugs, insufficient diet and substandard working conditions. Hence, all of these stimuli have the potential to alter health later in life. The placenta plays a key role in regulating the nutrient supply to the fetus and producing hormones that control the fetal as well as the maternal metabolism. Thus, any factor or stimulus that alters the function of the hormone producing placental trophoblast will provoke critical alterations of placental function and hence could induce programming of the fetus. The factors that change placental development may interfere with nutrient and oxygen supply to the fetus. This may be achieved by a direct disturbance of the placental barrier or more indirectly by, e. g., disturbing trophoblast invasion. For both path-ways, the respective pathologies are known: while preeclampsia is caused by alterations of the villous trophoblast, intra-uterine growth restriction is caused by insufficient invasion of the extravillous trophoblast. In both cases the effect can be undernutrition and/or fetal hypoxia, both of which adversely affect organ development, especially of brain and heart. However, the mechanisms responsible for disturbances of trophoblast differentiation and function remain elusive. © Georg Thieme Verlag KG Stuttgart · New York.

  14. Effect of incubation system on the development of intestinal villi, metabolism, and performance of one- to forty-day-old broiler chickens

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    Araceli Pacheco Villanueva

    Full Text Available ABSTRACT An experiment was performed to evaluate the effect of the incubation system ― multiple-stage (MS and single-stage (SS ― on the characteristics at hatching, intestinal morphology, metabolism, and performance of Cobb-500 chickens from 1 to 40 d of age. A total of 1,968 fertile eggs were incubated in two setters under commercial conditions. Birds hatched in SS were longer than those hatched in MS, and the females had higher relative intestinal weight compared with males. However, at hatching, there were no differences in BW and yolk-free body mass from incubation system or sex. In the period from 1-40 d, the birds hatched in SS were heavier, had higher weight gain and better adjusted feed conversion, without differences in feed intake and feed conversion. This result is due mainly to MS females, which always, although in some periods only numerically, exhibited worse responses than the other treatment, lowering the average MS bird performance. Sex influenced the duodenal villi height in chickens at 0 d; females showed larger villi than males. Moreover, the birds hatched in SS had deeper crypts than those hatched in MS. At 7 d, because males had higher feed intake, the differences in duodenal villi height found at hatching disappeared, leaving only a gender effect on jejunum crypt depth: females showed deeper crypts. As regards the metabolism coefficients of nutrients from 5 to 7 d, females were more efficient in metabolizing energy and showed higher apparent metabolizable energy corrected for nitrogen values than males, with no differences caused by the incubation system. The best incubation conditions are obtained with the single-stage system, based on the improved broiler performance (2.98%, especially in the females (5.04%.

  15. Contribution of different placental cells to the expression and stimulation of antimicrobial proteins (AMPs).

    Science.gov (United States)

    Klaffenbach, D; Friedrich, D; Strick, R; Strissel, P L; Beckmann, M W; Rascher, W; Gessner, A; Dötsch, J; Meissner, U; Schnare, M

    2011-11-01

    The placenta is a major barrier that prevents potentially infectious agents from causing fetal diseases or related complications during pregnancy. Therefore, we postulated that the placenta might express a broad repertoire of antimicrobial proteins as well as inflammatory chemokines and cytokines to combat invading microorganisms. Here we demonstrate that placental cells indeed express a wide range of AMPs (antimicrobial peptides and proteins) including bactericidal/permeability-increasing protein (BPI), secretory leukocyte protease inhibitor (SLPI), human β-defensin 2 (hBD2), acyloxyacyl hydrolase (AOAH), and cathelicidin (CAP18). In addition, these cells also secrete pro-inflammatory cytokines and chemokines upon stimulation with bacterial ligands. Notably, we show that BPI expression by placental cells could be completely attributed to granulocytes while highly purified placental trophoblasts expressed only a subset of the AMPs like SLPI. Unexpectedly, trophoblast AMPs did not exhibit inducible secretion in response to various TLR ligands and further investigations showed that the unresponsiveness of trophoblasts to lipopolysaccharide (LPS) was due to a lack of TLR4 expression. In summary, we have shown that the expression of different AMPs can be allocated to various cells in the placenta and the repertoire of the AMPs expressed by placental cells is a result of a cooperation of leukocytes as well as cells from embryonic origin. Copyright © 2011 Elsevier Ltd. All rights reserved.

  16. Placental syncytiotrophoblast constitutes a major barrier to vertical transmission of Listeria monocytogenes.

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    Jennifer R Robbins

    2010-01-01

    Full Text Available Listeria monocytogenes is an important cause of maternal-fetal infections and serves as a model organism to study these important but poorly understood events. L. monocytogenes can infect non-phagocytic cells by two means: direct invasion and cell-to-cell spread. The relative contribution of each method to placental infection is controversial, as is the anatomical site of invasion. Here, we report for the first time the use of first trimester placental organ cultures to quantitatively analyze L. monocytogenes infection of the human placenta. Contrary to previous reports, we found that the syncytiotrophoblast, which constitutes most of the placental surface and is bathed in maternal blood, was highly resistant to L. monocytogenes infection by either internalin-mediated invasion or cell-to-cell spread. Instead, extravillous cytotrophoblasts-which anchor the placenta in the decidua (uterine lining and abundantly express E-cadherin-served as the primary portal of entry for L. monocytogenes from both extracellular and intracellular compartments. Subsequent bacterial dissemination to the villous stroma, where fetal capillaries are found, was hampered by further cellular and histological barriers. Our study suggests the placenta has evolved multiple mechanisms to resist pathogen infection, especially from maternal blood. These findings provide a novel explanation why almost all placental pathogens have intracellular life cycles: they may need maternal cells to reach the decidua and infect the placenta.

  17. Prediction and prevention of ischemic placental disease.

    Science.gov (United States)

    Friedman, Alexander M; Cleary, Kirsten L

    2014-04-01

    Preeclampsia, intrauterine growth restriction (IUGR), and placental abruption are obstetrical conditions that constitute the syndrome of ischemic placental disease or IPD, the leading cause of indicated preterm birth and an important cause of neonatal morbidity and mortality. While the phenotypic manifestations vary significantly for preeclampsia, IUGR, and abruption, these conditions may share a common underlying etiology as evidenced by: (1) shared clinical risk factors, (2) increased recurrence risk across pregnancies as well as increased co-occurrence of IPD conditions within a pregnancy, and (3) findings that suggest the underlying pathophysiologic processes may be similar. IPD is of major clinical importance and accounts for a large proportion of indicated preterm delivery ranging from the periviable to late preterm period. Successful prevention of IPD and resultant preterm delivery could substantially improve neonatal and maternal outcomes. This article will review the following topics: (1) The complicated research literature on aspirin and the prevention of preeclampsia and IUGR. (2) Research evidence on other medical interventions to prevent IPD. (3) New clinical interventions currently under investigations, including statins. (4) Current clinical recommendations for prevention of ischemic placental disease. Copyright © 2014 Elsevier Inc. All rights reserved.

  18. Intrauterine growth restriction and placental angiogenesis

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    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.

  19. Placental mesenchymal dysplasia: What every radiologist needs to know

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    Disha Mittal

    2017-01-01

    Full Text Available Placental mesenchymal dysplasia (PMD is an uncommon vascular anomaly of the placenta characterized by placentomegaly with multicystic placental lesion on ultrasonography and mesenchymal stem villous hyperplasia on histopathology. Placental mesenchymal dysplasia should be considered in the differential diagnosis of cases of multicystic placental lesion such as molar pregnancy, chorioangioma, subchorionic hematoma, and spontaneous abortion with hydropic placental changes. However, lack of high-velocity signals inside the lesion and a normal karyotype favor a diagnosis of PMD. PMD must be differentiated from gestational trophoblastic disease because management and outcomes differ. We report the case of an 18-year-old female at 15 weeks of gestation with sonographic findings suggestive of placental mesenchymal dysplasia. The diagnosis was confirmed on histopathology.

  20. Rheological and physiological consequences of conversion of the maternal spiral arteries for uteroplacental blood flow during human pregnancy.

    Science.gov (United States)

    Burton, G J; Woods, A W; Jauniaux, E; Kingdom, J C P

    2009-06-01

    Physiological conversion of the maternal spiral arteries is key to a successful human pregnancy. It involves loss of smooth muscle and the elastic lamina from the vessel wall as far as the inner third of the myometrium, and is associated with a 5-10-fold dilation at the vessel mouth. Failure of conversion accompanies common complications of pregnancy, such as early-onset preeclampsia and fetal growth restriction. Here, we model the effects of terminal dilation on inflow of blood into the placental intervillous space at term, using dimensions in the literature derived from three-dimensional reconstructions. We observe that dilation slows the rate of flow from 2 to 3m/s in the non-dilated part of an artery of 0.4-0.5mm diameter to approximately 10 cm/s at the 2.5mm diameter mouth, depending on the exact radius and viscosity. This rate predicts a transit time through the intervillous space of approximately 25s, which matches observed times closely. The model shows that in the absence of conversion blood will enter the intervillous space as a turbulent jet at rates of 1-2m/s. We speculate that the high momentum will damage villous architecture, rupturing anchoring villi and creating echogenic cystic lesions as evidenced by ultrasound. The retention of smooth muscle will also increase the risk of spontaneous vasoconstriction and ischaemia-reperfusion injury, generating oxidative stress. Dilation has a surprisingly modest impact on total blood flow, and so we suggest the placental pathology associated with deficient conversion is dominated by rheological consequences rather than chronic hypoxia.

  1. Evidence for placental compensation in cattle.

    Science.gov (United States)

    Van Eetvelde, M; Kamal, M M; Hostens, M; Vandaele, L; Fiems, L O; Opsomer, G

    2016-08-01

    Prenatal development is known to be extremely sensitive to maternal and environmental challenges. In this study, we hypothesize that body growth and lactation during gestation in cattle reduce nutrient availability for the pregnant uterus, with consequences for placental development. Fetal membranes of 16 growing heifers and 27 fully grown cows of the Belgian Blue (BB) breed were compared to determine the effect of body growth on placental development. Furthermore, the fetal membranes of 49 lactating Holstein Friesian (HF) cows and 27 HF heifers were compared to study the impact of dam lactation compared to dam body growth. After parturition, calf birth weight and body measurements of dam and calf were recorded, as well as weight of total fetal membranes, cotyledons and intercotyledonary membranes. All cotyledons were individually measured to calculate both the surface of each individual cotyledon and the total cotyledonary surface per placenta. Total cotyledonary surface was unaffected by breed or the breed×parity interaction. Besides a 0.3 kg lower cotyledonary weight (P=0.007), heifer placentas had a smaller total cotyledonary surface compared with placentas of cows (0.48±0.017 v. 0.54±0.014 m2, respectively, P<0.001). Within the BB breed, fetal membranes of heifers had a 1.5 kg lower total weight and 1.0 kg lower intercotyledonary membrane weight (P<0.005) compared with cows. A cotyledon number of only 91±5.4 was found in multiparous BB dams, while growing BB heifers had a higher cotyledon number (126±6.7, P<0.001), but a greater proportion of smaller cotyledons (<40 cm2). Within the HF breed, no parity effect on intercotyledonary membrane weight, cotyledon number and individual cotyledonary surface was found. Placental efficiency (calf weight/total cotyledonary surface) was similar in HF and BB heifers but significantly higher in multiparous BB compared with multiparous HF dams (106.0±20.45 v. 74.3±12.27 kg/m2, respectively, P<0.001). Furthermore, a

  2. Presentation of Placental Site Trophoblastic Tumor with Amenorrhea

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    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.

  3. Placental weight in pregnancies with high or low hemoglobin concentrations.

    Science.gov (United States)

    Larsen, Sandra; Bjelland, Elisabeth Krefting; Haavaldsen, Camilla; Eskild, Anne

    2016-11-01

    To study the associations of maternal hemoglobin concentrations with placental weight and placental to birthweight ratio. In this retrospective cohort study, we included all singleton pregnancies during the years 1998-2013 at a large public hospital in Norway (n=57062). We compared mean placental weight and placental to birthweight ratio according to maternal hemoglobin concentrations: 13.5g/dl. The associations of maternal hemoglobin concentrations with placental weight and placental to birthweight ratio were estimated by linear regression analyses, and adjustments were made for gestational age at birth, preeclampsia, parity, maternal age, diabetes, body mass index, smoking, offspring sex and year of birth. In pregnancies with maternal hemoglobin concentrations hemoglobin concentrations 9-13.5g/dl and 655.5g (SD 147.7g) for hemoglobin concentrations >13.5g/dl (ANOVA, phemoglobin concentrations hemoglobin concentrations 9-13.5g/dl (0.193 (SD 0.040)) and >13.5g/dl (0.193 (SD 0.043)). Adjustments for our study factors did not alter the estimates notably. Placental weight decreased with increasing maternal hemoglobin concentrations. The high placental to birthweight ratio with low maternal hemoglobin concentrations suggests differences in placental growth relative to fetal growth across maternal hemoglobin concentrations. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

  4. Iron homeostasis in mother and child during placental malaria infection.

    Science.gov (United States)

    Van Santen, Susanne; de Mast, Quirijn; Luty, Adrian J F; Wiegerinck, Erwin T; Van der Ven, Andre J A M; Swinkels, Dorine W

    2011-01-01

    In malaria-endemic areas, iron deficiency and placental Plasmodium falciparum infection commonly coexist. In primigravidae and their newborns, hepcidin and other iron parameters were evaluated in groups and classified according to placental P. falciparum and maternal anemia status. Mothers had relatively high hepcidin levels considering their low iron status. In cord blood, levels of hepcidin, hemoglobin, and other iron parameters were also similar for groups. We conclude that maternal hepcidin is not significantly altered as a function of placental infection and/or anemia. Importantly, fetal hemoglobin and iron status were also unaffected, regardless of the presence of placental infection or maternal anemia.

  5. Iron Homeostasis in Mother and Child during Placental Malaria Infection

    Science.gov (United States)

    Van Santen, Susanne; de Mast, Quirijn; Luty, Adrian J. F.; Wiegerinck, Erwin T.; Van der Ven, Andre J. A. M.; Swinkels, Dorine W.

    2011-01-01

    In malaria-endemic areas, iron deficiency and placental Plasmodium falciparum infection commonly coexist. In primigravidae and their newborns, hepcidin and other iron parameters were evaluated in groups and classified according to placental P. falciparum and maternal anemia status. Mothers had relatively high hepcidin levels considering their low iron status. In cord blood, levels of hepcidin, hemoglobin, and other iron parameters were also similar for groups. We conclude that maternal hepcidin is not significantly altered as a function of placental infection and/or anemia. Importantly, fetal hemoglobin and iron status were also unaffected, regardless of the presence of placental infection or maternal anemia. PMID:21212218

  6. Placental Abnormalities and Preeclampsia in Trisomy 13 Pregnancies

    Directory of Open Access Journals (Sweden)

    Chih-Ping Chen

    2009-03-01

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

  7. 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

  8. Mitogenomic relationships of placental mammals and molecular estimates of their divergences.

    Science.gov (United States)

    Arnason, Ulfur; Adegoke, Joseph A; Gullberg, Anette; Harley, Eric H; Janke, Axel; Kullberg, Morgan

    2008-09-15

    divergences among recent humans become placed approximately 270,000 years ago, i.e. approximately 100,000 years earlier than the traditional age of "Mitochondrial Eve". Comparison between the two new mt genomes of Hylomys suillus (short-tailed gymnure) patently demonstrates the inconsistency that may exist between taxonomic designations and molecular difference, as the distance between these two supposedly conspecific genomes exceeds that of the three elephantid genera Elephas, Mammuthus and Loxodonta. In accordance with the progressive use of the term Placentalia for extant orders and extinct taxa falling within this group we forward new proposals for the names of some superordinal clades of placental mammals.

  9. 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

  10. Adrenomedullin 2/intermedin regulates HLA-G in human trophoblasts.

    Science.gov (United States)

    Chauhan, Madhu; Balakrishnan, Meena; Yallampalli, Uma; Endsley, Janice; Hankins, Gary D V; Theiler, Regan; Yallampalli, Chandra

    2011-12-01

    Adrenomedullin 2 (ADM2), also referred to as intermedin (IMD), is expressed in trophoblast cells in human placenta and enhances the invasion and migration of first-trimester HTR-8SV/neo cells. Further infusion of ADM2 antagonist in pregnant rat causes fetoplacental growth restriction, suggesting a role for ADM2 in maintaining a successful pregnancy. This study was undertaken to assess whether ADM2 protein is present in decidual tissue and colocalized with HLA-G-positive cytotrophoblast cells and natural killer cells; to assess whether ADM2 regulates expression of HLA-G in trophoblast cells; and to identify whether mitogen-activated protein kinase (MAPK) signaling pathway is involved in ADM2-induced trophoblast cell invasion and migration. Using immunohistochemical methods and RT-PCR, this study shows that ADM2 protein is colocalized with HLA-G-expressing cytotrophoblast cells as well as with NCAM1 (CD56) immunoreactivity in human first-trimester decidual tissue, and that ADM2 mRNA is expressed in peripheral blood natural killer cells. Further, ADM2 dose dependently increases the expression of HLA-G antigen in HTR-8SV/neo cells as well as in term placental villi explants, suggesting involvement of ADM2 in the regulation of HLA-G in trophoblast cells. In addition, interference with the activity of RAF and MAPK3/1 by their inhibitors, manumycin and U0126, respectively, reduces ADM2-induced HTR-8SV/neo cell invasion and migration. In summary, this study suggests a potential involvement for ADM2 in regulating HLA-G antigen at the maternal-fetal interface in human pregnancy and facilitating trophoblast invasion and migration via MAPK3/1 phosphorylation.

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

    NARCIS (Netherlands)

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

    2013-01-01

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

  12. 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

  13. Role of the placental Vitamin D receptor in modulating feto-placental growth in Fetal growth restriction and Preeclampsia-affected pregnancies.

    Directory of Open Access Journals (Sweden)

    Padma eMurthi

    2016-02-01

    Full Text Available Fetal growth restriction (FGR is a common pregnancy complication that affects up to 5% of pregnancies worldwide. Recent studies demonstrate that Vitamin D deficiency is implicated in reduced fetal growth, which may be rescued by supplementation of Vitamin D. Despite this, the pathway(s by which Vitamin D modulate fetal growth remains to be investigated. Our own studies demonstrate that the Vitamin D receptor (VDR is significantly decreased in placentae from human pregnancies complicated by FGR and contributes to abnormal placental trophoblast apoptosis and differentiation and regulation of cell-cycle genes in vitro. Thus, Vitamin D signalling is important for normal placental function and fetal growth. This review discusses the association of Vitamin D with fetal growth, the function of Vitamin D and its receptor in pregnancy, as well as the functional significance of a placental source of Vitamin D in FGR. Additionally, we propose that for Vitamin D to be clinically effective to prevent and manage FGR, the molecular mechanisms of Vitamin D and its receptor in modulating fetal growth requires further investigation.

  14. Invasión trofoblástica en el embarazo normal (II: Placentación profunda (Trophoblastic invasion in normal pregnancy (II: Deep placentation

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    Eduardo Reyna-Villasmil

    2015-01-01

    Full Text Available Deep placentation in human pregnancy is done by deep invasion of the placental bed by the extravillous trophoblast, involving the decidua and the inner (junctional zone myometrium. Interstitial invasion of the stroma and endovascular trophoblast invasion of the spiral arteries both occur. Deep endovascular trophoblast invasion into the myometrial segments of spiral arteries is important for proper placental functioning. Decidua-associated vascular remodeling, which includes swelling and disorganization of the vascular smooth muscle, occurs during a period of rising placental oxygen. This early remodeling step may accommodate the progressively increasing maternal blood flow to the developing placenta. The subsequent trophoblast-associated remodeling step enhances and stabilizes the widening of the vessels, whereas the vascular smooth muscle and elastic lamina are replaced by a fibrinoid matrix with embedded trophoblast

  15. Disruption of lactogenesis by retained placental fragments.

    Science.gov (United States)

    Anderson, A M

    2001-05-01

    This case report describes a situation in which lack of milk production led the mother to seek help from a lactation consultant in private practice. Despite extensive breast stimulation with the baby at breast and mechanical breast expression, no milk was produced. Retained placenta was suspected by the lactation consultant. The mother was later diagnosed with placenta increta. Only when this condition was diagnosed and resolved did milk onset occur. It is important to evaluate for retained placental fragments when lactation appears to be delayed.

  16. Placental findings in late-onset SGA births without Doppler signs of placental insufficiency.

    Science.gov (United States)

    Parra-Saavedra, M; Crovetto, F; Triunfo, S; Savchev, S; Peguero, A; Nadal, A; Parra, G; Gratacos, E; Figueras, F

    2013-12-01

    To describe placental pathological findings in late-onset small-for-gestational age (SGA) births for which Doppler signs of placental insufficiency are lacking. A series of placentas were evaluated from singleton pregnancies of SGA births (birth weight below the 10th percentile) delivered after 34 weeks with normal umbilical artery Doppler (pulsatility index below the 95th percentile), that were matched by gestational age with adequate-for-gestational age (AGA) controls. Using a hierarchical and standardized system, placental lesions were classified histologically as consequence of maternal underperfusion, fetal underperfusion or inflammation. A total of 284 placentas were evaluated (142 SGA and 142 AGA). In the SGA group, 54.2% (77/142) of the placentas had weights below the 3rd percentile for GA while it was a 9.9% (14/142) in the AGA group (p SGA placentas were free of histological abnormalities, while it was 74.6% (106/142) in the AGA group (p SGA placentas (111/142) there were a total of 161 lesions, attributable to MUP in 64% (103/161), FUP in 15.5% (25/161), and inflammation in 20.5% (33/161). In most placentas of term SGA neonates with normal UA Doppler histological abnormalities secondary to maternal underperfusion prevail, reflecting latent insufficiency in uteroplacental blood supply. This is consistent with the higher risk of adverse perinatal outcome reported in this population and underscores a need for new markers of placental disease. A significant proportion of late-onset SGA births with normal umbilical artery Doppler may still be explained by placental insufficiency. Copyright © 2013 Elsevier Ltd. All rights reserved.

  17. Relationship between placental thickness and growth parameters in ...

    African Journals Online (AJOL)

    STORAGESEVER

    2009-01-19

    Jan 19, 2009 ... weight (Hebbar, 2003). These growth parameters are adversely affected by insufficient nutrients reaching the foetus through the placenta. In these foetuses the placental is often thin. A placental thickness of less than. 2.5 cm is usually associated with intrauterine growth retardation (IUGR) (Kunlmann and ...

  18. Maternal placental syndromes: pathological mechanisms and long-term consequences

    NARCIS (Netherlands)

    Veerbeek, J.H.W.

    2015-01-01

    Preeclampsia, intra uterine growth restriction (IUGR) and placental abruption are major contributors to maternal and perinatal morbidity and mortality. In these disorders the placenta is a key aetiological factor and therefore preeclampsia, IUGR and placental abruption are also referred to as

  19. Evaluation of Relationship between Opioid Addiction and Placental Abruption

    Directory of Open Access Journals (Sweden)

    Z. Salari

    2007-04-01

    Full Text Available Introduction & Objective: Placental abruption is one of the most common causes of bleeding during pregnancy. Multiple factors are known to be associated with increased risk of placental abruption as alcohol and cocaine use and cigarette smoking but there are fewer studies about the importance of opioid abuse in placental abruption. The aim of this study was to determine the relationship between opioid addiction and placental abruption occurrence. Materials & Methods: In this case-control study 51 women with placental abruption and 147 women with normal pregnancy were studied. Data were collected using questionnaire and were analyzed using SPSS12. Odds ratio was used for standing the relation of demographic factors and risk factors with incidence of placental abruption, logistic regression analysis was applied to identify the confounding factors. Results: Results showed that 37.3% of the women in the case group and 14.3% of women in the control-group were opioid addiction (P=0.001. The mean of gestational age was 36-41 weeks. 31.3% of the women with placental abruption and 1.3% of the women in the control group had delivery before 36 weeks gestation (P=0. Conclusion: Our results showed that opioid addiction increases of placental abruption probability 2.6 times.

  20. Relación entre Área Total y Área Epitelial de vellosidades placentarias porcinas en diferentes estadíos gestacionales Relationship between Total area and Epithelial area of porcine placental villi at different gestational periods

    OpenAIRE

    Merkis, C. I.; Cristofolini, A. L.; M. A Franchino; E Moschetti; M. A Koncurat

    2005-01-01

    La placenta porcina es epiteliocorial y no invasiva. Las interdigitaciones entre el epitelio trofoblástico fetal y el epitelio uterino conforman vellosidades de las cuales depende el crecimiento y desarrollo fetal. El objetivo fue determinar el Área Total y el Área Epitelial de vellosidades placentarias porcinas en diferentes períodos gestacionales mediante un analizador digital de imágenes. Se realizaron preparados histológicos de 5 placentas porcinas de cada período gestacional estudiado: 2...

  1. 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.

  2. In vitro placental pressure-flow behaviour is non-linear and depends on the external pressure

    NARCIS (Netherlands)

    Kranenburg-Lakeman, P.; Boer, K.; van Gemert, M. J.; Vergroesen, I.

    2001-01-01

    OBJECTIVE: To study pressure-flow behaviour of in vitro placentas under normal simulated conditions and during raised external pressures, to simulate in vivo placental hemodynamic function, and as a model for polyhydramnios and the supine hypotension syndrome. DESIGN: Eleven normal term human

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

    DEFF Research Database (Denmark)

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

    2002-01-01

    Placental GH is thought to be responsible for the rise in maternal IGF-I during pregnancy and is considered to be important for fetal growth. In this prospective longitudinal study of healthy pregnant women, we investigated determinants of placental GH in maternal serum. Serum was obtained from 455...... women with normal singleton pregnancies at approximately 19 and 28 wk gestation. Serum placental GH concentrations were measured by a highly specific immunoradiometric assay, and fetal size was measured by ultrasound. Data on birth weight, gender, prepregnancy body mass index (BMI), parity, and smoking.......002). Placental GH at second examination was positively correlated with gestational age (P = 0.002) and negatively correlated with prepregnancy BMI (P = 0.039). Placental GH correlated with fetal weight at approximately 28 wk gestation (P = 0.002) but did not predict birth weight at term. Our study supports...

  4. Clinical development of placental malaria vaccines and immunoassays harmonization

    DEFF Research Database (Denmark)

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

    2016-01-01

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

  5. 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.

  6. Placental growth response to maternal insulin in early pregnancy.

    Science.gov (United States)

    O'Tierney-Ginn, Perrie; Presley, Larraine; Myers, Stephen; Catalano, Patrick

    2015-01-01

    The sensitivity of the placenta to maternal insulin remains controversial. Early pregnancy may be a time of increased placental sensitivity to maternal insulin because insulin receptors are abundant on the syncytiotrophoblast in the first trimester but are far fewer at term. Maternal insulin secretory response in early, but not late, pregnancy is positively associated with placental growth. This is a secondary analysis of a cohort of women (n = 40) recruited before pregnancy. An iv glucose tolerance test was administered before pregnancy and in early (12-14 weeks) and late (34-36 weeks) pregnancy. Placental volume throughout gestation (in a subset of women via 3-dimensional ultrasound) and weight at birth were recorded. Total insulin secretory response in early pregnancy was positively associated with placental volume in early pregnancy (R = 0.79, P = 0.04) and placental weight at term (R = 0.42, P = 0.007). Insulin secretory response before and in late pregnancy was not significantly associated with placental growth. Although neonatal fat mass was strongly correlated with placental weight at term (R = 0.449, P = 0.0003), maternal insulin secretory response was related to neonatal fat mass only at birth in male offspring (R = 0.59, P = 0.008). Maternal insulin secretory response in early pregnancy was strongly related to placental weight at birth. Thus, in early pregnancy, increased maternal insulin response as seen in obesity and gestational diabetes mellitus may be a key influence on placental growth, possibly due to the enhanced presence of placental insulin receptors on the maternal villous membrane early in gestation.

  7. Exercise in pregnancy: an association with placental weight?

    Science.gov (United States)

    Hilde, Gunvor; Eskild, Anne; Owe, Katrine Mari; Bø, Kari; Bjelland, Elisabeth K

    2017-02-01

    Women with high levels of physical exercise have an increased demand for oxygen and nutrients. Thus, in pregnancies of women with high levels of exercise, it is conceivable that the supply of oxygen and nutrients to the placenta is suboptimal, and growth could be impaired. The objective was to study the association of frequency of exercise during pregnancy with placental weight and placental to birthweight ratio. This was a prospective study of 80,515 singleton pregnancies in the Norwegian Mother and Child Cohort Study. Frequency of exercise was self-reported by a questionnaire at pregnancy weeks 17 and 30. Information on placental weight and birthweight was obtained by linkage to the Medical Birth Registry of Norway. Placental weight decreased with increasing frequency of exercise (tests for trend, P pregnancy week 17, the crude mean placental weight was 686.1 g compared with 667.3 g in women exercising ≥6 times weekly (difference, 18.8 g; 95% confidence interval, 12.0-25.5). Likewise, in nonexercisers in pregnancy week 30, crude mean placental weight was 684.9 g compared with 661.6 g in women exercising ≥6 times weekly (difference, 23.3 g; 95% confidence interval, 14.9-31.6). The largest difference in crude mean placental weight was seen between nonexercisers at both time points and women exercising ≥6 times weekly at both time points (difference, 31.7 g; 95% confidence interval, 19.2-44.2). Frequency of exercise was not associated with placental to birthweight ratio. We found decreasing placental weight with increasing frequency of exercise in pregnancy. The difference in placental weight between nonexercisers and women with exercising ≥6 times weekly was small and may have no clinical implications. Copyright © 2016 Elsevier Inc. All rights reserved.

  8. 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.

  9. Hypoxia: From Placental Development to Fetal Programming.

    Science.gov (United States)

    Fajersztajn, Lais; Veras, Mariana Matera

    2017-10-16

    Hypoxia may influence normal and different pathological processes. Low oxygenation activates a variety of responses, many of them regulated by hypoxia-inducible factor 1 complex, which is mostly involved in cellular control of O 2 consumption and delivery, inhibition of growth and development, and promotion of anaerobic metabolism. Hypoxia plays a significant physiological role in fetal development; it is involved in different embryonic processes, for example, placentation, angiogenesis, and hematopoiesis. More recently, fetal hypoxia has been associated directly or indirectly with fetal programming of heart, brain, and kidney function and metabolism in adulthood. In this review, the role of hypoxia in fetal development, placentation, and fetal programming is summarized. Hypoxia is a basic mechanism involved in different pregnancy disorders and fetal health developmental complications. Although there are scientific data showing that hypoxia mediates changes in the growth trajectory of the fetus, modulates gene expression by epigenetic mechanisms, and determines the health status later in adulthood, more mechanistic studies are needed. Furthermore, if we consider that intrauterine hypoxia is not a rare event, and can be a consequence of unavoidable exposures to air pollution, nutritional deficiencies, obesity, and other very common conditions (drug addiction and stress), the health of future generations may be damaged and the incidence of some diseases will markedly increase as a consequence of disturbed fetal programming. Birth Defects Research 109:1377-1385, 2017.© 2017 Wiley Periodicals, Inc. © 2017 Wiley Periodicals, Inc.

  10. 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.

  11. Protein Profiling of Preeclampsia Placental Tissues

    Science.gov (United States)

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

    2014-01-01

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

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

    DEFF Research Database (Denmark)

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

    2017-01-01

    and the CSA binding region of VAR2CSA has been identified as a promising vaccine target against placental malaria. Here we designed adenovirus encoded virus-like particles (VLP) by co-encoding Simian Immunodeficiency Virus (SIV) gag and VAR2CSA. The VAR2CSA antigen was fused to the transmembrane (TM......The malaria parasite Plasmodium falciparum presents antigens on the infected erythrocyte surface that bind human receptors expressed on the vascular endothelium. The VAR2CSA mediated binding to a distinct chondroitin sulphate A (CSA) is a crucial step in the pathophysiology of placental malaria......CSA fused to HA TM-CT was significantly superior in inducing ID1-ID2a specific antibodies after the first immunization. A sequential study was performed to include a comparison to the soluble VAR2CSA protein vaccine, which has entered a phase I clinical trial (NCT02647489). The results revealed...

  13. Prognosis after maternal placental events and revascularization: PAMPER study.

    Science.gov (United States)

    Ray, Joel G; Booth, Gillian L; Alter, David A; Vermeulen, Marian J

    2016-01-01

    Middle-aged women are at higher risk than men of death after coronary artery revascularization. Maternal placental syndromes (gestational hypertension, preeclampsia, placental abruption, and placental infarction) are associated with premature coronary artery disease, but their influence on survival after coronary artery revascularization is unknown. The purpose of this study was to determine whether a history of maternal placental syndromes alters the risk of death after coronary artery revascularization in middle-aged women. We completed a population-based retrospective cohort study among all hospitals in Ontario, Canada, where universal health care includes all aspects of antenatal and delivery care as well as all outpatient and inpatient health care, which includes coronary revascularization. We included 1985 middle-aged women who underwent a first percutaneous coronary intervention or coronary artery bypass grafting between 1993 and 2012 and who had ≥1 previous delivery. We excluded those with cardiovascular disease ≤1 year before or coronary revascularization ≤90 days after any delivery. The main study outcome, determined a priori, was all-cause death. Hazard ratios were adjusted for age, socioeconomic status, parity, revascularization type, time since last delivery, hypertension, diabetes mellitus, obesity, dyslipidemia, tobacco or drug dependence, and kidney disease. Three hundred sixty-two of 1985 women (18.2%) who underwent coronary artery revascularization had a previous maternal placental syndrome event. The mean age at index coronary revascularization was 45 years; percutaneous coronary intervention comprised approximately 80% of procedures. After a mean follow-up time of approximately 5 years, 41 deaths (2.2 per 100 person-years) occurred in women with previous maternal placental syndromes and 83 deaths (1.1 per 100 person-years) in women without maternal placental syndrome (adjusted hazard ratio, 1.96; 95% confidence interval, 1.29-2.99). Of the

  14. In vitro fertilization and embryo culture strongly impact the placental transcriptome in the mouse model.

    Directory of Open Access Journals (Sweden)

    Patricia Fauque

    Full Text Available BACKGROUND: Assisted Reproductive Technologies (ART are increasingly used in humans; however, their impact is now questioned. At blastocyst stage, the trophectoderm is directly in contact with an artificial medium environment, which can impact placental development. This study was designed to carry out an in-depth analysis of the placental transcriptome after ART in mice. METHODOLOGY/PRINCIPAL FINDINGS: Blastocysts were transferred either (1 after in vivo fertilization and development (control group or (2 after in vitro fertilization and embryo culture. Placentas were then analyzed at E10.5. Six percent of transcripts were altered at the two-fold threshold in placentas of manipulated embryos, 2/3 of transcripts being down-regulated. Strikingly, the X-chromosome harbors 11% of altered genes, 2/3 being induced. Imprinted genes were modified similarly to the X. Promoter composition analysis indicates that FOXA transcription factors may be involved in the transcriptional deregulations. CONCLUSIONS: For the first time, our study shows that in vitro fertilization associated with embryo culture strongly modify the placental expression profile, long after embryo manipulations, meaning that the stress of artificial environment is memorized after implantation. Expression of X and imprinted genes is also greatly modulated probably to adapt to adverse conditions. Our results highlight the importance of studying human placentas from ART.

  15. Expression of the vascular endothelial growth factor receptor neuropilin-1 at the human embryo-maternal interface.

    Science.gov (United States)

    Baston-Buest, Dunja M; Porn, Anne C; Schanz, Andrea; Kruessel, Jan-S; Janni, Wolfgang; Hess, Alexandra P

    2011-02-01

    Angiogenesis is required for successful implantation of the invading blastocyst. Vascular endothelial growth factor (VEGF) is an important key player in angiogenesis and vascular remodeling during the implantation process. Besides its well-characterized receptors VEGFR1 and VEGFR2, neuropilin-1 (NRP-1) has been shown to play an additional role in the signaling process of angiogenesis in human endometrium during the menstrual cycle, as a co-receptor of VEGF. These findings led to the hypothesis that NRP-1 might play a role in the vascular remodeling process during embryo implantation and the establishment of a pregnancy. NRP-1 mRNA transcript and protein expression were investigated in human choriocarcinoma cell lines (JEG-3, Jar and BeWo) aiming to evaluate the expression of NRP-1 in vitro, as well as in human decidua of all three trimesters of pregnancy, by western blot analysis (three samples of each trimester of pregnancy). The localization of NRP-1 in human decidua of all three trimesters of pregnancy was analyzed by immunohistochemistry (five samples of each trimester of pregnancy). NRP-1 transcript and protein were expressed in all cell lines examined. Corresponding to the analysis of human tissue by western blot and the localization by immunohistochemistry, NRP-1 protein higher expressed in samples of early pregnancy in comparison to the end of pregnancy. NRP-1 was expressed in the decidua, villi and invading cytotrophoblast of all samples investigated. This is the first study clearly showing the expression of NRP-1 in human decidua and trophoblast, suggesting an important role for the VEGF co-receptor NRP-1 besides the established receptor VEGFR2 at the embryo-maternal interface during embryonic implantation and placentation. Copyright © 2010 Elsevier Ireland Ltd. All rights reserved.

  16. DC-SIGN expression in Hofbauer cells may play an important role in immune tolerance in fetal chorionic villi during the development of preeclampsia.

    Science.gov (United States)

    Yang, Seung Woo; Cho, Eun Hee; Choi, So Young; Lee, Yun Kyung; Park, Jae Hyun; Kim, Min Kyung; Park, Jin Yeon; Choi, Hyeong Jwa; Lee, Jeong Ik; Ko, Hyun Myung; Park, Seung Hwa; Hwang, Han Sung; Kang, Young Sun

    2017-11-01

    Immune tolerance at feto-maternal interfaces is a complex phenomenon. Although maternal decidual macrophages are well-known immune cells, little is known about fetal-derived macrophages (Hofbauer cells) within chorionic villi. Preeclampsia (PE) is a major cause of maternal mortality in the field of obstetrics, and the innate immunological role of maternal decidual macrophages is well known. In this study, we assessed the differential phenotypes and marker expression in fetal macrophages, known as dendritic cell-specific ICAM-grabbing non-integrin (DC-SIGN)-positive Hofbauer cells. We compared Hofbauer cell properties between normal and PE placenta chorionic villi and performed sequential staining of DC-SIGN, CD14, and CD68 to evaluate the existence of Hofbauer cells. Furthermore, to evaluate the immunological function of these cells, we stained the cells for CD163, a marker of immunoregulatory type 2 (M2) macrophages. Additionally, we examined the expression of the immunosuppressive cytokine interleukin (IL)-10, which is known to be produced by M2 macrophages. DC-SIGN+/CD14+, DC-SIGN+/CD68+, and CD163+/DC-SIGN+ cells were quantified based on photomicrographs. The results showed that CD14, CD163, DC-SIGN, and IL-10 levels were significantly downregulated in PE compared with normal. Additionally, CD163+/DC-SIGN+ Hofbauer cells were significantly less frequent in PE than in normal. DC-SIGN Hofbauer cells produced IL-10 at lower levels in the PE than in the normal. Thus, we speculate that fetal-derived Hofbauer cells may play an important role in normal pregnancy with immunosuppressive effects based on their M2 macrophage characteristics to maintain immune tolerance during pregnancy. Additionally, in PE, these functions were defective, supporting the roles of these macrophages in PE development. Copyright © 2017 Elsevier B.V. All rights reserved.

  17. Placental defects in alpha7 integrin null mice.

    Science.gov (United States)

    Welser, J V; Lange, N D; Flintoff-Dye, N; Burkin, H R; Burkin, D J

    2007-01-01

    The alpha7beta1 integrin is a heterodimeric transmembrane receptor that links laminin in the extracellular matrix to the cell cytoskeleton. Loss of the alpha7 integrin chain results in partial embryonic lethality. We have previously shown that alpha7 integrin null embryos exhibit vascular smooth muscle cell defects that result in cerebral vascular hemorrhaging. Since the placenta is highly vascularized, we hypothesized that placental vascular defects in alpha7 integrin null embryos may contribute to the partial embryonic lethality. Placentae from embryonic day (ED) 9.5 and 13.5 alpha7 integrin knockout embryos showed structural defects including infiltration of the spongiotrophoblast layer into the placental labyrinth, a reduction in the placental labyrinth and loss of distinct placental layers. Embryos and placentae that lacked the alpha7 integrin weighed less compared to wild-type controls. Blood vessels within the placental labyrinth of alpha7 integrin null embryos exhibited fewer differentiated vascular smooth muscle cells compared to wild-type. Loss of the alpha7 integrin resulted in altered extracellular matrix deposition and reduced expression of alpha5 integrin. Together our results confirm a role for the alpha7beta1 integrin in placental vascular development and demonstrate for the first time that loss of the alpha7 integrin results in placental defects.

  18. Correlation with placental kisspeptin in postterm pregnancy and apoptosis.

    Science.gov (United States)

    Torricelli, Michela; Novembri, Romina; Conti, Nathalie; De Falco, Giulia; De Bonis, Maria; Petraglia, Felice

    2012-10-01

    Postterm pregnancy represents a condition associated with trophoblast apoptosis. Kisspeptin is a peptide able to induce apoptosis by a specific receptor, GPR54, through the upregulation of proapoptotic genes. The aims of the study were to evaluate (1) the messenger RNA (mRNA) expression of kisspeptin, GPR54, Bax/Bcl2, and p21 in postterm placentas and (2) kisspeptin ability to act on apoptosis in the third trimester placental explants. Placental specimens were collected from spontaneous term and postterm delivery and kisspeptin, GPR54, Bax/Bcl2, and p21 mRNA expression levels were analyzed by real-time polymerase chain reaction. Placental explants, collected from elective term cesarean sections, treated with different doses of kisspeptin were analyzed by terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL). The expression levels of all the genes studied in postterm placentas were significantly higher than in-term placentas. Kisspeptin-induced apoptosis in placental explants with a dose-dependent effect, and TUNEL assay demonstrated the kisspeptin involvement in the apoptotic placental processes. Our present findings led us to hypothesize that kisspeptin may represent a placental proapoptotic agent acting in physiological and/or pathological pregnancy conditions in which placental apoptosis mechanisms are increased.

  19. Placental exosomes in normal and complicated pregnancy.

    Science.gov (United States)

    Mitchell, Murray D; Peiris, Hassendrini N; Kobayashi, Miharu; Koh, Yong Q; Duncombe, Gregory; Illanes, Sebastian E; Rice, Gregory E; Salomon, Carlos

    2015-10-01

    While there is considerable contemporary interest in elucidating the role of placenta-derived extracellular vesicles in normal and complicated pregnancies and their utility as biomarkers and therapeutic interventions, progress in the field is hindered by a lack of standardized extracellular vesicle taxonomy and isolation protocols. The term "extracellular vesicle" is nonspecific and refers to all membrane-bound vesicles from nanometer to micrometer diameters and of different biogenic origins. To meaningfully ascribe biological function and/or diagnostic and therapeutic utility to extracellular vesicles, and in particular exosomes, greater specificity and vesicle characterization is required. The current literature relating to exosome biology must be interpreted in this context. Exosomes are a subtype of extracellular vesicle that are specifically defined by an endosomal biogenesis and particle size (40-120 nm) and density (1.13-1.19 g/mL(-1)). Exosomes are specifically package with signaling molecules (including protein, messenger RNA, microRNA, and noncoding RNA) and are released by exocytosis into biofluid compartments. Exosomes regulate the activity of both proximal and distal target cells, including translational activity, angiogenesis, proliferation, metabolism, and apoptosis. As such, exosomal signaling represents an integral pathway mediating intercellular communication. During pregnancy, the placenta releases exosomes into the maternal circulation from as early as 6 weeks of gestation. Release is regulated by factors that include both oxygen tension and glucose concentration and correlates with placental mass and perfusion. The concentration of placenta-derived exosomes in maternal plasma increases progressively during gestation. Exosomes isolated from maternal plasma are bioactive in vitro and are incorporated into target cells by endocytosis. While the functional significance of placental exosomes in pregnancy remains to be fully elucidated, available

  20. Risk of placental abruption in relation to migraines and headaches

    Directory of Open Access Journals (Sweden)

    Ananth Cande V

    2010-10-01

    Full Text Available Abstract Background Migraine, a common chronic-intermittent disorder of idiopathic origin characterized by severe debilitating headaches and autonomic nervous system dysfunction, and placental abruption, the premature separation of the placenta, share many common pathophysiological characteristics. Moreover, endothelial dysfunction, platelet activation, hypercoagulation, and inflammation are common to both disorders. We assessed risk of placental abruption in relation to maternal history of migraine before and during pregnancy in Peruvian women. Methods Cases were 375 women with pregnancies complicated by placental abruption, and controls were 368 women without an abruption. During in-person interviews conducted following delivery, women were asked if they had physician-diagnosed migraine, and they were asked questions that allowed headaches and migraine to be classified according to criteria established by the International Headache Society. Logistic regression procedures were used to calculate odds ratios (aOR and 95% confidence intervals (CI adjusted for confounders. Results Overall, a lifetime history of any headaches or migraine was associated with an increased odds of placental abruption (aOR = 1.60; 95% CI 1.16-2.20. A lifetime history of migraine was associated with a 2.14-fold increased odds of placental abruption (aOR = 2.14; 95% CI 1.22-3.75. The odds of placental abruption was 2.11 (95% CI 1.00-4.45 for migraineurs without aura; and 1.59 (95% 0.70-3.62 for migraineurs with aura. A lifetime history of tension-type headache was also increased with placental abruption (aOR = 1.61; 95% CI 1.01-2.57. Conclusions This study adds placental abruption to a growing list of pregnancy complications associated with maternal headache/migraine disorders. Nevertheless, prospective cohort studies are needed to more rigorously evaluate the extent to which migraines and/or its treatments are associated with the occurrence of placental abruption.

  1. 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.

  2. Functional Differences Between Placental Micro- and Macrovascular Endothelial Colony-Forming Cells

    Science.gov (United States)

    Solomon, Ioana; O’Reilly, Megan; Ionescu, Lavinia; Alphonse, Rajesh S.; Rajabali, Saima; Zhong, Shumei; Vadivel, Arul; Shelley, W. Chris; Yoder, Mervin C.

    2016-01-01

    Alterations in the development of the placental vasculature can lead to pregnancy complications, such as preeclampsia. Currently, the cause of preeclampsia is unknown, and there are no specific prevention or treatment strategies. Further insight into the placental vasculature may aid in identifying causal factors. Endothelial colony-forming cells (ECFCs) are a subset of endothelial progenitor cells capable of self-renewal and de novo vessel formation in vitro. We hypothesized that ECFCs exist in the micro- and macrovasculature of the normal, term human placenta. Human placentas were collected from term pregnancies delivered by cesarean section (n = 16). Placental micro- and macrovasculature was collected from the maternal and fetal side of the placenta, respectively, and ECFCs were isolated and characterized. ECFCs were CD31+, CD105+, CD144+, CD146+, CD14−, and CD45−, took up 1,1′-dioctadecyl-3,3,3′,3′-tetramethyl-indocarbocyanine perchlorate-labeled acetylated low-density lipoprotein, and bound Ulex europaeus agglutinin 1. In vitro, macrovascular ECFCs had a greater potential to generate high-proliferative colonies and formed more complex capillary-like networks on Matrigel compared with microvascular ECFCs. In contrast, in vivo assessment demonstrated that microvascular ECFCs had a greater potential to form vessels. Macrovascular ECFCs were of fetal origin, whereas microvascular ECFCs were of maternal origin. ECFCs exist in the micro- and macrovasculature of the normal, term human placenta. Although macrovascular ECFCs demonstrated greater vessel and colony-forming potency in vitro, this did not translate in vivo, where microvascular ECFCs exhibited a greater vessel-forming ability. These important findings contribute to the current understanding of normal placental vascular development and may aid in identifying factors involved in preeclampsia and other pregnancy complications. Significance This research confirms that resident endothelial colony

  3. [How to stimulate the placental function (author's transl)].

    Science.gov (United States)

    Fanard, A; Picazo, J J

    1976-01-01

    Imminent abortion, habitual abortion and threatened premature labor, all constitute difficult clinical problems. Those cases require on every occasion a diagnosis as acurate as possible, and unfortunately our present methods of biochemical determinations only represent a means to evaluate placental function. On those cases where a faulty placental function is detected thru the tests presently available, the authors recommend the utilization of a placentotropic substance, Gestanon, that is capable to stimulate and normalize the placental function, a is demostrated by the statistical results published in the international medical bibliography.

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

    Directory of Open Access Journals (Sweden)

    Qun Shu

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

  5. 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.

  6. Translocation of positively and negatively charged polystyrene nanoparticles in an in vitro placental model.

    Science.gov (United States)

    Kloet, Samantha K; Walczak, Agata P; Louisse, Jochem; van den Berg, Hans H J; Bouwmeester, Hans; Tromp, Peter; Fokkink, Remco G; Rietjens, Ivonne M C M

    2015-10-01

    To obtain insight in translocation of nanoparticles across the placental barrier, translocation was studied for one positively and two negatively charged polystyrene nanoparticles (PS-NPs) of similar size in an in vitro model. The model consisted of BeWo b30 cells, derived from a human choriocarcinoma grown on a transwell insert forming a cell layer that separates an apical from a basolateral compartment. PS-NPs were characterized with respect to size, surface charge, morphology and protein corona. Translocation of PS-NPs was not related to PS-NP charge. Two PS-NPs were translocated across the BeWo transwell model to a lower extent than amoxicillin, a model compound known to be translocated over the placental barrier to only a limited extent, whereas one PS-NP showed a slightly higher translocation. Studies on the effect of transporter inhibitors on the translocation of the PS-NPs indicated that their translocation was not mediated by known transporters and mainly dependent on passive diffusion. It is concluded that the BeWo b30 model can be used as an efficient method to get an initial qualitative impression about the capacity of NPs to translocate across the placental barrier and set priorities in further in vivo studies on translocation of NPs to the fetus. Copyright © 2015 The Authors. Published by Elsevier Ltd.. All rights reserved.

  7. The formation and transformation of hormones in maternal, placental and fetal compartments: biological implications.

    Science.gov (United States)

    Pasqualini, Jorge R; Chetrite, Gérard S

    2016-07-01

    The fetal endocrine system constitutes the earliest system developing in fetal life and operates during all the steps of gestation. Its regulation is in part dependent on the secretion of placental and/or maternal precursors emanating across the feto-maternal interface. Human fetal and placental compartments possess all the enzymatic systems necessary to produce steroid hormones. However, their activities are different and complementary: the fetus is very active in converting acetate into cholesterol, in transforming pregnanes to androstanes, various hydroxylases, sulfotransferases, while all these transformations are absent or very limited in the placenta. This compartment can transform cholesterol to C21-steroids, convert 5-ene to 4-ene steroids, and has a high capacity to aromatize C19 precursors and to hydrolyze sulfates. Steroid hormone receptors are present at an early stage of gestation and are functional for important physiological activities. The production rate of some steroids greatly increases with fetal evolution (e.g. estriol increases 500-1000 times in relation to non-pregnant women). Other hormones, such as glucocorticoids, in particular the stress hormone cortisol, adipokines (e.g. leptin, adiponectin), insulin-like growth factors, are also a key factor for regulating reproduction, metabolism, appetite and may be significant in programming the fetus and its growth. We can hypothesize that the fetal and placental factors controlling hormonal levels in the fetal compartment can be of capital importance in the normal development of extra-uterine life.

  8. Evolutionary history of LINE-1 in the major clades of placental mammals.

    Directory of Open Access Journals (Sweden)

    Paul D Waters

    2007-01-01

    Full Text Available LINE-1 constitutes an important component of mammalian genomes. It has a dynamic evolutionary history characterized by the rise, fall and replacement of subfamilies. Most data concerning LINE-1 biology and evolution are derived from the human and mouse genomes and are often assumed to hold for all placentals.To examine LINE-1 relationships, sequences from the 3' region of the reverse transcriptase from 21 species (representing 13 orders across Afrotheria, Xenarthra, Supraprimates and Laurasiatheria were obtained from whole genome sequence assemblies, or by PCR with degenerate primers. These sequences were aligned and analysed.Our analysis reflects accepted placental relationships suggesting mostly lineage-specific LINE-1 families. The data provide clear support for several clades including Glires, Supraprimates, Laurasiatheria, Boreoeutheria, Xenarthra and Afrotheria. Within the afrotherian LINE-1 (AfroLINE clade, our tree supports Paenungulata, Afroinsectivora and Afroinsectiphillia. Xenarthran LINE-1 (XenaLINE falls sister to AfroLINE, providing some support for the Atlantogenata (Xenarthra+Afrotheria hypothesis.LINEs and SINEs make up approximately half of all placental genomes, so understanding their dynamics is an essential aspect of comparative genomics. Importantly, a tree of LINE-1 offers a different view of the root, as long edges (branches such as that to marsupials are shortened and/or broken up. Additionally, a robust phylogeny of diverse LINE-1 is essential in testing that site-specific LINE-1 insertions, often regarded as homoplasy-free phylogenetic markers, are indeed unique and not convergent.

  9. Hypoxia and Reoxygenation: a Possible Mechanism for Placental Oxidative Stress in Preeclampsia

    Directory of Open Access Journals (Sweden)

    Tai-Ho Hung

    2006-09-01

    Full Text Available Preeclampsia is a human pregnancy-specific disorder that is diagnosed by the new appearance of hypertension and proteinuria after 20 weeks' gestation. It is a leading cause of perinatal morbidity and mortality, and the only intervention that effectively reverses the syndrome is delivery. Oxidative stress of the placenta is considered to be a key intermediary step in the pathogenesis of preeclampsia, but the cause for the stress remains unknown. Hypoxia-reoxygenation (H/R injury, as a result of intermittent placental perfusion secondary to deficient trophoblast invasion of the endometrial arteries, is a possible mechanism. In this review, we present evidence to show that there is a plausible basis from which to assume that blood flow in the intervillous space will be intermittent in all normal pregnancies. The intermittency will be exacerbated by impaired conversion of the spiral arteries, or by the presence of atherotic changes that reduce their caliber as seen in preeclampsia. Placental oxidative stress can be the consequences of fluctuations in oxygen concentrations after H/R through the actions of reactive oxygen species. On this basis, there will be a complete spectrum of placental changes among the normal, the late onset and the early onset preeclamptic states. Viewing the syndrome as a continuum of H/R insults provides new insight into the pathophysiology of pregnancy that will hopefully lead to improved clinical interventions.

  10. 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

  11. Placental chorangioma | Rabiu | Tropical Journal of Obstetrics and ...

    African Journals Online (AJOL)

    Fetal complications associated with placental chorangiomas include polyhydromnios, nonimmune fetal hydrops, fetal heart failure, cardiomegaly, intrauterine growth restriction, fetal anemia, thrombocytopenia, and fetal demise. Maternal complications such as preeclampsia, preterm delivery, and maternal mirror syndrome ...

  12. Placental fetal vascular thrombosis lesions and maternal thrombophilia

    NARCIS (Netherlands)

    Beeksma, F. A.; Erwich, J. J. H. M.; Khong, T. Y.

    Aims: Following intrauterine fetal death (IUFD), the placental fetal vessels undergo regressive changes. These changes are virtually indistinguishable from lesions that are the result of fetal vascular thrombosis (FVT). This study investigated the relation between these lesions and maternal

  13. Placental histopathology after Coxiella burnetii infection during pregnancy

    NARCIS (Netherlands)

    Munster, J. M.; Leenders, A. C. A. P.; Hamilton, C. J. C. M.; Hak, E.; Aarnoudse, J. G.; Timmer, A.

    Symptomatic and asymptomatic Coxiella burnetii infection during pregnancy have been associated with obstetric complications. We described placental histopathology and clinical outcome of five cases with asymptomatic C burnetii infection during pregnancy and compared these cases with four symptomatic

  14. First evidence of placental transfer of ochratoxin A in horses

    National Research Council Canada - National Science Library

    Minervini, Fiorenza; Giannoccaro, Alessandra; Nicassio, Michele; Panzarini, Giuseppe; Lacalandra, Giovanni Michele

    2013-01-01

    Ochratoxin A (OTA) is a renal mycotoxin and transplacental genotoxic carcinogen. The aim of this study was to evaluate the natural occurrence of OTA in equine blood samples and its placental transfer...

  15. 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...

  16. Microvessel density in the placental bed among preeclampsia patients

    Directory of Open Access Journals (Sweden)

    Tarcisio Mota Coelho

    Full Text Available CONTEXT AND OBJECTIVE: Morphological changes in the spiral arteries of the placental bed have been studied in patients with preeclampsia, one of the largest causes of maternal and perinatal morbidity and mortality. The reports show that vasospasm and vascular endothelial injury were two major pathological conditions for preeclampsia. The aim of this study was to investigate the microvessel density of spiral arteries in the placental bed, in pregnancies complicated by hypertension and proteinuria, and in normal pregnancies. DESIGN AND SETTING: This was a cross-sectional survey of immunohistochemical studies on biopsies from the spiral arteries of the placental bed, among women undergoing cesarean sections for clinical and obstetrical reasons at Universidade Federal de São Paulo, São Paulo, Brazil. METHODS: Placental bed biopsies were obtained during cesarean section after placenta removal, with direct viewing of the central area of placenta insertion. The microvessel density of spiral arteries was measured by immunohistochemical methods in decidual and myometrial segments, using CD34 antibody. RESULTS: Biopsies containing spiral arteries were obtained from 34 hypertensive pregnant women with proteinuria, and 26 normotensive pregnant women. The microvessel densities in decidual and myometrial segments of the placental bed were compared between the groups. It was observed that, with increasing blood pressure and proteinuria, the microvessel density gradually decreased. CONCLUSION: The presence of high levels of hypertension and proteinuria may be associated with a progressive decrease in microvessel density in the placental bed.

  17. Microvessel density in the placental bed among preeclampsia patients.

    Science.gov (United States)

    Coelho, Tarcisio Mota; Sass, Nelson; Camano, Luiz; Moron, Antonio Fernandes; Mattar, Rosiane; Stávale, João Noberto; Silva, Maria Regina Régis; Martins, Marília da Glória; Nogueira Neto, João

    2006-03-02

    Morphological changes in the spiral arteries of the placental bed have been studied in patients with preeclampsia, one of the largest causes of maternal and perinatal morbidity and mortality. The reports show that vasospasm and vascular endothelial injury were two major pathological conditions for preeclampsia. The aim of this study was to investigate the microvessel density of spiral arteries in the placental bed, in pregnancies complicated by hypertension and proteinuria, and in normal pregnancies. This was a cross-sectional survey of immunohistochemical studies on biopsies from the spiral arteries of the placental bed, among women undergoing cesarean sections for clinical and obstetrical reasons at Universidade Federal de São Paulo, São Paulo, Brazil. Placental bed biopsies were obtained during cesarean section after placenta removal, with direct viewing of the central area of placenta insertion. The microvessel density of spiral arteries was measured by immunohistochemical methods in decidual and myometrial segments, using CD34 antibody. Biopsies containing spiral arteries were obtained from 34 hypertensive pregnant women with proteinuria, and 26 normotensive pregnant women. The microvessel densities in decidual and myometrial segments of the placental bed were compared between the groups. It was observed that, with increasing blood pressure and proteinuria, the microvessel density gradually decreased. The presence of high levels of hypertension and proteinuria may be associated with a progressive decrease in microvessel density in the placental bed.

  18. Use of biochemical tests of placental function for improving pregnancy outcome.

    Science.gov (United States)

    Heazell, Alexander E P; Whitworth, Melissa; Duley, Lelia; Thornton, Jim G

    2015-11-25

    The placenta has an essential role in determining the outcome of pregnancy. Consequently, biochemical measurement of placentally-derived factors has been suggested as a means to improve fetal and maternal outcome of pregnancy. To assess whether clinicians' knowledge of the results of biochemical tests of placental function is associated with improvement in fetal or maternal outcome of pregnancy. We searched the Cochrane Pregnancy and Childbirth Group's Trials Register (31 July 2015) and reference lists of retrieved studies. Randomised, cluster-randomised or quasi-randomised controlled trials assessing the merits of the use of biochemical tests of placental function to improve pregnancy outcome.Studies were eligible if they compared women who had placental function tests and the results were available to their clinicians with women who either did not have the tests, or the tests were done but the results were not available to the clinicians. The placental function tests were any biochemical test of placental function carried out using the woman's maternal biofluid, either alone or in combination with other placental function test/s. Two review authors independently assessed trials for inclusion, extracted data and assessed trial quality. Authors of published trials were contacted for further information. Three trials were included, two quasi-randomised controlled trials and one randomised controlled trial. One trial was deemed to be at low risk of bias while the other two were at high risk of bias. Different biochemical analytes were measured - oestrogen was measured in one trial and the other two measured human placental lactogen (hPL). One trial did not contribute outcome data, therefore, the results of this review are based on two trials with 740 participants.There was no evidence of a difference in the incidence of death of a baby (risk ratio (RR) 0.88, 95% confidence interval (CI) 0.36 to 2.13, two trials, 740 participants (very low quality evidence)) or the

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

    Science.gov (United States)

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

    2013-01-30

    Poor success rates in somatic cell cloning are often attributed to abnormal early embryonic development as well as late abnormal fetal growth and placental development. Although promising results have been reported following chromatin transfer (CT), a novel cloning method that includes the remodeling of the donor nuclei in vitro prior to their transfer into enucleated oocytes, animals cloned by CT show placental abnormalities similar to those observed following conventional nuclear transfer. We hypothesized that the placental gene expression pattern from cloned fetuses was ontologically related to the frequently observed placental phenotype. The aim of the present study was to compare global gene expression by microarray analysis of Day 44-47 cattle placentas derived from CT cloned fetuses with those derived from in vitro fertilization (i.e. control), and confirm the altered mRNA and protein expression of selected molecules by qRT-PCR and immunohistochemistry, respectively. The differentially expressed genes identified in the present study are known to be involved in a range of activities associated with cell adhesion, cell cycle control, intracellular transport and proteolysis. Specifically, an imprinted gene, involved with cell proliferation and placentomegaly in humans (CDKN1C) and a peptidase that serves as a marker for non-invasive trophoblast cells in human placentas (DPP4), had mRNA and protein altered in CT placentas. It was concluded that the altered pattern of gene expression observed in CT samples may contribute to the abnormal placental development phenotypes commonly identified in cloned offspring, and that expression of imprinted as well as trophoblast invasiveness-related genes is altered in cattle cloned by CT. Copyright © 2012 Elsevier B.V. All rights reserved.

  20. Paternal allele of IGF2 gene haplotype CTG is associated with fetal and placental growth in Japanese.

    Science.gov (United States)

    Nagaya, Ken; Makita, Yoshio; Taketazu, Genya; Okamoto, Toshio; Nakamura, Eiki; Hayashi, Tokitsugi; Fujieda, Kenji

    2009-08-01

    IGF-II associates with feto-placental growth in rodent and human. We determined three tag-single nucleotide polymorphisms (SNPs) to investigate haplotype frequency of IGF2 relative to size at birth in 134 healthy Japanese infants. In addition, a total of 276 healthy infants were investigated to determine whether common genetic variation of IGF2 might contribute to feto-placental growth using haplotype analysis. Further, quantitative methylation analysis of the IGF2/H19 was performed using the MassARRAY Compact system. In the initial study, the frequency of haplotype CTG from the paternal allele in small for date (SFD) infants was significantly higher than that in non-SFD infants (p = 0.03). In a second study, the CTG haplotype infants exhibited significantly lower birth length, weight, and placental weight compared with non-CTG infants. Further, the number of infants less than -1.5 SD (SD) birth weight in CTG haplotype was higher than those in non-CTG infants. There was no significant difference in the methylation status of H19/IGF2 in the two haplotypes. In conclusion, inheriting the IGF2 CTG haplotype from a paternal allele results in reduced feto-placental growth, but it is not associated with the methylation status of IGF2/H19.

  1. 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.

  2. Placental Induced Growth Factor (PIGf) in Coronary Artery Disease

    Science.gov (United States)

    Sundaresan, Alamelu; Carabello, Blaise; Mehta, Satish; Schlegel, Todd; Pellis, Neal; Ott, Mark; Pierson, Duane

    2010-01-01

    Our previous studies on normal human lymphocytes have shown a five-fold increase (p less than 0.001) in angiogenic inducers such as Placental Induced Growth Factor (PIGf) in physiologically stressful environments such as modeled microgravity, a space analog. This suggests de-regulation of cardiovascular signalling pathways indicated by upregulation of PIGf. In the current study, we measured PIGf in the plasma of 33 patients with and without coronary artery disease (CAD) to investigate whether such disease is associated with increased levels of PIGf. A control consisting of 31 sex matched apparently healthy subjects was also included in the study. We observed that the levels of PIGf in CAD patients were significantly increased compared to those in healthy control subjects (p less than 0.001) and usually increased beyond the clinical threshold level (greater than 27ng/L). The mechanisms leading to up-regulation of angiogenic factors and the adaptation of organisms to stressful environments such as isolation, high altitude, hypoxia, ischemia, microgravity, increased radiation, etc are presently unknown and require further investigation in spaceflight and these other physiologically stressed environments.

  3. Specific Immunoassays for Placental Alkaline Phosphatase As a Tumor Marker

    Science.gov (United States)

    Stinghen, Sérvio T.; Moura, Juliana F.; Zancanella, Patrícia; Rodrigues, Giovanna A.; Pianovski, Mara A.; Lalli, Enzo; Arnold, Dodie L.; Minozzo, João C.; Callefe, Luis G.; Ribeiro, Raul C.; Figueiredo, Bonald C.

    2006-01-01

    Human placental (hPLAP) and germ cell (PLAP-like) alkaline phosphatases are polymorphic and heat-stable enzymes. This study was designed to develop specific immunoassays for quantifying hPLAP and PLAP-like enzyme activity (EA) in sera of cancer patients, pregnant women, or smokers. Polyclonal sheep anti-hPLAP antibodies were purified by affinity chromatography with whole hPLAP protein (ICA-PLAP assay) or a synthetic peptide (aa 57–71) of hPLAP (ICA-PEP assay); the working range was 0.1–11 U/L and cutoff value was 0.2 U/L EA for nonsmokers. The intra- and interassay coefficients of variation were 3.7%–6.5% (ICA-PLAP assay) and 9.0%–9.9% (ICA-PEP assay). An insignificant cross-reactivity was noted for high levels of unheated intestinal alkaline phosphatase in ICA-PEP assay. A positive correlation between the regression of tumor size and EA was noted in a child with embryonal carcinoma. It can be concluded that ICA-PEP assay is more specific than ICA-PLAP, which is still useful to detect other PLAP/PLAP-like phenotypes. PMID:17489017

  4. Influences of placental growth factor on mouse retinal vascular development.

    Science.gov (United States)

    Kay, Vanessa R; Tayade, Chandrakant; Carmeliet, Peter; Croy, B Anne

    2017-09-01

    Placental growth factor (PGF) is important for wound-healing and vascular collaterogenesis. PGF deficiency is associated with preeclampsia, a hypertensive disease of human pregnancy. Offspring born to preeclamptic mothers display cognitive impairments and brain vascular and neurostructural deviations. Low PGF production during development may contribute to alterations in offspring cerebrovascular beds. Retina is a readily accessible part of the central nervous system with a well-described pattern of vascular development in mice. Impacts of PGF deficiency were addressed during mouse retinal vascularization. Retinal vessels were compared between Pgf-/- and congenic C57BL/6 (B6) mice. PGF deficiency altered neonatal retinal vascularization patterns. Some anatomic alterations persisted into adulthood, particularly in males. Greater arterial wall collagen IV expression was found in adult Pgf-/- females. Pregnancy (studied in adult females at gestational days 11.5 or 18.5) induced subtle changes upon the mother's retinal vasculature but these pregnancy-induced changes did not differ between genotypes. Significant sex-related differences occurred between adult male and female B6 although sexually dimorphic retinal vascular differences were absent in B6 neonates. Overall, PGF has a role in retinal vascular angiogenesis and vessel organization during development but does not affect retinal vessel adaptations in adult females during pregnancy. Developmental Dynamics 246:700-712, 2017. © 2017 Wiley Periodicals, Inc. © 2017 Wiley Periodicals, Inc.

  5. Placental and fetal hemodynamics after labetalol or pindolol in a sheep model of increased placental vascular resistance and maternal hypertension.

    Science.gov (United States)

    Erkinaro, Tiina; Kavasmaa, Tomi; Ylikauma, Laura; Mäkikallio, Kaarin; Haapsamo, Mervi; Acharya, Ganesh; Ohtonen, Pasi; Alahuhta, Seppo; Räsänen, Juha

    2009-08-01

    We investigated the effects of labetalol and pindolol on uterine, placental, and fetal hemodynamics following norepinephrine-induced maternal hypertension in a sheep model of increased placental vascular resistance. Also, we examined fetal and placental hemodynamic responses to acute hypoxemia after antihypertensive medication. Norepinephrine increased maternal heart rate (HR), mean arterial pressure (MAP) and uterine vascular resistance (R(UtA)), and decreased uterine volume blood flow (Q(UtA)). Both labetalol and pindolol decreased maternal HR, MAP, and R(UtA), but did not restore Q(UtA). Fetal MAP was unaffected while fetal HR and placental volume blood flow (Q(UA)) decreased and placental vascular resistance increased. During hypoxemia, which was induced by decreasing maternal inspiratory oxygen fraction, all these parameters remained unchanged in the labetalol group while fetal HR increased and Q(UA) further decreased in the pindolol group. We conclude that labetalol and pindolol may compromise uterine and placental hemodynamics. Hypoxemic stress provokes divergent hemodynamic responses in fetuses exposed to these differently acting adrenoceptor antagonists.

  6. BMP4-directed trophoblast differentiation of human embryonic stem cells is mediated through a ΔNp63+ cytotrophoblast stem cell state.

    Science.gov (United States)

    Li, Yingchun; Moretto-Zita, Matteo; Soncin, Francesca; Wakeland, Anna; Wolfe, Lynlee; Leon-Garcia, Sandra; Pandian, Raj; Pizzo, Donald; Cui, Li; Nazor, Kristopher; Loring, Jeanne F; Crum, Christopher P; Laurent, Louise C; Parast, Mana M

    2013-10-01

    The placenta is a transient organ that is necessary for proper fetal development. Its main functional component is the trophoblast, which is derived from extra-embryonic ectoderm. Little is known about early trophoblast differentiation in the human embryo, owing to lack of a proper in vitro model system. Human embryonic stem cells (hESCs) differentiate into functional trophoblast following BMP4 treatment in the presence of feeder-conditioned media; however, this model has not been widely accepted, in part owing to a lack of proof for a trophoblast progenitor population. We have previously shown that p63, a member of the p53 family of nuclear proteins, is expressed in proliferative cytotrophoblast (CTB), precursors to terminally differentiated syncytiotrophoblast (STB) in chorionic villi and extravillous trophoblast (EVT) at the implantation site. Here, we show that BMP4-treated hESCs differentiate into bona fide CTB by direct comparison with primary human placental tissues and isolated CTB through gene expression profiling. We show that, in primary CTB, p63 levels are reduced as cells differentiate into STB, and that forced expression of p63 maintains cyclin B1 and inhibits STB differentiation. We also establish that, similar to in vivo events, hESC differentiation into trophoblast is characterized by a p63(+)/KRT7(+) CTB stem cell state, followed by formation of functional KLF4(+) STB and HLA-G(+) EVT. Finally, we illustrate that downregulation of p63 by shRNA inhibits differentiation of hESCs into functional trophoblast. Taken together, our results establish that BMP4-treated hESCs are an excellent model of human trophoblast differentiation, closely mimicking the in vivo progression from p63(+) CTB stem cells to terminally differentiated trophoblast subtypes.

  7. Rising maternal circulating GH during murine pregnancy suggests placental regulation

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    Kathryn L Gatford

    2017-06-01

    Full Text Available Placenta-derived hormones including growth hormone (GH in humans contribute to maternal adaptation to pregnancy, and intermittent maternal GH administration increases foetal growth in several species. Both patterns and abundance of circulating GH are important for its activity, but their changes during pregnancy have only been reported in humans and rats. The aim of the present study was to characterise circulating profiles and secretory characteristics of GH in non-pregnant female mice and throughout murine pregnancy. Circulating GH concentrations were measured in whole blood (2 μL collected every 10 min for 6 h in non-pregnant diestrus female C57Bl/6J mice (n = 9, and pregnant females at day 8.5–9.5 (early pregnancy, n = 8, day 12.5–13.5 (mid-pregnancy, n = 7 and day 17.5 after mating (late pregnancy, n = 7. Kinetics and secretory patterns of GH secretion were determined by deconvolution analysis, while orderliness and regularity of serial GH concentrations were calculated by approximate entropy analysis. Circulating GH was pulsatile in all groups. Mean circulating GH and total and basal GH secretion rates increased markedly from early to mid-pregnancy, and then remained elevated. Pulse frequency and pulsatile GH secretion rate were similar between groups. The irregularity of GH pulses was higher in all pregnant groups than that in non-pregnant mice. Increased circulating GH in murine pregnancy is consistent with an important role for this hormone in maternal adaptation to pregnancy and placental development. The timing of increased basal secretion from mid-pregnancy, concurrent with the formation of the chorioallantoic placenta and initiation of maternal blood flow through it, suggests regulation of pituitary secretion by placenta-derived factors.

  8. A higher-level MRP supertree of placental mammals

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    Bininda-Emonds Olaf RP

    2006-11-01

    Full Text Available Abstract Background The higher-level phylogeny of placental mammals has long been a phylogenetic Gordian knot, with disagreement about both the precise contents of, and relationships between, the extant orders. A recent MRP supertree that favoured 'outdated' hypotheses (notably, monophyly of both Artiodactyla and Lipotyphla has been heavily criticised for including low-quality and redundant data. We apply a stringent data selection protocol designed to minimise these problems to a much-expanded data set of morphological, molecular and combined source trees, to produce a supertree that includes every family of extant placental mammals. Results The supertree is well-resolved and supports both polyphyly of Lipotyphla and paraphyly of Artiodactyla with respect to Cetacea. The existence of four 'superorders' – Afrotheria, Xenarthra, Laurasiatheria and Euarchontoglires – is also supported. The topology is highly congruent with recent (molecular phylogenetic analyses of placental mammals, but is considerably more comprehensive, being the first phylogeny to include all 113 extant families without making a priori assumptions of suprafamilial monophyly. Subsidiary analyses reveal that the data selection protocol played a key role in the major changes relative to a previously published higher-level supertree of placentals. Conclusion The supertree should provide a useful framework for hypothesis testing in phylogenetic comparative biology, and supports the idea that biogeography has played a crucial role in the evolution of placental mammals. Our results demonstrate the importance of minimising poor and redundant data when constructing supertrees.

  9. Epigenetic regulation of placental endocrine lineages and complications of pregnancy.

    Science.gov (United States)

    John, Rosalind M

    2013-06-01

    A defining feature of mammals is the development in utero of the fetus supported by the constant flow of nutrients from the mother obtained via a specialized organ: the placenta. The placenta is also a major endocrine organ that synthesizes vast quantities of hormones and cytokines to instruct both maternal and fetal physiology. Nearly 20 years ago, David Haig and colleagues proposed that placental hormones were likely targets of the epigenetic process of genomic imprinting in response to the genetic conflicts imposed by in utero development [Haig (1993) Q. Rev. Biol. 68, 495-532]. There are two simple mechanisms through which genomic imprinting could regulate placental hormones. First, imprints could directly switch on or off alleles of specific genes. Secondly, imprinted genes could alter the expression of placental hormones by regulating the development of placental endocrine lineages. In mice, the placental hormones are synthesized in the trophoblast giant cells and spongiotrophoblast cells of the mature placenta. In the present article, I review the functional role of imprinted genes in regulating these endocrine lineages, which lends support to Haig's original hypothesis. I also discuss how imprinting defects in the placenta may adversely affect the health of the fetus and its mother during pregnancy and beyond.

  10. 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.

  11. Social disparity affects the incidence of placental abruption among multiparous but not nulliparous women

    DEFF Research Database (Denmark)

    Räisänen, Sari; Gissler, Mika; Nielsen, Henriette Svarre

    2013-01-01

    To identify risk factors for placental abruption and to evaluate associations between adverse perinatal outcomes and placental abruption stratified by parity among women with singleton births from 1991 to 2010 in Finland....

  12. Blocking Endogenous Leukemia Inhibitory Factor During Placental Development in Mice Leads to Abnormal Placentation and Pregnancy Loss.

    Science.gov (United States)

    Winship, Amy; Correia, Jeanne; Krishnan, Tara; Menkhorst, Ellen; Cuman, Carly; Zhang, Jian-Guo; Nicola, Nicos A; Dimitriadis, Evdokia

    2015-08-14

    The placenta forms the interface between the maternal and fetal circulation and is critical for the establishment of a healthy pregnancy. Specialized trophoblast cells derived from the embryonic trophectoderm play a pivotal role in the establishment of the placenta. Leukemia inhibitory factor (LIF) is one of the predominant cytokines present in the placenta during early pregnancy. LIF has been shown to regulate trophoblast adhesion and invasion in vitro, however its precise role in vivo is unknown. We hypothesized that LIF would be required for normal placental development in mice. LIF and LIFRα were immunolocalized to placental trophoblasts and fetal vessels in mouse implantation sites during mid-gestation. Temporally blocking LIF action during specific periods of placental development via intraperitoneal administration of our specific LIFRα antagonist, PEGLA, resulted in abnormal placental trophoblast and vascular morphology and reduced activated STAT3 but not ERK. Numerous genes regulating angiogenesis and oxidative stress were altered in the placenta in response to LIF inhibition. Pregnancy viability was also significantly compromised in PEGLA treated mice. Our data suggest that LIF plays an important role in placentation in vivo and the maintenance of healthy pregnancy.

  13. The evolution of fetal membranes and placentation in carnivores and ungulates (Ferungulata)

    DEFF Research Database (Denmark)

    Carter, Anthony Michael; Mess, Andrea

    2017-01-01

    of the chorioallantoic placenta are derived, including the diffuse and cotyledonary placental types in ungulates and zonary placenta in carnivores, specializations of the interhaemal barrier, the presence of areolae or haemophagous regions and lack of stromal decidual cells. Ungulates produce large amounts of placental...... proteins including placental lactogens and pregnancy-associated glycoproteins. Evolutionary innovations of the placental system may contribute to the high diversity of lifestyles within Ferungulata and be linked to the evolution of highly precocial offspring in ungulates....

  14. Epigenetic regulation and related diseases during placental development.

    Science.gov (United States)

    Liu, Fu-lin; Zhou, Jin; Zhang, Wei; Wang, Hui

    2017-04-20

    The placenta is vital to fetal growth and development, as it bridges the fetus and the mother. Genome-wide epigenetic regulations (e.g., DNA methylation, histone modifications, non-coding RNAs) participate in many aspects of placenta development, including decidua of the uterus, trophoblast cell adhesion and invasion, angiogenesis and placental imprinted gene expression. Environmental factors during pregnancy, such as heavy metals, chemical compounds, modern assisted reproductive technology and the nutrient conditions, may cause abnormal placental epigenetics. Furthermore, sex differential expression of placental genes also contributes to epigenetic modifications. As prenatal DNA methylation analysis can detect abnormal epigenetic modifications, it is a potential diagnosis tool for early stage diseases and may help disease intervention and treatment. Here, we review not only regulations of epigenetic modifications during development of the placenta, but also the influences of environmental factors. The potential value for diagnosis and treatment is also discussed.

  15. Indications of anti-HY immunity in recurrent placental abruption

    DEFF Research Database (Denmark)

    Nielsen, Henriette Svarre; Mogensen, Marie; Steffensen, Rudi

    2007-01-01

    PROBLEM: Placental abruption is a potential life-threatening condition for both the fetus and the mother, being significantly more common in pregnancies with male fetuses. The pathogenesis of placental abruption remains unknown. However, some recent reports point toward a maternal immune response...... the fetus died. Seven patients (88%) had first-born boys, and 15 abruptions (68%) involved male fetuses. All patients with a first-born boy, except one, had HLA-class II alleles known to restrict CD4+ T-cell responses against male-specific minor histocompatibility (HY)-antigens (HLA-DRB1*15, HLA-DRB3...... abruption is exclusively almost preceded by the birth of a boy and the majority of patients have HLA-class II known to restrict CD4 T-cell reactions against HY-antigens. This indicates that maternal immunological responses against HY-antigens play a role in recurrent placental abruption. Udgivelsesdato...

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

    Science.gov (United States)

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

    2014-03-01

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

  17. Association between PAPP-A and placental thickness

    Directory of Open Access Journals (Sweden)

    Elaheh Mesdaghi-nia

    2016-06-01

    Full Text Available Background: Measuring of maternal serum pregnancy-associated plasma protein-A (PAPP-A in first trimester can be a way for early detection of adverse prenatal outcome due to faulty placenta. Objective: The aim was to Determination of association between placental thickness in second trimester with low level of PAPP-A in first trimester. Materials and Methods: In this cohort study, serum PAPP-A of 187 pregnant women was measured in the first trimester of pregnancy. Patients who had PAPP-A ≤0.8 MOM were in exposed and others who had PAPP-A >0.8 defined as unexposed group. The criteria of placental thickness in ultrasound study was thickness of 4 cm or more than 50% of placental length. Results: Of 187 patients, 87 patients had PAPP-A >0.8 and 93 patients had PAPP-A ≤0.8. Women with low levels of PAPP-A in the first trimester, had an increased incidence placental thickness of 34.4%, whereas another group had about 15% (p=0.002. Also, PAPP-A levels had acceptable sensitivity and specificity for placental thickness detection (71.1% and 54.8%, respectively. Conclusion: Our study showed that serum level of PAPP-A generally was low (≤0.8 in women with a thick placenta (>4 cm or >50% of placental length. The first trimester of pregnancy measurement of PAPP-A will be more predictable for healthy placenta.

  18. Macrosomia has its roots in early placental development.

    Science.gov (United States)

    Schwartz, N; Quant, H S; Sammel, M D; Parry, S

    2014-09-01

    We sought to determine if early placental size, as measured by 3-dimensional ultrasonography, is associated with an increased risk of delivering a macrosomic or large-for-gestational age (LGA) infant. We prospectively collected 3-dimensional ultrasound volume sets of singleton pregnancies at 11-14 weeks and 18-24 weeks. Birth weights were collected from the medical records. After delivery, the ultrasound volume set were used to measure the placental volume (PV) and placental quotient (PQ = PV/gestational age), as well as the mean placental and chorionic diameters (MPD and MCD, respectively). Placental measures were analyzed as predictors of macrosomia (birth weight ≥4000 g) and LGA (birth weight ≥90th percentile). The 578 pregnancies with first trimester volumes included 44 (7.6%) macrosomic and 43 (7.4%) LGA infants. 373 subjects also had second trimester volumes available. A higher PV and PQ were both significantly associated with macrosomia and LGA in both the first and second trimesters. Second trimester MPD was significantly associated with both outcomes as well, while second trimester MCD was only associated with LGA. The above associations remained significant after adjusting for maternal demographic variables such as race, ethnicity, age and diabetes. Adjusted models yielded moderate prediction of macrosomia and LGA (AUC: 0.71-0.77). Sonographic measurement of the early placenta can identify pregnancies at greater risk of macrosomia and LGA. Macrosomia and LGA are already determined in part by early placental growth and development. Copyright © 2014 Elsevier Ltd. All rights reserved.

  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. Antimutagenic action of mammalian placental extracts on mutations induced in Escherichia coli by UV radiation,. gamma. -rays and N-methyl-N'-nitro-N-nitrosoguanidine

    Energy Technology Data Exchange (ETDEWEB)

    Mochizuki, H.; Kada, T. (National Inst. of Genetics, Mishima, Shizuoka (Japan). Dept. of Induced Mutation)

    1982-01-01

    Mammalian placental extracts prepared from human, monkey, dog, rat and mouse had strong antimutagenic activities for reverse mutations induced in Escherichia coli B/r WP2 trp/sup -/ by UV radiation, ..gamma..-rays and N-methyl-N'-nitro-N-nitrosoguanidine (MNNG).

  1. Placental malaria and pre-eclampsia through the looking glass backwards?

    NARCIS (Netherlands)

    Brabin, Bernard J.; Johnson, Peter M.

    2005-01-01

    Placental malaria and pre-eclampsia occur frequently in women in developing countries and are leading causes of fetal growth restriction. Reduced placental perfusion, loss of placental integrity and endothelial cell dysfunction are characteristics of both conditions, and several common factors can

  2. Placental pathology and clinical trials : Histopathology data from prior and study pregnancies may improve analysis

    NARCIS (Netherlands)

    Khong, T. Y.; Ting, M.; Gordijn, S. J.

    Placental pathology may explain adverse outcomes and reveal likely recurrent lesions. Stratifying women into intervention arms of a perinatal trial on the basis of the placental histopathological findings of the index pregnancy and evaluating the effect of the interventions against the placental

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

    Directory of Open Access Journals (Sweden)

    Chen Chun-Hung

    2011-08-01

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

  4. 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...

  5. Infant sex-specific placental cadmium and DNA methylation associations

    Energy Technology Data Exchange (ETDEWEB)

    Mohanty, April F., E-mail: april.mohanty@va.gov [Cardiovascular Health Research Unit, University of Washington, 1730 Minor Ave, Seattle, WA 98101 (United States); Department of Epidemiology, School of Public Health, University of Washington, Seattle, WA (United States); Farin, Fred M., E-mail: freddy@u.washington.edu [Department of Environmental and Occupational Health Sciences, School of Public Health, University of Washington, 4225 Roosevelt Way N.E., Suite #100, Seattle, WA 98105 (United States); Bammler, Theo K., E-mail: tbammler@u.washington.edu [Department of Environmental and Occupational Health Sciences, School of Public Health, University of Washington, 4225 Roosevelt Way N.E., Suite #100, Seattle, WA 98105 (United States); MacDonald, James W., E-mail: jmacdon@uw.edu [Department of Environmental and Occupational Health Sciences, School of Public Health, University of Washington, 4225 Roosevelt Way N.E., Suite #100, Seattle, WA 98105 (United States); Afsharinejad, Zahra, E-mail: zafshari@u.washington.edu [Department of Environmental and Occupational Health Sciences, School of Public Health, University of Washington, 4225 Roosevelt Way N.E., Suite #100, Seattle, WA 98105 (United States); Burbacher, Thomas M., E-mail: tmb@uw.edu [Department of Environmental and Occupational Health Sciences, School of Public Health, University of Washington, Box: 357234, 1705 N.E. Pacific Street, Seattle, WA 98195 (United States); Siscovick, David S., E-mail: dsiscovick@nyam.org [Cardiovascular Health Research Unit, University of Washington, 1730 Minor Ave, Seattle, WA 98101 (United States); Department of Epidemiology, School of Public Health, University of Washington, Seattle, WA (United States); Department of Medicine, University of Washington, Seattle, WA (United States); and others

    2015-04-15

    Background: Recent evidence suggests that maternal cadmium (Cd) burden and fetal growth associations may vary by fetal sex. However, mechanisms contributing to these differences are unknown. Objectives: Among 24 maternal-infant pairs, we investigated infant sex-specific associations between placental Cd and placental genome-wide DNA methylation. Methods: We used ANOVA models to examine sex-stratified associations of placental Cd (dichotomized into high/low Cd using sex-specific Cd median cutoffs) with DNA methylation at each cytosine-phosphate-guanine site or region. Statistical significance was defined using a false discovery rate cutoff (<0.10). Results: Medians of placental Cd among females and males were 5 and 2 ng/g, respectively. Among females, three sites (near ADP-ribosylation factor-like 9 (ARL9), siah E3 ubiquitin protein ligase family member 3 (SIAH3), and heparin sulfate (glucosamine) 3-O-sulfotransferase 4 (HS3ST4) and one region on chromosome 7 (including carnitine O-octanoyltransferase (CROT) and TP5S target 1 (TP53TG1)) were hypomethylated in high Cd placentas. Among males, high placental Cd was associated with methylation of three sites, two (hypomethylated) near MDS1 and EVI1 complex locus (MECOM) and one (hypermethylated) near spalt-like transcription factor 1 (SALL1), and two regions (both hypomethylated, one on chromosome 3 including MECOM and another on chromosome 8 including rho guanine nucleotide exchange factor (GEF) 10 (ARHGEF10). Differentially methylated sites were at or close to transcription start sites of genes involved in cell damage response (SIAH3, HS3ST4, TP53TG1) in females and cell differentiation, angiogenesis and organ development (MECOM, SALL1) in males. Conclusions: Our preliminary study supports infant sex-specific placental Cd-DNA methylation associations, possibly accounting for previously reported differences in Cd-fetal growth associations across fetal sex. Larger studies are needed to replicate and extend these

  6. IFPA Meeting 2011 workshop report I: Placenta: Predicting future health; roles of lipids in the growth and development of feto-placental unit; placental nutrient sensing; placental research to solve clinical problems--a translational approach.

    Science.gov (United States)

    Acharya, G; Albrecht, C; Benton, S J; Cotechini, T; Dechend, R; Dilworth, M R; Duttaroy, A K; Grotmol, T; Heazell, A E; Jansson, T; Johnstone, E D; Jones, H N; Jones, R L; Lager, S; Laine, K; Nagirnaja, L; Nystad, M; Powell, T; Redman, C; Sadovsky, Y; Sibley, C; Troisi, R; Wadsack, C; Westwood, M; Lash, G E

    2012-02-01

    Workshops are an important part of the IFPA annual meeting as they allow for discussion of specialized topics. At IFPA meeting 2011 there were twelve themed workshops, four of which are summarized in this report. These workshops related to both basic science and clinical research into placental growth and nutrient sensing and were divided into 1) placenta: predicting future health; 2) roles of lipids in the growth and development of feto-placental unit; 3) placental nutrient sensing; 4) placental research to solve clinical problems: a translational approach. Copyright © 2012 Elsevier Ltd. All rights reserved.

  7. Evidence of sexual dimorphism in placental vitamin D metabolism: Testosterone inhibits calcitriol-dependent cathelicidin expression.

    Science.gov (United States)

    Olmos-Ortiz, Andrea; García-Quiroz, Janice; López-Marure, Rebeca; González-Curiel, Irma; Rivas-Santiago, Bruno; Olivares, Aleida; Avila, Euclides; Barrera, David; Halhali, Ali; Caldiño, Felipe; Larrea, Fernando; Díaz, Lorenza

    2016-10-01

    Male fetus and neonates show increased immune vulnerability compared to females, which results in a higher risk of perinatal infections. These differences could partially be due to sex steroids differential modulation of vitamin D metabolism; since calcitriol, the most active vitamin D metabolite, regulates immune responses and transcriptionally induces the antimicrobial peptide cathelicidin in the human placenta. Calcitriol availability depends on CYP27B1 and CYP24A1 expression, the cytochromes involved in its synthesis and degradation, respectively. However, the effects of testosterone upon these enzymes and the final biological outcome upon the calcitriol-dependent immune-target cathelicidin in the placenta have not been studied. In this study we show that testosterone significantly inhibited CYP27B1 while stimulated CYP24A1 gene expression in cultured trophoblasts. These effects were accompanied by CREB activation through cAMP-independent and androgen receptor-dependent mechanisms. Male placental cotyledons showed reduced basal CYP27B1 and cathelicidin gene expression compared to females (PTestosterone concentration was higher in the cord blood of male neonates (P=0.007), whereas cathelicidin levels were lesser compared to females (P=0.002). Altogether our results suggest that male placentas produce less cathelicidin due to decreased calcitriol bioavailability. We propose that the observed sex-dependent differences in placental vitamin D metabolism contribute in fetal responses to infections and could partially explain why the increased male fetuses immune vulnerability. Moreover, gestational hyperandrogenemia could adversely affect placental vitamin D metabolism independently of fetal sex. Copyright © 2016 Elsevier Ltd. All rights reserved.

  8. 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.

  9. Epigenetic regulation of fetal bone development and placental transfer of nutrients: progress for osteoporosis.

    Science.gov (United States)

    Bocheva, Georgeta; Boyadjieva, Nadka

    2011-12-01

    Osteoporosis is a common age-related disorder and causes acute and long-term disability and economic cost. Many factors influence the accumulation of bone minerals, including heredity, diet, physical activity, gender, endocrine functions, and risk factors such as alcohol, drug abuse, some pharmacological drugs or cigarette smoking. The pathology of bone development during intrauterine life is a factor for osteoporosis. Moreover, the placental transfer of nutrients plays an important role in the building of bones of fetuses. The importance of maternal calcium intake and vitamin D status are highlighted in this review. Various environmental factors including nutrition state or maternal stress may affect the epigenetic state of a number of genes during fetal development of bones. Histone modifications as histone hypomethylation, histone hypermethylation, hypoacetylation, etc. are involved in chromatin remodeling, known to contribute to the epigenetic landscape of chromosomes, and play roles in both fetal bone development and osteoporosis. This review will give an overview of epigenetic modulati