WorldWideScience

Sample records for human placental development

  1. 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.

  2. STEREOLOGICAL STUDIES ON FETAL VASCULAR DEVELOPMENT IN HUMAN PLACENTAL VILLI

    Directory of Open Access Journals (Sweden)

    Terry M Mayhew

    2011-05-01

    Full Text Available In human pregnancy, fetal well-being depends on the development of placental villi and the creation and maintenance of fetal microvessels within them. The aim of this study was to define stereological measures of the growth, capillarization and maturation of villi and of fetoplacental angiogenesis and capillary remodelling. Placentas were collected at 12-41 weeks of gestation and assigned to six age groups spanning equal age ranges. Tissue samples were randomised for position and orientation. Overall growth of peripheral (intermediate and terminal villi and their capillaries was evaluated using total volumes, surface areas and lengths. Measures of villous capillarization comprised capillary volume, surface and length densities and capillary:villus surface and length ratios. Size and shape remodelling of villi and capillaries was assessed using mean cross-sectional areas, perimeters and shape coefficients (perimeter2/area. Group comparisons were drawn by analysis of variance. Villous and capillary volumes, surfaces and lengths increased significantly throughout gestation. Villous maturation involved phasic (capillary:villus surface and length ratios or progressive (volume, surface and length densities increases in indices of villous capillarization. It also involved isomorphic thinning (cross-sectional areas and perimeters declined but shape coefficients did not alter. In contrast, growth of capillaries did not involve changes in luminal areas or perimeters. The results show that villous growth and fetal angiogenesis involve increases in overall length rather than calibre and that villous differentiation involves increased capillarization. Although they do not distinguish between increases in the lengths versus numbers of capillary segments, other studies have shown that capillaries switch from branching to non-branching angiogenesis during gestation. Combined with maintenance of capillary calibres, these processes will contribute to the reduced

  3. Placental perfusion - a human alternative

    DEFF Research Database (Denmark)

    Mose, Tina; Knudsen, Lisbeth E

    2006-01-01

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

  4. 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...... and endometrium is similar in macaques and baboons, as is the subsequent lacunar stage. The absence of interstitial trophoblast cells in the monkey is an important difference from human placentation. However, there is a strong resemblance in the way spiral arteries are invaded and transformed in the macaque...

  5. A stochastic model for early placental development.

    KAUST Repository

    Cotter, Simon L; Klika, Vá clav; Kimpton, Laura; Collins, Sally; Heazell, Alexander E P

    2014-01-01

    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

  6. 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.

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

    Directory of Open Access Journals (Sweden)

    Francesca Romana Grati

    2014-07-01

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

  8. IMMUNOLOGICAL MECHANISMS OF APOPTOSIS IN PLACENTAL DEVELOPMENT

    Directory of Open Access Journals (Sweden)

    D. I. Sokolov

    2008-01-01

    Full Text Available Abstract. In present review, the data are considered that concern a role of immunological mechanisms controlling the events of apoptosis at different stages of development of placenta. Intensity of apoptotic process in human placenta is progressively increasing in the course of pregnancy, until delivery act. The processes of apoptosis induction and its prevention in placental cells are inseparably linked to development of placenta and formation of vascular system, as controlled by trophoblast cells, as well as by maternal fetal immune cells. T-lymphocytes, natural killer cells, NKT-cells and macrophages that perform surveillance over the processes of angiogenesis and apoptosis in placental tissue, thus providing its normal development and functioning.

  9. 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

  10. Human placentation from nidation to 5 weeks of gestation. Part I: What do we know about formative placental development following implantation?

    DEFF Research Database (Denmark)

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

    2012-01-01

    limited for ethical reasons. In this review we discuss our current knowledge of early placental formation from the time of implantation at 3 weeks of gestation to approximately 5-6 weeks of gestation, encompassing both the significant anatomical findings derived from the unique specimens obtained...

  11. 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 ...

  12. Comparative intrauterine development and placental function of ART concepti: implications for human reproductive medicine and animal breeding.

    Science.gov (United States)

    Bloise, Enrrico; Feuer, Sky K; Rinaudo, Paolo F

    2014-01-01

    The number of children conceived using assisted reproductive technologies (ART) has reached >5 million worldwide and continues to increase. Although the great majority of ART children are healthy, many reports suggest a forthcoming risk of metabolic complications, which is further supported by the Developmental Origins of Health and Disease hypothesis of suboptimal embryo/fetal conditions predisposing adult cardiometabolic pathologies. Accumulating evidence suggests that fetal and placental growth kinetics are important features predicting post-natal health, but the relationship between ART and intrauterine growth has not been systematically reviewed. Relevant studies describing fetoplacental intrauterine phenotypes of concepti generated by in vitro fertilization (IVF), intracytoplasmic sperm injection (ICSI) and somatic cell nuclear transfer (SCNT) in the mouse, bovine and human were comprehensively researched using PubMed and Google Scholar. Intrauterine growth plots were created from tabular formatted data available in selected reports. ART pregnancies display minor but noticeable alterations in fetal and placental growth curves across mammalian species. In all species, there is evidence of fetal growth restriction in the earlier stages of pregnancy, followed by significant increases in placental size and accelerated fetal growth toward the end of gestation. However, there is a species-specific effect of ART on birthweights, that additionally vary in a culture condition-, strain-, and/or stage at transfer-specific manner. We discuss the potential mechanisms that underlie these changes, and how they are affected by specific components of ART procedures. ART may promote measurable alterations to intrauterine growth trajectory and placental function. Key findings include evidence that birthweight is not a reliable marker of fetal stress, and that increases in embryo manipulation result in more deviant fetal growth curves. Because growth kinetics in early life are

  13. Comparative intrauterine development and placental function of ART concepti: implications for human reproductive medicine and animal breeding

    Science.gov (United States)

    Bloise, Enrrico; Feuer, Sky K.; Rinaudo, Paolo F.

    2014-01-01

    BACKGROUND The number of children conceived using assisted reproductive technologies (ART) has reached >5 million worldwide and continues to increase. Although the great majority of ART children are healthy, many reports suggest a forthcoming risk of metabolic complications, which is further supported by the Developmental Origins of Health and Disease hypothesis of suboptimal embryo/fetal conditions predisposing adult cardiometabolic pathologies. Accumulating evidence suggests that fetal and placental growth kinetics are important features predicting post-natal health, but the relationship between ART and intrauterine growth has not been systematically reviewed. METHODS Relevant studies describing fetoplacental intrauterine phenotypes of concepti generated by in vitro fertilization (IVF), intracytoplasmic sperm injection (ICSI) and somatic cell nuclear transfer (SCNT) in the mouse, bovine and human were comprehensively researched using PubMed and Google Scholar. Intrauterine growth plots were created from tabular formatted data available in selected reports. RESULTS ART pregnancies display minor but noticeable alterations in fetal and placental growth curves across mammalian species. In all species, there is evidence of fetal growth restriction in the earlier stages of pregnancy, followed by significant increases in placental size and accelerated fetal growth toward the end of gestation. However, there is a species-specific effect of ART on birthweights, that additionally vary in a culture condition-, strain-, and/or stage at transfer-specific manner. We discuss the potential mechanisms that underlie these changes, and how they are affected by specific components of ART procedures. CONCLUSIONS ART may promote measurable alterations to intrauterine growth trajectory and placental function. Key findings include evidence that birthweight is not a reliable marker of fetal stress, and that increases in embryo manipulation result in more deviant fetal growth curves

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

    African Journals Online (AJOL)

    2016-02-16

    Feb 16, 2016 ... development of placental malaria in HIV‑positive women (odds ratio: 21.60; 95% ..... Marital status. Single. 6 (5.9). 4 (3.9). Married. 96 (94.1). 98 (96.1) ... χ2=16.65; df=2; P=<0.001. df=Degrees of freedom; HIV=Human.

  15. 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....

  16. Triazole fungicide tebuconazole disrupts human placental trophoblast cell functions

    International Nuclear Information System (INIS)

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

    2016-01-01

    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.

  17. Triazole fungicide tebuconazole disrupts human placental trophoblast cell functions

    Energy Technology Data Exchange (ETDEWEB)

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

    2016-05-05

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

  18. Human placental perfusion method in the assessment of transplacental passage of antiepileptic drugs

    International Nuclear Information System (INIS)

    Myllynen, Paeivi; Pienimaeki, Paeivi; Vaehaekangas, Kirsi

    2005-01-01

    Epilepsy is one of the most common neurological diseases, affecting about 0.5 to 1% of pregnant women. It is commonly accepted that older antiepileptic drugs bear teratogenic potential. So far, no agreement has been reached about the safest antiepileptic drug during pregnancy. It is known that nearly all drugs cross the placenta at least to some extent. Nowadays, there is very little information available of the pharmacokinetics of drugs in the feto-placental unit. Detailed information about drug transport across the placenta would be valuable for the development of safe and effective treatments. For reasons of safety, human studies on placental transfer are restricted to a limited number of drugs. Interspecies differences limit the extrapolation of animal data to humans. Several in vitro methods for the study of placental transfer have been developed over the past decades. The placental perfusion method is the only experimental method that has been used to study human placental transfer of substances in organized placental tissue. The aim of this article is to review human placental perfusion data on antiepileptic drugs. According to perfusion data, it seems that most of the antiepileptic drugs are transferred across the placenta meaning significant fetal exposure

  19. 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.

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

    NARCIS (Netherlands)

    Roescher, Annemiek

    2014-01-01

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

  1. Effects of maternal obesity on placental function and fetal development

    Science.gov (United States)

    Howell, Kristy R.; Powell, Theresa L.

    2017-01-01

    Obesity has reached epidemic proportions and pregnancies in obese mothers have increased risk for complications including gestational diabetes, hypertensive disorders, preterm birth and caesarian section. Children born to obese mothers are at increased risk of obesity and metabolic disease and are susceptible to develop neuropsychiatric and cognitive disorders. Changes in placental function not only play a critical role in the development of pregnancy complications but may also be involved in linking maternal obesity to long-term health risks in the infant. Maternal adipokines i.e., interleukin 6 (IL-6), tumor necrosis factor alpha (TNF-α), leptin and adiponectin link maternal nutritional status and adipose tissue metabolism to placental function. Adipokines and metabolic hormones have direct impact on placental function by modulating placental nutrient transport. Nutrient delivery to the fetus is regulated by a complex interaction between insulin signaling, cytokine profile and insulin responsiveness, which is modulated by adiponectin and IL-1β. In addition, obese pregnant women are at risk for hypertension and preeclampsia with reduced placental vascularity and blood flow, which would restrict placental nutrient delivery to the developing fetus. These sometimes opposing signals regulating placental function may contribute to the diversity of short and long-term outcomes observed in pregnant obese women. This review focuses on the changes in adipokines and obesity-related metabolic hormones, how these factors influence placental function and fetal development to contribute to long-term metabolic and behavioral consequences of children born to obese mothers. PMID:27864335

  2. 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...

  3. 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

    , 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...... 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....

  4. Oxcarbazepine-loaded polymeric nanoparticles: development and permeability studies across in vitro models of the blood-brain barrier and human placental trophoblast.

    Science.gov (United States)

    Lopalco, Antonio; Ali, Hazem; Denora, Nunzio; Rytting, Erik

    2015-01-01

    Encapsulation of antiepileptic drugs (AEDs) into nanoparticles may offer promise for treating pregnant women with epilepsy by improving brain delivery and limiting the transplacental permeability of AEDs to avoid fetal exposure and its consequent undesirable adverse effects. Oxcarbazepine-loaded nanoparticles were prepared by a modified solvent displacement method from biocompatible polymers (poly(lactic-co-glycolic acid) [PLGA] with or without surfactant and PEGylated PLGA [Resomer(®) RGPd5055]). The physical properties of the developed nanoparticles were determined with subsequent evaluation of their permeability across in vitro models of the blood-brain barrier (hCMEC/D3 cells) and human placental trophoblast cells (BeWo b30 cells). Oxcarbazepine-loaded nanoparticles with encapsulation efficiency above 69% were prepared with sizes ranging from 140-170 nm, polydispersity indices below 0.3, and zeta potential values below -34 mV. Differential scanning calorimetry and X-ray diffraction studies confirmed the amorphous state of the nanoencapsulated drug. The apparent permeability (Pe ) values of the free and nanoencapsulated oxcarbazepine were comparable across both cell types, likely due to rapid drug release kinetics. Transport studies using fluorescently-labeled nanoparticles (loaded with coumarin-6) demonstrated increased permeability of surfactant-coated nanoparticles. Future developments in enzyme-prodrug therapy and targeted delivery are expected to provide improved options for pregnant patients with epilepsy.

  5. Oxcarbazepine-loaded polymeric nanoparticles: development and permeability studies across in vitro models of the blood–brain barrier and human placental trophoblast

    Science.gov (United States)

    Lopalco, Antonio; Ali, Hazem; Denora, Nunzio; Rytting, Erik

    2015-01-01

    Encapsulation of antiepileptic drugs (AEDs) into nanoparticles may offer promise for treating pregnant women with epilepsy by improving brain delivery and limiting the transplacental permeability of AEDs to avoid fetal exposure and its consequent undesirable adverse effects. Oxcarbazepine-loaded nanoparticles were prepared by a modified solvent displacement method from biocompatible polymers (poly(lactic-co-glycolic acid) [PLGA] with or without surfactant and PEGylated PLGA [Resomer® RGPd5055]). The physical properties of the developed nanoparticles were determined with subsequent evaluation of their permeability across in vitro models of the blood–brain barrier (hCMEC/D3 cells) and human placental trophoblast cells (BeWo b30 cells). Oxcarbazepine-loaded nanoparticles with encapsulation efficiency above 69% were prepared with sizes ranging from 140–170 nm, polydispersity indices below 0.3, and zeta potential values below -34 mV. Differential scanning calorimetry and X-ray diffraction studies confirmed the amorphous state of the nanoencapsulated drug. The apparent permeability (Pe) values of the free and nanoencapsulated oxcarbazepine were comparable across both cell types, likely due to rapid drug release kinetics. Transport studies using fluorescently-labeled nanoparticles (loaded with coumarin-6) demonstrated increased permeability of surfactant-coated nanoparticles. Future developments in enzyme-prodrug therapy and targeted delivery are expected to provide improved options for pregnant patients with epilepsy. PMID:25792832

  6. 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

  7. A novel mechanism of angiotensin II-regulated placental vascular tone in the development of hypertension in preeclampsia.

    Science.gov (United States)

    Gao, Qinqin; Tang, Jiaqi; Li, Na; Zhou, Xiuwen; Li, Yongmei; Liu, Yanping; Wu, Jue; Yang, Yuxian; Shi, Ruixiu; He, Axin; Li, Xiang; Zhang, Yingying; Chen, Jie; Zhang, Lubo; Sun, Miao; Xu, Zhice

    2017-05-09

    The present study tested the hypothesis that angiotensin II plays a role in the regulation of placental vascular tone, which contributes to hypertension in preeclampsia. Functional and molecular assays were performed in large and micro placental and non-placental vessels from humans and animals. In human placental vessels, angiotensin II induced vasoconstrictions in 78.7% vessels in 155 tests, as referenced to KCl-induced contractions. In contrast, phenylephrine only produced contractions in 3.0% of 133 tests. In non-placental vessels, phenylephrine induced contractions in 76.0% of 67 tests, whereas angiotensin II failed to produce contractions in 75 tests. Similar results were obtained in animal placental and non-placental vessels. Compared with non-placental vessels, angiotensin II receptors and β-adrenoceptors were significantly increased in placental vessels. Compared to the vessels from normal pregnancy, angiotensin II-induced vasoconstrictions were significantly reduced in preeclamptic placentas, which was associated with a decrease in angiotensin II receptors. In addition, angiotensin II and angiotensin converting enzyme in the maternal-placenta circulation in preeclampsia were increased, whereas angiotensin I and angiotensin1-7 concentrations were unchanged. The study demonstrates a selective effect of angiotensin II in maintaining placental vessel tension, which may play an important role in development of hypertension in preeclampsia.

  8. EG-VEGF: a key endocrine factor in placental development.

    Science.gov (United States)

    Brouillet, Sophie; Hoffmann, Pascale; Feige, Jean-Jacques; Alfaidy, Nadia

    2012-10-01

    Endocrine gland-derived vascular endothelial growth factor (EG-VEGF), also named prokineticin 1, is the canonical member of the prokineticin family. Numerous reports suggest a direct involvement of this peptide in normal and pathological reproductive processes. Recent advances propose EG-VEGF as a key endocrine factor that controls many aspects of placental development and suggest its involvement in the development of preeclampsia (PE), the most threatening pathology of human pregnancy. This review describes the finely tuned action and regulation of EG-VEGF throughout human pregnancy, argues for its clinical relevance as a potential diagnostic marker of the onset of PE, and discusses future research directions for therapeutic targeting of EG-VEGF. Copyright © 2012 Elsevier Ltd. All rights reserved.

  9. 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.

  10. Maternal serum placental growth hormone, but not human placental lactogen or insulin growth factor-1, is positively associated with fetal growth in the first half of pregnancy

    DEFF Research Database (Denmark)

    Pedersen, N G; Juul, A; Christiansen, M

    2010-01-01

    To investigate if maternal levels of human placental lactogen (hPL), placental growth hormone (PGH) and insulin-like growth factor-1 (IGF-1) are associated with growth rate of the biparietal diameter (BPD) in the first half of pregnancy.......To investigate if maternal levels of human placental lactogen (hPL), placental growth hormone (PGH) and insulin-like growth factor-1 (IGF-1) are associated with growth rate of the biparietal diameter (BPD) in the first half of pregnancy....

  11. Oxcarbazepine-loaded polymeric nanoparticles: development and permeability studies across in vitro models of the blood–brain barrier and human placental trophoblast

    Directory of Open Access Journals (Sweden)

    Lopalco A

    2015-03-01

    Full Text Available Antonio Lopalco,1–3,* Hazem Ali,1,* Nunzio Denora,3 Erik Rytting1,4,5 1Department of Obstretrics and Gynecology, University of Texas Medical Branch, Galveston, TX, USA; 2Department of Pharmaceutical Chemistry, University of Kansas, Lawrence, KS, USA; 3Department of Pharmacy – Drug Sciences, University of Bari Aldo Moro, Bari, Italy; 4Center for Biomedical Engineering, University of Texas Medical Branch, Galveston, TX, USA; 5Department of Pharmacology and Toxicology, University of Texas Medical Branch, Galveston, TX, USA *These authors contributed equally to this work Abstract: Encapsulation of antiepileptic drugs (AEDs into nanoparticles may offer promise for treating pregnant women with epilepsy by improving brain delivery and limiting the transplacental permeability of AEDs to avoid fetal exposure and its consequent undesirable adverse effects. Oxcarbazepine-loaded nanoparticles were prepared by a modified solvent displacement method from biocompatible polymers (poly(lactic-co-glycolic acid [PLGA] with or without surfactant and PEGylated PLGA [Resomer® RGPd5055]. The physical properties of the developed nanoparticles were determined with subsequent evaluation of their permeability across in vitro models of the blood–brain barrier (hCMEC/D3 cells and human placental trophoblast cells (BeWo b30 cells. Oxcarbazepine-loaded nanoparticles with encapsulation efficiency above 69% were prepared with sizes ranging from 140–170 nm, polydispersity indices below 0.3, and zeta potential values below −34 mV. Differential scanning calorimetry and X-ray diffraction studies confirmed the amorphous state of the nanoencapsulated drug. The apparent permeability (Pe values of the free and nanoencapsulated oxcarbazepine were comparable across both cell types, likely due to rapid drug release kinetics. Transport studies using fluorescently-labeled nanoparticles (loaded with coumarin-6 demonstrated increased permeability of surfactant-coated nanoparticles

  12. Identification of Novel Placentally Expressed Aspartic Proteinase in Humans

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    Marta Majewska

    2017-06-01

    Full Text Available This study presents pioneering data concerning the human pregnancy-associated glycoprotein-Like family, identified in the genome, of the term placental transcriptome and proteome. RNA-seq allowed the identification of 1364 bp hPAG-L/pep cDNA with at least 56.5% homology with other aspartic proteinases (APs. In silico analyses revealed 388 amino acids (aa of full-length hPAG-L polypeptide precursor, with 15 aa-signal peptide, 47 aa-blocking peptide and 326 aa-mature protein, and two Asp residues (D, specific for a catalytic cleft of the APs (VVFDTGSSNLWV91-102 and AIVDTGTSLLTG274-285. Capillary sequencing identified 9330 bp of the hPAG-L gene (Gen Bank Acc. No. KX533473, composed of nine exons and eight introns. Heterologous Western blotting revealed the presence of one dominant 60 kDa isoform of the hPAG-L amongst cellular placental proteins. Detection with anti-pPAG-P and anti-Rec pPAG2 polyclonals allowed identification of the hPAG-L proteins located within regions of chorionic villi, especially within the syncytiotrophoblast of term singleton placentas. Our novel data extend the present knowledge about the human genome, as well as placental transcriptome and proteome during term pregnancy. Presumably, this may contribute to establishing a new diagnostic tool for examination of some disturbances during human pregnancy, as well as growing interest from both scientific and clinical perspectives.

  13. Does malaria affect placental development? Evidence from in vitro models.

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    Alexandra J Umbers

    Full Text Available BACKGROUND: Malaria in early pregnancy is difficult to study but has recently been associated with fetal growth restriction (FGR. The pathogenic mechanisms underlying malarial FGR are poorly characterized, but may include impaired placental development. We used in vitro methods that model migration and invasion of placental trophoblast into the uterine wall to investigate whether soluble factors released into maternal blood in malaria infection might impair placental development. Because trophoblast invasion is enhanced by a number of hormones and chemokines, and is inhibited by pro-inflammatory cytokines, many of which are dysregulated in malaria in pregnancy, we further compared concentrations of these factors in blood between malaria-infected and uninfected pregnancies. METHODOLOGY/PRINCIPAL FINDINGS: We measured trophoblast invasion, migration and viability in response to treatment with serum or plasma from two independent cohorts of Papua New Guinean women infected with Plasmodium falciparum or Plasmodium vivax in early pregnancy. Compared to uninfected women, serum and plasma from women with P. falciparum reduced trophoblast invasion (P = .06 and migration (P = .004. P. vivax infection did not alter trophoblast migration (P = .64. The P. falciparum-specific negative effect on placental development was independent of trophoblast viability, but associated with high-density infections. Serum from P. falciparum infected women tended to have lower levels of trophoblast invasion promoting hormones and factors and higher levels of invasion-inhibitory inflammatory factors. CONCLUSION/SIGNIFICANCE: We demonstrate that in vitro models of placental development can be adapted to indirectly study the impact of malaria in early pregnancy. These infections could result in impaired trophoblast invasion with reduced transformation of maternal spiral arteries due to maternal hormonal and inflammatory disturbances, which may contribute to FGR by

  14. Endoplasmic reticulum stress disrupts placental morphogenesis: implications for human intrauterine growth restriction.

    Science.gov (United States)

    Yung, Hong Wa; Hemberger, Myriam; Watson, Erica D; Senner, Claire E; Jones, Carolyn P; Kaufman, Randal J; Charnock-Jones, D Stephen; Burton, Graham J

    2012-12-01

    We recently reported the first evidence of placental endoplasmic reticulum (ER) stress in the pathophysiology of human intrauterine growth restriction. Here, we used a mouse model to investigate potential underlying mechanisms. Eif2s1(tm1RjK) mice, in which Ser51 of eukaryotic initiation factor 2 subunit alpha (eIF2α) is mutated, display a 30% increase in basal translation. In Eif2s1(tm1RjK) placentas, we observed increased ER stress and anomalous accumulation of glycoproteins in the endocrine junctional zone (Jz), but not in the labyrinthine zone where physiological exchange occurs. Placental and fetal weights were reduced by 15% (97 mg to 82 mg, p growth factor for placental development; indeed, activity in the Pdk1-Akt-mTOR pathways was decreased in Eif2s1(tm1RjK) placentas, indicating loss of Igf2 signalling. Furthermore, we observed premature differentiation of trophoblast progenitors at E9.5 in mutant placentas, consistent with the in vitro results and with the disproportionate development of the labyrinth and Jz seen in placentas at E18.5. Similar disproportion has been reported in the Igf2-null mouse. These results demonstrate that ER stress adversely affects placental development, and that modulation of post-translational processing, and hence bioactivity, of secreted growth factors contributes to this effect. Placental dysmorphogenesis potentially affects fetal growth through reduced exchange capacity. Copyright © 2012 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.

  15. Mammalian Placentation

    DEFF Research Database (Denmark)

    Carter, Anthony Michael; Mess, A. M.

    2014-01-01

    This guide to animal models of human placentation assesses the strengths and weaknesses of species in common use. We argue that structural differences from human placenta, though important in some contexts, are less of a drawback than differences in reproductive strategy. Many laboratory rodents...... of the placenta. This information is collated both to assess common animal models such as mouse, sheep, and primates and to introduce some alternatives that we consider worthy of attention....... 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...

  16. Oxidation of eugenol by purified human term placental peroxidase.

    Science.gov (United States)

    Zhang, R; Kulkarni, K A; Kulkarni, A P

    2000-01-01

    The oxidation of eugenol by purified human term placental peroxidase (HTPP) was examined. Spectral analyses indicated that, similar to horseradish peroxidase, HTPP is capable of catalyzing the oxidation of eugenol. The accumulated stable product in the reaction medium due to eugenol oxidation by HTPP was tentatively identified as quinone methide of eugenol (EQM). The EQM formation exhibited a pH optimum of 8.0 and was dependent on incubation time, amount of HTPP and the concentration of both eugenol and hydrogen peroxide. The specific activity of approx 2.8 micromoles of EQM/min/mg protein was observed with different preparations of HTPP. The EQM formation was significantly suppressed by glutathione and ascorbic acid. The classical peroxidase inhibitors viz. potassium cyanide and sodium azide blocked the reaction in a concentration manner. Collectively, the results suggest that eugenol may undergo peroxidative metabolism in human placenta. Copyright 2000 Harcourt Publishers Ltd.

  17. 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

  18. Impaired Angiogenic Potential of Human Placental Mesenchymal Stromal Cells in Intrauterine Growth Restriction.

    Science.gov (United States)

    Mandò, Chiara; Razini, Paola; Novielli, Chiara; Anelli, Gaia Maria; Belicchi, Marzia; Erratico, Silvia; Banfi, Stefania; Meregalli, Mirella; Tavelli, Alessandro; Baccarin, Marco; Rolfo, Alessandro; Motta, Silvia; Torrente, Yvan; Cetin, Irene

    2016-04-01

    Human placental mesenchymal stromal cells (pMSCs) have never been investigated in intrauterine growth restriction (IUGR). We characterized cells isolated from placental membranes and the basal disc of six IUGR and five physiological placentas. Cell viability and proliferation were assessed every 7 days during a 6-week culture. Expression of hematopoietic, stem, endothelial, and mesenchymal markers was evaluated by flow cytometry. We characterized the multipotency of pMSCs and the expression of genes involved in mitochondrial content and function. Cell viability was high in all samples, and proliferation rate was lower in IUGR compared with control cells. All samples presented a starting heterogeneous population, shifting during culture toward homogeneity for mesenchymal markers and occurring earlier in IUGR than in controls. In vitro multipotency of IUGR-derived pMSCs was restricted because their capacity for adipocyte differentiation was increased, whereas their ability to differentiate toward endothelial cell lineage was decreased. Mitochondrial content and function were higher in IUGR pMSCs than controls, possibly indicating a shift from anaerobic to aerobic metabolism, with the loss of the metabolic characteristics that are typical of undifferentiated multipotent cells. This study demonstrates that the loss of endothelial differentiation potential and the increase of adipogenic ability are likely to play a significant role in the vicious cycle of abnormal placental development in intrauterine growth restriction (IUGR). This is the first observation of a potential role for placental mesenchymal stromal cells in intrauterine growth restriction, thus leading to new perspectives for the treatment of IUGR. ©AlphaMed Press.

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

    DEFF Research Database (Denmark)

    Mathiesen, Line

    2011-01-01

    be used as a negative control when adding a small amount to the fetal reservoir. To be able to detect any trace of dextran in the maternal reservoir in case of a leakage, the dextran is labeled with FITC and analyzed by fluorescence measurement (Paper I). Inter-laboratory comparisons have confirmed...... 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...

  20. 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.

  1. Dickkopf-1 induced apoptosis in human placental choriocarcinoma is independent of canonical Wnt signaling

    International Nuclear Information System (INIS)

    Peng Sha; Miao Chenglin; Li Jing; Fan Xiujun; Cao Yujing; Duan Enkui

    2006-01-01

    Placental choriocarcinoma, a reproductive system carcinoma in women, has about 0.81% occurrence frequency in China, which leads to over 90% lethality due to indistinct pathogenesis and the absence of efficient therapeutic treatment. In the present study, using immunostaining and reverse transcription PCR, we reported that Dickkopf-1 (Dkk-1) is prominently expressed in human cytotrophoblast (CTB) cell, but absent in the human placental choriocarcinoma cell line JAR and JEG3, implicating an unknown correlation between Dkk-1 and carcinogenesis of placental choriocarcinoma. Further, through exogenous introduction of Dkk-1, we found repressed proliferation in JAR and JEG3, induced apoptosis in JAR, and discovered significant tumor suppression effects of Dkk-1 in placental choriocarcinoma. Moreover we found that this function of Dkk-1 is achieved through c-Jun N-terminal kinase (JNK), whereas the canonical Wnt pathway may not have a great role. This discovery is not symphonic to previous functional understanding of Dkk-1, a canonical Wnt signaling antagonist. Together, our data indicate the possible correlation between Dkk-1 and human placental choriocarcinoma and suggest potential applications of Dkk-1 in treatment of human placental choriocarcinomas

  2. Placental Drug Transport-on-a-Chip: A Microengineered In Vitro Model of Transporter-Mediated Drug Efflux in the Human Placental Barrier.

    Science.gov (United States)

    Blundell, Cassidy; Yi, Yoon-Suk; Ma, Lin; Tess, Emily R; Farrell, Megan J; Georgescu, Andrei; Aleksunes, Lauren M; Huh, Dongeun

    2018-01-01

    The current lack of knowledge about the effect of maternally administered drugs on the developing fetus is a major public health concern worldwide. The first critical step toward predicting the safety of medications in pregnancy is to screen drug compounds for their ability to cross the placenta. However, this type of preclinical study has been hampered by the limited capacity of existing in vitro and ex vivo models to mimic physiological drug transport across the maternal-fetal interface in the human placenta. Here the proof-of-principle for utilizing a microengineered model of the human placental barrier to simulate and investigate drug transfer from the maternal to the fetal circulation is demonstrated. Using the gestational diabetes drug glyburide as a model compound, it is shown that the microphysiological system is capable of reconstituting efflux transporter-mediated active transport function of the human placental barrier to limit fetal exposure to maternally administered drugs. The data provide evidence that the placenta-on-a-chip may serve as a new screening platform to enable more accurate prediction of drug transport in the human placenta. © 2017 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  3. Comparative N-glycoproteomic and phosphoproteomic profiling of human placental plasma membrane between normal and preeclampsia pregnancies with high-resolution mass spectrometry.

    Directory of Open Access Journals (Sweden)

    Fuqiang Wang

    Full Text Available Preeclampsia is a serious complication of pregnancy, which affects 2-8% of all pregnancies and is one of the leading causes of maternal and perinatal mortality and morbidity worldwide. To better understand the molecular mechanisms involved in pathological development of placenta in preeclampsia, we used high-resolution LC-MS/MS technologies to construct a comparative N-glycoproteomic and phosphoproteomic profiling of human placental plasma membrane in normal and preeclamptic pregnancies. A total of 1027 N-glyco- and 2094 phospho- sites were detected in human placental plasma membrane, and 5 N-glyco- and 38 phospho- proteins, respectively, with differentially expression were definitively identified between control and preeclamptic placental plasma membrane. Further bioinformatics analysis indicated that these differentially expressed proteins correlate with several specific cellular processes occurring during pathological changes of preeclamptic placental plasma membrane.

  4. PPARγ controls pregnancy outcome through activation of EG-VEGF: new insights into the mechanism of placental development.

    Science.gov (United States)

    Garnier, Vanessa; Traboulsi, Wael; Salomon, Aude; Brouillet, Sophie; Fournier, Thierry; Winkler, Carine; Desvergne, Beatrice; Hoffmann, Pascale; Zhou, Qun-Yong; Congiu, Cenzo; Onnis, Valentina; Benharouga, Mohamed; Feige, Jean-Jacques; Alfaidy, Nadia

    2015-08-15

    PPARγ-deficient mice die at E9.5 due to placental abnormalities. The mechanism by which this occurs is unknown. We demonstrated that the new endocrine factor EG-VEGF controls the same processes as those described for PPARγ, suggesting potential regulation of EG-VEGF by PPARγ. EG-VEGF exerts its functions via prokineticin receptor 1 (PROKR1) and 2 (PROKR2). This study sought to investigate whether EG-VEGF mediates part of PPARγ effects on placental development. Three approaches were used: 1) in vitro, using human primary isolated cytotrophoblasts and the extravillous trophoblast cell line (HTR-8/SVneo); 2) ex vivo, using human placental explants (n = 46 placentas); and 3) in vivo, using gravid wild-type PPARγ(+/-) and PPARγ(-/-) mice. Major processes of placental development that are known to be controlled by PPARγ, such as trophoblast proliferation, migration, and invasion, were assessed in the absence or presence of PROKR1 and PROKR2 antagonists. In both human trophoblast cell and placental explants, we demonstrated that rosiglitazone, a PPARγ agonist, 1) increased EG-VEGF secretion, 2) increased EG-VEGF and its receptors mRNA and protein expression, 3) increased placental vascularization via PROKR1 and PROKR2, and 4) inhibited trophoblast migration and invasion via PROKR2. In the PPARγ(-/-) mouse placentas, EG-VEGF levels were significantly decreased, supporting an in vivo control of EG-VEGF/PROKRs system during pregnancy. The present data reveal EG-VEGF as a new mediator of PPARγ effects during pregnancy and bring new insights into the fine mechanism of trophoblast invasion. Copyright © 2015 the American Physiological Society.

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

    DEFF Research Database (Denmark)

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

    2014-01-01

    expressing VAR2CSA on the erythrocyte surface. This protein adheres to a low-sulfated chondroitin sulfate-A found in placental tissue causing great harm to both mother and developing fetus. In rare cases, the localization of infected erythrocytes to the placenta can even result in the vertical transmission...... placental tissue accessible to parasites in the bloodstream, suggesting it is the primary receptor for parasite infected red blood cells....

  6. 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 modulation of bone development and placental transfer of nutrients. In addition, the data from animal and human studies support the role of epigenetic modulation of calcium and vitamin D in the pathogenesis of osteoporosis. We review the evidence suggesting that various genes are involved in regulation of osteoclast formation and differentiation by osteoblasts and stem cells. Epigenetic changes in growth factors as well as cytokines play a rol in fetal bone development. On balance, the data suggest that there is a link between epigenetic changes in placental transfer of nutrients, including calcium and vitamin D, abnormal intrauterine bone development and pathogenesis of osteoporosis.

  7. Maternal HtrA3 optimizes placental development to influence offspring birth weight and subsequent white fat gain in adulthood.

    Science.gov (United States)

    Li, Ying; Salamonsen, Lois A; Hyett, Jonathan; Costa, Fabricio da Silva; Nie, Guiying

    2017-07-04

    High temperature requirement factor A3 (HtrA3), a member of the HtrA protease family, is highly expressed in the developing placenta, including the maternal decidual cells in both mice and humans. In this study we deleted the HtrA3 gene in the mouse and crossed females carrying zero, one, or two HtrA3-expressing alleles with HtrA3 +/- males to investigate the role of maternal vs fetal HtrA3 in placentation. Although HtrA3 -/- mice were phenotypically normal and fertile, HtrA3 deletion in the mother resulted in intra-uterine growth restriction (IUGR). Disorganization of labyrinthine fetal capillaries was the major placental defect when HtrA3 was absent. The IUGR caused by maternal HtrA3 deletion, albeit being mild, significantly altered offspring growth trajectory long after birth. By 8 months of age, mice born to HtrA3-deficient mothers, independent of their own genotype, were significantly heavier and contained a larger mass of white fat. We further demonstrated that in women serum levels of HtrA3 during early pregnancy were significantly lower in IUGR pregnancies, establishing an association between lower HtrA3 levels and placental insufficiency in the human. This study thus revealed the importance of maternal HtrA3 in optimizing placental development and its long-term impact on the offspring well beyond in utero growth.

  8. Pre-clinical and clinical development of the first placental malaria vaccine

    DEFF Research Database (Denmark)

    Pehrson, Caroline; Salanti, Ali; Theander, Thor G

    2017-01-01

    the condition.  Areas covered: Pub Med was searched using the broad terms 'malaria parasite placenta' to identify studies of interactions between parasite and host, 'prevention of placental malaria' to identify current strategies to prevent placental malaria, and 'placental malaria vaccine' to identify pre-clinical...... vaccine development. However, all papers from these searches were not systematically included.  Expert commentary: The first phase I clinical trials of vaccines are well underway. Trials testing efficacy are more complicated to carry out as only women that are exposed to parasites during pregnancy...

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

    International Nuclear Information System (INIS)

    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 (θ) with tabulated values for fractional absorption (f 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

  10. Plutonium content of human placental tissues after occupational exposure

    International Nuclear Information System (INIS)

    Russell, J.J.; Sikov, M.R.; Kathren, R.L.

    2003-01-01

    The placenta and umbilical cord were obtained following a normal live delivery from a volunteer donor who had received an accidental inhalation intake of plutonium 12 years prior to her pregnancy (Case 0777). Her employer estimated the intake to be about 73 Bq Class W plutonium. Based on bioassay results and clearance models in use at that time, they calculated her body content at the beginning of pregnancy to be about 5.6 Bq with an average concentration of approximately 60 mBq kg -1 . The placenta and cord from this pregnancy, along with the placenta and cord from a donor with no known exposure to plutonium (Case 0835), were divided and assayed for plutonium by ultrasensitive fission track analysis at two collaborating laboratories. Placental 239 Pu concentration values obtained by the two laboratories for Case 0777 agreed within a factor of 2 and were several-fold greater than for the control, Case 0835, as well as values that had been reported by others for unexposed populations. There was no elevated concentration of plutonium in the umbilical cord from the exposed person. The data yielded values of 0.16 and 0.27 for placental to maternal concentrations (C PI :C M ) that were of the same order of magnitude as the value of 0.1 the ICRP calculated for intakes before pregnancy. (author)

  11. Plutonium content of human placental tissues after occupational exposure

    Energy Technology Data Exchange (ETDEWEB)

    Russell, J.J.; Sikov, M.R.; Kathren, R.L

    2003-07-01

    The placenta and umbilical cord were obtained following a normal live delivery from a volunteer donor who had received an accidental inhalation intake of plutonium 12 years prior to her pregnancy (Case 0777). Her employer estimated the intake to be about 73 Bq Class W plutonium. Based on bioassay results and clearance models in use at that time, they calculated her body content at the beginning of pregnancy to be about 5.6 Bq with an average concentration of approximately 60 mBq kg{sup -1}. The placenta and cord from this pregnancy, along with the placenta and cord from a donor with no known exposure to plutonium (Case 0835), were divided and assayed for plutonium by ultrasensitive fission track analysis at two collaborating laboratories. Placental {sup 239}Pu concentration values obtained by the two laboratories for Case 0777 agreed within a factor of 2 and were several-fold greater than for the control, Case 0835, as well as values that had been reported by others for unexposed populations. There was no elevated concentration of plutonium in the umbilical cord from the exposed person. The data yielded values of 0.16 and 0.27 for placental to maternal concentrations (C{sub PI}:C{sub M}) that were of the same order of magnitude as the value of 0.1 the ICRP calculated for intakes before pregnancy. (author)

  12. 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

    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....... 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...

  13. 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

  14. 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

  15. Effect of young maternal age and skeletal growth on placental growth and development.

    Science.gov (United States)

    Hayward, C E; Greenwood, S L; Sibley, C P; Baker, P N; Jones, R L

    2011-12-01

    Teenagers are susceptible to delivering small-for-gestational-age infants. Previous studies implicate continued skeletal growth as a contributory factor, and impaired placental development was the primary cause of fetal growth restriction in growing adolescent sheep. The aims of this study were to examine the impact of young maternal age and growth on placental development. Placentas were collected from 31 teenagers, of which 12 were growing and 17 non-growing based on knee height measurements. An adult control group (n = 12) was included. Placental weight and morphometric measurements of villous, syncytiotrophoblast, fibrin and vessel areas, as well as indices of proliferation and apoptosis, were analysed in relation to maternal growth and age. Growing teenagers had a higher birthweight:placental weight ratio than non-growing teenagers (p adult and teenage pregnancies. Maternal smoking, a potential confounding factor, did not exert a major influence on the placental parameters examined, except for a stimulatory effect on placental proliferation (p development, and is consistent with our recent observations that maternal growth was not detrimental to fetal growth. Copyright © 2011 Elsevier Ltd. All rights reserved.

  16. 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.

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

    International Nuclear Information System (INIS)

    Prouillac, Caroline; Koraichi, Farah; Videmann, Bernadette; Mazallon, Michelle; Rodriguez, Frédéric; Baltas, Michel; Lecoeur, Sylvaine

    2012-01-01

    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. 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......-eclampsia also occurs in these species, such information may reveal the evolutionary roots of this disease of impaired maternal-fetal interaction....

  19. Characterization of receptors for recombinant human tumor necrosis factor-alpha from human placental membranes

    International Nuclear Information System (INIS)

    Aiyer, R.A.; Aggarwal, B.B.

    1990-01-01

    High affinity receptors for recombinant human tumor necrosis factor-alpha (rhTNF-alpha) were identified on membranes prepared from full term human placenta. Highly purified rhTNF-alpha iodinated by the iodogen method was found to bind placental membranes in a displaceable manner with an approximate dissociation constant (KD) of 1.9 nM. The membrane bound TNF-alpha receptor could be solubilized by several detergents with optimum extraction being obtained with 1% Triton X-100. The binding of 125I-rhTNF-alpha to the solubilized receptor was found to be time and temperature dependent, yielding maximum binding within 1 h, 24 h and 48 h at 37 degrees C, 24 degrees C and 4 degrees C, respectively. However, the maximum binding obtainable at 4 degrees C was only 40% of that at 37 degrees C. The binding 125I-rhTNF-alpha to solubilized placental membrane extracts was displaceable by unlabeled rhTNF-alpha, but not by a related protein recombinant human tumor necrosis factor-beta (rhTNF-beta; previously called lymphotoxin). This is similar to the behavior of TNF-alpha receptors derived from detergent-solubilized cell extracts, although on intact cells, both rhTNF-alpha and rhTNF-beta bind with equal affinity to TNF receptors. The Scatchard analysis of the binding data of the solubilized receptor revealed high affinity binding sites with a KD of approximately 0.5 nM and a receptor concentration of about 1 pmole/mg protein. Gel filtration of the solubilized receptor-ligand complexes on Sephacryl S-300 revealed two different peaks of radioactivity at approximate molecular masses of 50,000 Da and 400,000 Da. The 400,000 dalton peak corresponded to the receptor-ligand complex. Overall, our results suggest that high affinity receptors for TNF-alpha are present on human placental membranes and provide evidence that these receptors may be different from that of rhTNF-beta

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

    Science.gov (United States)

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

    2012-01-01

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

  1. Conversion of ethanol to acetaldehyde by human placental homogenates and villi in vitro

    International Nuclear Information System (INIS)

    Blomquist, C.H.; Lindemann, N.J.; Hakanson, E.Y.

    1986-01-01

    The authors have previously reported that placental villi in vitro metabolize acetaldehyde (Ach), and that Ach forms adducts with placental subcellular fractions. In the experiments reported here the authors have investigated the capacity of placental homogenates and villi to generate Ach from ethanol (EtOH). When placental homogenates (0.5 g wet weight) prepared in 50 mM Tris. pH 7.5, were incubated with 20 μM [1- 14 C]ethanol and an NADP- generating system, Ach was formed at the rate of 0.18 nmol/h/g wet weight of tissue, based on counts trappable with semicarbazide. NAD was as effective as NADP. Omission of cofactor resulted in a 69% decrease in activity. The addition of a human serum ultrafiltrate (25,000 m.w. cut-off) to 20% had no effect on Ach formation, whole serum at 20% reduced reaction by 60%. Sodium azide at 40 mM completely abolished Ach formation, 1,10-phenanthroline at 0.4 mM inhibited approximately 50%. In contrast, no Ach formation was detected when 1.0-g fragments of villous tissue were incubated with 20 μM [1- 14 C]EtOH. The data suggest that villous tissue is capable of Ach formation by a catalase-like activity, but the capacity of intact villi for EtOH oxidation is low

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

    International Nuclear Information System (INIS)

    Tetz, Lauren M.; Cheng, Adrienne A.; Korte, Cassandra S.; Giese, Roger W.; Wang, Poguang; Harris, Craig; Meeker, John D.; Loch-Caruso, Rita

    2013-01-01

    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

  3. A microprocessor-controlled assay for the estimation of human placental lactogen

    International Nuclear Information System (INIS)

    Adam, T.; Roulston, J.E.; Bagshawe, K.D.

    1979-01-01

    A radioimmunoassay for human placental lactogen (HPL) is described using the KEMTEK 3000, which is a modular radioimmunoassay apparatus controlled by a microprocessor. Operation of the KEMTEK 3000 is largely automatic and it requires minimal intervention from the operator. It is capable of 300 reactions per hour so that a large number of estimations can readily be performed. HPL was assayed by a double antibody method on serum samples from pregnant women and patients with trophoblastic tumours. (Auth.)

  4. 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

  5. Concentrations of Polybrominated Diphenyl Ethers (PBDEs) and 2,4,6-Tribromophenol in Human Placental Tissues

    Science.gov (United States)

    Leonetti, Christopher; Butt, Craig M.; Hoffman, Kate; Miranda, Marie Lynn; Stapleton, Heather M.

    2015-01-01

    Legacy environmental contaminants such as polybrominated diphenyl ethers (PBDEs) are widely detected in human tissues. However, few studies have measured PBDEs in placental tissues, and there are no reported measurements of 2,4,6-tribromophenol (2,4,6-TBP) in placental tissues. Measurements of these contaminants are important for understanding potential fetal exposures, as these compounds have been shown to alter thyroid hormone regulation in vitro and in vivo. In this study, we measured a suite of PBDEs and 2,4,6-TBP in 102 human placental tissues collected between 2010–2011 in Durham County, North Carolina, USA. The most abundant PBDE congener detected was BDE-47, with a mean concentration of 5.09 ng/g lipid (range: 0.12–141 ng/g lipid; detection frequency 91%); however, 2,4,6-TBP was ubiquitously detected and present at higher concentrations with a mean concentration of 15.4 ng/g lipid (range:1.31–316 ng/g lipid; detection frequency 100%). BDE-209 was also detected in more than 50% of the samples, and was significantly associated with 2,4,6-TBP in placental tissues, suggesting they may have a similar source, or that 2,4,6-TBP may be a degradation product of BDE-209. Interestingly, BDE-209 and 2,4,6-TBP were negatively associated with age (rs=−0.16; p=0.10 and rs=−0.17; p=0.08, respectively). The results of this work indicate that PBDEs and 2,4,6-TBP bioaccumulate in human placenta tissue and likely contribute to prenatal exposures to these environmental contaminants. Future studies are needed to determine if these joint exposures are associated with any adverse health measures in infants and children. PMID:26700418

  6. Induced Human Decidual NK-Like Cells Improve Utero-Placental Perfusion in Mice.

    Directory of Open Access Journals (Sweden)

    Ricardo C Cavalli

    Full Text Available Decidual NK (dNK cells, a distinct type of NK cell, are thought to regulate uterine spiral artery remodeling, a process that allows for increased blood delivery to the fetal-placental unit. Impairment of uterine spiral artery remodeling is associated with decreased placental perfusion, increased uterine artery resistance, and obstetric complications such as preeclampsia and intrauterine growth restriction. Ex vivo manipulation of human peripheral blood NK (pNK cells by a combination of hypoxia, TGFß-1 and 5-aza-2'-deoxycytidine yields cells with phenotypic and in vitro functional similarities to dNK cells, called idNK cells. Here, gene expression profiling shows that CD56Bright idNK cells derived ex vivo from human pNK cells, and to a lesser extent CD56Dim idNK cells, are enriched in the gene expression signature that distinguishes dNK cells from pNK cells. When injected into immunocompromised pregnant mice with elevated uterine artery resistance, idNK cells homed to the uterus and reduced the uterine artery resistance index, suggesting improved placental perfusion.

  7. 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.

  8. Placental markers of human exposure to polychlorinated biphenyls and polychlorinated dibenzofurans

    International Nuclear Information System (INIS)

    Lucier, G.W.; Nelson, K.G.; Everson, R.B.; Wong, T.K.; Philpot, R.M.; Tiernan, T.; Taylor, M.; Sunahara, G.I.

    1987-01-01

    These studies have evaluated biochemical changes in placentae from humans exposed to rice oil contaminated with polychlorinated biphenyls (PCBs) and polychlorinated dibenzofurans (PCDFs) in Taiwan. Placentae were obtained from nonsmoking women 4 to 5 years after the exposure had occurred. The exposed individuals ingested approximately 1 to 3 g PCBs and 5 mg PCDFs, and many exhibited symptoms characteristic of PCB poisoning. This disease was termed Yu-Cheng in Chinese. Based on data from experimental animals models, the authors examined a number of parameters in placentae from control and exposed women, including arylhydrocarbon hydroxylase (AHH) activity, cytochrome P-450 isozymes, epidermal growth factor (EGF) receptor binding properties and actions, and Ah receptor. They also quantified concentrations of various PCB and PCDF congeners known to be present in the contaminated rice oil. The results revealed a dramatic elevation in placental AHH activity in samples from PCB/PCDF-exposed women. This increase in enzyme activity was associated with a parallel increase in placental microsomal protein immunochemically related to cytochrome P-450 form 6. EGF receptor-mediated autophosphorylation capacity was significantly diminished in PCB/PCDF placentae, but this effect was not associated with changes in plasma membrane EGF receptor binding properties. Two PCDF congeners were detected in Yu-Cheng placentae but not controls. Several PCBs were also detected in much higher concentrations in Yu-Cheng placentae. Surprisingly, placental concentrations of PCBs correlated better with effects than did the PCDFs. The findings are discussed in relation to the risk assessment process

  9. The relationship between human placental morphometry and ultrasonic measurements of utero-placental blood flow and fetal growth.

    Science.gov (United States)

    Salavati, N; Sovio, U; Mayo, R Plitman; Charnock-Jones, D S; Smith, G C S

    2016-02-01

    Ultrasonic fetal biometry and arterial Doppler flow velocimetry are widely used to assess the risk of pregnancy complications. There is an extensive literature on the relationship between pregnancy outcomes and the size and shape of the placenta. However, ultrasonic fetal biometry and arterial Doppler flow velocimetry have not previously been studied in relation to postnatal placental morphometry in detail. We conducted a prospective cohort study of nulliparous women in The Rosie Hospital, Cambridge (UK). We studied a group of 2120 women who had complete data on uterine and umbilical Doppler velocimetry and fetal biometry at 20, 28 and 36 weeks' gestational age, digital images of the placenta available, and delivered a liveborn infant at term. Associations were expressed as the difference in the standard deviation (SD) score of the gestational age adjusted ultrasound measurement (z-score) comparing the lowest and highest decile of the given placental morphometric measurement. The lowest decile of placental surface area was associated with 0.87 SD higher uterine artery Doppler mean pulsatility index (PI) at 20 weeks (95% CI: 0.68 to 1.07, P flow, respectively, and both are associated with fetal growth rate. Copyright © 2015 Elsevier Ltd. All rights reserved.

  10. Oxygen-Sensitive K+ Channels Modulate Human Chorionic Gonadotropin Secretion from Human Placental Trophoblast

    Science.gov (United States)

    Díaz, Paula; Sibley, Colin P.; Greenwood, Susan L.

    2016-01-01

    Human chorionic gonadotropin (hCG) is a key autocrine/paracrine regulator of placental syncytiotrophoblast, the transport epithelium of the human placenta. Syncytiotrophoblast hCG secretion is modulated by the partial pressure of oxygen (pO2), reactive oxygen species (ROS) and potassium (K+) channels. Here we test the hypothesis that K+ channels mediate the effects of pO2 and ROS on hCG secretion. Placental villous explants from normal term pregnancies were cultured for 6 days at 6% (normoxia), 21% (hyperoxia) or 1% (hypoxia) pO2. On days 3–5, explants were treated with 5mM 4-aminopyridine (4-AP) or tetraethylammonium (TEA), blockers of pO2-sensitive voltage-gated K+ (KV) channels, or ROS (10–1000μM H2O2). hCG secretion and lactate dehydrogenase (LDH) release, a marker of necrosis, were determined daily. At day 6, hCG and LDH were measured in tissue lysate and 86Rb (K+) efflux assessed to estimate syncytiotrophoblast K+ permeability. hCG secretion and 86Rb efflux were significantly greater in explants maintained in 21% pO2 than normoxia. 4-AP/TEA inhibited hCG secretion to a greater extent at 21% than 6% and 1% pO2, and reduced 86Rb efflux at 21% but not 6% pO2. LDH release and tissue LDH/hCG were similar in 6%, 21% and 1% pO2 and unaffected by 4-AP/TEA. H2O2 stimulated 86Rb efflux and hCG secretion at normoxia but decreased 86Rb efflux, without affecting hCG secretion, at 21% pO2. 4-AP/TEA-sensitive K+ channels participate in pO2-sensitive hCG secretion from syncytiotrophoblast. ROS effects on both hCG secretion and 86Rb efflux are pO2-dependent but causal links between the two remain to be established. PMID:26863525

  11. Androgen dependent mechanisms of pro-angiogenic networks in placental and tumor development.

    Science.gov (United States)

    Metzler, Veronika M; de Brot, Simone; Robinson, Robert S; Jeyapalan, Jennie N; Rakha, Emad; Walton, Thomas; Gardner, David S; Lund, Emma F; Whitchurch, Jonathan; Haigh, Daisy; Lochray, Jack M; Robinson, Brian D; Allegrucci, Cinzia; Fray, Rupert G; Persson, Jenny L; Ødum, Niels; Miftakhova, Regina R; Rizvanov, Albert A; Hughes, Ieuan A; Tadokoro-Cuccaro, Rieko; Heery, David M; Rutland, Catrin S; Mongan, Nigel P

    2017-08-01

    The placenta and tumors share important characteristics, including a requirement to establish effective angiogenesis. In the case of the placenta, optimal angiogenesis is required to sustain the blood flow required to maintain a successful pregnancy, whereas in tumors establishing new blood supplies is considered a key step in supporting metastases. Therefore the development of novel angiogenesis inhibitors has been an area of active research in oncology. A subset of the molecular processes regulating angiogenesis are well understood in the context of both early placentation and tumorigenesis. In this review we focus on the well-established role of androgen regulation of angiogenesis in cancer and relate these mechanisms to placental angiogenesis. The physiological actions of androgens are mediated by the androgen receptor (AR), a ligand dependent transcription factor. Androgens and the AR are essential for normal male embryonic development, puberty and lifelong health. Defects in androgen signalling are associated with a diverse range of clinical disorders in men and women including disorders of sex development (DSD), polycystic ovary syndrome in women and many cancers. We summarize the diverse molecular mechanisms of androgen regulation of angiogenesis and infer the potential significance of these pathways to normal and pathogenic placental function. Finally, we offer potential research applications of androgen-targeting molecules developed to treat cancer as investigative tools to help further delineate the role of androgen signalling in placental function and maternal and offspring health in animal models. Copyright © 2017 Elsevier Ltd. All rights reserved.

  12. Control of growth and development of the feto-placental unit

    DEFF Research Database (Denmark)

    Han, V K; Carter, Anthony Michael

    2001-01-01

    Classical gene targeting has identified many genes important for fetal and placental development. Null mutation of these genes may lead to fetal growth restriction, malformation or embryonic death. Growth restriction of epigenetic basis can predispose to adult-onset diseases. The mechanisms...

  13. Human trophoblast-derived hydrogen sulfide stimulates placental artery endothelial cell angiogenesis.

    Science.gov (United States)

    Chen, Dong-Bao; Feng, Lin; Hodges, Jennifer K; Lechuga, Thomas J; Zhang, Honghai

    2017-09-01

    Endogenous hydrogen sulfide (H2S), mainly synthesized by cystathionine β-synthase (CBS) and cystathionine γ-lyase (CTH), has been implicated in regulating placental angiogenesis; however, the underlying mechanisms are unknown. This study was to test a hypothesis that trophoblasts synthesize H2S to promote placental angiogenesis. Human choriocarcinoma-derived BeWo cells expressed both CBS and CTH proteins, while the first trimester villous trophoblast-originated HTR-8/SVneo cells expressed CTH protein only. The H2S producing ability of BeWo cells was significantly inhibited by either inhibitors of CBS (carboxymethyl hydroxylamine hemihydrochloride, CHH) or CTH (β-cyano-L-alanine, BCA) and that in HTR-8/SVneo cells was inhibited by CHH only. H2S donors stimulated cell proliferation, migration, and tube formation in ovine placental artery endothelial cells (oFPAECs) as effectively as vascular endothelial growth factor. Co-culture with BeWo and HTR-8/SVneo cells stimulated oFPAEC migration, which was inhibited by CHH or BCA in BeWo but CHH only in HTR-8/SVneo cells. Primary human villous trophoblasts (HVT) were more potent than trophoblast cell lines in stimulating oFPAEC migration that was inhibited by CHH and CHH/BCA combination in accordance with its H2S synthesizing activity linked to CBS and CTH expression patterns. H2S donors activated endothelial nitric oxide synthase (NOS3), v-AKT murine thymoma viral oncogene homolog 1 (AKT1), and extracellular signal-activated kinase 1/2 (mitogen-activated protein kinase 3/1, MAPK3/1) in oFPAECs. H2S donor-induced NOS3 activation was blocked by AKT1 but not MAPK3/1 inhibition. In keeping with our previous studies showing a crucial role of AKT1, MAPK3/1, and NOS3/NO in placental angiogenesis, these data show that trophoblast-derived endogenous H2S stimulates placental angiogenesis, involving activation of AKT1, NOS3/NO, and MAPK3/1. © The Authors 2017. Published by Oxford University Press on behalf of Society for the Study

  14. N-carbamylglutamate and L-arginine improved maternal and placental development in underfed ewes.

    Science.gov (United States)

    Zhang, Hao; Sun, Lingwei; Wang, Ziyu; Deng, Mingtian; Nie, Haitao; Zhang, Guomin; Ma, Tiewei; Wang, Feng

    2016-06-01

    The objectives of this study were to determine how dietary supplementation of N-carbamylglutamate (NCG) and rumen-protected L-arginine (RP-Arg) in nutrient-restricted pregnant Hu sheep would affect (1) maternal endocrine status; (2) maternal, fetal, and placental antioxidation capability; and (3) placental development. From day 35 to day 110 of gestation, 32 Hu ewes carrying twin fetuses were allocated randomly into four groups: 100% of NRC-recommended nutrient requirements, 50% of NRC recommendations, 50% of NRC recommendations supplemented with 20g/day RP-Arg, and 50% of NRC recommendations supplemented with 5g/day NCG product. The results showed that in maternal and fetal plasma and placentomes, the activities of total antioxidant capacity and superoxide dismutase were increased (Pewes. The mRNA expression of vascular endothelial growth factor and Fms-like tyrosine kinase 1 was increased (Pewes than in 100% NRC ewes, and had no effect (P>0.05) in both NCG- and RP-Arg-treated underfed ewes. A supplement of RP-Arg and NCG reduced (Pewes. These results indicate that dietary supplementation of NCG and RP-Arg in underfed ewes could influence maternal endocrine status, improve the maternal-fetal-placental antioxidation capability, and promote fetal and placental development during early-to-late gestation. © 2016 Society for Reproduction and Fertility.

  15. Structural comparisons of two allelic variants of human placental alkaline phosphatase.

    Science.gov (United States)

    Millán, J L; Stigbrand, T; Jörnvall, H

    1985-01-01

    A simple immunosorbent purification scheme based on monoclonal antibodies has been devised for human placental alkaline phosphatase. The two most common allelic variants, S and F, have similar amino acid compositions with identical N-terminal amino acid sequences through the first 13 residues. Both variants have identical lectin binding properties towards concanavalin A, lentil-lectin, wheat germ agglutinin, phytohemagglutinin and soybean agglutinin, and identical carbohydrate contents as revealed by methylation analysis. CNBr fragments of the variants demonstrate identical high performance liquid chromatography patterns. The carbohydrate containing fragment is different from the 32P-labeled active site fragment and the N-terminal fragment.

  16. Rac1 Regulates Endometrial Secretory Function to Control Placental Development.

    Directory of Open Access Journals (Sweden)

    Juanmahel Davila

    2015-08-01

    Full Text Available During placenta development, a succession of complex molecular and cellular interactions between the maternal endometrium and the developing embryo ensures reproductive success. The precise mechanisms regulating this maternal-fetal crosstalk remain unknown. Our study revealed that the expression of Rac1, a member of the Rho family of GTPases, is markedly elevated in mouse decidua on days 7 and 8 of gestation. To investigate its function in the uterus, we created mice bearing a conditional deletion of the Rac1 gene in uterine stromal cells. Ablation of Rac1 did not affect the formation of the decidua but led to fetal loss in mid gestation accompanied by extensive hemorrhage. To gain insights into the molecular pathways affected by the loss of Rac1, we performed gene expression profiling which revealed that Rac1 signaling regulates the expression of Rab27b, another GTPase that plays a key role in targeting vesicular trafficking. Consequently, the Rac1-null decidual cells failed to secrete vascular endothelial growth factor A, which is a critical regulator of decidual angiogenesis, and insulin-like growth factor binding protein 4, which regulates the bioavailability of insulin-like growth factors that promote proliferation and differentiation of trophoblast cell lineages in the ectoplacental cone. The lack of secretion of these key factors by Rac1-null decidua gave rise to impaired angiogenesis and dysregulated proliferation of trophoblast cells, which in turn results in overexpansion of the trophoblast giant cell lineage and disorganized placenta development. Further experiments revealed that RAC1, the human ortholog of Rac1, regulates the secretory activity of human endometrial stromal cells during decidualization, supporting the concept that this signaling G protein plays a central and conserved role in controlling endometrial secretory function. This study provides unique insights into the molecular mechanisms regulating endometrial secretions

  17. Rac1 Regulates Endometrial Secretory Function to Control Placental Development

    Science.gov (United States)

    Davila, Juanmahel; Laws, Mary J.; Kannan, Athilakshmi; Li, Quanxi; Taylor, Robert N.; Bagchi, Milan K.; Bagchi, Indrani C.

    2015-01-01

    During placenta development, a succession of complex molecular and cellular interactions between the maternal endometrium and the developing embryo ensures reproductive success. The precise mechanisms regulating this maternal-fetal crosstalk remain unknown. Our study revealed that the expression of Rac1, a member of the Rho family of GTPases, is markedly elevated in mouse decidua on days 7 and 8 of gestation. To investigate its function in the uterus, we created mice bearing a conditional deletion of the Rac1 gene in uterine stromal cells. Ablation of Rac1 did not affect the formation of the decidua but led to fetal loss in mid gestation accompanied by extensive hemorrhage. To gain insights into the molecular pathways affected by the loss of Rac1, we performed gene expression profiling which revealed that Rac1 signaling regulates the expression of Rab27b, another GTPase that plays a key role in targeting vesicular trafficking. Consequently, the Rac1-null decidual cells failed to secrete vascular endothelial growth factor A, which is a critical regulator of decidual angiogenesis, and insulin-like growth factor binding protein 4, which regulates the bioavailability of insulin-like growth factors that promote proliferation and differentiation of trophoblast cell lineages in the ectoplacental cone. The lack of secretion of these key factors by Rac1-null decidua gave rise to impaired angiogenesis and dysregulated proliferation of trophoblast cells, which in turn results in overexpansion of the trophoblast giant cell lineage and disorganized placenta development. Further experiments revealed that RAC1, the human ortholog of Rac1, regulates the secretory activity of human endometrial stromal cells during decidualization, supporting the concept that this signaling G protein plays a central and conserved role in controlling endometrial secretory function. This study provides unique insights into the molecular mechanisms regulating endometrial secretions that mediate stromal

  18. Effect of placental factors on growth and function of the human fetal adrenal in vitro.

    Science.gov (United States)

    Riopel, L; Branchaud, C L; Goodyer, C G; Zweig, M; Lipowski, L; Adkar, V; Lefebvre, Y

    1989-11-01

    Conditioned medium from human placental monolayer cultures (PM) had a marked stimulatory effect on proliferation (3H-thymidine uptake) of human fetal zone adrenal cells in primary monolayer culture, even in the absence of serum. Epidermal growth factor (EGF) and fibroblast growth factor (FGF) also significantly stimulated fetal adrenal cell growth. However, the effects of PM differed from those of EGF and FGF in several respects: 1) maximal response to PM was 2-5 times greater; 2) mitogenic effects of EGF and FGF were suppressed by adrenocorticotropic hormone (ACTH), whereas that of 50% PM was not; 3) PM inhibited ACTH-stimulated steroidogenesis (dehydroepiandrosterone sulfate and cortisol), but EGF and FGF did not. Preliminary characterization studies have indicated that approximately half of the placental growth-promoting activity is heat resistant and sensitive to bacterial proteases, and that 50-60% of the activity is lost after dialysis with membranes having a molecular weight cutoff of 3500. These findings suggest a role for the placenta in the growth and differentiated function of the human fetal adrenal gland.

  19. Effect of placental factors on growth and function of the human fetal adrenal in vitro

    Energy Technology Data Exchange (ETDEWEB)

    Riopel, L.; Branchaud, C.L.; Goodyer, C.G.; Zweig, M.; Lipowski, L.; Adkar, V.; Lefebvre, Y. (McGill Univ.-Montreal Children' s Hospital Research Institute, Quebec (Canada))

    1989-11-01

    Conditioned medium from human placental monolayer cultures (PM) had a marked stimulatory effect on proliferation (3H-thymidine uptake) of human fetal zone adrenal cells in primary monolayer culture, even in the absence of serum. Epidermal growth factor (EGF) and fibroblast growth factor (FGF) also significantly stimulated fetal adrenal cell growth. However, the effects of PM differed from those of EGF and FGF in several respects: (1) maximal response to PM was 2-5 times greater; (2) mitogenic effects of EGF and FGF were suppressed by adrenocorticotropic hormone (ACTH), whereas that of 50% PM was not; (3) PM inhibited ACTH-stimulated steroidogenesis (dehydroepiandrosterone sulfate and cortisol), but EGF and FGF did not. Preliminary characterization studies have indicated that approximately half of the placental growth-promoting activity is heat resistant and sensitive to bacterial proteases, and that 50-60% of the activity is lost after dialysis with membranes having a molecular weight cutoff of 3500. These findings suggest a role for the placenta in the growth and differentiated function of the human fetal adrenal gland.

  20. Effect of placental factors on growth and function of the human fetal adrenal in vitro

    International Nuclear Information System (INIS)

    Riopel, L.; Branchaud, C.L.; Goodyer, C.G.; Zweig, M.; Lipowski, L.; Adkar, V.; Lefebvre, Y.

    1989-01-01

    Conditioned medium from human placental monolayer cultures (PM) had a marked stimulatory effect on proliferation (3H-thymidine uptake) of human fetal zone adrenal cells in primary monolayer culture, even in the absence of serum. Epidermal growth factor (EGF) and fibroblast growth factor (FGF) also significantly stimulated fetal adrenal cell growth. However, the effects of PM differed from those of EGF and FGF in several respects: (1) maximal response to PM was 2-5 times greater; (2) mitogenic effects of EGF and FGF were suppressed by adrenocorticotropic hormone (ACTH), whereas that of 50% PM was not; (3) PM inhibited ACTH-stimulated steroidogenesis (dehydroepiandrosterone sulfate and cortisol), but EGF and FGF did not. Preliminary characterization studies have indicated that approximately half of the placental growth-promoting activity is heat resistant and sensitive to bacterial proteases, and that 50-60% of the activity is lost after dialysis with membranes having a molecular weight cutoff of 3500. These findings suggest a role for the placenta in the growth and differentiated function of the human fetal adrenal gland

  1. Androgen dependent mechanisms of pro-angiogenic networks in placental and tumor development

    DEFF Research Database (Denmark)

    Metzler, Veronika M.; de Brot, Simone; Robinson, Robert S.

    2017-01-01

    molecular mechanisms of androgen regulation of angiogenesis and infer the potential significance of these pathways to normal and pathogenic placental function. Finally, we offer potential research applications of androgen-targeting molecules developed to treat cancer as investigative tools to help further...... supplies is considered a key step in supporting metastases. Therefore the development of novel angiogenesis inhibitors has been an area of active research in oncology. A subset of the molecular processes regulating angiogenesis are well understood in the context of both early placentation and tumorigenesis...... are essential for normal male embryonic development, puberty and lifelong health. Defects in androgen signalling are associated with a diverse range of clinical disorders in men and women including disorders of sex development (DSD), polycystic ovary syndrome in women and many cancers. We summarize the diverse...

  2. 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

    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....

  3. Primary Human Placental Trophoblasts are Permissive for Zika Virus (ZIKV) Replication.

    Science.gov (United States)

    Aagaard, Kjersti M; Lahon, Anismrita; Suter, Melissa A; Arya, Ravi P; Seferovic, Maxim D; Vogt, Megan B; Hu, Min; Stossi, Fabio; Mancini, Michael A; Harris, R Alan; Kahr, Maike; Eppes, Catherine; Rac, Martha; Belfort, Michael A; Park, Chun Shik; Lacorazza, Daniel; Rico-Hesse, Rebecca

    2017-01-27

    Zika virus (ZIKV) is an emerging mosquito-borne (Aedes genus) arbovirus of the Flaviviridae family. Although ZIKV has been predominately associated with a mild or asymptomatic dengue-like disease, its appearance in the Americas has been accompanied by a multi-fold increase in reported incidence of fetal microcephaly and brain malformations. The source and mode of vertical transmission from mother to fetus is presumptively transplacental, although a causal link explaining the interval delay between maternal symptoms and observed fetal malformations following infection has been missing. In this study, we show that primary human placental trophoblasts from non-exposed donors (n = 20) can be infected by primary passage ZIKV-FLR isolate, and uniquely allowed for ZIKV viral RNA replication when compared to dengue virus (DENV). Consistent with their being permissive for ZIKV infection, primary trophoblasts expressed multiple putative ZIKV cell entry receptors, and cellular function and differentiation were preserved. These findings suggest that ZIKV-FLR strain can replicate in human placental trophoblasts without host cell destruction, thereby serving as a likely permissive reservoir and portal of fetal transmission with risk of latent microcephaly and malformations.

  4. Toxic effects of low doses of Bisphenol-A on human placental cells

    International Nuclear Information System (INIS)

    Benachour, Nora; Aris, Aziz

    2009-01-01

    Humans are exposed daily to a great number of xenobiotics and their metabolites present as pollutants. Bisphenol-A (BPA) is extensively used in a broad range of products including baby bottles, food-storage containers, medical equipment, and consumer electronics. Thus, BPA is the most common monomer for polycarbonates intended for food contact. Levels of this industrial product are found in maternal blood, amniotic fluid, follicular fluid, placental tissue, umbilical cord blood, and maternal urine. In this study, we investigated toxic effects of BPA concentrations close to levels found in serum of pregnant women on human cytotrophoblasts (CTB). These cells were isolated from fresh placentas and exposed to BPA for 24 h. Our results showed that very low doses of BPA induce apoptosis (2 to 3 times) as assessed using M30 antibody immunofluorescent detection, and necrosis (1.3 to 1.7 times) as assessed through the cytosolic Adenylate Kinase (AK) activity after cell membrane damage. We also showed that BPA increased significantly the tumor-necrosis factor alpha (TNF-α) gene expression and protein excretion as measured by real-time RT-PCR and ELISA luminescent test, respectively. Moreover, we observed that induction of AK activation and TNF-α gene expression require lower levels of BPA than apoptosis or TNF-α protein excretion. Our findings suggest that exposure of placental cells to low doses of BPA may cause detrimental effects, leading in vivo to adverse pregnancy outcomes such as preeclampsia, intrauterine growth restriction, prematurity and pregnancy loss.

  5. Role of the BAHD1 Chromatin-Repressive Complex in Placental Development and Regulation of Steroid Metabolism.

    Directory of Open Access Journals (Sweden)

    Goran Lakisic

    2016-03-01

    Full Text Available BAHD1 is a vertebrate protein that promotes heterochromatin formation and gene repression in association with several epigenetic regulators. However, its physiological roles remain unknown. Here, we demonstrate that ablation of the Bahd1 gene results in hypocholesterolemia, hypoglycemia and decreased body fat in mice. It also causes placental growth restriction with a drop of trophoblast glycogen cells, a reduction of fetal weight and a high neonatal mortality rate. By intersecting transcriptome data from murine Bahd1 knockout (KO placentas at stages E16.5 and E18.5 of gestation, Bahd1-KO embryonic fibroblasts, and human cells stably expressing BAHD1, we also show that changes in BAHD1 levels alter expression of steroid/lipid metabolism genes. Biochemical analysis of the BAHD1-associated multiprotein complex identifies MIER proteins as novel partners of BAHD1 and suggests that BAHD1-MIER interaction forms a hub for histone deacetylases and methyltransferases, chromatin readers and transcription factors. We further show that overexpression of BAHD1 leads to an increase of MIER1 enrichment on the inactive X chromosome (Xi. In addition, BAHD1 and MIER1/3 repress expression of the steroid hormone receptor genes ESR1 and PGR, both playing important roles in placental development and energy metabolism. Moreover, modulation of BAHD1 expression in HEK293 cells triggers epigenetic changes at the ESR1 locus. Together, these results identify BAHD1 as a core component of a chromatin-repressive complex regulating placental morphogenesis and body fat storage and suggest that its dysfunction may contribute to several human diseases.

  6. The Elsevier trophoblast research award lecture: Impacts of placental growth factor and preeclampsia on brain development, behaviour, and cognition.

    Science.gov (United States)

    Rätsep, Matthew T; Hickman, Andrew F; Croy, B Anne

    2016-12-01

    Preeclampsia (PE) is a significant gestational disorder affecting 3-5% of all human pregnancies. In many PE pregnancies, maternal plasma is deficient in placental growth factor (PGF), a placentally-produced angiokine. Beyond immediate fetal risks associated with acute termination of the pregnancy, offspring of PE pregnancies (PE-F1) have higher long-term risks for hypertension, stroke, and cognitive impairment compared to F1s from uncomplicated pregnancies. At present, mechanisms that explain PE-F1 gains in postpartum risks are poorly understood. Our laboratory found that mice genetically-deleted for Pgf have altered fetal and adult brain vascular development. This is accompanied by sexually dimorphic alterations in anatomic structure in the adult Pgf -/- brain and impaired cognitive functions. We hypothesize that cerebrovascular and neurological aberrations occur in fetuses exposed to the progressive development of PE and that these brain changes impair cognitive functioning, enhance risk for stroke, elevate severity of stroke, and lead to worse stroke outcomes. These brain and placental outcomes may be linked to down-regulated PGF gene expression in early pre-implantation embryos, prior to gastrulation. This review explores our hypothesis that there are mechanistic links between low PGF detection in maternal plasma prodromal to PE, PE, and altered brain vascular, structural, and functional development amongst PE-F1s. We also include a summary of preliminary outcomes from a pilot study of 7-10 year old children that is the first to report magnetic resonance imaging, magnetic resonance angiography, and functional brain region assessment by eye movement control studies in PE-F1s. Copyright © 2016 Elsevier Ltd. All rights reserved.

  7. 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...... transfer of BPA was observed across the term placentae and the BeWo cell monolayer. Further, transdermal transport of BPA was observed. These results indicate that fetal BPA exposure through placental exchange occurs with potential adverse implications for placental and fetal development. This battery...

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

    Science.gov (United States)

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

    2017-10-01

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

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

    Directory of Open Access Journals (Sweden)

    Frederiksen Marie

    2010-07-01

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

  10. Ubiquitin-Like Protein from Human Placental Extract Exhibits Collagenase Activity

    Science.gov (United States)

    De, Debashree; Datta Chakraborty, Piyali; Mitra, Jyotirmoy; Sharma, Kanika; Mandal, Somnath; Das, Aneesha; Chakrabarti, Saikat; Bhattacharyya, Debasish

    2013-01-01

    An aqueous extract of human placenta exhibits strong gelatinase/collagenase activity in zymography. 2-D gel electrophoresis of the extract with gelatin zymography in the second dimension displayed a single spot, identified as ubiquitin-like component upon MALDI/TOF MS/MS analysis. Immunoblot indicated presence of ubiquitin and absence of collagenase in the extract. Collagenase activity of the ubiquitin-like component was confirmed from the change in solubility of collagen in aqueous buffer, degradation of collagen by size-exclusion HPLC and atomic force microscopy. Quantification with DQ-gelatin showed that the extract contains 0.04 U/ml of collagenase activity that was inhibited up to 95% by ubiquitin antibody. Ubiquitin from bovine erythrocytes demonstrated mild collagenase activity. Bioinformatics studies suggest that placental ubiquitin and collagenase follow structurally divergent evolution. This thermostable intrinsic collagenase activity of placental extract might have wide physiological relevance in degrading and remodeling collagen as it is used as a drug for wound healing and pelvic inflammatory diseases. PMID:23555718

  11. Pst I restriction fragment length polymorphism of the human placental alkaline phosphatase gene in normal placentae and tumors

    International Nuclear Information System (INIS)

    Tsavaler, L.; Penhallow, R.C.; Kam, W.; Sussman, H.H.

    1987-01-01

    The structure of the human placental alkaline phosphatase gene from normal term placentae was studied by restriction enzyme digestion and Southern blot analysis using a cDNA probe to the gene for the placental enzyme. The DNA digests fall into three distinct patterns based on the presence and intensity of an extra 1.1-kilobase Pst I Band. The extra 1.1-kilobase band is present in 9 of 27 placenta samples, and in 1 of these samples the extra band is present at double intensity. No polymorphism was revealed by digestion with restriction enzymes EcoRI, Sma I, BamHI, or Sac I. The extra Pst I-digestion site may lie in a noncoding region of the gene because no correlation was observed between the restriction fragment length polymorphism and the common placental alkaline phosphatase alleles identified by starch gel electrophoresis. In addition, because placental alkaline phosphatase is frequently re-expressed in neoplasms, the authors examined tissue from ovarian, testicular, and endometrial tumors and from BeWo choriocarcinoma cells in culture. The Pst I-DNA digestion patterns from these cells and tissues were identical to those seen in the normal ovary and term placentae. The consistent reproducible digestion patterns seen in DNA from normal and tumor tissue indicate that a major gene rearrangement is not the basis for the ectopic expression of placental alkaline phosphatase in neoplasia

  12. Estrogen regulates progesterone production by human placental trophoblast cells in culture

    International Nuclear Information System (INIS)

    Grimes, R.W.

    1990-01-01

    We have suggested that estrogen regulates placental low-density lipoprotein (LDL) uptake and thus progesterone (P 4 ) production during primate pregnancy based on results obtained in antiestrogen-treated baboons. The objectives of the present study, were to determine whether estrogen is also important to regulation of P 4 formation by the human placenta, and whether effects of estrogen were mediated by availability of cholesterol substrate via the LDL, de novo, or deesterification pathways. Term human placenta were dispersed in 0.125% trypsin, cytotrophoblasts were purified via a 70-5% Percoll gradient, incubated 72 h in DMEM with 10% FBS to stimulate formation of syncytia, then incubated an additional 48 h with estradiol (E2). In Experiment 1, 1 μg/ml E 2 and 500 μg/MI LDL-protein, stimulated P 4 (P 2 increased LDL uptake. Scatchard analysis indicated that trophoblast uptake of [ 125 I]LDL (ng/mg cell protein) was 50% greater (P 2 (mean ± SE, 638 +/- 23; n = 6) than DMEM in the presence of antiestrogen MER-25. Moreover, uptake and degradation of LDL, and cellular content of free and esterified cholesterol, increased in a dose-dependent manner with 0.1 to 1000 ng/ml E 2 . These results suggest that estrogen regulates placental cell uptake of LDL and thus availability of cholesterol for P 4 biosynthesis during human pregnancy. In Experiment 2, E 2 Stimulated P 4 formation (ng/mg cell protein/48 h) from a control level of 194 ± 25 to 357 ± 62, in the absence of LDL. Under these conditions, cholesterol for P 4 biosynthesis must have been derived from de novo synthesis and/or deesterification of cholesteryl ester stores

  13. Placental growth factor deficiency is associated with impaired cerebral vascular development in mice.

    Science.gov (United States)

    Luna, Rayana Leal; Kay, Vanessa R; Rätsep, Matthew T; Khalaj, Kasra; Bidarimath, Mallikarjun; Peterson, Nichole; Carmeliet, Peter; Jin, Albert; Croy, B Anne

    2016-02-01

    Placental growth factor (PGF) is expressed in the developing mouse brain and contributes to vascularization and vessel patterning. PGF is dynamically expressed in fetal mouse brain, particularly forebrain, and is essential for normal cerebrovascular development. PGF rises in maternal plasma over normal human and mouse pregnancy but is low in many women with the acute onset hypertensive syndrome, pre-eclampsia (PE). Little is known about the expression of PGF in the fetus during PE. Pgf  (-/-) mice appear normal but recently cerebral vascular defects were documented in adult Pgf  (-/-) mice. Here, temporal-spatial expression of PGF is mapped in normal fetal mouse brains and cerebral vasculature development is compared between normal and congenic Pgf  (-/-) fetuses to assess the actions of PGF during cerebrovascular development. Pgf/PGF, Vegfa/VEGF, Vegf receptor (Vegfr)1 and Vegfr2 expression were examined in the brains of embryonic day (E)12.5, 14.5, 16.5 and 18.5 C57BL/6 (B6) mice using quantitative PCR and immunohistochemistry. The cerebral vasculature was compared between Pgf  (-/-) and B6 embryonic and adult brains using whole mount techniques. Vulnerability to cerebral ischemia was investigated using a left common carotid ligation assay. Pgf/PGF and Vegfr1 are highly expressed in E12.5-14.5 forebrain relative to VEGF and Vegfr2. Vegfa/VEGF is relatively more abundant in hindbrain (HB). PGF and VEGF expression were similar in midbrain. Delayed HB vascularization was seen at E10.5 and 11.5 in Pgf  (-/-) brains. At E14.5, Pgf  (-/-) circle of Willis showed unilateral hypoplasia and fewer collateral vessels, defects that persisted post-natally. Functionally, adult Pgf  (-/-) mice experienced cerebral ischemia after left common carotid arterial occlusion while B6 mice did not. Since Pgf  (-/-) mice were used, consequences of complete absence of maternal and fetal PGF were defined. Therefore, the effects of maternal versus fetal PGF

  14. Placental chorangioma

    African Journals Online (AJOL)

    Key words: Kano; live birth; placental chorangioma; Pregnancy. Introduction. Placental ... single live intrauterine fetus in longitudinal lie and breech presentation with ... Pelvic examination revealed normal external genitalia; the cervix was ...

  15. Translational analysis of mouse and human placental protein and mRNA reveals distinct molecular pathologies in human preeclampsia.

    Science.gov (United States)

    Cox, Brian; Sharma, Parveen; Evangelou, Andreas I; Whiteley, Kathie; Ignatchenko, Vladimir; Ignatchenko, Alex; Baczyk, Dora; Czikk, Marie; Kingdom, John; Rossant, Janet; Gramolini, Anthony O; Adamson, S Lee; Kislinger, Thomas

    2011-12-01

    Preeclampsia (PE) adversely impacts ~5% of pregnancies. Despite extensive research, no consistent biomarkers or cures have emerged, suggesting that different molecular mechanisms may cause clinically similar disease. To address this, we undertook a proteomics study with three main goals: (1) to identify a panel of cell surface markers that distinguish the trophoblast and endothelial cells of the placenta in the mouse; (2) to translate this marker set to human via the Human Protein Atlas database; and (3) to utilize the validated human trophoblast markers to identify subgroups of human preeclampsia. To achieve these goals, plasma membrane proteins at the blood tissue interfaces were extracted from placentas using intravascular silica-bead perfusion, and then identified using shotgun proteomics. We identified 1181 plasma membrane proteins, of which 171 were enriched at the maternal blood-trophoblast interface and 192 at the fetal endothelial interface with a 70% conservation of expression in humans. Three distinct molecular subgroups of human preeclampsia were identified in existing human microarray data by using expression patterns of trophoblast-enriched proteins. Analysis of all misexpressed genes revealed divergent dysfunctions including angiogenesis (subgroup 1), MAPK signaling (subgroup 2), and hormone biosynthesis and metabolism (subgroup 3). Subgroup 2 lacked expected changes in known preeclampsia markers (sFLT1, sENG) and uniquely overexpressed GNA12. In an independent set of 40 banked placental specimens, GNA12 was overexpressed during preeclampsia when co-incident with chronic hypertension. In the current study we used a novel translational analysis to integrate mouse and human trophoblast protein expression with human microarray data. This strategy identified distinct molecular pathologies in human preeclampsia. We conclude that clinically similar preeclampsia patients exhibit divergent placental gene expression profiles thus implicating divergent

  16. 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.

  17. Identification and characterization of a novel nanobody against human placental growth factor to modulate angiogenesis.

    Science.gov (United States)

    Arezumand, Roghaye; Mahdian, Reza; Zeinali, Sirous; Hassanzadeh-Ghassabeh, Gholamreza; Mansouri, Kamran; Khanahmad, Hossein; Namvar-Asl, Nabiollah; Rahimi, Hamzeh; Behdani, Mahdi; Cohan, Reza Ahangari; Eavazalipour, Mehdi; Ramazani, Ali; Muyldermans, Serge

    2016-10-01

    Placental growth factor (PlGF), a member of vascular endothelial growth factors (VEGF) family, is considered as an important antigen associated with pathological conditions such as cancer cell growth, and metastasis. PlGF-targeting via nanobody (Nb) therefore could be beneficial to modulate these pathologies. In this work, phage-display and computational approach was employed to develop a high affinity PlGF-specific Nb. An Nb library was constructed against human recombinant PlGF (rPlGF). After panning on immobilized rPlGF the periplasmic-extract (PE) of individual colonies were screened by ELISA (PE-ELISA). The 3D structures of selected Nbs were then homology modeled and energy minimized using the AMBER force field. Binding score calculations were also assessed to reveal possible Nb-PlGF interactions. Via ELISA-based affinity/specificity determinations, the best-qualified Nb was further evaluated by proliferation, migration, 3D capillary formation, invasion assays and on Chick chorioallantoic membrane (CAM) model. An immune library of 1.5×10 7 individual Nb clones was constructed. By PE-ELISA 12 clones with strong signals were selected. Three out of 12 sequenced Nbs (Nb-C13, Nb-C18 and Nb-C62) showed high binding scores ranging between -378.7 and -461kcal/mol. Compared to a control Nb, Nb-C18 significantly inhibited proliferation, migration and the 3D-capillary formation of HUVEC cells (p<0.05) with an EC 50 of 35nM, 42nM and 24nM and invasion of MDA-MB231was significantly suppressed (p<0.05) with an EC 50 of57nM. The result of the CAM assay shows that Nb-C18 could inhibit the vascular formation in the chicken chorioallantoic membrane. This Nb can be used as anti-angiogenesis agent in future. Copyright © 2016 Elsevier Ltd. All rights reserved.

  18. Sequence of interleukin-2 isolated from human placental poly A+ RNA: possible role in maintenance of fetal allograft.

    Science.gov (United States)

    Chernicky, C L; Tan, H; Burfeind, P; Ilan, J; Ilan, J

    1996-02-01

    There are several cell types within the placenta that produce cytokines which can contribute to the regulatory mechanisms that ensure normal pregnancy. The immunological milieu at the maternofetal interface is considered to be crucial for survival of the fetus. Interleukin-2 (IL-2) is expressed by the syncytiotrophoblast, the cell layer between the mother and the fetus. IL-2 appears to be a key factor in maintenance of pregnancy. Therefore, it was important to determine the sequence of human placental interleukin-2. Direct sequencing of human placental IL-2 cDNA was determined for the coding region. Subclone sequencing was carried out for the 5'- and 3'-untranslated regions (5'-UTR and 3'-UTR). The 5'-UTR for human placental IL-2 cDNA is 294 bp, which is 247 nucleotides longer than that reported for cDNA IL-2 derived from T cells. The sequence of the coding region is identical to that reported for T cell IL-2, while sequence analysis of the polymerase chain reaction (PCR) product showed that the cDNA from the 3' end was the same as that reported for cDNA from T cells. Human placental IL-2 cDNA is 1,028 base pairs (excluding the poly A tail), which is 247 bp longer at the 5' end than that reported for IL-2 T cell cDNA. Therefore, the extended 5'-UTR of the placental IL-2 cDNA may be a consequence of alternative promoter utilization in the placenta.

  19. Inhibition of human placental aromatase activity by hydroxylated polybrominated diphenyl ethers (OH-PBDEs).

    Science.gov (United States)

    Cantón, Rocío F; Scholten, Deborah E A; Marsh, Göran; de Jong, Paul C; van den Berg, Martin

    2008-02-15

    Polybrominated diphenyl ethers (PBDEs) are widely used as flame retardants in many different polymers, resins and substrates. Due to their widespread production and use, their high binding affinity to particles, and their lipophilic properties, several PBDE congeners can bioaccumulate in the environment. As a result, PBDEs and their hydroxylated metabolites (OH-PBDEs) have been detected in humans and various wildlife samples, such as birds, seals, and whales. Furthermore, certain OH-PBDEs and their methoxylated derivatives (MeO-PBDEs) are natural products in the marine environment. Recently, our laboratory focused on the possible effects on steroidogenesis of PBDEs and OH-PBDEs, e.g. in the human adrenocortical carcinoma (H295R) cell line indicating that some OH-PBDEs can significantly influence steroidogenic enzymes like CYP19 (aromatase) and CYP17. In the present study, human placental microsomes have been used to study the possible interaction of twenty two OH-PBDEs and MeO-PBDEs with aromatase, the enzyme that mediates the conversion of androgens into estrogens. All OH-PBDE derivates showed significant inhibition of placental aromatase activity with IC(50) values in the low micromolar range, while the MeO-PBDEs did not have any effect on this enzyme activity. Enzyme kinetics studies indicated that two OH-PBDEs, 5-hydroxy-2,2',4,4'-tetrabromodiphenyl ether (5-OH-BDE47) and 6-hydroxy-2,2',4,4'-tetrabromodiphenyl ether (6-OH-BDE47), had a mixed-type inhibition of aromatase activity with apparent K(i)/K(i)' of 7.68/0,02 microM and 5.01/0.04 microM respectively. For comparison, some structurally related compounds, a dihydroxylated polybrominated biphenyl, which is a natural product (2,2'-dihyroxy-3,3',5,5'-tetrabromobiphenyl (2,2'-diOH-BB80)) and its non-bromo derivative were also included in the study. Again inhibition of aromatase activity could be measured, but their potency was significantly less than those observed for the OH-PBDEs. These results show that a

  20. Inhibition of human placental aromatase activity by hydroxylated polybrominated diphenyl ethers (OH-PBDEs)

    International Nuclear Information System (INIS)

    Canton, Rocio F.; Scholten, Deborah E.A.; Marsh, Goeran; Jong, Paul C. de; Berg, Martin van den

    2008-01-01

    Polybrominated diphenyl ethers (PBDEs) are widely used as flame retardants in many different polymers, resins and substrates. Due to their widespread production and use, their high binding affinity to particles, and their lipophilic properties, several PBDE congeners can bioaccumulate in the environment. As a result, PBDEs and their hydroxylated metabolites (OH-PBDEs) have been detected in humans and various wildlife samples, such as birds, seals, and whales. Furthermore, certain OH-PBDEs and their methoxylated derivatives (MeO-PBDEs) are natural products in the marine environment. Recently, our laboratory focused on the possible effects on steroidogenesis of PBDEs and OH-PBDEs, e.g. in the human adrenocortical carcinoma (H295R) cell line indicating that some OH-PBDEs can significantly influence steroidogenic enzymes like CYP19 (aromatase) and CYP17. In the present study, human placental microsomes have been used to study the possible interaction of twenty two OH-PBDEs and MeO-PBDEs with aromatase, the enzyme that mediates the conversion of androgens into estrogens. All OH-PBDE derivates showed significant inhibition of placental aromatase activity with IC 50 values in the low micromolar range, while the MeO-PBDEs did not have any effect on this enzyme activity. Enzyme kinetics studies indicated that two OH-PBDEs, 5-hydroxy-2,2',4,4'-tetrabromodiphenyl ether (5-OH-BDE47) and 6-hydroxy-2,2',4,4'-tetrabromodiphenyl ether (6-OH-BDE47), had a mixed-type inhibition of aromatase activity with apparent K i /K i ' of 7.68/0,02 μM and 5.01/0.04 μM respectively. For comparison, some structurally related compounds, a dihydroxylated polybrominated biphenyl, which is a natural product (2,2'-dihyroxy-3,3',5,5'-tetrabromobiphenyl (2,2'-diOH-BB80)) and its non-bromo derivative were also included in the study. Again inhibition of aromatase activity could be measured, but their potency was significantly less than those observed for the OH-PBDEs. These results show that a wide

  1. In vivo dendritic cell depletion reduces breeding efficiency, affecting implantation and early placental development in mice.

    Science.gov (United States)

    Krey, Gesa; Frank, Pierre; Shaikly, Valerie; Barrientos, Gabriela; Cordo-Russo, Rosalia; Ringel, Frauke; Moschansky, Petra; Chernukhin, Igor V; Metodiev, Metodi; Fernández, Nelson; Klapp, Burghard F; Arck, Petra C; Blois, Sandra M

    2008-09-01

    Implantation of mammalian embryos into their mother's uterus ensures optimal nourishment and protection throughout development. Complex molecular interactions characterize the implantation process, and an optimal synchronization of the components of this embryo-maternal dialogue is crucial for a successful reproductive outcome. In the present study, we investigated the role of dendritic cells (DC) during implantation process using a transgenic mouse system (DTRtg) that allows transient depletion of CD11c+ cells in vivo through administration of diphtheria toxin. We observed that DC depletion impairs the implantation process, resulting in a reduced breeding efficiency. Furthermore, the maturity of uterine natural killer cells at dendritic cell knockout (DCKO) implantation sites was affected as well; as demonstrated by decreased perforin expression and reduced numbers of periodic-acid-Schiff (PAS)-positive cells. This was accompanied by disarrangements in decidual vascular development. In the present study, we were also able to identify a novel DC-dependent protein, phosphatidylinositol transfer protein beta (PITPbeta), involved in implantation and trophoblast development using a proteomic approach. Indeed, DCKO mice exhibited substantial anomalies in placental development, including hypocellularity of the spongiotrophoblast and labyrinthine layers and reduced numbers of trophoblast giant cells. Giant cells also down-regulated their expression of two characteristic markers of trophoblast differentiation, placental lactogen 1 and proliferin. In view of these findings, dendritic cells emerge as possible modulators in the orchestration of events leading to the establishment and maintenance of pregnancy.

  2. Pkd1 and Pkd2 are required for normal placental development.

    Directory of Open Access Journals (Sweden)

    Miguel A Garcia-Gonzalez

    2010-09-01

    Full Text Available Autosomal dominant polycystic kidney disease (ADPKD is a common cause of inherited renal failure that results from mutations in PKD1 and PKD2. The disorder is characterized by focal cyst formation that involves somatic mutation of the wild type allele in a large fraction of cysts. Consistent with a two-hit mechanism, mice that are homozygous for inactivating mutations of either Pkd1 or Pkd2 develop cystic kidneys, edema and hemorrhage and typically die in midgestation. Cystic kidney disease is unlikely to be the cause of fetal loss since renal function is not required to complete gestation. One hypothesis is that embryonic demise is due to leaky vessels or cardiac pathology.In these studies we used a series of genetically modified Pkd1 and Pkd2 murine models to investigate the cause of embryonic lethality in mutant embryos. Since placental defects are a frequent cause of fetal loss, we conducted histopathologic analyses of placentas from Pkd1 null mice and detected abnormalities of the labyrinth layer beginning at E12.5. We performed placental rescue experiments using tetraploid aggregation and conditional inactivation of Pkd1 with the Meox2 Cre recombinase. We found that both strategies improved the viability of Pkd1 null embryos. Selective inactivation of Pkd1 and Pkd2 in endothelial cells resulted in polyhydramnios and abnormalities similar to those observed in Pkd1(-/- placentas. However, endothelial cell specific deletion of Pkd1 or Pkd2 did not yield the dramatic vascular phenotypes observed in null animals.Placental abnormalities contribute to the fetal demise of Pkd(-/- embryos. Endothelial cell specific deletion of Pkd1 or Pkd2 recapitulates a subset of findings seen in Pkd null animals. Our studies reveal a complex role for polycystins in maintaining vascular integrity.

  3. Placental Adaptations in Growth Restriction

    Science.gov (United States)

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

    2015-01-01

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

  4. The effects of sildenafil citrate on feto-placental development and haemodynamics in a rabbit model of intrauterine growth restriction.

    Science.gov (United States)

    López-Tello, Jorge; Arias-Álvarez, María; Jiménez-Martínez, Maria-Ángeles; Barbero-Fernández, Alicia; García-García, Rosa María; Rodríguez, María; Lorenzo, Pedro L; Torres-Rovira, Laura; Astiz, Susana; González-Bulnes, Antonio; Rebollar, Pilar G

    2017-06-01

    The present study evaluated the effectiveness of sildenafil citrate (SC) to improve placental and fetal growth in a diet-induced rabbit model of intrauterine growth restriction (IUGR). Pregnant rabbits were fed either ad libitum (Group C) or restricted to 50% of dietary requirements (Group R) or restricted and treated with SC (Group SC). The treatment with SC improved placental development by increasing vascularity and vessel hypertrophy in the decidua. The assessment of feto-placental haemodynamics showed higher resistance and pulsatility indices at the middle cerebral artery (MCA) in fetuses treated with SC when compared with Group R, which had increased systolic peak and time-averaged mean velocities at the MCA. Furthermore, fetuses in the SC group had significantly higher biparietal and thoracic diameters and longer crown-rump lengths than fetuses in Group R. Hence, the SC group had a reduced IUGR rate and a higher kit size at birth compared with Group R. In conclusion, SC may provide potential benefits in pregnancies with placental insufficiency and IUGR, partially counteracting the negative effects of food restriction on placental development and fetal growth. However, the present study also found evidence of a possible blood overflow in the brain that warrants further investigation.

  5. Hypoxia and the anticoagulants dalteparin and acetylsalicylic acid affect human placental amino acid transport.

    Directory of Open Access Journals (Sweden)

    Marc-Jens Kleppa

    Full Text Available BACKGROUND: Anticoagulants, e.g. low-molecular weight heparins (LMWHs and acetylsalicylic acid (ASA are prescribed to women at risk for pregnancy complications that are associated with impaired placentation and placental hypoxia. Beyond their role as anticoagulants these compounds exhibit direct effects on trophoblast but their impact on placental function is unknown. The amino acid transport systems A and L, which preferably transfer essential amino acids, are well-described models to study placental nutrient transport. We aimed to examine the effect of hypoxia, LMWHs and ASA on the activity of the placental amino acid transport systems A and L and associated signalling mechanisms. METHODS: The uptake of C14-MeAIB (system A or H3-leucin (system L was investigated after incubation of primary villous fragments isolated from term placentas. Villous tissue was incubated at 2% O2 (hypoxia, 8% O2 and standard culture conditions (21% O2 or at 2% O2 and 21% O2 with dalteparin or ASA. Activation of the JAK/STAT or mTOR signalling pathways was determined by Western analysis of total and phosphorylated STAT3 or Raptor. RESULTS: Hypoxia decreased system A mediated MeAIB uptake and increased system L mediated leucine uptake compared to standard culture conditions (21% O2. This was accompanied by an impairment of STAT3 and a stimulation of Raptor signalling. System L activity increased at 8% O2. Dalteparin treatment reduced system A and system L activity under normoxic conditions and ASA (1 mM decreased system A and L transporter activity under normoxic and hypoxic conditions. CONCLUSIONS: Our data underline the dependency of placental function on oxygen supply. LMWHs and ASA are not able to reverse the effects of hypoxia on placental amino acid transport. These findings and the uncovering of the signalling mechanisms in more detail will help to understand the impact of LMWHs and ASA on placental function and fetal growth.

  6. Maternal hemoglobin concentration and hematocrit values may affect fetus development by influencing placental angiogenesis.

    Science.gov (United States)

    Stangret, Aleksandra; Wnuk, Anna; Szewczyk, Grzegorz; Pyzlak, Michał; Szukiewicz, Dariusz

    2017-01-01

    Vasculogenesis and angiogenesis are crucial for maintaining proper placental perfusion and optimal fetal development. Among other physical and chemical factors, hypoxia is known to stimulate angiogenic processes. Preplacental type of hypoxia is often associated with maternal anemia and is thought to enhance vascularization within the fetoplacental unit. The goal of this study was to establish the correlation between the local expression of vascular endothelial growth factor (VEGF) and placenta growth factor (PlGF) receptors (flt-1, flk-1) with maternal hemoglobin (Hb) concentration, hematocrit (Ht) values and the infant birthweight. In total, 43 specimens of term placentas obtained from normal course pregnancies delivered at term were included in the study. The expression of flt-1 and flk-1 receptors was analyzed by immunohistochemical staining. Vascular/extravascular tissular index (V/EVTI) was measured by assessing a total vascular area. Nonparametric Mann-Whitney U-test and Spearman's rank correlation were used to compare the various parameters and their differences between the groups. Among the patients with low Hb concentration, nearly 2-fold greater expression of the flt-1 receptor was positively correlated with infants birthweight (p = 0.028). Increased placental vascular density (increased flt-1 expression), during a physiological course of gestation, may be an adaptive response to lowered maternal Hb concentration and Ht values encountered during pregnancy.

  7. 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.

  8. Elevated levels of beta-human chorionic gonadotropin and human placental lactogen between 11-13 week's gestation and subsequent pregnancy complications in Oman i women

    International Nuclear Information System (INIS)

    Krolikowski, Andrzej; Al-Busaidi, Fikra; Al-Wahaibi, Adil

    2004-01-01

    The association between abnormal levels of maternal serum b-human chorionic gonadotrophin (b-HCG) and human placental lactogen (HPL) measured in early pregnancy and future poor pregnancy outcome is fairly well established. Little is known on how such prognostic information can be used to avoid future complications of pregnancy and improve their outcome. We undertook a prospective study, which was designed to assess the efficiency of maternal serum biochemical markers b-HCG and HPL for the detection of different pregnancy and labor complications. The blood samples were taken from pregnant patients who attended the antenatal clinic at Sultan Qaboos University Hospital in Muscat, Sultanate of Oman, from December 2001 to October 2002. These patients were selected randomly. A total of 200 Omani women, none diabetic, with singleton pregnancies between 11 and 13 weeks gestation were recruited into the study. Gestational age was calculated from the first day of the last menstrual period, unless ultrasonography showed a discrepancy of more than 14 days. Excluded from the study were pregnancies with fetal anomalies, multiple gestations and insulin dependent maternal diabetes. Biochemical analysis of both maternal serum markers was performed in the clinical biochemistry laboratory using an automated immunometric technique supplied by Beckman Coulter for b-HCG and manual radioimmunoassay utilizing a gamma radiation scintillation counter for HPL. Both assays underwent internal, trilevel quality controls. The selected patients were monitored for the following complications: pregnancy induced hypertension (PIH), gestational diabetes, polyhydramnios, antepartum hemorrhage, intrauterine growth retardation (IUGR) (birth weight <10th per centile for gestation), low Apgar score (7 or less) and emergency cesarean section. 75 patients did not develop any pregnancy complications and delivered vaginally. This was our control group. 85 patients developed one of the above mentioned problems

  9. Effect of Human Placental Extract on Health Status in Elderly Koreans

    Directory of Open Access Journals (Sweden)

    Mihee Kong

    2012-01-01

    Full Text Available Objectives. Human placental extract (HPE has begun to be used in Korea in various ways to improve health, even though evidence-based data is insufficient. This study investigated the effects of HPE on health status in elderly Koreans. Design. Randomized, single-blind, and case-control study design. Setting and Participants. Thirty-nine community-dwelling healthy Koreans ≥65 years of age. Intervention. The participants were randomly categorized into a placebo group (=17 and HPE group (=22. The HPE group received abdominal subcutaneous injections of HPE for 8 weeks. The placebo group was injected with normal saline. Measurements. The degree of health status was surveyed by the Korean health status measure for the elderly (KoHSME V1.0 at baseline and the end of the study. Results. In the HPE group, the scores of physical function, sexual life, and general heath perception at the end of the study period were significantly improved from baseline (=.007, .020, and .005, resp., while the health status of the placebo group remained unchanged during the study period. There was a significant difference over the study period between the two groups in the mean change of the physical function score (=.036. Conclusion. A HPE injection regimen can improve the health status in elderly Koreans.

  10. 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.

  11. Correlation Between Placental Matrix Metalloproteinase 9 and Tumor Necrosis Factor-α Protein Expression Throughout Gestation in Normal Human Pregnancy.

    Science.gov (United States)

    Basu, Jayasri; Agamasu, Enyonam; Bendek, Bolek; Salafia, Carolyn M; Mishra, Aruna; Lopez, Julia Vasquez; Kroes, Jessica; Dragich, Sharon Claire; Thakur, Ashley; Mikhail, Magdy

    2018-04-01

    Matrix metalloproteinases (MMPs), specifically MMP-9 plays a role in human placentation. The enzyme confers an invasive ability to cytotrophoblasts and degrades the endometrial matrix as the cells infiltrate the decidua to keep up with placental growth. Since tumor necrosis factor-α (TNF-α) can induce the synthesis of MMP-9, we investigated the patterns of changes in and correlation between placental villous MMP-9 and TNF-α expressions throughout normal human gestation. Placentas were obtained from 179 normal pregnant women who underwent elective abortion or term delivery. Chorionic villi isolated from placental samples were grouped as first, second, and third trimester (7 0/7 -13 0/7 , 13 1/7 -23 6/7 , and 37 0/7 -42 4/7 weeks, respectively). Chorionic villous TNF-α and MMP-9 proteins were assayed using enzyme immunoassay kits. There were significant differences in MMP-9 and TNF-α protein expressions among the trimester groups ( P = .001). The MMP-9 protein increased progressively with an increase in gestational age (GA), but TNF-α peaked in the second trimester. Within each trimester group, we searched for the effects of variation of GA in days on the 2 variables. A significant positive correlation between MMP-9 and GA was noted in the first trimester ( r = 0.364, P = .005). No other comparisons were significant. When GA was controlled for, partial correlation revealed a significant positive correlation between TNF-α and MMP-9 only in the second trimester ( r = 0.300, P = .018). We hypothesize that the TNF-α peak and the positive correlation between TNF-α and MMP-9 in the second trimester of normal human gestation could contribute toward a successful pregnancy outcome.

  12. Maternal exposure to di-(2-ethylhexyl) phthalate disrupts placental growth and development in pregnant mice

    Energy Technology Data Exchange (ETDEWEB)

    Zong, Teng; Lai, Lidan [Department of Physiology, School of Medicine, Nanchang University, Nanchang, Jiangxi 330006 (China); Hu, Jia [Department of Obstetrics and Gynecology, The First Affiliated Hospital of Nanchang University, Nanchang, Jiangxi (China); Guo, Meijun; Li, Mo; Zhang, Lu; Zhong, Chengxue; Yang, Bei; Wu, Lei; Zhang, Dalei; Tang, Min [Department of Physiology, School of Medicine, Nanchang University, Nanchang, Jiangxi 330006 (China); Kuang, Haibin, E-mail: kuanghaibin@ncu.edu.cn [Department of Physiology, School of Medicine, Nanchang University, Nanchang, Jiangxi 330006 (China)

    2015-10-30

    Highlights: • The influence of DEHP on the development of placenta was investigated. • DEHP disrupts the growth and development of placenta. • DEHP disrupts the formation of labyrinth vascularization. • DEHP inhibits the proliferation of ectoplacental cone and placenta. • DEHP induces the apoptosis of placenta via activated MAPK signaling pathway. - Abstract: Di-(2-ethylhexyl) phthalate (DEHP) is used as a plasticizer and widely dispersed in the environment. DEHP exposure reduces embryo implantations, increases embryonic loss, and decreases fetal body weights. However, no detailed information is available about the effect of DEHP on the placentation during pregnancy. Thus, our aim was to explore the effect of DEHP on the growth and development of placenta in vivo. Mice were administered DEHP by gavages at 125, 250, 500 mg/kg/day from gestational days (GD) 1 until sacrifice. Results showed that DEHP treatment significantly reduced the weight of placenta at GD 13. Histopathologically, in DEHP-treated group, the ectoplacental cones significantly became smaller at GD9, and total area of placenta and area of spongiotrophoblast were significantly reduced at GD 13. Expression levels of Ascl2, Esx1 and Fosl1 mRNA dramatically decreased in DEHP-treated placenta at GD 13. DEHP administration disrupted labyrinth vascularization of placentas, and inhibited proliferation and induced apoptosis of placenta by the activation of caspase-3 and -8, up-regulation of Bax and down-regulation of Bcl-2 mRNA and protein at GD 13. In conclusion, these results suggest that adverse pregnancy outcomes including low birth-weight and pregnancy loss exposed to DEHP are possibly mediated, at least in part, via the suppression of placental growth and development.

  13. Abnormal placental development and early embryonic lethality in EpCAM-null mice.

    Directory of Open Access Journals (Sweden)

    Keisuke Nagao

    Full Text Available BACKGROUND: EpCAM (CD326 is encoded by the tacstd1 gene and expressed by a variety of normal and malignant epithelial cells and some leukocytes. Results of previous in vitro experiments suggested that EpCAM is an intercellular adhesion molecule. EpCAM has been extensively studied as a potential tumor marker and immunotherapy target, and more recent studies suggest that EpCAM expression may be characteristic of cancer stem cells. METHODOLOGY/PRINCIPAL FINDINGS: To gain insights into EpCAM function in vivo, we generated EpCAM -/- mice utilizing an embryonic stem cell line with a tacstd1 allele that had been disrupted. Gene trapping resulted in a protein comprised of the N-terminus of EpCAM encoded by 2 exons of the tacstd1 gene fused in frame to betageo. EpCAM +/- mice were viable and fertile and exhibited no obvious abnormalities. Examination of EpCAM +/- embryos revealed that betageo was expressed in several epithelial structures including developing ears (otocysts, eyes, branchial arches, gut, apical ectodermal ridges, lungs, pancreas, hair follicles and others. All EpCAM -/- mice died in utero by E12.5, and were small, developmentally delayed, and displayed prominent placental abnormalities. In developing placentas, EpCAM was expressed throughout the labyrinthine layer and by spongiotrophoblasts as well. Placentas of EpCAM -/- embryos were compact, with thin labyrinthine layers lacking prominent vascularity. Parietal trophoblast giant cells were also dramatically reduced in EpCAM -/- placentas. CONCLUSION: EpCAM was required for differentiation or survival of parietal trophoblast giant cells, normal development of the placental labyrinth and establishment of a competent maternal-fetal circulation. The findings in EpCAM-reporter mice suggest involvement of this molecule in development of vital organs including the gut, kidneys, pancreas, lungs, eyes, and limbs.

  14. Abnormal placental development and early embryonic lethality in EpCAM-null mice.

    Science.gov (United States)

    Nagao, Keisuke; Zhu, Jianjian; Heneghan, Mallorie B; Hanson, Jeffrey C; Morasso, Maria I; Tessarollo, Lino; Mackem, Susan; Udey, Mark C

    2009-12-31

    EpCAM (CD326) is encoded by the tacstd1 gene and expressed by a variety of normal and malignant epithelial cells and some leukocytes. Results of previous in vitro experiments suggested that EpCAM is an intercellular adhesion molecule. EpCAM has been extensively studied as a potential tumor marker and immunotherapy target, and more recent studies suggest that EpCAM expression may be characteristic of cancer stem cells. To gain insights into EpCAM function in vivo, we generated EpCAM -/- mice utilizing an embryonic stem cell line with a tacstd1 allele that had been disrupted. Gene trapping resulted in a protein comprised of the N-terminus of EpCAM encoded by 2 exons of the tacstd1 gene fused in frame to betageo. EpCAM +/- mice were viable and fertile and exhibited no obvious abnormalities. Examination of EpCAM +/- embryos revealed that betageo was expressed in several epithelial structures including developing ears (otocysts), eyes, branchial arches, gut, apical ectodermal ridges, lungs, pancreas, hair follicles and others. All EpCAM -/- mice died in utero by E12.5, and were small, developmentally delayed, and displayed prominent placental abnormalities. In developing placentas, EpCAM was expressed throughout the labyrinthine layer and by spongiotrophoblasts as well. Placentas of EpCAM -/- embryos were compact, with thin labyrinthine layers lacking prominent vascularity. Parietal trophoblast giant cells were also dramatically reduced in EpCAM -/- placentas. EpCAM was required for differentiation or survival of parietal trophoblast giant cells, normal development of the placental labyrinth and establishment of a competent maternal-fetal circulation. The findings in EpCAM-reporter mice suggest involvement of this molecule in development of vital organs including the gut, kidneys, pancreas, lungs, eyes, and limbs.

  15. 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.

  16. 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.

  17. Elemental maps in human allantochorial placental vessels cells: 1. High K{sup +} and acetylcholine effects

    Energy Technology Data Exchange (ETDEWEB)

    Michelet-Habchi, C. E-mail: michelet@cenbg.in2p3.fr; Barberet, Ph.; Dutta, R.K.; Guiet-Bara, A.; Bara, M.; Moretto, Ph

    2003-09-01

    Regulation of vascular tone in the fetal extracorporeal circulation most likely depends on circulating hormones, local paracrine mechanisms and changes in membrane potential of vascular smooth muscle cells (VSMCs) and of vascular endothelial cells (VECs). The membrane potential is a function of the physiological activities of ionic channels (particularly, K{sup +} and Ca{sup 2+} channels in these cells). These channels regulate the ionic distribution into these cells. Micro-particle induced X-ray emission (PIXE) analysis was applied to determine the ionic composition of VSMC and of VEC in the placental human allantochorial vessels in a physiological survival medium (Hanks' solution) modified by the addition of acetylcholine (ACh: which opens the calcium-sensitive K{sup +} channels, K{sub Ca}) and of high concentration of K{sup +} (which blocks the voltage-sensitive K{sup +} channels, K{sub df}). In VSMC (media layer), the addition of ACh induced no modification of the Na, K, Cl, P, S, Mg and Ca concentrations and high K{sup +} medium increased significantly the Cl and K concentrations, the other ion concentrations remaining constant. In endothelium (VEC), ACh addition implicated a significant increase of Na and K concentration, and high K{sup +} medium, a significant increase in Cl and K concentration. These results indicated the importance of K{sub df}, K{sub Ca} and K{sub ATP} channels in the regulation of K{sup +} intracellular distribution in VSMC and VEC and the possible intervention of a Na-K-2Cl cotransport and corroborated the previous electrophysiological data.

  18. Role of EG-VEGF in human placentation: Physiological and pathological implications.

    Science.gov (United States)

    Hoffmann, Pascale; Saoudi, Yasmina; Benharouga, Mohamed; Graham, Charles H; Schaal, Jean-Patrick; Mazouni, Chafika; Feige, Jean-Jacques; Alfaidy, Nadia

    2009-08-01

    Pre-eclampsia (PE), the major cause of maternal morbidity and mortality, is thought to be caused by shallow invasion of the maternal decidua by extravillous trophoblasts (EVT). Data suggest that a fine balance between the expressions of pro- and anti-invasive factors might regulate EVT invasiveness. Recently, we showed that the expression of the new growth factor endocrine gland-derived vascular endothelial growth factor (EG-VEGF) is high in early pregnancy but falls after 11 weeks, suggesting an essential role for this factor in early pregnancy. Using human villous explants and HTR-8/SVneo, a first trimester extravillous trophoblast cell line, we showed differential expression of EG-VEGF receptors, PKR1 and PKR2, in the placenta and demonstrated that EG-VEGF inhibits EVT migration, invasion and tube-like organisation. EG-VEGF inhibitory effect on invasion was supported by a decrease in matrix metalloproteinase (MMP)-2 and MMP-9 production. Interference with PKR2 expression, using specific siRNAs, reversed the EG-VEGF-induced inhibitory effects. Furthermore, we determined EG-VEGF circulating levels in normal and PE patients. Our results showed that EG-VEGF levels were highest during the first trimester of pregnancy and decreased thereafter to non-pregnant levels. More important, EG-VEGF levels were significantly elevated in PE patients compared with age-matched controls. These findings identify EG-VEGF as a novel paracrine regulator of trophoblast invasion. We speculate that a failure to correctly down-regulate placental expression of EG-VEGF at the end of the first trimester of pregnancy might lead to PE.

  19. 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

    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...... 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...

  20. 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.

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

    Directory of Open Access Journals (Sweden)

    Y.K. Sinzato

    2011-03-01

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

  2. Matrix Metalloproteinase-3 (MMP-3) Is an Endogenous Activator of the MMP-9 Secreted by Placental Leukocytes: Implication in Human Labor.

    Science.gov (United States)

    Flores-Pliego, Arturo; Espejel-Nuñez, Aurora; Castillo-Castrejon, Marisol; Meraz-Cruz, Noemi; Beltran-Montoya, Jorge; Zaga-Clavellina, Veronica; Nava-Salazar, Sonia; Sanchez-Martinez, Maribel; Vadillo-Ortega, Felipe; Estrada-Gutierrez, Guadalupe

    2015-01-01

    The activity of matrix degrading enzymes plays a leading role in the rupture of the fetal membranes under normal and pathological human labor, and matrix metalloproteinase-9 (MMP-9) it is considered a biomarker of this event. To gain further insight into local MMP-9 origin and activation, in this study we analyzed the contribution of human placental leukocytes to MMP-9 secretion and explored the local mechanisms of the pro-enzyme activation. Placental blood leukocytes were obtained from women at term gestation without labor and maintained in culture up to 72 h. MMP-9 activity in the culture supernatants was determined by zymography and using a specific substrate. The presence of a potential pro-MMP-9 activator in the culture supernatants was monitored using a recombinant biotin-labeled human pro-MMP-9. To characterize the endogenous pro-MMP-9 activator, MMP-1, -3, -7 and -9 were measured by multiplex assay in the supernatants, and an inhibition assay of MMP-9 activation was performed using an anti-human MMP-3 and a specific MMP-3 inhibitor. Finally, production of MMP-9 and MMP-3 in placental leukocytes obtained from term pregnancies with and without labor was assessed by immunofluorescence. Placental leukocytes spontaneously secreted pro-MMP-9 after 24 h of culture, increasing significantly at 48 h (P≤0.05), when the active form of MMP-9 was detected. Culture supernatants activated the recombinant pro-MMP-9 showing that placental leukocytes secrete the activator. A significant increase in MMP-3 secretion by placental leukocytes was observed since 48 h in culture (P≤0.05) and up to 72 h (P≤0.001), when concentration reached its maximum value. Specific activity of MMP-9 decreased significantly (P≤0.005) when an anti-MMP-3 antibody or a specific MMP-3 inhibitor were added to the culture media. Placental leukocytes from term labor produced more MMP-9 and MMP-3 compared to term non-labor cells. In this work we confirm that placental leukocytes from human term

  3. 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

  4. First trimester serum placental growth factor and hyperglycosylated human chorionic gonadotropin are associated with pre-eclampsia: a case control study.

    Science.gov (United States)

    Keikkala, Elina; Koskinen, Sini; Vuorela, Piia; Laivuori, Hannele; Romppanen, Jarkko; Heinonen, Seppo; Stenman, Ulf-Håkan

    2016-11-25

    To study whether maternal serum hyperglycosylated human chorionic gonadotropin (hCG-h) improves first trimester prediction of pre-eclampsia when combined with placental growth factor (PlGF), pregnancy-associated plasma protein-A (PAPP-A) and maternal risk factors. Gestational-age-adjusted concentrations of hCG, hCG-h, PlGF and PAPP-A were analysed in serum samples by time-resolved immunofluorometric assays at 8-13 weeks of gestation. The case-control study included 98 women who developed pre-eclampsia, 25 who developed gestational hypertension, 41 normotensive women with small-for-gestational-age (SGA) infants and 177 controls. Of 98 women with pre-eclampsia, 24 women developed preterm pre-eclampsia (diagnosis factors.

  5. Computational modeling of the structure-function relationship in human placental terminal villi.

    OpenAIRE

    Plitman, Mayo R; Olsthoorn, Jason; Charnock-Jones, David Stephen; Burton, Graham James; Oyen, Michelle Lynn

    2016-01-01

    Placental oxygen transport takes place at the final branches of the villous tree and is dictated by the relative arrangement of the maternal and fetal circulations. Modeling techniques have failed to accurately assess the structure-function relationship in the terminal villi due to the geometrical complexity. Three-dimensional blood flow and oxygen transport was modeled in four terminal villi reconstructed from confocal image stacks. The blood flow was analyzed along the center lines of capil...

  6. Intravenous maternal -arginine administration to twin-bearing ewes during late pregnancy enhances placental growth and development.

    Science.gov (United States)

    van der Linden, D S; Sciascia, Q; Sales, F; Wards, N J; Oliver, M H; McCoard, S A

    2015-10-01

    This study aimed to investigate if intravenous maternal Arg administration to well-fed twin-bearing ewes, from 100 to 140 d of gestation or birth, could enhance placental development and placental nutrient transport. Ewes received intravenous infusions of saline (control) or 345 μmol Arg HCl/kg of BW 3 times daily from d 100 of pregnancy (P100) to d 140 of pregnancy (P140; cohort 1) or from P100 to birth (cohort 2). At P140, ewes in cohort 1 were euthanized and individual placentae per fetus were dissected and placentomes were classed per type (A to D) and size (light to heavy). Placentome number and individual weight were recorded. As an indicator of placental nutrient transport, blood plasma was collected from the uterine ovarian vein (UOV), uterine artery (UA), and umbilical vein and artery at the time of euthanasia and analyzed for metabolites and free AA concentrations. The ewes in cohort 2 were allowed to lamb and lambs were weighed at birth. The expelled placenta was dissected and number of cotyledons and weights of total cotyledons, remaining fetal membranes, and total placenta were recorded. At P140, Arg-infused ewes had a 63% ( = 0.03) greater number of unoccupied caruncles than control ewes. No differences were observed for placental weight at P140. At birth, lambs from Arg-infused ewes tended to have 11% ( = 0.09) greater placental weight and 34% ( = 0.03) greater total cotyledon weight compared with control lambs. Arginine-infused ewes (Arg-infused) had increased concentrations of Arg ( = 0.0001) and ornithine (Orn; = 0.004) but decreased concentrations of Met ( = 0.01) and His ( = 0.02 and = 0.09, respectively) compared with control ewes in plasma UOV and UA. Fetuses from Arg-infused ewes had increased concentrations of Orn ( = 0.005) and decreased concentrations of His ( = 0.006), Met ( = 0.003), and Lys ( = 0.01) but no differences in Arg ( > 0.10) concentrations were found compared with control fetuses in umbilical artery and vein plasma. This

  7. 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

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

    International Nuclear Information System (INIS)

    Gorrochategui, Eva; Pérez-Albaladejo, Elisabet; Casas, Josefina; Lacorte, Sílvia; Porte, Cinta

    2014-01-01

    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

  9. Ott1 (Rbm15) is essential for placental vascular branching morphogenesis and embryonic development of the heart and spleen.

    Science.gov (United States)

    Raffel, Glen D; Chu, Gerald C; Jesneck, Jonathan L; Cullen, Dana E; Bronson, Roderick T; Bernard, Olivier A; Gilliland, D Gary

    2009-01-01

    The infant leukemia-associated gene Ott1 (Rbm15) has broad regulatory effects within murine hematopoiesis. However, germ line Ott1 deletion results in fetal demise prior to embryonic day 10.5, indicating additional developmental requirements for Ott1. The spen gene family, to which Ott1 belongs, has a transcriptional activation/repression domain and RNA recognition motifs and has a significant role in the development of the head and thorax in Drosophila melanogaster. Early Ott1-deficient embryos show growth retardation and incomplete closure of the notochord. Further analysis demonstrated placental defects in the spongiotrophoblast and syncytiotrophoblast layers, resulting in an arrest of vascular branching morphogenesis. The rescue of the placental defect using a conditional allele with a trophoblast-sparing cre transgene allowed embryos to form a normal placenta and survive gestation. This outcome showed that the process of vascular branching morphogenesis in Ott1-deficient animals was regulated by the trophoblast compartment rather than the fetal vasculature. Mice surviving to term manifested hyposplenia and abnormal cardiac development. Analysis of global gene expression of Ott1-deficient embryonic hearts showed an enrichment of hypoxia-related genes and a significant alteration of several candidate genes critical for cardiac development. Thus, Ott1-dependent pathways, in addition to being implicated in leukemogenesis, may also be important for the pathogenesis of placental insufficiency and cardiac malformations.

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

    Directory of Open Access Journals (Sweden)

    Alejandra Perez-Sepulveda

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

  11. Effect of Macrophage Migration Inhibitory Factor (MIF) in Human Placental Explants Infected with Toxoplasma gondii Depends on Gestational Age

    Science.gov (United States)

    de Oliveira Gomes, Angelica; de Oliveira Silva, Deise Aparecida; Silva, Neide Maria; de Freitas Barbosa, Bellisa; Franco, Priscila Silva; Angeloni, Mariana Bodini; Fermino, Marise Lopes; Roque-Barreira, Maria Cristina; Bechi, Nicoletta; Paulesu, Luana Ricci; dos Santos, Maria Célia; Mineo, José Roberto; Ferro, Eloisa Amália Vieira

    2011-01-01

    Because macrophage migration inhibitory factor (MIF) is a key cytokine in pregnancy and has a role in inflammatory response and pathogen defense, the objective of the present study was to investigate the effects of MIF in first- and third-trimester human placental explants infected with Toxoplasma gondii. Explants were treated with recombinant MIF, IL-12, interferon-γ, transforming growth factor-β1, or IL-10, followed by infection with T. gondii RH strain tachyzoites. Supernatants of cultured explants were assessed for MIF production. Explants were processed for morphologic analysis, immunohistochemistry, and real-time PCR analysis. Comparison of infected and stimulated explants versus noninfected control explants demonstrated a significant increase in MIF release in first-trimester but not third-trimester explants. Tissue parasitism was higher in third- than in first-trimester explants. Moreover, T. gondii DNA content was lower in first-trimester explants treated with MIF compared with untreated explants. However, in third-trimester explants, MIF stimulus decreased T. gondii DNA content only at the highest concentration of the cytokine. In addition, high expression of MIF receptor was observed in first-trimester placental explants, whereas MIF receptor expression was low in third-trimester explants. In conclusion, MIF was up-regulated and demonstrated to be important for control of T. gondii infection in first-trimester explants, whereas lack of MIF up-regulation in third-trimester placentas may be involved in higher susceptibility to infection at this gestational age. PMID:21641401

  12. Co-ordinated expression of MMP-2 and its putative activator, MT1-MMP, in human placentation.

    Science.gov (United States)

    Bjørn, S F; Hastrup, N; Lund, L R; Danø, K; Larsen, J F; Pyke, C

    1997-08-01

    The spatial expression of mRNA for matrix metalloproteinase 2 (MMP-2), its putative activator, the membrane-type 1 matrix metalloproteinase (MT1-MMP), and the MMP-2 substrate type IV collagen was investigated in human placentas of both normal and tubal ectopic pregnancies and in cyclic endometrium using in-situ hybridization. Cytokeratin staining applied to adjacent sections was used to identify epithelial and trophoblast cells. In both normal and tubal pregnancies MT1-MMP, MMP-2 and type IV collagen mRNA were highly expressed and co-localized in the extravillous cytotrophoblasts of anchoring villi, in cytotrophoblasts that had penatrated into the placental bed and in cytotrophoblastic cell islands. In addition, the decidual cells of normal pregnancies in some areas co-expressed MT1-MMP and MMP-2 mRNA, with moderate signals for both components. Fibroblast-like stromal cells in tubal pregnancies were positive for MMP-2 mRNA but generally negative for MT1-MMP mRNA. The consistent co-localization of MT1-MMP with MMP-2 and type IV collagen in the same subset of cytotrophoblasts strongly suggests that all three components co-operate in the tightly regulated fetal invasion process. The co-expression of MT1-MMP and MMP-2 mRNA in some of the decidual cells indicates that these cells are also actively involved in the placentation process.

  13. 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...... pregnancy in type 1 diabetic subjects could not be related to hPGH levels.......Human placental GH (hPGH) replaces pituitary GH during pregnancy. hPGH is correlated to serum IGF-I in normal pregnancies and in pregnancies complicated by fetoplacental disorders. In gestational diabetes and type 2 diabetes no correlation between hPGH and IGF-I has been found. The relationship...

  14. Placental macrophage contact potentiates the complete replicative cycle of human cytomegalovirus in syncytiotrophoblast cells: role of interleukin-8 and transforming growth factor-beta1.

    Science.gov (United States)

    Bácsi, A; Aranyosi, J; Beck, Z; Ebbesen, P; Andirkó, I; Szabó, J; Lampé, L; Kiss, J; Gergely, L; Tóth, F D

    1999-10-01

    Although syncytiotrophoblast (ST) cells can be infected by human cytomegalovirus (HCMV), in vitro studies have indicated that ST cells do not support the complete viral reproductive cycle, or HCMV replication may occur in less than 3% of ST cells. The present study tested the possibility that placental macrophages might enhance activation of HCMV carried in ST cells and, further, that infected ST cells would be capable of transmitting virus to neighboring macrophages. For this purpose, we studied HCMV replication in ST cells grown alone or cocultured with uninfected placental macrophages. Our results demonstrated that HCMV gene expression in ST cells was markedly upregulated by coculture with macrophages, resulting in release of substantial amounts of infectious virus from HCMV-infected ST cells. After having become permissive for viral replication, ST cells delivered HCMV to the cocultured macrophages, as evidenced by detection of virus-specific antigens in these cells. The stimulatory effect of coculture on HCMV gene expression in ST cells was mediated by marked interleukin-8 (IL-8) and transforming growth factor-beta1 (TGF-beta1) release from macrophages, an effect caused by contact between the different placental cells. Our findings indicate an interactive role for the ST layer and placental macrophages in the dissemination of HCMV among placental tissue. Eventually, these interactions may contribute to the transmission of HCMV from mother to the fetus.

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

    DEFF Research Database (Denmark)

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

    2017-01-01

    BACKGROUND: Malaria in pregnancy is associated with significant morbidity in pregnant women and their offspring. Plasmodium falciparum infected erythrocytes (IE) express VAR2CSA that mediates binding to chondroitin sulphate A (CSA) in the placenta. Two VAR2CSA-based vaccines for placental malaria...

  16. Calcitonin gene related family peptides: importance in normal placental and fetal development.

    Science.gov (United States)

    Yallampalli, Chandra; Chauhan, Madhu; Endsley, Janice; Sathishkumar, Kunju

    2014-01-01

    Synchronized molecular and cellular events occur between the uterus and the implanting embryo to facilitate successful pregnancy outcome. Nevertheless, the molecular signaling network that coordinates strategies for successful decidualization, placentation and fetal growth are not well understood. The discovery of calcitonin/calcitonin gene-related peptides (CT/CGRP) highlighted new signaling mediators in various physiological processes, including reproduction. It is known that CGRP family peptides including CGRP, adrenomedulin and intermedin play regulatory functions during implantation, trophoblast proliferation and invasion, and fetal organogenesis. In addition, all the CGRP family peptides and their receptor components are found to be expressed in decidual, placental and fetal tissues. Additionally, plasma levels of peptides of the CGRP family were found to fluctuate during normal gestation and to induce placental cellular differentiation, proliferation, and critical hormone signaling. Moreover, aberrant signaling of these CGRP family peptides during gestation has been associated with pregnancy disorders. It indicates the existence of a possible regulatory role for these molecules during decidualization and placentation processes, which are known to be particularly vulnerable. In this review, the influence of the CGRP family peptides in these critical processes is explored and discussed.

  17. ATP-dependent calcium transport across basal plasma membranes of human placental trophoblast

    International Nuclear Information System (INIS)

    Fisher, G.J.; Kelley, L.K.; Smith, C.H.

    1987-01-01

    As a first step in understanding the cellular basis of maternal-fetal calcium transfer, the authors examined the characteristics of calcium uptake by a highly purified preparation of the syncytiotrophoblast basal (fetal facing) plasma membrane. In the presence of nanomolar concentrations of free calcium, basal membranes demonstrated substantial ATP-dependent calcium uptake. This uptake required magnesium, was not significantly affected by Na + or K + (50 mM), or sodium azide (10 mM). Intravesicular calcium was rapidly and completely released by the calcium ionophore rapidly and completely released by the calcium ionophore A23187. Calcium transport was significantly stimulated by the calcium-dependent regulatory protein calmodulin. Placental membrane fractions enriched in endoplasmic reticulum (ER) and mitochondria also demonstrated ATP-dependent calcium uptake. In contrast to basal membrane, mitochondrial calcium uptake was completely inhibited by azide. The rate of calcium uptake was completely inhibited by azide. The rate of calcium uptake by the ER was only 20% of that of basal membranes. They conclude that the placental basal plasma membrane possesses a high-affinity calcium transport system similar to that found in plasma membranes of a variety of cell types. This transporter is situated to permit it to function in vivo in maternal-fetal calcium transfer

  18. The Elsevier Trophoblast Research Award Lecture: Importance of metzincin proteases in trophoblast biology and placental development: a focus on ADAM12.

    Science.gov (United States)

    Aghababaei, Mahroo; Beristain, Alexander G

    2015-04-01

    Placental development is a highly regulated process requiring signals from both fetal and maternal uterine compartments. Within this complex system, trophoblasts, placental cells of epithelial lineage, form the maternal-fetal interface controlling nutrient, gas and waste exchange. The commitment of progenitor villous cytotrophoblasts to differentiate into diverse trophoblast subsets is a fundamental process in placental development. Differentiation of trophoblasts into invasive stromal- and vascular-remodeling subtypes is essential for uterine arterial remodeling and placental function. Inadequate placentation, characterized by defects in trophoblast differentiation, may underlie the earliest cellular events driving pregnancy disorders such as preeclampsia and fetal growth restriction. Molecularly, invasive trophoblasts acquire characteristics defined by profound alterations in cell-cell and cell-matrix adhesion, cytoskeletal reorganization and production of proteolytic factors. To date, most studies have investigated the importance of the matrix metalloproteinases (MMPs) and their ability to efficiently remodel components of the extracellular matrix (ECM). However, it is now becoming clear that besides MMPs, other related proteases regulate trophoblast invasion via mechanisms other than ECM turnover. In this review, we will summarize the current knowledge on the regulation of trophoblast invasion by members of the metzincin family of metalloproteinases. Specifically, we will discuss the emerging roles that A Disintegrin and Metalloproteinases (ADAMs) play in placental development, with a particular focus on the ADAM subtype, ADAM12. Copyright © 2015 Elsevier Ltd. All rights reserved.

  19. Comparative toxicity and endocrine disruption potential of urban and rural atmospheric organic PM1 in JEG-3 human placental cells

    International Nuclear Information System (INIS)

    Drooge, Barend L. van; Marqueño, Anna; Grimalt, Joan O.; Fernández, Pilar; Porte, Cinta

    2017-01-01

    Outdoor ambient air particulate matter and air pollution are related to adverse effects on human health. The present study assesses the cytotoxicity and ability to disrupt aromatase activity of organic PM 1 extracts from rural and urban areas at equivalent air volumes from 2 to 30 m 3 , in human placental JEG-3 cells. Samples were chemically analyzed for particle bounded organic compounds with endocrine disrupting potential, i.e. PAH, O-PAH, phthalate esters, but also for organic molecular tracer compounds for the emission source identification. Rural samples collected in winter were cytotoxic at the highest concentration tested and strongly inhibited aromatase activity in JEG-3 cells. No cytotoxicity was detected in summer samples from the rural site and the urban samples, while aromatase activity was moderately inhibited in these samples. In the urban area, the street site samples, collected close to intensive traffic, showed stronger inhibition of aromatase activity than the samples simultaneously collected at a roof site, 50 m above ground level. The cytotoxicity and endocrine disruption potential of the samples were linked to combustion products, i.e. PAH and O-PAH, especially from biomass burning in the rural site in winter. - Highlights: • Organic extracts of outdoor ambient air PM1 showed aromatase activity inhibition in exposed human placental JEG-3 cells. • Cytotoxicity and strongest endocrine disruption was observed in rural winter samples, while lowest inhibition was observed in urban background site 50 m above a busy street. • Cytotoxicity and aromatase activity inhibition in the samples were linked to combustion products, i.e. PAH and O-PAH, especially from biomass burning. - Organic extracts from ambient air PM 1 related to biomass burning are more cytotoxic and have stronger endocrine disruption potential than urban PM 1 .

  20. Characterization of cDNA encoding human placental anticoagulant protein (PP4): Homology with the lipocortin family

    International Nuclear Information System (INIS)

    Grundmann, U.; Abel, K.J.; Bohn, H.; Loebermann, H.; Lottspeich, F.; Kuepper, H.

    1988-01-01

    A cDNA library prepared from human placenta was screened for sequences encoding the placental protein 4 (PP4). PP4 is an anticoagulant protein that acts as an indirect inhibitor of the thromboplastin-specific complex, which is involved in the blood coagulation cascade. Partial amino acid sequence information from PP4-derived cyanogen bromide fragments was used to design three oligonucleotide probes for screening the library. From 10 6 independent recombinants, 18 clones were identified that hybridized to all three probes. These 18 recombinants contained cDNA inserts encoding a protein of 320 amino acid residues. In addition to the PP4 cDNA the authors identified 9 other recombinants encoding a protein with considerable similarity (74%) to PP4, which was termed PP4-X. PP4 and PP4-X belong to the lipocortin family, as judged by their homology to lipocortin I and calpactin I

  1. 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.

  2. Metabolism of 19-methyl-substituted steroids by human placental aromatase

    International Nuclear Information System (INIS)

    Beusen, D.D.; Carrell, H.L.; Covey, D.F.

    1987-01-01

    The 19-methyl analogues of androstenedione and its aromatization intermediates (19-hydroxyandrostenedione and 19-oxoandrostenedione) were evaluated as substrates of microsomal aromatase in order to determine the effect of a 19-alkyl substituent on the enzyme's regiospecificity. Neither the androstenedione analog [10-ethylestr-4-ene-3,17-dione (1c) nor the 19-oxoandrostenedione analog [10-acetylestr-4-ene-3,17-dione (3c)] was converted to estrogens or oxygenated metabolites by placental microsomes. In contrast, both analogues of 19-hydroxyandrostenedione [10-[(1S)-1-hydroxyethyl] extr-4-ene-3,17-dione (2c) and 10-[(1R)-1-hydroxyethyl]estr-4-ene-3,17-dione (2e)] were converted to the intermediate analog 3c in a process requiring O 2 and either NADH or NADPH. No change in enzyme regiospecificity was detected. The absolute configuration of 2e was determined by X-ray crystallography. Experiments with 18 O 2 established that 3c generated from 2c retained little 18 O ( 18 O (≅ 70%). All four 19-methyl steroids elicited type I difference spectra from placental microsomes in addition to acting as competitive inhibitors of aromatase. Pretreatment of microsomes with 4-hydroxyandrostenedione (a suicide inactivator of aromatase) abolished the metabolism of 2c and 2e to 3c, as well as the type I difference spectrum elicited by 2c and 2e. The failure of 2c, 2e, and 3c to undergo aromatization was rationalized in the context of a mechanistic proposal for the third oxygenation of aromatase requiring hydrogen abstraction at C 1 of 19,19-dihydroxyandrostenedione, homolytic cleavage of the C 10 -C 19 bond, and oxygen rebound at C 19

  3. Placental abruption possibly due to parvovirus B19 infection.

    Science.gov (United States)

    Kawabe, Ayaka; Takai, Yasushi; Tamaru, Jun-Ichi; Samejima, Kouki; Seki, Hiroyuki

    2016-01-01

    There is concern about the development of anemia-associated fetal hydrops associated with maternal parvovirus B19 infection. Parvovirus B19 infection occurs via the globoside (P antigen) receptor, the main glycolipid of erythroid cells, which induces apoptosis. Similar findings have been reported for the P antigen of globoside-containing placental trophoblast cells. A 32-year-old woman was infected with human parvovirus B19 at week 32 of pregnancy, and had severe anemia at week 34. At week 37, an emergency cesarean section was performed because of sudden abdominal pain and fetal bradycardia; placental abruption was found. A live male infant was delivered with no sign of fetal hydrops or fetal infection. Placental tissue was positive for parvovirus B19 according to polymerase chain reaction. Immunohistochemical analysis using caspase-related M30 CytoDEATH monoclonal antibody revealed M30 staining of the placental villous trophoblasts. Placental trophoblasts and erythroid precursor cells have been reported to express globoside (P antigen), which is necessary for parvovirus B19 infectivity, and to show apoptotic activity as a result of infection. Placentas from three other pregnancies with documented abruption showed no M30 staining. The present case strongly suggests an association between placental abruption and apoptosis resulting from parvovirus B19 infection.

  4. 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

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

    Directory of Open Access Journals (Sweden)

    Ramazan Demir

    2011-07-01

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

  6. Human pituitary and placental hormones control human insulin-like growth factor II secretion in human granulosa cells

    International Nuclear Information System (INIS)

    Ramasharma, K.; Li, C.H.

    1987-01-01

    Human granulosa cells cultured with calf serum actively proliferated for 18-20 generations and secreted progesterone into the medium; progesterone levels appeared to decline with increase in generation number. Cells cultured under serum-free conditions secreted significant amounts of progesterone and insulin-like growth factor II (IGF-II). The progesterone secretion was enhanced by the addition of human follitropin, lutropin, and chorionic gonadotropin but not by growth hormone. These cells, when challenged to varying concentrations of human growth hormone, human chorionic somatomammotropin, human prolactin, chorionic gonadotropin, follitropin, and lutropin, secreted IGF-II into the medium as measured by specific IGF-II RIA. Among these human hormones, chorionic gonadotropin, follitropin, and lutropin were most effective in inducing IGF-II secretion from these cells. When synthetic lutropin-releasing hormone and α-inhibin-92 were tested, only lutropin-releasing hormone was effective in releasing IGF-II. The results described suggest that cultured human granulosa cells can proliferate and actively secrete progesterone and IGF-II into the medium. IGF-II production in human granulosa cells was influenced by a multi-hormonal complex including human growth hormone, human chorionic somatomammotropin, and prolactin

  7. 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).

  8. Comparative toxicity and endocrine disruption potential of urban and rural atmospheric organic PM1 in JEG-3 human placental cells.

    Science.gov (United States)

    van Drooge, Barend L; Marqueño, Anna; Grimalt, Joan O; Fernández, Pilar; Porte, Cinta

    2017-11-01

    Outdoor ambient air particulate matter and air pollution are related to adverse effects on human health. The present study assesses the cytotoxicity and ability to disrupt aromatase activity of organic PM 1 extracts from rural and urban areas at equivalent air volumes from 2 to 30 m 3 , in human placental JEG-3 cells. Samples were chemically analyzed for particle bounded organic compounds with endocrine disrupting potential, i.e. PAH, O-PAH, phthalate esters, but also for organic molecular tracer compounds for the emission source identification. Rural samples collected in winter were cytotoxic at the highest concentration tested and strongly inhibited aromatase activity in JEG-3 cells. No cytotoxicity was detected in summer samples from the rural site and the urban samples, while aromatase activity was moderately inhibited in these samples. In the urban area, the street site samples, collected close to intensive traffic, showed stronger inhibition of aromatase activity than the samples simultaneously collected at a roof site, 50 m above ground level. The cytotoxicity and endocrine disruption potential of the samples were linked to combustion products, i.e. PAH and O-PAH, especially from biomass burning in the rural site in winter. Copyright © 2017 Elsevier Ltd. All rights reserved.

  9. The genetics of feto-placental development: A study of acid phosphatase locus 1 and adenosine deaminase polymorphisms in a consecutive series of newborn infants

    Directory of Open Access Journals (Sweden)

    Bergamaschi Antonio

    2008-09-01

    Full Text Available Abstract Background Acid phosphatase locus 1 and adenosine deaminase locus 1 polymorphisms show cooperative effects on glucose metabolism and immunological functions. The recent observation of cooperation between the two systems on susceptibility to repeated spontaneous miscarriage prompted us to search for possible interactional effects between these genes and the correlation between birth weight and placental weight. Deviation from a balanced development of the feto-placental unit has been found to be associated with perinatal morbidity and mortality and with cardiovascular diseases in adulthood. Methods We examined 400 consecutive newborns from the Caucasian population of Rome. Birth weight, placental weight, and gestational length were registered. Acid phosphatase locus 1 and adenosine deaminase locus 1 phenotypes were determined by starch gel electrophoresis and correlation analysis was performed by SPSS programs. Informed verbal consent to participate in the study was obtained from the mothers. Results Highly significant differences in birth weight-placental weight correlations were observed among acid phosphatase locus 1 phenotypes (p = 0.005. The correlation between birth weight and placental weight was markedly elevated in subjects carrying acid phosphatase locus 1 phenotypes with medium-low F isoform concentration (A, CA and CB phenotypes compared to those carrying acid phosphatase locus 1 phenotypes with medium-high F isoform concentration (BA and B phenotypes (p = 0.002. Environmental and developmental variables were found to exert a significant effect on birth weight-placental weight correlation in subjects with medium-high F isoform concentrations, but only a marginal effect was observed in those with medium-low F isoform concentrations. The correlation between birth weight and placental weight is higher among carriers of the adenosine deaminase locus 1 allele*2, which is associated with low activity, than in homozygous adenosine

  10. The Shared Pathoetiological Effects of Particulate Air Pollution and the Social Environment on Fetal-Placental Development

    Science.gov (United States)

    2014-01-01

    Exposure to particulate air pollution and socioeconomic risk factors are shown to be independently associated with adverse pregnancy outcomes; however, their confounding relationship is an epidemiological challenge that requires understanding of their shared etiologic pathways affecting fetal-placental development. The purpose of this paper is to explore the etiological mechanisms associated with exposure to particulate air pollution in contributing to adverse pregnancy outcomes and how these mechanisms intersect with those related to socioeconomic status. Here we review the role of oxidative stress, inflammation and endocrine modification in the pathoetiology of deficient deep placentation and detail how the physical and social environments can act alone and collectively to mediate the established pathology linked to a spectrum of adverse pregnancy outcomes. We review the experimental and epidemiological literature showing that diet/nutrition, smoking, and psychosocial stress share similar pathways with that of particulate air pollution exposure to potentially exasperate the negative effects of either insult alone. Therefore, socially patterned risk factors often treated as nuisance parameters should be explored as potential effect modifiers that may operate at multiple levels of social geography. The degree to which deleterious exposures can be ameliorated or exacerbated via community-level social and environmental characteristics needs further exploration. PMID:25574176

  11. PKA tightly bound to human placental mitochondria participates in steroidogenesis and is not modified by cAMP.

    Science.gov (United States)

    Gomez-Chang, E; Espinosa-Garcia, M T; Olvera-Sanchez, S; Flores-Herrera, O; Martinez, F

    2014-09-01

    Protein phosphorylation plays an important role in the modulation of steroidogenesis and it depends on the activation of different signaling cascades. Previous data showed that PKA activity is related to steroidogenesis in mitochondria from syncytiotrophoblast of human placenta (HPM). PKA localization and contribution in progesterone synthesis and protein phosphorylation of HPM was assessed in this work. Placental mitochondria and submitochondrial fractions were used. Catalytic and regulatory PKA subunits were identified by Western blot. PKA activity was determined by the incorporation of (32)P into proteins in the presence or absence of specific inhibitors. The effect of PKA activators and inhibitors on steroidogenesis and protein phosphorylation in HPM was tested by radioimmunoassay and autoradiography. The PKAα catalytic subunit was distributed in all the submitochondrial fractions whereas βII regulatory subunit was the main isoform observed in both the outer and inner membranes of HPM. PKA located in the inner membrane showed the highest activity. Progesterone synthesis and mitochondrial protein phosphorylation are modified by inhibitors of PKA catalytic subunit but are neither sensitive to inhibitors of the regulatory subunit nor to activators of the holoenzyme. The lack of response in the presence of PKA activators and inhibitors of the regulatory subunit suggests that the activation of intramitochondrial PKA cannot be prevented or further activated. The phosphorylating activity of PKA inside HPM could be an important component of the steroidogenesis transduction cascade, probably exerting its effects by direct phosphorylation of its substrates or by modulating other kinases and phosphatases. Copyright © 2014 Elsevier Ltd. All rights reserved.

  12. Myricetin suppresses invasion and promotes cell death in human placental choriocarcinoma cells through induction of oxidative stress.

    Science.gov (United States)

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

    2017-07-28

    Myricetin is a bioactive compound found in a variety of vegetables and fruits, and its anti-cancer effects are well known. In this study, we confirmed that myricetin reduced proliferation of two choriocarcinoma cell lines (JAR and JEG-3) and also promoted apoptosis and regulated cell cycle progression in a dose-dependent manner in JAR and JEG-3 cells. In addition, we found that invasive and pro-angiogenic properties of malignant JAR and JEG-3 trophoblast cells were attenuated by myricetin treatment via MAPK and PI3K/AKT signaling pathways. In addition, we found that ROS production, lipid peroxidation, glutathione depletion, and loss of mitochondrial membrane potentials were enhanced in JAR and JEG-3 cells treated with myricetin. Moreover, myricetin augmented cytosolic Ca 2+ release from the endoplasmic reticulum associated with modulation of ER stress in JAR and JEG-3 cells. Our results also revealed that myricetin had synergistic antiproliferative effects with current chemotherapeutics, etoposide and cisplatin, on choriocarcinoma cells. Collectively, results of the present study provide strong evidence for the potential of myricetin to be an effective therapeutic for the prevention of human placental choriocarcinomas. Copyright © 2017 Elsevier B.V. All rights reserved.

  13. {sup 26}Al incorporation into the brain of rat fetuses through the placental barrier and subsequent metabolism in postnatal development

    Energy Technology Data Exchange (ETDEWEB)

    Yumoto, Sakae, E-mail: yumoto-s@viola.ocn.ne.j [Yumoto Institute of Neurology, Kawadacho 6-11, Shinjuku-ku, Tokyo 162-0054 (Japan); Nagai, Hisao [College of Humanities and Sciences, Nihon University, Tokyo (Japan); Kakimi, Shigeo [Faculty of Medicine, Nihon University, Tokyo (Japan); Matsuzaki, Hiroyuki [School of Engineering, The University of Tokyo, Tokyo (Japan)

    2010-04-15

    Aluminium (Al) inhibits prenatal and postnatal development of the brain. We used {sup 26}Al as a tracer, and measured {sup 26}Al incorporation into rat fetuses through the placental barrier by accelerator mass spectrometry (AMS). From day 15 to day 18 of gestation, {sup 26}AlCl{sub 3} was subcutaneously injected into pregnant rats. Considerable amounts of {sup 26}Al were measured in the tissues of newborn rats immediately after birth. The amounts of {sup 26}Al in the liver and kidneys decreased rapidly during postnatal development. However, approximately 15% of {sup 26}Al incorporated into the brain of fetuses remained in the brain of adult rats 730 days after birth.

  14. 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.

  15. 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.

  16. 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 M.M.; Leonhard, Anne K.; Widen Zakhary, Carina

    2017-01-01

    INTRODUCTION: Recently, an association between human papillomavirus (HPV) infection and both spontaneous abortion and spontaneous preterm delivery was suggested. However, the reported HPV prevalence in pregnant women varies considerably and reliable conclusions are difficult. We aimed to investig......INTRODUCTION: Recently, an association between human papillomavirus (HPV) infection and both spontaneous abortion and spontaneous preterm delivery was suggested. However, the reported HPV prevalence in pregnant women varies considerably and reliable conclusions are difficult. We aimed...... (n=103), spontaneous preterm delivery (n=69), elective abortion (n=54), and spontaneous abortion (n=44). Moreover, HPV cellular target was identified by the use of in situ hybridization. RESULTS: HPV 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. 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...

  17. 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

  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. Placental Nutrient Transport in Gestational Diabetic Pregnancies

    Directory of Open Access Journals (Sweden)

    Marisol Castillo-Castrejon

    2017-11-01

    Full Text Available Maternal obesity during pregnancy is rising and is associated with increased risk of developing gestational diabetes mellitus (GDM, defined as glucose intolerance first diagnosed in pregnancy (1. Fetal growth is determined by the maternal nutrient supply and placental nutrient transfer capacity. GDM-complicated pregnancies are more likely to be complicated by fetal overgrowth or excess adipose deposition in utero. Infants born from GDM mothers have an increased risk of developing cardiovascular and metabolic disorders later in life. Diverse factors, such as ethnicity, age, fetal sex, clinical treatment for glycemic control, gestational weight gain, and body mass index among others, represent a challenge for studying underlying mechanisms in GDM subjects. Determining the individual roles of glucose intolerance, obesity, and other factors on placental function and fetal growth remains a challenge. This review provides an overview of changes in placental macronutrient transport observed in human pregnancies complicated by GDM. Improved knowledge and understanding of the alterations in placenta function that lead to pathological fetal growth will allow for development of new therapeutic interventions and treatments to improve pregnancy outcomes and lifelong health for the mother and her children.

  20. 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.

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

    Science.gov (United States)

    Denier, Colette C; Brisson-Lougarre, Andrée A; Biasini, Ghislaine G; Grozdea, Jean J; Fournier, Didier D

    2002-01-01

    In humans, there are four alkaline phosphatases, and each form exhibits 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 pregnant 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. 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. 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.

  2. Pst I restriction fragment length polymorphism of human placental alkaline phosphatase gene: Mendelian in segregation and localization of mutation site in the gene

    International Nuclear Information System (INIS)

    Tsavaler, L.; Penhallow, R.C.; Sussman, H.H.

    1988-01-01

    The pattern of inheritance of a Pst I restriction fragment length polymorphism (RFLP) of the human placental alkaline phosphatase gene was studied in nine nuclear families by Southern blot hybridization analysis of genomic DNA. The dimorphic RFLP is defined by the presence of allelic fragments 1.0 kilobase and 0.8 kilobase long. The results of this study show that the two alleles of the Pst I RFLP of the placental alkaline phosphatase gene segregate as codominant traits according to Mendelian expectations. For a polymorphism to be useful as a genetic marker the probability that an offspring is informative (PIC) must be at least 0.15. The allelic frequency of the 1.0-kilobase allele is 0.21, which correlates to a probability that an offspring is informative of 0.275 and is indicative of a useful polymorphism. By using probes derived from different regions of the placental alkaline phosphatase cDNA, the mutated Pst I site causing the RFLP was located in the penultimate intron 2497 base pairs downstream from the transcriptional initiation site

  3. 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 h...... transcription of var2csa. The results corroborate current efforts to develop PAM-specific vaccines based on VAR2CSA....

  4. Arsenic exposure in pregnant mice disrupts placental vasculogenesis and causes spontaneous abortion.

    Science.gov (United States)

    He, Wenjie; Greenwell, Robert J; Brooks, Diane M; Calderón-Garcidueñas, Lilian; Beall, Howard D; Coffin, J Douglas

    2007-09-01

    Arsenic is an abundant toxicant in ground water and soil around areas with extractive industries. Human epidemiological studies have shown that arsenic exposure is linked to developmental defects and miscarriage. The placenta is known to utilize vasculogenesis to develop its circulation. The hypothesis tested here states the following: arsenic exposure causes placental dysmorphogenesis and defective placental vasculogenesis resulting in placental insufficiency and subsequent spontaneous abortion. To test this hypothesis, pregnant mice were exposed to sodium arsenite (AsIII) through drinking water from conception through weanling stages. Neonatal assessment of birth rates, pup weights, and litter sizes in arsenic exposed and control mothers revealed that AsIII-exposed mothers had only 40% the fecundity of controls. Preterm analysis at E12.5 revealed a loss of fecundity at E12.5 from either 20 ppm or greater exposures to AsIII. There was no loss of fecundity at E7.5 suggesting that spontaneous abortion occurs during placentation. Histomorphometry on E12.5 placentae from arsenic-exposed mice revealed placental dysplasia especially in the vasculature. These results suggest that arsenic toxicity is causative for mammalian spontaneous abortion by virtue of aberrant placental vasculogenesis and placental insufficiency.

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

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    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

  6. Intrapritoneal Hemorrhage after Placental Abruption

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    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.

  7. 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.

  8. Placental iron uptake and its regulation

    NARCIS (Netherlands)

    M. Bierings (Marc)

    1989-01-01

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

  9. Purification of human placental aromatase cytochrome P-450 with monoclonal antibody and its characterization

    International Nuclear Information System (INIS)

    Yoshida, Nobutaka; Osawa, Yoshio

    1991-01-01

    A simple and efficient method is described for the purification of microsomal aromatase cytochrome P-450 from human placenta. The enzyme was solubilized with Emulgen 913 and sodium cholate and subjected to chromatography on a column of Sepharose 4B couples with a specific monoclonal antibody, followed by hydroxyapatite column chromatography. The specific cytochrome P-450 content of purified aromatase was 13.1 (12-14.8) nmol/mg of protein. Aromatase assays were carried out with reconstituted systems of bovine liver P-450 reductase and dilauroyl-L-α-phosphatidylcholine with [1β- 3 H,4- 14 C]androstenedione as substrate. The total recovery of purified aromatase activity was 32.2%, and P-450 recovery was 17.6%. The very high K m value for 16α-hydroxytestosterone aromatization gives a reasonable indication that estriol is not the directly aromatized product in the fetoplacental unit of human pregnancy. The aromatase P-450 was subjected to SDS-polyacrylamide gel electrophoresis in increasing quantities. Silver stain detection techniques indicated a single band having a molecular mass of 55 kDa with greater than 97% purity. The stability analysis showed a half-life of over 4 years on storage at -80C

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

    Science.gov (United States)

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

    2016-12-01

    Chronic placental hypoxia is one of the root causes of placental insufficiencies that result in pre-eclampsia and maternal hypertension. Chronic hypoxia causes disruption of trophoblast (TB) development, invasion into maternal decidua, and remodeling of maternal spiral arteries. The pregnant guinea pig shares several characteristics with humans such as hemomonochorial placenta, villous subplacenta, deep TB invasion, and remodeling of maternal arteries, and is an ideal animal model to study placental development. We hypothesized that chronic placental hypoxia of the pregnant guinea pig inhibits TB invasion and alters spiral artery remodeling. Time-mated pregnant guinea pigs were exposed to either normoxia (NMX) or three levels of hypoxia (HPX: 16%, 12%, or 10.5% O 2 ) from 20 day gestation until midterm (39-40 days) or term (60-65 days). At term, HPX (10.5% O 2 ) increased maternal arterial blood pressure (HPX 57.9 ± 2.3 vs. NMX 40.4 ± 2.3, P < 0.001), decreased fetal weight by 16.1% (P < 0.05), and increased both absolute and relative placenta weights by 10.1% and 31.8%, respectively (P < 0.05). At midterm, there was a significant increase in TB proliferation in HPX placentas as confirmed by increased PCNA and KRT7 staining and elevated ESX1 (TB marker) gene expression (P < 0.05). Additionally, quantitative image analysis revealed decreased invasion of maternal blood vessels by TB cells. In summary, this animal model of placental HPX identifies several aspects of abnormal placental development, including increased TB proliferation and decreased migration and invasion of TBs into the spiral arteries, the consequences of which are associated with maternal hypertension and fetal growth restriction. © 2016 by the Society for the Study of Reproduction, Inc.

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

    International Nuclear Information System (INIS)

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

    1992-01-01

    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 with values for fractional absorption from gastrointestinal tract or lung for most substances. Information about three elements - cesium, strontium, and iodine - serve to present comparative approaches to predicting radiation dose and effect. 25 refs., 11 figs., tab

  12. Prognostic significance of the radioimmunoassay of human serum placental lactogen during the last stage of pregnancy

    International Nuclear Information System (INIS)

    Kleinert, P.

    1980-01-01

    995 HPL analyses have been carried out in 185 pregnant women in order to assess the role of routine HPL determination in the second phase of pregnancy. The pregnancies were retrospectively grouped as follows: - Normal pregnancies; deficient intrauterine development - heparinisation in cases of intrauterine development - premature infants - giant growth - gemini. A normal range of HPL concentrations was established on the basis of the normal pregnancies and compared with the other collectives. It was found that routine HPL determination alone is of little value as a monitoring parameter for the second phase of pregnancy. On the other hand, it is indispensible for further clinical diagnosis and therapy. (orig./MG) [de

  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. 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.

  15. 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.

  16. Down-Regulation of Placental Transport of Amino Acids Precedes the Development of Intrauterine Growth Restriction in Maternal Nutrient Restricted Baboons.

    Science.gov (United States)

    Pantham, Priyadarshini; Rosario, Fredrick J; Weintraub, Susan T; Nathanielsz, Peter W; Powell, Theresa L; Li, Cun; Jansson, Thomas

    2016-11-01

    Intrauterine growth restriction (IUGR) is an important risk factor for perinatal complications and adult disease. IUGR is associated with down-regulation of placental amino acid transporter expression and activity at birth. It is unknown whether these changes are a cause or a consequence of human IUGR. We hypothesized that placental amino acid transport capacity is reduced prior to onset of reduced fetal growth in baboons with maternal nutrient restriction (MNR). Pregnant baboons were fed either a control (n = 8) or MNR diet (70% of control diet, n = 9) from Gestational Day 30. At Gestational Day 120 (0.65 of gestation), fetuses and placentas were collected. Microvillous (MVM) and basal (BM) plasma membrane vesicles were isolated. System A and system L transport activity was determined in MVM, and leucine transporter activity was assessed in BM using radiolabeled substrates. MVM amino acid transporter isoform expression (SNAT1, SNAT2, and SNAT4 and LAT1 and LAT2) was measured using Western blots. LAT1 and LAT2 expression were also determined in BM. Maternal and fetal plasma amino acids concentrations were determined using mass spectrometry. Fetal and placental weights were unaffected by MNR. MVM system A activity was decreased by 37% in MNR baboon placentas (P = 0.03); however MVM system A amino acid transporter protein expression was unchanged. MVM system L activity and BM leucine transporter activity were not altered by MNR. Fetal plasma concentrations of essential amino acids isoleucine and leucine were reduced, while citrulline increased (P growth trajectory. The reduction in plasma leucine and isoleucine in MNR fetuses may be caused by reduced activity of MVM system A, which is strongly coupled with system L essential amino acid uptake. Our findings indicate that reduced placental amino acid transport may be a cause rather than a consequence of IUGR due to inadequate maternal nutrition. © 2016 by the Society for the Study of Reproduction, Inc.

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

    Science.gov (United States)

    Denier, Colette C; Brisson-Lougarre, Andrée A; Biasini, Ghislaine G; Grozdea, Jean J; Fournier, Didier D

    2002-01-01

    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. PMID:11818032

  18. 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.

  19. 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.

    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

  20. 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

  1. Tumour necrosis factor-α stimulates HIV-1 replication in single-cycle infection of human term placental villi fragments in a time, viral dose and envelope dependent manner

    Directory of Open Access Journals (Sweden)

    Barré-Sinoussi Françoise

    2006-06-01

    Full Text Available Abstract Background The placenta plays an important role in the control of in utero HIV-1 mother-to-child transmission (MTCT. Proinflammatory cytokines in the placental environment are particularly implicated in this control. We thus investigated the effect of TNF-α on HIV-1 expression in human placental tissues in vitro. Results Human placental chorionic villi fragments were infected with varying doses of luciferase reporter HIV-1 pseudotypes with the R5, X4-Env or the vesicular stomatitis virus protein G (VSV-G. Histocultures were then performed in the presence or absence of recombinant human TNF-α. Luciferase activity was measured at different time points in cell lysates or on whole fragments using ex vivo imaging systems. A significant increase in viral expression was detected in placental fragments infected with 0.2 ng of p24 antigen/fragment (P = 0.002 of VSV-G pseudotyped HIV-1 in the presence of TNF-α seen after 120 hours of culture. A time independent significant increase of viral expression by TNF-α was observed with higher doses of VSV-G pseudotyped HIV-1. When placental fragments were infected with R5-Env pseudotyped HIV-1, a low level of HIV expression at 168 hours of culture was detected for 3 of the 5 placentas tested, with no statistically significant enhancement by TNF-α. Infection with X4-Env pseudotyped HIV-1 did not lead to any detectable luciferase activity at any time point in the absence or in the presence of TNF-α. Conclusion TNF-α in the placental environment increases HIV-1 expression and could facilitate MTCT of HIV-1, particularly in an inflammatory context.

  2. Exploring the world of human development and reproduction.

    Science.gov (United States)

    Red-Horse, Kristy; Drake, Penelope M; Fisher, Susan

    2014-01-01

    Susan Fisher has spent her career studying human development, proteomics, and the intersection between the two. When she began studying human placentation, there had been extensive descriptive studies of this fascinating organ that intertwines with the mother's vasculature during pregnancy. Susan can be credited with numerous major findings on the mechanisms that regulate placental cytotrophoblast invasion. These include the discovery that cytotrophoblasts undergo vascular mimicry to insert themselves into uterine arteries, the finding that oxygen tension greatly effects placentation, and identifying how these responses go awry in pregnancy complications such as preeclamsia. Other important work has focused on the effect of post-translational modifications such as glycosylation on bacterial adhesion and reproduction. Susan has also forayed into the world of proteomics to identify cancer biomarkers. Because her work is truly groundbreaking, many of these findings inspire research in other laboratories around the world resulting in numerous follow up papers. Likewise, her mentoring and support inspires young scientists to go on and make their own important discoveries. In this interview, Susan shares what drove her science, how she continued to do important research while balancing other aspects of life, and provides insights for the next generation.

  3. Review: Maternal health and the placental microbiome.

    Science.gov (United States)

    Pelzer, Elise; Gomez-Arango, Luisa F; Barrett, Helen L; Nitert, Marloes Dekker

    2017-06-01

    Over the past decade, the role of the microbiome in regulating metabolism, immune function and behavior in humans has become apparent. It has become clear that the placenta is not a sterile organ, but rather has its own endogenous microbiome. The composition of the placental microbiome is distinct from that of the vagina and has been reported to resemble the oral microbiome. Compared to the gut microbiome, the placental microbiome exhibits limited microbial diversity. This review will focus on the current understanding of the placental microbiota in normal healthy pregnancy and also in disease states including preterm birth, chorioamnionitis and maternal conditions such as obesity, gestational diabetes mellitus and preeclampsia. Factors known to alter the composition of the placental microbiota will be discussed in the final part of this review. Copyright © 2016. Published by Elsevier Ltd.

  4. 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

  5. Correlation between human maternal-fetal placental transfer and molecular weight of PCB and dioxin congeners/isomers.

    Science.gov (United States)

    Mori, Chisato; Nakamura, Noriko; Todaka, Emiko; Fujisaki, Takeyoshi; Matsuno, Yoshiharu; Nakaoka, Hiroko; Hanazato, Masamichi

    2014-11-01

    Establishing methods for the assessment of fetal exposure to chemicals is important for the prevention or prediction of the child's future disease risk. In the present study, we aimed to determine the influence of molecular weight on the likelihood of chemical transfer from mother to fetus via the placenta. The correlation between molecular weight and placental transfer rates of congeners/isomers of polychlorinated biphenyls (PCBs) and dioxins was examined. Twenty-nine sample sets of maternal blood, umbilical cord, and umbilical cord blood were used to measure PCB concentration, and 41 sample sets were used to analyze dioxins. Placental transfer rates were calculated using the concentrations of PCBs, dioxins, and their congeners/isomers within these sample sets. Transfer rate correlated negatively with molecular weight for PCB congeners, normalized using wet and lipid weights. The transfer rates of PCB or dioxin congeners differed from those of total PCBs or dioxins. The transfer rate for dioxin congeners did not always correlate significantly with molecular weight, perhaps because of the small sample size or other factors. Further improvement of the analytical methods for dioxin congeners is required. The findings of the present study suggested that PCBs, dioxins, or their congeners with lower molecular weights are more likely to be transferred from mother to fetus via the placenta. Consideration of chemical molecular weight and transfer rate could therefore contribute to the assessment of fetal exposure. Copyright © 2014 Elsevier Ltd. All rights reserved.

  6. Clinical development of a VAR2CSA-based placental malaria vaccine PAMVAC

    DEFF Research Database (Denmark)

    Gbédandé, Komi; Fievet, Nadine; Viwami, Firmine

    2017-01-01

    Background  The antigen VAR2CSA plays a pivotal role in the pathophysiology of pregnancy-associated malaria (PAM) caused by Plasmodium falciparum. A VAR2CSA-based vaccine candidate, PAMVAC, is under development by an EU-funded multi-country consortium (PlacMalVac project). As part of PAMVAC...

  7. IFPA meeting 2014 workshop report : Animal models to study pregnancy pathologies; new approaches to study human placental exposure to xenobiotics; biomarkers of pregnancy pathologies; placental genetics and epigenetics; the placenta and stillbirth and fetal growth restriction

    NARCIS (Netherlands)

    Barbaux, S.; Erwich, J. J. H. M.; Favaron, P. O.; Gil, S.; Gallot, D.; Golos, T. G.; Gonzalez-Bulnes, A.; Guibourdenche, J.; Heazell, A. E. P.; Jansson, T.; Laprevote, O.; Lewis, R. M.; Miller, R. K.; Monk, D.; Novakovic, B.; Oudejans, C.; Parast, M.; Peugnet, P.; Pfarrer, C.; Pinar, H.; Roberts, C. T.; Robinson, W.; Saffery, R.; Salomon, C.; Sexton, A.; Staff, A. C.; Suter, M.; Tarrade, A.; Wallace, J.; Vaillancourt, C.; Vaiman, D.; Worton, S. A.; Lash, G. E.

    Workshops are an important part of the IFPA annual meeting as they allow for discussion of specialized topics. At IFPA meeting 2014 there were six themed workshops, five of which are summarized in this report. These workshops related to various aspects of placental biology but collectively covered

  8. Prediction of Placental Barrier Permeability: A Model Based on Partial Least Squares Variable Selection Procedure

    Directory of Open Access Journals (Sweden)

    Yong-Hong Zhang

    2015-05-01

    Full Text Available Assessing the human placental barrier permeability of drugs is very important to guarantee drug safety during pregnancy. Quantitative structure–activity relationship (QSAR method was used as an effective assessing tool for the placental transfer study of drugs, while in vitro human placental perfusion is the most widely used method. In this study, the partial least squares (PLS variable selection and modeling procedure was used to pick out optimal descriptors from a pool of 620 descriptors of 65 compounds and to simultaneously develop a QSAR model between the descriptors and the placental barrier permeability expressed by the clearance indices (CI. The model was subjected to internal validation by cross-validation and y-randomization and to external validation by predicting CI values of 19 compounds. It was shown that the model developed is robust and has a good predictive potential (r2 = 0.9064, RMSE = 0.09, q2 = 0.7323, rp2 = 0.7656, RMSP = 0.14. The mechanistic interpretation of the final model was given by the high variable importance in projection values of descriptors. Using PLS procedure, we can rapidly and effectively select optimal descriptors and thus construct a model with good stability and predictability. This analysis can provide an effective tool for the high-throughput screening of the placental barrier permeability of drugs.

  9. Study on the determination of human placental lactogen (HPL) using an enzyme-immunoassay. Comparison with a commercial radio-immunoassay in the course of normal pregnancies

    International Nuclear Information System (INIS)

    Schneider, B.

    1982-01-01

    A novel enzyme-immunoassay (EIA) for determining human placental lactogen (HPL) was studied for its practicability and quality. The precision of the system in series was tested by using a serum taken each in the 19th, 29th and 40th pregnancy week. A normal range graph between the 10th and the 40th pregnancy week (10 sera per pregnancy week) was established from 310 sera of normal-course pregnancies. The graph practically agreed with the known RIA-established graphs. When comparing with a radio-immunoassay for HPL of routine application and known quality criteria, r=0.93 indicated a close correlation of the values found. (orig./MG) [de

  10. Enzyme-immuno assay for total estrogens and human placental lactogen. Comparison with radio-immuno-assay in normal pregnancy-monitoring

    International Nuclear Information System (INIS)

    Raichvarg, D.; Tallet, F.; Lajeunie, E.; Bonnaire, Y.; Danglas, P.

    1980-01-01

    The concentrations of estrogens (E) and human placental lactogen (HLP) are estimated in sera by radio immuno-assay (RIA) and enzyme-immuno-assay (EIA). Statistical data indicate mean intra-assay variation coefficients of 7% and 12% for E and HLP tests, respectively. The correlation coefficient (RIA/EIA) are found higher than 0,9% for both hormonal assays. The dilution curves obtained by RIA and EIA are similar. However, Student'test gives a significant difference for E determination. In fact, total E and E 3 only are measured by EIA and RIA, respectively. In most cases biological interferences are negligible except for HLP in presence of higher protein or haemoglobin levels. RIA and EIA are performed to study serum HLP and E levels throughout normal pregnancies. Results allow to use EIA for HLP and E evaluations in pregnancy-monitoring [fr

  11. Placental gene expression of the placental growth factor (PlGF) in intrauterine growth restriction.

    Science.gov (United States)

    Joó, József Gábor; Rigó, János; Börzsönyi, Balázs; Demendi, Csaba; Kornya, László

    2017-06-01

    We analyzed changes in gene expression of placental growth factor (PIGF) in human placental samples obtained postpartum from pregnancies with IUGR. During a twelve-month study period representing the calendar year of 2012 placental samples from 101 pregnancies with IUGR and from 140 normal pregnancies were obtained for analysis of a potential difference in PIGF gene expression. There was no significant difference in gene activity of the PIGF gene between the IUGR versus normal pregnancy groups (Ln2 α : 0.92; p intrauterine growth restriction PIGF expression does show a significant decrease indicating its potential role in the profound defect in angiogenesis in these cases.

  12. Vitamin C supplementation ameliorates the adverse effects of nicotine on placental hemodynamics and histology in nonhuman primates.

    Science.gov (United States)

    Lo, Jamie O; Schabel, Matthias C; Roberts, Victoria H J; Morgan, Terry K; Rasanen, Juha P; Kroenke, Christopher D; Shoemaker, Sophie R; Spindel, Eliot R; Frias, Antonio E

    2015-03-01

    We previously demonstrated that prenatal nicotine exposure decreases neonatal pulmonary function in nonhuman primates, and maternal vitamin C supplementation attenuates these deleterious effects. However, the effect of nicotine on placental perfusion and development is not fully understood. This study utilizes noninvasive imaging techniques and histological analysis in a nonhuman primate model to test the hypothesis that prenatal nicotine exposure adversely effects placental hemodynamics and development but is ameliorated by vitamin C. Time-mated macaques (n = 27) were divided into 4 treatment groups: control (n = 5), nicotine only (n = 4), vitamin C only (n = 9), and nicotine plus vitamin C (n = 9). Nicotine animals received 2 mg/kg per day of nicotine bitartrate (approximately 0.7 mg/kg per day free nicotine levels in pregnant human smokers) from days 26 to 160 (term, 168 days). Vitamin C groups received ascorbic acid at 50, 100, or 250 mg/kg per day with or without nicotine. All underwent placental dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) at 135-140 days and Doppler ultrasound at 155 days to measure uterine artery and umbilical vein velocimetry and diameter to calculate uterine artery volume blood flow and placental volume blood flow. Animals were delivered by cesarean delivery at 160 days. A novel DCE-MRI protocol was utilized to calculate placental perfusion from maternal spiral arteries. Placental tissue was processed for histopathology. Placental volume blood flow was significantly reduced in nicotine-only animals compared with controls and nicotine plus vitamin C groups (P = .03). Maternal placental blood flow was not different between experimental groups by DCE-MRI, ranging from 0.75 to 1.94 mL/mL per minute (P = .93). Placental histology showed increased numbers of villous cytotrophoblast cell islands (P vitamin C. Prenatal nicotine exposure significantly decreased fetal blood supply via reduced placental volume blood flow, which

  13. Morphology, development, and evolution of fetal membranes and placentation in squamate reptiles.

    Science.gov (United States)

    Blackburn, Daniel G; Flemming, Alexander F

    2009-09-15

    Current studies on fetal membranes of reptiles are providing insight into three major historical transformations: evolution of the amniote egg, evolution of viviparity, and evolution of placentotrophy. Squamates (lizards and snakes) are ideal for such studies because their fetal membranes sustain embryos in oviparous species and contribute to placentas in viviparous species. Ultrastructure of the fetal membranes in oviparous corn snakes (Pituophis guttatus) shows that the chorioallantois is specialized for gas exchange and the omphalopleure, for water absorption. Transmission and scanning electron microscopic studies of viviparous thamnophine snakes (Thamnophis, Storeria) have revealed morphological specializations for gas exchange and absorption in the intra-uterine environment that represent modifications of features found in oviparous species. Thus, fetal membranes in oviparous species show morphological differentiation for distinct functions that have been recruited and enhanced under viviparous conditions. The ultimate in specialization of fetal membranes is found in viviparous skinks of South America (Mabuya) and Africa (Trachylepis, Eumecia), in which placentotrophy accounts for nearly all of the nutrients for development. Ongoing research on these lizards has revealed morphological specializations of the chorioallantoic placenta through which nutrient transfer is accomplished. In addition, African Trachylepis show an invasive form of implantation, in which uterine epithelium is replaced by invading chorionic cells. Ongoing analysis of these lizards shows how integration of multiple lines of evidence can provide insight into the evolution of developmental and reproductive specializations once thought to be confined to eutherian mammals.

  14. Placental fatty acid transport in maternal obesity.

    Science.gov (United States)

    Cetin, I; Parisi, F; Berti, C; Mandò, C; Desoye, G

    2012-12-01

    Pregestational obesity is a significant risk factor for adverse pregnancy outcomes. Maternal obesity is associated with a specific proinflammatory, endocrine and metabolic phenotype that may lead to higher supply of nutrients to the feto-placental unit and to excessive fetal fat accumulation. In particular, obesity may influence placental fatty acid (FA) transport in several ways, leading to increased diffusion driving force across the placenta, and to altered placental development, size and exchange surface area. Animal models show that maternal obesity is associated with increased expression of specific FA carriers and inflammatory signaling molecules in placental cotyledonary tissue, resulting in enhanced lipid transfer across the placenta, dislipidemia, fat accumulation and possibly altered development in fetuses. Cell culture experiments confirmed that inflammatory molecules, adipokines and FA, all significantly altered in obesity, are important regulators of placental lipid exchange. Expression studies in placentas of obese-diabetic women found a significant increase in FA binding protein-4 expression and in cellular triglyceride content, resulting in increased triglyceride cord blood concentrations. The expression and activity of carriers involved in placental lipid transport are influenced by the endocrine, inflammatory and metabolic milieu of obesity, and further studies are needed to elucidate the strong association between maternal obesity and fetal overgrowth.

  15. Expression patterns of ERVWE1/Syncytin-1 and other placentally expressed human endogenous retroviruses along the malignant transformation process of hydatidiform moles.

    Science.gov (United States)

    Bolze, Pierre-Adrien; Patrier, Sophie; Cheynet, Valérie; Oriol, Guy; Massardier, Jérôme; Hajri, Touria; Guillotte, Michèle; Bossus, Marc; Sanlaville, Damien; Golfier, François; Mallet, François

    2016-03-01

    Up to 20% of hydatidiform moles are followed by malignant transformation in gestational trophoblastic neoplasia and require chemotherapy. Syncytin-1 is involved in human placental morphogenesis and is also expressed in various cancers. We assessed the predictive value of the expression of Syncytin-1 and its interactants in the malignant transformation process of hydatidiform moles. Syncytin-1 glycoprotein was localized by immunohistochemistry in hydatidiform moles, gestational trophoblastic neoplasia and control placentas. The transcription levels of its locus ERVWE1, its interaction partners (hASCT1, hASCT2, TLR4 and DC-SIGN) and two loci (ERVFRDE1 and ERV3) involved the expression of other placental envelopes were assessed by real-time PCR. Syncytin-1 glycoprotein was expressed in syncytiotrophoblast of hydatidiform moles with an apical enhancement when compared with normal placentas. Moles with further malignant transformation had a higher staining intensity of Syncytin-1 surface unit C-terminus but the transcription level of its locus ERVWE1 was not different from that of moles with further remission and normal placentas. hASCT1 and TLR4, showed lower transcription levels in complete moles when compared to normal placentas. ERVWE1, ERVFRDE1 and ERV3 transcription was down-regulated in hydatidiform moles and gestational trophoblastic neoplasia. Variations of Syncytin-1 protein localization and down-regulation of hASCT1 and TLR4 transcription are likely to reflect altered functions of Syncytin-1 in the premalignant context of complete moles. The reduced transcription in gestational trophoblastic diseases of ERVWE1, ERVFRDE1 and ERV3, which expression during normal pregnancy is differentially regulated by promoter region methylation, suggest a joint dysregulation mechanism in malignant context. Copyright © 2016 Elsevier Ltd. All rights reserved.

  16. Placental Origins of Chronic Disease

    Science.gov (United States)

    Burton, Graham J.; Fowden, Abigail L.; Thornburg, Kent L.

    2016-01-01

    Epidemiological evidence links an individual's susceptibility to chronic disease in adult life to events during their intrauterine phase of development. Biologically this should not be unexpected, for organ systems are at their most plastic when progenitor cells are proliferating and differentiating. Influences operating at this time can permanently affect their structure and functional capacity, and the activity of enzyme systems and endocrine axes. It is now appreciated that such effects lay the foundations for a diverse array of diseases that become manifest many years later, often in response to secondary environmental stressors. Fetal development is underpinned by the placenta, the organ that forms the interface between the fetus and its mother. All nutrients and oxygen reaching the fetus must pass through this organ. The placenta also has major endocrine functions, orchestrating maternal adaptations to pregnancy and mobilizing resources for fetal use. In addition, it acts as a selective barrier, creating a protective milieu by minimizing exposure of the fetus to maternal hormones, such as glucocorticoids, xenobiotics, pathogens, and parasites. The placenta shows a remarkable capacity to adapt to adverse environmental cues and lessen their impact on the fetus. However, if placental function is impaired, or its capacity to adapt is exceeded, then fetal development may be compromised. Here, we explore the complex relationships between the placental phenotype and developmental programming of chronic disease in the offspring. Ensuring optimal placentation offers a new approach to the prevention of disorders such as cardiovascular disease, diabetes, and obesity, which are reaching epidemic proportions. PMID:27604528

  17. 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.

  18. 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.

  19. Adverse fetal and neonatal outcomes associated with a life-long high fat diet: role of altered development of the placental vasculature.

    Directory of Open Access Journals (Sweden)

    Emily K Hayes

    Full Text Available Maternal obesity results in a number of obstetrical and fetal complications with both immediate and long-term consequences. The increased prevalence of obesity has resulted in increasing numbers of women of reproductive age in this high-risk group. Since many of these obese women have been subjected to hypercaloric diets from early childhood we have developed a rodent model of life-long maternal obesity to more clearly understand the mechanisms that contribute to adverse pregnancy outcomes in obese women. Female Sprague Dawley rats were fed a control diet (CON--16% of calories from fat or high fat diet (HF--45% of calories from fat from 3 to 19 weeks of age. Prior to pregnancy HF-fed dams exhibited significant increases in body fat, serum leptin and triglycerides. A subset of dams was sacrificed at gestational day 15 to evaluate fetal and placental development. The remaining animals were allowed to deliver normally. HF-fed dams exhibited a more than 3-fold increase in fetal death and decreased neonatal survival. These outcomes were associated with altered vascular development in the placenta, as well as increased hypoxia in the labyrinth. We propose that the altered placental vasculature may result in reduced oxygenation of the fetal tissues contributing to premature demise and poor neonatal survival.

  20. Molecular cloning of the gene for the human placental GTP-binding protein Gp (G25K): Identification of this GTP-binding protein as the human homolog of the yeast cell-division-cycle protein CDC42

    International Nuclear Information System (INIS)

    Shinjo, K.; Koland, J.G.; Hart, M.J.; Narasimhan, V.; Cerione, R.A.; Johnson, D.I.; Evans, T.

    1990-01-01

    The authors have isolated cDNA clones from a human placental library that code for a low molecular weight GTP-binding protein originally designated G p (also called G25K). This identification is based on comparisons with the available peptide sequences for the purified human G p protein and the use of two highly specific anti-peptide antibodies. The predicted amino acid sequence of the protein is very similar to those of various members of the ras superfamily of low molecular weight GTP-binding proteins, including the N-, Ki-, and Ha-ras proteins (30-35% identical), the rho proteins and the rac proteins. The highest degree of sequence identity (80%) is found with the Saccharomyces cerevisiae cell division-cycle protein CDC42. The human placental gene, which they designate CDC42Hs, complements the cdc42-1 mutation in S. cerevisiae, which suggests that this GTP-binding protein is the human homolog of the yeast protein

  1. Human Rights, Human Needs, Human Development, Human Security

    OpenAIRE

    Gasper, Des

    2009-01-01

    Human rights, human development and human security form increasingly important, partly interconnected, partly competitive and misunderstood ethical and policy discourses. Each tries to humanize a pre-existing and unavoidable major discourse of everyday life, policy and politics; each has emerged within the United Nations world; each relies implicitly on a conceptualisation of human need; each has specific strengths. Yet mutual communication, understanding and co-operation are deficient, espec...

  2. 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.

  3. Tumor and placental histaminase. II

    International Nuclear Information System (INIS)

    Wellin, C.; Angellis, D.

    1981-01-01

    Histaminase (diamine oxidase) is an enzyme associated with pregnancy and with a number of human cancers. In pregnancy, the enzyme is produced by the decidual cells of the placenta. Histaminase of the placenta is biochemically and immunologically identical to that of cancer. Based on this, a radioimmunoassay procedure for histaminase has been developed. The high affinity monospecific antiserum for the assay was obtained from rabbits by injecting with homogeneous histaminase purified from placenta by affinity chromatography. Radioactive labelling of histaminase was carried out by iodination with 125 I using chloramine T as the oxidizing agent. The iodination yielded [ 125 I]-histaminase of high specific radioactivity (20 μCi/μg protein) with no apparent affect on the immunologic affinity. For separating the antibody-antigen complex from the unbound antigen, a second antibody bound to polyacrylamide beads was most effective at high antiserum dilutions. The assay had a working range of 0.3 to 80 ng/ml and a minimal detectable quantity of 0.15 ng/ml. Compared to the enzymatic assay with [ 14 C]putrescine as substrate, the radioimmunoassay procedure is about 70 times more sensitive. Measurements of histaminase in placental extracts and malignant effusions using both radioimmunoassay and enzyme assay demonstrated that the two methods were highly correlated, thus providing evidence for the specificity of the radioimmunoassay. This procedure will be useful in future studies of histaminase as a biochemical marker for human cancer and for the elucidation of the significance of this enzyme in pregnancy and in neoplasia. (Auth.)

  4. Maternal undernutrition during the pre- and post-conception periods in twin-bearing hairsheep ewes: effects on fetal and placental development at mid-gestation.

    Science.gov (United States)

    Macías-Cruz, Ulises; Vicente-Pérez, Ricardo; Mellado, Miguel; Correa-Calderón, Abelardo; Meza-Herrera, Cesar A; Avendaño-Reyes, Leonel

    2017-10-01

    To evaluate the effects of pre- and post-conception undernutrition (UN) on fetal and placental development at mid-gestation, 28 Katahdin × Pelibuey multiparous ewes were blocked by weight and assigned to the following four dietary treatments (n = 7 each): ewes fed 100% (control) or 60% of their nutritional requirements 30 days before mating (UNPre), 50 days after mating (UNPost) or during both periods (UNB). Four twin-bearing ewes were selected per treatment at day 50 post-conception and then slaughtered at day 75 of gestation to analyze their fetuses. Control fetuses were heavier (P ewes than UNB ewes, but not relative to ewes of other treatments. The number of placentomes per ewe and placental efficiency were unaffected by UN treatments. Compared to control, only UNB ewes exhibited variations (P ewes than placentas of control ewes (P ewes carrying twins is mainly altered when nutritional restriction occurs simultaneously before conception and during the first third of pregnancy.

  5. Marketing Human Resource Development.

    Science.gov (United States)

    Frank, Eric, Ed.

    1994-01-01

    Describes three human resource development activities: training, education, and development. Explains marketing from the practitioners's viewpoint in terms of customer orientation; external and internal marketing; and market analysis, research, strategy, and mix. Shows how to design, develop, and implement strategic marketing plans and identify…

  6. Cytomegalovirus Infection Triggers the Secretion of the PPARγ Agonists 15-Hydroxyeicosatetraenoic Acid (15-HETE and 13-Hydroxyoctadecadienoic Acid (13-HODE in Human Cytotrophoblasts and Placental Cultures.

    Directory of Open Access Journals (Sweden)

    Kaoutar Leghmar

    Full Text Available Congenital infection by human cytomegalovirus (HCMV is a leading cause of congenital abnormalities of the central nervous system. Placenta infection by HCMV allows for viral spread to fetus and may result in intrauterine growth restriction, preeclampsia-like symptoms, or miscarriages. We previously reported that HCMV activates peroxisome proliferator-activated receptor gamma (PPARγ for its own replication in cytotrophoblasts. Here, we investigated the molecular bases of PPARγ activation in infected cytotrophoblasts.We show that onboarded cPLA2 carried by HCMV particles is required for effective PPARγ activation in infected HIPEC cytotrophoblasts, and for the resulting inhibition of cell migration. Natural PPARγ agonists are generated by PLA2 driven oxidization of linoleic and arachidonic acids. Therefore, using HPLC coupled with mass spectrometry, we disclosed that cellular and secreted levels of 13-hydroxyoctadecadienoic acid (13-HODE and 15-hydroxyeicosatetraenoic acid (15-HETE were significantly increased in and from HIPEC cytotrophoblasts at soon as 6 hours post infection. 13-HODE treatment of uninfected HIPEC recapitulated the effect of infection (PPARγ activation, migration impairment. We found that infection of histocultures of normal, first-term, human placental explants resulted in significantly increased levels of secreted 15-HETE and 13-HODE.Our findings reveal that 15-HETE and 13-HODE could be new pathogenic effectors of HCMV congenital infection They provide a new insight about the pathogenesis of congenital infection by HCMV.

  7. A new recycling technique for human placental cotyledon perfusion: application to studies of the fetomaternal transfer of glucose, inulin, and antipyrine

    International Nuclear Information System (INIS)

    Brandes, J.M.; Tavoloni, N.; Potter, B.J.; Sarkozi, L.; Shepard, M.D.; Berk, P.D.

    1983-01-01

    A previously described technique has been modified to permit the continuously recirculating perfusion of the separate maternal and fetal circulations of an isolated cotyledon of human placenta. Viability of the perfused cotyledons was established by measurements of oxygen consumption (average, 0.18 ml/gm/hr), glucose utilization (average, 1.0 mg/gm/hr), and lactate production (less than 0.01 mumol/gm/hr), and integrity of the placental barrier by the failure of India ink, 125I-albumin, or 35S-sulfobromophthalein to cross from fetal to maternal circulation. Clearance of 3H-inulin from the fetal circuit, 0.0059 +/- 0.0005 (SE) ml/min/gm, corresponded to 2.5% of its clearance by the adult human kidney. Clearance of 14C-antipyrine was 0.013 +/- 0.003 ml/min/gm. After introduction into the fetal circuit, the observed appearance of both inulin and antipyrine in the maternal circuit closely paralleled curves predicted by a simple mathematical model. The use of a continuously recirculating perfusion system is technically feasible, and has advantages over the single-pass technique for studying transplacental transfer of metabolites with a low efficiency of extraction

  8. 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.

  9. Zika virus infection in immunocompetent pregnant mice causes fetal damage and placental pathology in the absence of fetal infection

    Science.gov (United States)

    Kummer, Lawrence W.; Lanthier, Paula; Kim, In-Jeong; Kuki, Atsuo; Thomas, Stephen J.

    2018-01-01

    Zika virus (ZIKV) infection during human pregnancy may cause diverse and serious congenital defects in the developing fetus. Previous efforts to generate animal models of human ZIKV infection and clinical symptoms often involved manipulating mice to impair their Type I interferon (IFN) signaling, thereby allowing enhanced infection and vertical transmission of virus to the embryo. Here, we show that even pregnant mice competent to generate Type I IFN responses that can limit ZIKV infection nonetheless develop profound placental pathology and high frequency of fetal demise. We consistently found that maternal ZIKV exposure led to placental pathology and that ZIKV RNA levels measured in maternal, placental or embryonic tissues were not predictive of the pathological effects seen in the embryos. Placental pathology included trophoblast hyperplasia in the labyrinth, trophoblast giant cell necrosis in the junctional zone, and loss of embryonic vessels. Our findings suggest that, in this context of limited infection, placental pathology rather than embryonic/fetal viral infection may be a stronger contributor to adverse pregnancy outcomes in mice. Our finding demonstrates that in immunocompetent mice, direct viral infection of the embryo is not essential for fetal demise. Our immunologically unmanipulated pregnancy mouse model provides a consistent and easily measurable congenital abnormality readout to assess fetal outcome, and may serve as an additional model to test prophylactic and therapeutic interventions to protect the fetus during pregnancy, and for studying the mechanisms of ZIKV congenital immunopathogenesis. PMID:29634758

  10. [Placental gene activity of significant angiogenetic factors in the background of intrauterine growth restriction].

    Science.gov (United States)

    Kovács, Péter; Rab, Attila; Szentpéteri, Imre; Joó, József Gábor; Kornya, László

    2017-04-01

    Placental vascular endothelial growth factor A (VEGF-A) gene and endoglin gene are both overexpressed in placental samples obtained from pregnancies with intrauterine growth restriction compared to normal pregnancies. In the background of these changes a mechanism can be supposed, in which the increased endoglin activity in intrauterine growth restriction (IUGR) leads to impaired placental circulation through an antioangiogenetic effect. This results in the development of placental vascular dysfunction and chronic fetal hypoxia. It is chronic hypoxia that turns on VEGF-A as a compensatory mechanism to improve fetal vascular blood supply by promoting placental blood vessel formation. Although the maternal serum placental growth factor (PlGF) level is a potential predictor for both IUGR and praeeclampsia, placental PlGF gene activity may be less of an active in the regulation of placental circulation in IUGR pregnancies during the later stages of gestation. Orv. Hetil., 2017, 158(16), 612-617.

  11. Regulation of estradiol and progesterone production by CRH-R1 and -R2 is through divergent signaling pathways in cultured human placental trophoblasts.

    Science.gov (United States)

    Gao, Lu; Tao, Yi; Hu, Tianxiao; Liu, Weina; Xu, Chen; Liu, Jie; You, Xingji; Gu, Hang; Ni, Xin

    2012-10-01

    CRH and its related peptides urocortins (UCN) have been identified in placenta and implicated to play pivotal roles in the regulation of pregnancy and parturition in humans. The objectives of present study were to investigate the effects of endogenous CRH and its related peptides in the regulation of steroid production in placenta. Placental trophoblasts were isolated from term placenta tissues and cultured for 72 h. Estradiol (E(2)) and progesterone (P(4)) contents in culture media were determined by radioimmunoassay. Treatment of cultured trophoblasts with CRH or UCNI antibody showed decreased E(2), whereas increased P(4) production. Treatment of cells with CRH receptor type 1 antagonist antalarmin or CRH receptor type 2 (CRH-R2) antagonist astressin-2b also decreased E(2) but increased P(4) production. Knockdown of CRH receptor type 1 or CRH-R2 cells showed a decrease in E(2) production and an increase in P(4) production. In CRH-R2 knockdown cells, CRH stimulated GTP-bound Gαs protein and phosphorylated phospholipase C-β3. Adenylyl cyclase and protein kinase A inhibitors blocked CRH-induced increased E(2) production but not decreased P(4) production. PLC inhibitor U73122 and protein kinase C inhibitor chelerythrine blocked the effects of CRH on E(2) and P(4) production in CRH-R2 knockdown cells. UCNIII, the specific CRH-R2 agonist, stimulated GTP-bound Gαi protein and phosphorylated phospholipase C-β3 expression. Both U73122 and chelerythrine blocked UCNIII-induced increased E(2) production and decreased P(4) production. We suggest that CRH and its related peptides might be involved in changes in the progesterone to estrogen ratio during human pregnancy.

  12. Development of human locomotion.

    Science.gov (United States)

    Lacquaniti, Francesco; Ivanenko, Yuri P; Zago, Myrka

    2012-10-01

    Neural control of locomotion in human adults involves the generation of a small set of basic patterned commands directed to the leg muscles. The commands are generated sequentially in time during each step by neural networks located in the spinal cord, called Central Pattern Generators. This review outlines recent advances in understanding how motor commands are expressed at different stages of human development. Similar commands are found in several other vertebrates, indicating that locomotion development follows common principles of organization of the control networks. Movements show a high degree of flexibility at all stages of development, which is instrumental for learning and exploration of variable interactions with the environment. Copyright © 2012 Elsevier Ltd. All rights reserved.

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

    Science.gov (United States)

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

    2016-08-29

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

  14. Probability distributions of placental morphological measurements and origins of variability of placental shapes.

    Science.gov (United States)

    Yampolsky, M; Salafia, C M; Shlakhter, O

    2013-06-01

    While the mean shape of human placenta is round with centrally inserted umbilical cord, significant deviations from this ideal are fairly common, and may be clinically meaningful. Traditionally, they are explained by trophotropism. We have proposed a hypothesis explaining typical variations in placental shape by randomly determined fluctuations in the growth process of the vascular tree. It has been recently reported that umbilical cord displacement in a birth cohort has a log-normal probability distribution, which indicates that the displacement between an initial point of origin and the centroid of the mature shape is a result of accumulation of random fluctuations of the dynamic growth of the placenta. To confirm this, we investigate statistical distributions of other features of placental morphology. In a cohort of 1023 births at term digital photographs of placentas were recorded at delivery. Excluding cases with velamentous cord insertion, or missing clinical data left 1001 (97.8%) for which placental surface morphology features were measured. Best-fit statistical distributions for them were obtained using EasyFit. The best-fit distributions of umbilical cord displacement, placental disk diameter, area, perimeter, and maximal radius calculated from the cord insertion point are of heavy-tailed type, similar in shape to log-normal distributions. This is consistent with a stochastic origin of deviations of placental shape from normal. Deviations of placental shape descriptors from average have heavy-tailed distributions similar in shape to log-normal. This evidence points away from trophotropism, and towards a spontaneous stochastic evolution of the variants of placental surface shape features. Copyright © 2013 Elsevier Ltd. All rights reserved.

  15. Potential roles of placental human beta-defensin-3 and apolipoprotein B mRNA-editing enzyme catalytic polypeptide 3G in prevention of intrauterine transmission of hepatitis B virus.

    Science.gov (United States)

    Bai, Xiaoxia; Tian, Ting; Wang, Peng; Yang, Xiaofu; Wang, Zhengping; Dong, Minyue

    2015-03-01

    Approximately 5% of newborns were infected by hepatitis B virus (HBV) via intrauterine transmission and this is the main reason for high prevalence of HBV in endemic regions. However, the mechanisms by which intrauterine transmission is avoided in most cases remain elusive and placental natural anti-microbial factors may play a role in the prevention of HBV intrauterine transmission. The expression levels of human β-defensin-3 (HBD-3), apolipoprotein B mRNA-editing enzyme catalytic polypeptide 3G (A3G) and mannose binding lectin (MBL) were determined in the placenta of 30 HBV-seronegative pregnant women (controls), 7 HBV-seropositive pregnant women with infants infected via intrauterine transmission (infected group) and 30 HBV-seropositive pregnant women with non-infected infants (non-infected group). The expression of HBD-3, A3G, and MBL of placental trophoblast cell line Swan71 was determined after exposed to HBV. There were significant differences in placental HBD-3 and A3G levels among three groups, but the expression of MBL did not significantly differ. The expressions of HBD-3 and A3G were higher in non-infected group than controls and infected group, but not significantly different between infected group and controls. The exposure to HBV increased significantly the expression of HBD-3, A3G, and MBL by Swan 71. It may be concluded HBV up-regulates HBD-3 and A3G expression in vivo and in vitro in placental trophoblast and lack of this up-regulation is possibly associated with intrauterine transmission of HBV. © 2014 Wiley Periodicals, Inc.

  16. Human placental Na+, K+-ATPase α subunit: cDNA cloning, tissue expression, DNA polymorphism, and chromosomal localization

    International Nuclear Information System (INIS)

    Chehab, F.F.; Kan, Y.W.; Law, M.L.; Hartz, J.; Kao, F.T.; Blostein, R.

    1987-01-01

    A 2.2-kilobase clone comprising a major portion of the coding sequence of the Na + , K + -ATPase α subunit was cloned from human placenta and its sequence was identical to that encoding the α subunit of human kidney and HeLa cells. Transfer blot analysis of the mRNA products of the Na + , K + -ATPase gene from various human tissues and cell lines revealed only one band (≅ 4.7 kilobases) under low and high stringency washing conditions. The levels of expression in the tissues were intestine > placenta > liver > pancreas, and in the cell lines the levels were human erythroleukemia > butyrate-induced colon > colon > brain > HeLa cells. mRNA was undetectable in reticulocytes, consistent with the authors failure to detect positive clones in a size-selected ( > 2 kilobases) λgt11 reticulocyte cDNA library. DNA analysis revealed by a polymorphic EcoRI band and chromosome localization by flow sorting and in situ hybridization showed that the α subunit is on the short is on the short arm (band p11-p13) of chromosome 1

  17. 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, especial...

  18. EG-VEGF controls placental growth and survival in normal and pathological pregnancies: case of fetal growth restriction (FGR).

    Science.gov (United States)

    Brouillet, S; Murthi, P; Hoffmann, P; Salomon, A; Sergent, F; De Mazancourt, P; Dakouane-Giudicelli, M; Dieudonné, M N; Rozenberg, P; Vaiman, D; Barbaux, S; Benharouga, M; Feige, J-J; Alfaidy, N

    2013-02-01

    Identifiable causes of fetal growth restriction (FGR) account for 30 % of cases, but the remainders are idiopathic and are frequently associated with placental dysfunction. We have shown that the angiogenic factor endocrine gland-derived VEGF (EG-VEGF) and its receptors, prokineticin receptor 1 (PROKR1) and 2, (1) are abundantly expressed in human placenta, (2) are up-regulated by hypoxia, (3) control trophoblast invasion, and that EG-VEGF circulating levels are the highest during the first trimester of pregnancy, the period of important placental growth. These findings suggest that EG-VEGF/PROKR1 and 2 might be involved in normal and FGR placental development. To test this hypothesis, we used placental explants, primary trophoblast cultures, and placental and serum samples collected from FGR and age-matched control women. Our results show that (1) EG-VEGF increases trophoblast proliferation ([(3)H]-thymidine incorporation and Ki67-staining) via the homeobox-gene, HLX (2) the proliferative effect involves PROKR1 but not PROKR2, (3) EG-VEGF does not affect syncytium formation (measurement of syncytin 1 and 2 and β hCG production) (4) EG-VEGF increases the vascularization of the placental villi and insures their survival, (5) EG-VEGF, PROKR1, and PROKR2 mRNA and protein levels are significantly elevated in FGR placentas, and (6) EG-VEGF circulating levels are significantly higher in FGR patients. Altogether, our results identify EG-VEGF as a new placental growth factor acting during the first trimester of pregnancy, established its mechanism of action, and provide evidence for its deregulation in FGR. We propose that EG-VEGF/PROKR1 and 2 increases occur in FGR as a compensatory mechanism to insure proper pregnancy progress.

  19. Disruption of var2csa gene impairs placental malaria associated adhesion phenotype.

    Directory of Open Access Journals (Sweden)

    Nicola K Viebig

    Full Text Available Infection with Plasmodium falciparum during pregnancy is one of the major causes of malaria related morbidity and mortality in newborn and mothers. The complications of pregnancy-associated malaria result mainly from massive adhesion of Plasmodium falciparum-infected erythrocytes (IE to chondroitin sulfate A (CSA present in the placental intervillous blood spaces. Var2CSA, a member of the P. falciparum erythrocyte membrane protein 1 (PfEMP1 family is the predominant parasite ligand mediating CSA binding. However, experimental evidence suggests that other host receptors, such as hyaluronic acid (HA and the neonatal Fc receptor, may also support placental binding. Here we used parasites in which var2csa was genetically disrupted to evaluate the contribution of these receptors to placental sequestration and to identify additional adhesion receptors that may be involved in pregnancy-associated malaria. By comparison to the wild-type parasites, the FCR3delta var2csa mutants could not be selected for HA adhesion, indicating that var2csa is not only essential for IE cytoadhesion to the placental receptor CSA, but also to HA. However, further studies using different pure sources of HA revealed that the previously observed binding results from CSA contamination in the bovine vitreous humor HA preparation. To identify CSA-independent placental interactions, FCR3delta var2csa mutant parasites were selected for adhesion to the human placental trophoblastic BeWo cell line. BeWo selected parasites revealed a multi-phenotypic adhesion population expressing multiple var genes. However, these parasites did not cytoadhere specifically to the syncytiotrophoblast lining of placental cryosections and were not recognized by sera from malaria-exposed women in a parity dependent manner, indicating that the surface molecules present on the surface of the BeWo selected population are not specifically expressed during the course of pregnancy-associated malaria. Taken

  20. 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.

  1. Induction of glutathione S-transferase placental form positive foci in liver and epithelial hyperplasia in urinary bladder, but no tumor development in male Fischer 344 rats treated with monomethylarsonic acid for 104 weeks

    International Nuclear Information System (INIS)

    Shen Jun; Wanibuchi, Hideki; Salim, Elsayed I.; Wei Min; Doi, Kenichiro; Yoshida, Kaoru; Endo, Ginji; Morimura,; Fukushima, Shoji

    2003-01-01

    The carcinogenicity of monomethylarsonic acid (MMA(V)), a major metabolite of inorganic arsenics in human and experimental animals, was investigated in male Fischer 344 rats. A total of 129 rats at 10 weeks of age were randomly divided into three groups and received drinking water containing MMA(V) at doses of 0 (Control), 50, and 200 ppm ad libitum for 104 weeks. No significant differences were found between the control and the MMA(V)-treated groups regarding clinical signs, mortality, hematological, and serum biochemistry findings. Quantitative analysis of glutathione S-transferase placental form (GST-P) positive foci in liver revealed a significant increase of numbers and areas in the 200 ppm MMA(V)-treated group. In the urinary bladder MMA(V) induced simple hyperplasia and significantly elevated the proliferating cell nuclear antigen (PCNA)-positive index in the urothelium. A variety of tumors developed in rats of all groups, including the controls, but all were histologically similar to those known to occur spontaneously in F344 rats and there were no significant differences among the groups. Thus, it could be concluded that, under the present experimental conditions, MMA(V) induced lesions in the liver and urinary bladder, but did not cause tumor development in male F344 rats even after 2 years exposure

  2. 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.

  3. 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

  4. Moderate folic acid supplementation and MTHFD1-synthetase deficiency in mice, a model for the R653Q variant, result in embryonic defects and abnormal placental development.

    Science.gov (United States)

    Christensen, Karen E; Hou, Wenyang; Bahous, Renata H; Deng, Liyuan; Malysheva, Olga V; Arning, Erland; Bottiglieri, Teodoro; Caudill, Marie A; Jerome-Majewska, Loydie A; Rozen, Rima

    2016-11-01

    incidence of defects in embryos. Although maternal circulating methylTHF was higher, it may not have reached the embryos because of abnormal placental development; abnormal placentas were observed predominantly in abnormally developed embryos. These findings have implications for women with high folate intakes, particularly if they are polymorphic for MTHFD1 R653Q. © 2016 American Society for Nutrition.

  5. Revisited the relationship between vitamin D level and receptors of BsmI- gene polymorphism with the pathogenetic mechanisms of placental dysfunction development

    Directory of Open Access Journals (Sweden)

    G. S. Manasova

    2018-03-01

    Full Text Available The role of the calcitriol / vitamin D receptor (VD endocrine system and the pleiotropic effects of this system in the pathogenetic mechanisms of various diseases development, in particular complications of pregnancy, has attracted researches’ increasing attention in recent years. The aim of the work: to compare the VD-status and frequency of occurrence of polymorphism of the VDR gene (BsmI (A> G, rs1544410 in patients with a physiological course of the gestation process and in patients with placental dysfunction (PD. Materials and methods. 56 pregnant women with PD (the main group and 40 patients with a physiological pregnancy (control group were examined. VD status was determined by ELISA at level 25 (OH D in serum, the frequency of BsmI polymorphism of the VDR gene (rs1544410 by polymerase chain reaction (PCR. Results. The average index of VD (31.40 ± 8.6 ng / ml in patients with PD is significantly lower than in patients with physiological pregnancy (43.54 ± 11.20 ng / ml, (p ≤ 0.05 . In patients with PD, homozygous carrier for the A-allele was found in 12% of cases, in healthy pregnant women - in 16.7%, (р ≥ 0.05, for the G-allele - in 20% and 47.20%, (р ≤ 0.01 cases, respectively to groups. Heterozygous combination of A / G alleles was noted in 68% of patients with PD and in 36.10% of the control group patients. In pregnant women with BsmI polymorphism of calcitriol gene (genotype A / G PD was 3.7 times more frequent (68% vs 36.10% : RR = 2.1, CI 1.0-6.6, OR = 3.7, CI 1.1-13.1. Conclusions. Vitamin D insufficiency or deficiency can be one of the reasons of PD formation. In carriers of BsmIgene’s polymorphism encoding VD receptor with genotype A / G, the course of pregnancy is complicated by placental dysfunction 3.7 times more often than in women without this polymorphism.

  6. Human Rights, Human Needs, Human Development, Human Security - Relationships between four international human discourses.

    NARCIS (Netherlands)

    D.R. Gasper (Des)

    2007-01-01

    markdownabstractAbstract: Human rights, human development and human security form increasingly important, partly interconnected, partly competitive and misunderstood ethical and policy discourses. Each tries to humanize a pre-existing and unavoidable major discourse of everyday life, policy and

  7. Placental methylome analysis from a prospective autism study.

    Science.gov (United States)

    Schroeder, Diane I; Schmidt, Rebecca J; Crary-Dooley, Florence K; Walker, Cheryl K; Ozonoff, Sally; Tancredi, Daniel J; Hertz-Picciotto, Irva; LaSalle, Janine M

    2016-01-01

    Autism spectrum disorders (ASD) are increasingly prevalent neurodevelopmental disorders that are behaviorally diagnosed in early childhood. Most ASD cases likely arise from a complex mixture of genetic and environmental factors, an interface where the epigenetic marks of DNA methylation may be useful as risk biomarkers. The placenta is a potentially useful surrogate tissue characterized by a methylation pattern of partially methylated domains (PMDs) and highly methylated domains (HMDs) reflective of methylation patterns observed in the early embryo. In this study, we investigated human term placentas from the MARBLES (Markers of Autism Risk in Babies: Learning Early Signs) prospective study by whole genome bisulfite sequencing. We also examined the utility of PMD/HMDs in detecting methylation differences consistent with ASD diagnosis at age three. We found that while human placental methylomes have highly reproducible PMD and HMD locations, there is a greater variation between individuals in methylation levels over PMDs than HMDs due to both sampling and individual variability. In a comparison of methylation differences in placental samples from 24 ASD and 23 typically developing (TD) children, a HMD containing a putative fetal brain enhancer near DLL1 was found to reach genome-wide significance and was validated for significantly higher methylation in ASD by pyrosequencing. These results suggest that the placenta could be an informative surrogate tissue for predictive ASD biomarkers in high-risk families.

  8. Effects from placental exposure

    Energy Technology Data Exchange (ETDEWEB)

    Kawamoto, S [Radiation Effect Research Foundation, Hiroshima (Japan)

    1975-12-01

    Investigations of the effects on the people who had received placental exposure at either Hiroshima or Nagasaki were discussed. All of the subjects were children who had been born at either Hiroshima or Nagasaki between noon of 31, May, 1946 and the atomic-bomb detornation. Deaths of embryos and neonates were determined by the radiation dosage and the growth phase of embryos. Bifid uvula and a slight decrease of number of lumbar vertebra were observed in 14 males and 3 females at Nagasaki. Mental deficiency occurred in 25% of the children whose mothers had received radiation at Nagasaki, and in 8% at Hiroshima. The occurrence of microcephaly was high at both places in the children who had received placental exposure of more than 150 rad. A significant retardation of growth was observed in those who had had a high radiation dosage. Congenitally abnormal persistence of pupillary membrane was very frequently observed in the group which had received a high dosage of radiation. Concerning progeria, mortality of infants under one year of age was increased in the group which had received a high dosage of radiation, but mortality statistics should continue to be observed.

  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. Selenomethionine Uptake Test as a Sensitive Indicator of Placental Function in the Last Trimester of Pregnancy

    Energy Technology Data Exchange (ETDEWEB)

    Garrow, J. S. [Medical Research Council, Department of Obstetrics, Royal Free Hospital, London (United Kingdom)

    1971-02-15

    During the last trimester of pregnancy the demands of the human foetus for nutrients can only just be met by the normal placenta. If the placenta is damaged or poorly developed foetal growth is impaired or, in severe cases, the baby dies. It is clinically important to detect placental failure as early as possible so that the underlying cause can be treated, or if this is not possible the baby can be delivered before term. {sup 75}Se-selenomethionine is one of the amino-acids which is taken up by the placenta from the mother's blood and actively transported against a concentration gradient to the foetus. In the selenomethionine uptake test two 3-in. diameter Nal detectors in cylindrical collimators are used; one is positioned over the mother's mediastinum and the other over her uterus. The output from each detector is fed through a pulse-height analyser to a recording ratemeter. A dose of 2 {mu}Ci of selenomethionine is given intravenously to the mother, and from the recorded count-rates during the next 15 minutes the efficiency of placental amino-acid transport can be assessed. The maximum radiation dose to the mother or foetus is 20 mrad. This test has been applied without ill effects to over 500 patients in whom there were clinical grounds for suspecting placental damage. Gross placental failure and intrauterine death were invariably associated with a very low selenomethionine-uptake over the uterus, and high uterine uptakes were always associated with good placental function. Misleading results may be obtained in cases with rhesus immunization or congenital defect in the foetus, since in such cases foetal growth failure is not due to a defect of transport in the placenta. Generally the test provides a quick, simple and reliable indication of the nutritive function of the placenta, and can be safely used to select those mothers who need particularly careful clinical management. (author)

  11. Developing human technology curriculum

    Directory of Open Access Journals (Sweden)

    Teija Vainio

    2012-10-01

    Full Text Available During the past ten years expertise in human-computer interaction has shifted from humans interacting with desktop computers to individual human beings or groups of human beings interacting with embedded or mobile technology. Thus, humans are not only interacting with computers but with technology. Obviously, this shift should be reflected in how we educate human-technology interaction (HTI experts today and in the future. We tackle this educational challenge first by analysing current Master’s-level education in collaboration with two universities and second, discussing postgraduate education in the international context. As a result, we identified core studies that should be included in the HTI curriculum. Furthermore, we discuss some practical challenges and new directions for international HTI education.

  12. Human Development and Economic Growth

    OpenAIRE

    Ranis, Gustav

    2004-01-01

    Recent literature has contrasted Human Development, described as the ultimate goal of the development process, with economic growth, described as an imperfect proxy for more general welfare, or as a means toward enhanced human development. This debate has broadened the definitions and goals of development but still needs to define the important interrelations between human development (HD) and economic growth (EG). To the extent that greater freedom and capabilities improve economic performan...

  13. Soluble FLT-1 rules placental destiny.

    Science.gov (United States)

    Yamashita, Michiko; Kumasawa, Keiichi; Nakamura, Hitomi; Kimura, Tadashi

    2018-02-19

    Placenta previa is an abnormality in which the placenta covers the internal uterine os, and it can cause serious morbidity and mortality in both mother and fetus due to catastrophic hemorrhage. Some pregnant women recover from placenta previa due to a phenomenon called "migration." However, the mechanism of "migration" of the placenta has not been elucidated. Human placentas were collected from patients with placenta previa and those with no abnormal placentation (control). A microarray analysis was performed to detect the genes up- or down-regulated only in the caudal part in the previa group. Specific mRNA expression was evaluated using real-time quantitative reverse transcription PCR (qRT-PCR). Unilateral uterine artery ablation of 8.5 dpc mice was performed to reproduce the reduction of placental blood supply, and weights of the placentas and fetuses were evaluated in 18.5 dpc. Specific mRNA expression was also evaluated in mice placentas. According to the result of the microarray analysis, we focused on soluble fms-like tyrosine kinase-1 (sFLT-1) and hypoxia-inducible factor-1 (HIF-1) alpha. The sFLT-1 expression level is locally high in the caudal part of the human placenta in patients with placenta previa. In mice experiments, the weights of the placentas and fetuses were significantly smaller in the ablation side than those in the control side, and the sFlt-1 expression level was significantly higher in the ablation side than in the control side. Our study suggests that "migration" of the placenta is derived from placental degeneration at the caudal part of the placenta, and sFlt-1 plays a role in this placental degeneration. Copyright © 2018 Elsevier Inc. All rights reserved.

  14. Is Placental Mitochondrial Function a Regulator that Matches Fetal and Placental Growth to Maternal Nutrient Intake in the Mouse?

    Directory of Open Access Journals (Sweden)

    Marcos R Chiaratti

    Full Text Available Effective fetal growth requires adequate maternal nutrition coupled to active transport of nutrients across the placenta, which, in turn requires ATP. Epidemiological and experimental evidence has shown that impaired maternal nutrition in utero results in an adverse postnatal phenotype for the offspring. Placental mitochondrial function might link maternal food intake to fetal growth since impaired placental ATP production, in response to poor maternal nutrition, could be a pathway linking maternal food intake to reduced fetal growth.We assessed the effects of maternal diet on placental water content, ATP levels and mitochondrial DNA (mtDNA content in mice at embryonic (E day 18 (E18. Females maintained on either low- (LPD or normal- (NPD protein diets were mated with NPD males.Fetal dry weight and placental efficiency (embryo/placental fresh weight were positively correlated (r = 0.53, P = 0.0001. Individual placental dry weight was reduced by LPD (P = 0.003, as was the expression of amino acid transporter Slc38a2 and of growth factor Igf2. Placental water content, which is regulated by active transport of solutes, was increased by LPD (P = 0.0001. However, placental ATP content was also increased (P = 0.03. To investigate the possibility of an underlying mitochondrial stress response, we studied cultured human trophoblast cells (BeWos. High throughput imaging showed that amino acid starvation induces changes in mitochondrial morphology that suggest stress-induced mitochondrial hyperfusion. This is a defensive response, believed to increase mitochondrial efficiency, that could underlie the increase in ATP observed in placenta.These findings reinforce the pathophysiological links between maternal diet and conceptus mitochondria, potentially contributing to metabolic programming. The quiet embryo hypothesis proposes that pre-implantation embryo survival is best served by a relatively low level of metabolism. This may extend to post

  15. Developing Human Resources through Actualizing Human Potential

    Science.gov (United States)

    Clarken, Rodney H.

    2012-01-01

    The key to human resource development is in actualizing individual and collective thinking, feeling and choosing potentials related to our minds, hearts and wills respectively. These capacities and faculties must be balanced and regulated according to the standards of truth, love and justice for individual, community and institutional development,…

  16. Measurement of Placental Blood Flow with {sup 133}Xe in Normal and Pathological Human Pregnancy; Mesure du Debit Placentaire dans les Grossesses Normales et Pathologiques

    Energy Technology Data Exchange (ETDEWEB)

    Pontonnier, G.; Delmas, H.; Farre, J.; Favretto, R. [Clinique Obstetricale, Hopital de la Grave, Toulouse (France)

    1971-02-15

    Most authors agree that changes in placental circulation play an important part in the genesis of chronic foetal disorders. However, until recently there was no technique by which a quantitative evaluation of placental haemodynamics could be obtained. Our method of measuring placental blood flow represents one application of the use of radioisotopes for measurements of local blood flows. We use {sup 133}Xe in solution in physiological serum. This radioactive gas has the advantage of being inert and instantly diffusible. After radiographic or ultrasonic localization of the placenta, 50 {mu}Ci of xenon are injected into it transabdominally. A scintillation detector is used to take the {sup 133}Xe clearance curve, which is recorded simultaneously on a linear writer and transmitted to a computer. We have made 111 measurements of placental blood flow - 45 in normal pregnancy, 59 in pathological pregnancy and 7 after perfusion of medication. The measurements made it possible to obtain, for the first time, a quantitative evaluation of placental blood flow in women. The value found for normal pregnancies between the thirty-second and the forty-first weeks was 145 ml/100 g per min. The measurements carried out in pathologically pregnant patients (with arterial hypertension, dysgravidity, urinary infection, diabetes, prolonged pregnancy) showed that such pregnancies are accompanied by a statistically significant diminution of placental blood flow, and that the magnitude of this diminution has a bearing on the clinical condition and the state of the child at birth. This method of measurement, which is easily reproducible in the same patient, is accordingly of interest from two points of view. As far as theoretical studies are concerned, it has made possible a quantitative evaluation of placental blood flow and has supplied proof that the maternal disorders which give rise to chronic foetal disorders are usually accompanied by a diminution in placental blood flow. From the

  17. 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.

  18. PLACENTAL WEIGHT AND ITS ASSOCIATION WITH MATERNAL AND NEONATAL CHARACTERISTICS

    Directory of Open Access Journals (Sweden)

    M Asgharnia

    2008-12-01

    Full Text Available "nPlacenta plays a vital role in normal fetal development and failure of placenta to gain weight and insufficiency of its function can result in fetal disorders. We performed this study to determine placental weight and factors associated with low weight placentas. In a longitudinal cross-sectional study, women with single pregnancy, and gestational age between 37-42 weeks were studied. The subjects were categorized in high (> 750 g, normal (330-750 g, and low placental weights (< 330 g. The placental weight, birth weight, maternal age, gestational age, parity, pre-eclampsia, history of maternal diabetes, delivery approaches, infants' gender; and Apgar score in 5th minutes after delivery were examined. One thousand-eighty eight pregnant women were included in the study. The mean and standard deviation for maternal ages and gestational ages at deliveries were 25.35 ± 5.6 and 247.51 ± 9.56 days, respectively. The mean and standard deviation of neonates' weights at birth and placental weights were 3214.28 ± 529 and 529.72 ± 113 g, respectively. The prevalences of low and high placental weights were 2% and 2.8%, respectively. There were statistically significant relationships between placental weight and birth weight, fetal distress, Apgar score, maternal diabetes, pre-eclampsia and approaches of deliveries (α = 0.05. Our findings indicate that placental weight can be associated with important variables influencing some maternal and neonatal outcomes and placental weight lower than 330 g can be a warning sign. Careful attention to placenta growth during pregnancy, for example by ultrasonography, can guide physicians to assess neonatal health.

  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. [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.

  1. Melatonin improves placental efficiency and birth weight and increases the placental expression of antioxidant enzymes in undernourished pregnancy.

    Science.gov (United States)

    Richter, Hans G; Hansell, Jeremy A; Raut, Shruti; Giussani, Dino A

    2009-05-01

    Melatonin participates in circadian, seasonal and reproductive physiology. Melatonin also acts as a potent endogenous antioxidant by scavenging free radicals and upregulating antioxidant pathways. The placenta expresses melatonin receptors and melatonin protects against oxidative damage induced in rat placenta by ischemia-reperfusion. One of the most common complications in pregnancy is a reduction in fetal nutrient delivery, which is known to promote oxidative stress. However, whether melatonin protects placental function and fetal development in undernourished pregnancy is unknown. Here, we investigated the effects of maternal treatment with melatonin on placental efficiency, fetal growth, birth weight and protein expression of placental oxidative stress markers in undernourished pregnancy. On day 15 of pregnancy, rats were divided into control and undernourished pregnancy (35% reduction in food intake), with and without melatonin treatment (5 microg/mL drinking water). On day 20 of gestation, fetal biometry was carried out, the placenta was weighed and subsequently analyzed by Western blot for xanthine oxidase, heat shock protein (HSP) 27 and 70, catalase, manganese superoxide dismutase (Mn-SOD) and glutathione peroxidase 1 (GPx-1). A separate cohort was allowed to deliver to assess effects on birth weight. Maternal undernutrition led to a fall in placental efficiency, disproportionate intrauterine growth retardation and a reduction in birth weight. Maternal treatment with melatonin in undernourished pregnancy improved placental efficiency and restored birth weight, and it increased the expression of placental Mn-SOD and catalase. The data show that in pregnancy complicated by undernutrition, melatonin may improve placental efficiency and birth weight by upregulating placental antioxidant enzymes.

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

    DEFF Research Database (Denmark)

    Brøgger, Torbjørn; Forman, Axel; Aalkjær, Christian

    2014-01-01

    is available. In-depth understanding of the mechanisms involved in control of placental vascular tone are needed to develop new tissue targets for therapeutic intervention. Method: From fresh born placentas segments of stem villous arteries were carefully dissected. The artery branches were divided....... The surrounding trophoblast was removed from one end and left intact in the other, and the segment was divided to give two ring preparations, with or without trophoblast. The preparations were mounted in wire myographs and responses to vasoactive agents were compared. Results: pD2values for PGF2α, Tx-analog U...... or endotheline-1. These differences partly disappeared in the presence of L-NAME. Conclusion: The perivascular tissue significantly reduces sensitivity and force development of stem villous arteries, partly due to release of NO This represents a new mechanism for control of human stem villous artery tone....

  3. 2011 and 2012 Early Careers Achievement Awards: Placental programming: how the maternal environment can impact placental function.

    Science.gov (United States)

    Vonnahme, K A; Lemley, C O; Shukla, P; O'Rourke, S T

    2013-06-01

    Proper establishment of the placenta is important for fetal survival; however, placental adaptations to inadequate maternal nutrition or other stressors are imperative for fetal growth to be optimal. The effects of maternal nutritional status and activity level on placental vascular function and uteroplacental blood flows are important to understand as improper placental function leads to reduced growth of the fetus. In environments where fetal growth can be compromised, potential therapeutics may augment placental function and delivery of nutrients to improve offspring performance during postnatal life. Factors that could enhance placental function include supplementation of specific nutrients, such as protein, hormone supplements, such as indolamines, and increased activity levels of the dam. To understand the mechanism of how the maternal environment can impact uterine or umbilical blood flows, assessment of placental vascular reactivity has been studied in several large animal models. As we begin to understand how the maternal environment impacts uterine and umbilical blood flows and other uteroplacental hemodynamic parameters, development of management methods and therapeutics for proper fetal growth can be achieved.

  4. Placental Barrier and Autism Spectrum Disorders: The Role of Prolactin and Dopamine on the Developing Fetal Brain.

    Science.gov (United States)

    Yarlagadda, Atmaram; Acharya, Ganesh; Kasaraneni, Jayaprada; Hampe, Christiane S; Clayton, Anita H

    2015-01-01

    Dopamine and prolactin exhibit opposite effects on lactation. However, a possible role for increased prolactin/dopamine ratio in postpartum mood and thought disorders and as a prognostic indicator of the mother's future mental health has not been well investigated. Postpartum depression is a serious condition with potentially devastating outcomes for both the mother and the infant. Early detection and treatment of this condition can have impressive results. Treatment options include antidepressant medications for mood disorders and use of antipsychotics and electroconvulsive therapy to address postpartum psychosis. Although there are obvious benefits of such treatments on the welfare of the mother and her child, broader implications of these treatments on lactation and child growth and development are not known. This review article explores a possible link between in-utero exposure to a high maternal prolactin/dopamine ratio and subsequent development of autism spectrum disorders. We hypothesize that a comprehensive, biologically oriented approach to the use of psychotropics in the regulation of neurotransmission during pre- and postpartum periods may result in better outcomes in this population.

  5. 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

  6. A Brief Account of the Discovery of the Fetal/Placental Unit for Estrogen Production in Equine and Human Pregnancies: Relation to Human Medicine.

    Science.gov (United States)

    Raeside, James I

    2017-09-01

    The role of steroids in human medicine is well recognized, but the major contributions made by the large domestic animals as a source of material in the discovery, isolation, and determination of the structure of the steroid hormones is less well appreciated. After a brief reminder of the early efforts to obtain a reliable source of steroids for clinical use, the narrative here is to outline one example where success was ultimately achieved for estrogen replacement therapy. Whereas knowledge of the high concentrations of estrogens in urine of pregnant women and mares dates from the late 1920s, it was not until the 1940s that the latter was shown to be a practical source. Initially, the placenta was held to be responsible, but the involvement of the fetus in each case was eventually established. The remarkable enlargement of the human fetal adrenal glands and the fetal gonads in the horse, with characteristic features of steroid secreting tissues, suggested their participation. Ultimately, it was 16-hydroxylation by the fetal liver that resulted in estriol being the major estrogen type, by far, in late human pregnancy. In the mare, the pattern of estrogen production reflected that of the growth and later regression of the fetal gonads. The characteristic production ring-B, unsaturated estrogens in the mare is derived from an alternative pathway involving retention of the additional double bond in the biosynthesis of equilin.

  7. Relationship between Plasma D-Dimer Concentration and Three-Dimensional Ultrasound Placental Volume in Women at Risk for Placental Vascular Diseases: A Monocentric Prospective Study.

    Directory of Open Access Journals (Sweden)

    Cécile Fanget

    Full Text Available The aim of this study was to correlate placental volumes deduced from three-dimensional ultrasound and virtual organ computer-aided analysis (VOCAL software with systemic concentrations of D-dimer and soluble endothelial protein C receptor (sEPCR.This was a monocentric experimental prospective study conducted from October 2008 to July 2009. Forty consecutive patients at risk of placental vascular pathology (PVP recurrence or occurrence were included. Placental volumes were systematically measured three times (11-14, 16-18 and 20-22 weeks of gestation (WG by two independent sonographers. D-dimers and sEPCR plasma concentrations were measured using ELISA kits (Enzyme Linked ImmunoSorbent Assay.Eleven patients had a PVP. The plasma D-dimer level was positively correlated with placental volume (r = 0.45, p < 0.001. A smaller placental volume and placental quotient was evidenced in women who developed a PVP at the three gestational ages, and the difference was more pronounced during the third exam (20 WG. No obvious correlation could be demonstrated between the development of a PVP and the levels of D-dimer and sEPCR. There was no significant difference in the values of placental volumes measured by the two sonographers.The placenta growth could be a major determinant of the elevation of D-dimer during pregnancy. Consideration of placental volume could allow for modulation of the D-dimer concentrations for restoring their clinical interest.

  8. Human Rights, Human Needs, Human Development, Human Security : Relationships between four international 'human' discourses

    NARCIS (Netherlands)

    D.R. Gasper (Des)

    2007-01-01

    textabstractHuman rights, human development and human security form increasingly important, partly interconnected, partly competitive and misunderstood ethical and policy discourses. Each tries to humanize a pre-existing and unavoidable major discourse of everyday life, policy and politics; each

  9. Gender equity & human development.

    Science.gov (United States)

    Vepa, Swarna S

    2007-10-01

    The welfare of both women and men constitutes the human welfare. At the turn of the century amidst the glory of unprecedented growth in national income, India is experiencing the spread of rural distress. It is mainly due to the collapse of agricultural economy. Structural adjustments and competition from large-scale enterprises result in loss of rural livelihoods. Poor delivery of public services and safety nets, deepen the distress. The adverse impact is more on women than on men. This review examines the adverse impact of the events in terms of endowments, livelihood opportunities and nutritional outcomes on women in detail with the help of chosen indicators at two time-periods roughly representing mid nineties and early 2000. The gender equality index computed and the major indicators of welfare show that the gender gap is increasing in many aspects. All the aspects of livelihoods, such as literacy, unemployment and wages now have larger gender gaps than before. Survival indicators such as juvenile sex ratio, infant mortality, child labour have deteriorated for women, compared to men, though there has been a narrowing of gender gaps in life expectancy and literacy. The overall gender gap has widened due to larger gaps in some indicators, which are not compensated by the smaller narrowing in other indicators both in the rural and urban context.

  10. 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.

  11. Embodiment and Human Development.

    Science.gov (United States)

    Marshall, Peter J

    2016-12-01

    We are recognizing increasingly that the study of cognitive, social, and emotional processes must account for their embodiment in living, acting beings. The related field of embodied cognition (EC) has coalesced around dissatisfaction with the lack of attention to the body in cognitive science. For developmental scientists, the emphasis in the literature on adult EC on the role of the body in cognition may not seem particularly novel, given that bodily action was central to Piaget's theory of cognitive development. However, as the influence of the Piagetian account waned, developmental notions of embodiment were shelved in favor of mechanical computational approaches. In this article, I argue that by reconsidering embodiment, we can address a key issue with computational accounts: how meaning is constructed by the developing person. I also suggest that the process-relational approach to developmental systems can provide a system of concepts for framing a fully embodied, integrative developmental science.

  12. 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

    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....

  13. Early studies of placental ultrastructure by electron microscopy

    DEFF Research Database (Denmark)

    Carter, A M; Enders, A C

    2016-01-01

    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......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...

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

    DEFF Research Database (Denmark)

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

    2010-01-01

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

  15. Placental adaptations to micronutrient dysregulation in the programming of chronic disease.

    Science.gov (United States)

    Hofstee, Pierre; McKeating, Daniel; Perkins, Anthony V; Cuffe, James S M

    2018-04-21

    Poor nutrition during pregnancy is known to impair foetal development and increase the risk of chronic disease in offspring. Both macronutrients and micronutrients are required for a healthy pregnancy although significantly less is understood about the role of micronutrients in the programming of chronic disease. This is despite the fact that modern calorie rich diets are often also deficient in key micronutrients. The importance of micronutrients in gestational disorders is clearly understood but how they impact long term disease in humans requires further investigation. In contrast, animal studies have demonstrated how diets high or low in specific micronutrients influence offspring physiology. Many of these studies highlight the importance of the placenta in determining disease risk. This review will explore the effects of individual vitamins, minerals and trace elements on offspring disease outcomes and discuss several key placental adaptations that are affected by multiple micronutrients. These placental adaptations include micronutrient induced dysregulation of oxidative stress, altered methyl donor availability and its impact on epigenetic mechanisms as well as endocrine dysfunction. Critical gaps in our current knowledge and the relative importance of different micronutrients at different gestational ages will also be highlighted. Finally, this review will discuss the need for further studies to characterise the micronutrient status of Australian women of reproductive age and correlate micronutrient status to placental adaptations, pregnancy complications and offspring disease. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.

  16. Review: Alterations in placental glycogen deposition in complicated pregnancies: Current preclinical and clinical evidence.

    Science.gov (United States)

    Akison, Lisa K; Nitert, Marloes Dekker; Clifton, Vicki L; Moritz, Karen M; Simmons, David G

    2017-06-01

    Normal placental function is essential for optimal fetal growth. Transport of glucose from mother to fetus is critical for fetal nutrient demands and can be stored in the placenta as glycogen. However, the function of this glycogen deposition remains a matter of debate: It could be a source of fuel for the placenta itself or a storage reservoir for later use by the fetus in times of need. While the significance of placental glycogen remains elusive, mounting evidence indicates that altered glycogen metabolism and/or deposition accompanies many pregnancy complications that adversely affect fetal development. This review will summarize histological, biochemical and molecular evidence that glycogen accumulates in a) placentas from a variety of experimental rodent models of perturbed pregnancy, including maternal alcohol exposure, glucocorticoid exposure, dietary deficiencies and hypoxia and b) placentas from human pregnancies with complications including preeclampsia, gestational diabetes mellitus and intrauterine growth restriction (IUGR). These pregnancies typically result in altered fetal growth, developmental abnormalities and/or disease outcomes in offspring. Collectively, this evidence suggests that changes in placental glycogen deposition is a common feature of pregnancy complications, particularly those associated with altered fetal growth. Crown Copyright © 2017. Published by Elsevier Ltd. All rights reserved.

  17. New Humanism and Sustainable Development

    Directory of Open Access Journals (Sweden)

    Han d'Orville

    2015-10-01

    Full Text Available The call for a new humanism in the 21st century roots in the conviction that the moral, intellectual and political foundations of globalization and international cooperation have to be rethought. Whilst the historic humanism was set out to resolve tensions between tradition and modernity and to reconcile individual rights with newly emerging duties of citizenship, the new humanism approach goes beyond the level of the nation state in seeking to unite the process of globalization with its complex and sometimes contradictory manifestations. The new humanism therefore advocates the social inclusion of every human being at all levels of society and underlines the transformative power of education, sciences, culture and communications. Therefore, humanism today needs to be perceived as a collective effort that holds governments, civil society, the private sector and human individuals equally responsible to realize its values and to design creatively and implement a humanist approach to a sustainable society, based on economic, social and environmental development. New humanism describes the only way forward for a world that accounts for the diversity of identities and the heterogeneity of interests and which is based on inclusive, democratic, and, indeed, humanist values. Humanism did evolve into the grand movement of human spiritual and creative liberation, which enabled an unparalleled acceleration of prosperity and transformation of civilizations. In line with humanist ethics, the material growth was understood as a collective good, which was to serve all participants of a community and meant to enable the socio-economic progress of society. The exact definition of humanism has historically fluctuated in accordance with successive and diverse strands of intellectual thought. The underlying concept rests on the universal ideas of human emancipation, independence and social justice. Humanism can hence be understood as a moral inspiration for

  18. Angiogenesis inhibition causes hypertension and placental dysfunction in a rat model of preeclampsia

    DEFF Research Database (Denmark)

    Carlström, Mattias; Wentzel, Parri; Skøtt, Ole

    2009-01-01

    in the mesometrial triangle was smaller in the pregnant Suramin-treated rats group than in the pregnant control rats group. CONCLUSION: The inhibition of uterine angiogenesis increases maternal blood pressure and compromises fetal and placental development. Placental hypoxia and subsequent activation of the renin...

  19. High-Throughput Testing of Antibody-Dependent Binding Inhibition of Placental Malaria Parasites

    DEFF Research Database (Denmark)

    Nielsen, Morten A; Salanti, Ali

    2015-01-01

    The particular virulence of Plasmodium falciparum manifests in diverse severe malaria syndromes as cerebral malaria, severe anemia and placental malaria. The cause of both the severity and the diversity of infection outcome, is the ability of the infected erythrocyte (IE) to bind a range......-throughput assay used in the preclinical and clinical development of a VAR2CSA based vaccine against placental malaria....

  20. Placental Dysfunction Underlies Increased Risk of Fetal Growth Restriction and Stillbirth in Advanced Maternal Age Women.

    Science.gov (United States)

    Lean, Samantha C; Heazell, Alexander E P; Dilworth, Mark R; Mills, Tracey A; Jones, Rebecca L

    2017-08-29

    Pregnancies in women of advanced maternal age (AMA) are susceptible to fetal growth restriction (FGR) and stillbirth. We hypothesised that maternal ageing is associated with utero-placental dysfunction, predisposing to adverse fetal outcomes. Women of AMA (≥35 years) and young controls (20-30 years) with uncomplicated pregnancies were studied. Placentas from AMA women exhibited increased syncytial nuclear aggregates and decreased proliferation, and had increased amino acid transporter activity. Chorionic plate and myometrial artery relaxation was increased compared to controls. AMA was associated with lower maternal serum PAPP-A and sFlt and a higher PlGF:sFlt ratio. AMA mice (38-41 weeks) at E17.5 had fewer pups, more late fetal deaths, reduced fetal weight, increased placental weight and reduced fetal:placental weight ratio compared to 8-12 week controls. Maternofetal clearance of 14 C-MeAIB and 3 H-taurine was reduced and uterine arteries showed increased relaxation. These studies identify reduced placental efficiency and altered placental function with AMA in women, with evidence of placental adaptations in normal pregnancies. The AMA mouse model complements the human studies, demonstrating high rates of adverse fetal outcomes and commonalities in placental phenotype. These findings highlight placental dysfunction as a potential mechanism for susceptibility to FGR and stillbirth with AMA.

  1. Creative Trade for Human Development

    OpenAIRE

    Kabanda, Patrick

    2016-01-01

    In recent years, international trade in creative goods and services has been expanding. But this upward march is not lifting all boats. Although many developing countries are endowed with vast cultural wealth, they still lag behind. In addition, women are not faring well. Much needs to be done to expand creative trade for human development. Suggestions here include implementing a Women Art...

  2. Extracellular RNAs: development as biomarkers of human disease

    Directory of Open Access Journals (Sweden)

    Joseph F. Quinn

    2015-08-01

    Full Text Available Ten ongoing studies designed to test the possibility that extracellular RNAs may serve as biomarkers in human disease are described. These studies, funded by the NIH Common Fund Extracellular RNA Communication Program, examine diverse extracellular body fluids, including plasma, serum, urine and cerebrospinal fluid. The disorders studied include hepatic and gastric cancer, cardiovascular disease, chronic kidney disease, neurodegenerative disease, brain tumours, intracranial haemorrhage, multiple sclerosis and placental disorders. Progress to date and the plans for future studies are outlined.

  3. Energetic consumption levels and human development indexes

    International Nuclear Information System (INIS)

    Boa Nova, Antonio Carlos

    1999-01-01

    The article overviews the energetic consumption levels and human development indexes. The human development indexes are described based on the United Nations Development Programme. A comparison between the energetic consumption levels and human development indexes is also presented

  4. The golden triangle of human dignity: human security, human development and human rights

    NARCIS (Netherlands)

    Gaay Fortman, B. de

    2004-01-01

    The success or failure of processes of democratization cannot be detached from processes of development related to the aspirations of people at the grassroots. Human rights, in a more theoretical terminology, require human development in order to enhance human security.

  5. 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.

  6. Human development recruiting and selection

    Directory of Open Access Journals (Sweden)

    Maksimović Marijana

    2002-01-01

    Full Text Available Along with the development of trends towards internationalization and globalization, human resource management and, especially, international human resource management, attracted overall theoretical and practical interest. International environment is complex, made of numerous elements like social organization, laws, education, values and attitudes, religion language, politics, material and technological culture. In multicultural environment, strategic activities could be multiplied through economical political, cultural, social and technological spheres of action, making the recruitment, selection and successful resource allocation in the international human resource management a real challenge for top management. In international human resource management practice, several approaches to the recruitment have differentiated, playing the key roles in hiring talented individuals and retaining efficient workforce KW resources, labor force, recruiting, managers, education

  7. Low birth weight in response to salt restriction during pregnancy is not due to alterations in uterine-placental blood flow or the placental and peripheral renin-angiotensin system.

    Science.gov (United States)

    Leandro, Sandra Márcia; Furukawa, Luzia Naôko Shinohara; Shimizu, Maria Heloisa Massola; Casarini, Dulce Elena; Seguro, Antonio Carlos; Patriarca, Giuliana; Coelho, Michella Soares; Dolnikoff, Miriam Sterman; Heimann, Joel Claudio

    2008-09-03

    A number of studies conducted in humans and in animals have observed that events occurring early in life are associated with the development of diseases in adulthood. Salt overload and restriction during pregnancy and lactation are responsible for functional (hemodynamic and hormonal) and structural alterations in adult offspring. Our group observed that lower birth weight and insulin resistance in adulthood is associated with salt restriction during pregnancy. On the other hand, perinatal salt overload is associated with higher blood pressure and higher renal angiotensin II content in adult offspring. Therefore, we hypothesised that renin-angiotensin system (RAS) function is altered by changes in sodium intake during pregnancy. Such changes may influence fetoplacental blood flow and thereby fetal nutrient supply, with effects on growth in utero and, consequently, on birth weight. Female Wistar rats were fed low-salt (LS), normal-salt (NS), or high-salt (HS) diet, starting before conception and continuing until day 19 of pregnancy. Blood pressure, heart rate, fetuses and dams' body weight, placentae weight and litter size were measured on day 19 of pregnancy. Cardiac output, uterine and placental blood flow were also determined on day 19. Expressions of renin-angiotensin system components and of the TNF-alpha gene were evaluated in the placentae. Plasma renin activity (PRA) and plasma and tissue angiotensin-converting enzyme (ACE) activity, as well as plasma and placental levels of angiotensins I, II, and 1-7 were measured. Body weight and kidney mass were greater in HS than in NS and LS dams. Food intake did not differ among the maternal groups. Placental weight was lower in LS dams than in NS and HS dams. Fetal weight was lower in the LS group than in the NS and HS groups. The PRA was greater in LS dams than in NS and HS dams, although ACE activity (serum, cardiac, renal, and placental) was unaffected by the level of sodium intake. Placental levels of

  8. Increased placental trophoblast inclusions in placenta accreta.

    Science.gov (United States)

    Adler, E; Madankumar, R; Rosner, M; Reznik, S E

    2014-12-01

    Trophoblast inclusions (TIs) are often found in placentas of genetically abnormal gestations. Although best documented in placentas from molar pregnancies and chromosomal aneuploidy, TIs are also associated with more subtle genetic abnormalities, and possibly autism. Less than 3% of non-aneuploid, non-accreta placentas have TIs. We hypothesize that placental genetics may play a role in the development of placenta accreta and aim to study TIs as a potential surrogate indicator of abnormal placental genetics. Forty cases of placenta accreta in the third trimester were identified in a search of the medical records at one institution. Forty two third trimester control placentas were identified by a review of consecutively received single gestation placentas with no known genetic abnormalities and no diagnosis of placenta accreta. Forty percent of cases with placenta accreta demonstrated TIs compared to 2.4% of controls. More invasive placenta accretas (increta and percreta) were more likely to demonstrate TIs than accreta (47% versus 20%). Prior cesarean delivery was more likely in accreta patients than controls (67% versus 9.5%). Placenta accreta is thought to be the result of damage to the endometrium predisposing to abnormal decidualization and invasive trophoblast growth into the myometrium. However, the etiology of accreta is incompletely understood with accreta frequently occurring in women without predisposing factors and failing to occur in predisposed patients. This study has shown that TIs are present at increased rates in cases of PA. Further studies are needed to discern what underlying pathogenic mechanisms are in common between abnormal placentation and the formation of TIs. Published by Elsevier Ltd.

  9. Towards Improved Human Resource Development In Nigeria ...

    African Journals Online (AJOL)

    Towards Improved Human Resource Development In Nigeria: Challenges And Prospects. ... Journal of Research in National Development ... Consequently, the paper recommended; improved investment in education, implementable policies on human resource development, involvement of private organization in human ...

  10. Growth charts of human development

    NARCIS (Netherlands)

    Van Buuren, Stef

    2014-01-01

    This article reviews and compares two types of growth charts for tracking human development over age. Both charts assume the existence of a continuous latent variable, but relate to the observed data in different ways. The D-score diagram summarizes developmental indicators into a single aggregate

  11. 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

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

    International Nuclear Information System (INIS)

    Mohanty, April F.; Farin, Fred M.; Bammler, Theo K.; MacDonald, James W.; Afsharinejad, Zahra; Burbacher, Thomas M.; Siscovick, David S.

    2015-01-01

    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

  13. Economic Development and Development of Human Resources

    Directory of Open Access Journals (Sweden)

    Metod Černetič

    1998-12-01

    Full Text Available Černetič deals with certain dilemmas and problems related to employee training within companies, and discusses the complexity of the relationship between technological development and education, developmental gap between the developed and underdevdoped economies, and the goals of social development in Slovenia. Cernetič stresses that training programmes should above all provide flexibility of employment; the competitive edge of an entire state actually depends on effective use of human resources. Slovenia cannot exert any substantial influence on the global economy, it can only follow the main market trends. Knowledge is therefore of great importance, as the wealth of smaller nations is primarily based on the education level of their inhabitants.

  14. 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...

  15. MRI of placental adhesive disorder

    Science.gov (United States)

    Prapaisilp, P; Bangchokdee, S

    2014-01-01

    Placental adhesive disorder (PAD) is a serious pregnancy complication that occurs when the chorionic villi invade the myometrium. Placenta praevia and prior caesarean section are the two important risk factors. PAD is classified on the basis of the depth of myometrial invasion (placenta accreta, placenta increta and placenta percreta). MRI is the preferred image modality for pre-natal diagnosis of PAD and as complementary technique when ultrasonography is inconclusive. Imaging findings that are helpful for the diagnosis include dark intraplacental bands, direct invasion of adjacent structures by placental tissue, interruption of normal trilayered myometrium and uterine bulging. Clinicians should be aware of imaging features of PAD to facilitate optimal patient management. PMID:25060799

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

    Directory of Open Access Journals (Sweden)

    Rodrigo M Souza

    Full Text Available Histological evidence of Plasmodium in the placenta is indicative of placental malaria, a condition associated with severe outcomes for mother and child. Histological lesions found in placentas from Plasmodium-exposed women include syncytial knotting, syncytial rupture, thickening of the placental barrier, necrosis of villous tissue and intervillositis. These histological changes have been associated with P. falciparum infections, but little is known about the contribution of P. vivax to such changes. We conducted a cross-sectional study with pregnant women at delivery and assigned them to three groups according to their Plasmodium exposure during pregnancy: no Plasmodium exposure (n = 41, P. vivax exposure (n = 59 or P. falciparum exposure (n = 19. We evaluated their placentas for signs of Plasmodium and placental lesions using ten histological parameters: syncytial knotting, syncytial rupture, placental barrier thickness, villi necrosis, intervillous space area, intervillous leucocytes, intervillous mononucleates, intervillous polymorphonucleates, parasitized erythrocytes and hemozoin. Placentas from P. vivax-exposed women showed little evidence of Plasmodium or hemozoin but still exhibited more lesions than placentas from women not exposed to Plasmodium, especially when infections occurred twice or more during pregnancy. In the Brazilian state of Acre, where diagnosis and primary treatment are readily available and placental lesions occur in the absence of detected placental parasites, relying on the presence of Plasmodium in the placenta to evaluate Plasmodium-induced placental pathology is not feasible. Multivariate logistic analysis revealed that syncytial knotting (odds ratio [OR], 4.21, P = 0.045, placental barrier thickness (OR, 25.59, P = 0.021 and mononuclear cells (OR, 4.02, P = 0.046 were increased in placentas from P. vivax-exposed women when compared to women not exposed to Plasmodium during pregnancy. A

  17. Educational Solutions for Human Development

    Directory of Open Access Journals (Sweden)

    Inês Kisil Miskalo

    2009-06-01

    Full Text Available The biggest challenge for education in Brazil is not only to popularize school access, but also to provide conditions for students to remain at school successfully. Therefore, it is necessary to invest in teachers qualification and in the adoption of efficient and effective public policies based on managerial patterns designed to cater to human resources articulations, equipment, finance and, mainly, to methodologies focused on results. Quality reorganization of public policy will only be possible through a triplet effort involving political will from public government, cooperation from the private sector and contribution from civil society. These partnerships assure public sphere the development of essential projects to enable the country to grow. They also allow Education to occupy the important place it deserves in the national agenda as a tool to foster human development. It is essential to guarantee to people knowledge and abilities that enable them to make sensible choices, have their health improved and thus, take part in the society actively. This essay intends to provide information on Instituto Ayrton Senna´s mission to boost quality education for new Brazilian generations as a precondition for human development. Its education programs supply managerial praxes to state and municipal public school systems that warrant conceptual changes and alter the school failure vicious cycle.

  18. Increased Levels of Cell-Free Human Placental Lactogen mRNA at 28-32 Gestational Weeks in Plasma of Pregnant Women With Placenta Previa and Invasive Placenta

    Science.gov (United States)

    Sekizawa, Akihiko; Ventura, Walter; Koide, Keiko; Hori, Kyouko; Okai, Takashi; Masashi, Yoshida; Furuya, Kenichi; Mizumoto, Yoshifumi

    2014-01-01

    We compared the levels of cell-free human placental lactogen (hPL) messenger RNA (mRNA) in maternal plasma at 28 to 32 weeks of gestation between women with diagnosis of placenta previa or invasive placenta and women with an uneventful pregnancy. Sensitivity and specificity of hPL mRNA for the prediction of invasive placenta were further explored. Plasma hPL mRNA were quantified by real-time reverse-transcriptase polymerase chain reaction in women with placenta previa (n = 13), invasive placenta (n = 5), and normal pregnancies (n = 92). Median (range) hPL mRNA was significantly higher in women with placenta previa, 782 (10-2301) copies/mL of plasma, and in those with invasive placenta, 615 (522-2102) copies/mL of plasma, when compared to normal pregnancies, 90 (4-4407) copies/mL of plasma, P < .01 and P < .05, respectively. We found a sensitivity of 100% and a specificity of 61.5% for the prediction of invasive placenta among women with placenta previa. In conclusion, expression of hPL mRNA is increased in plasma of women with placenta previa and invasive placenta at 28 to 32 weeks of gestation. PMID:23744883

  19. 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 shape...... of the most important findings made by Strahl including work on placentation in carnivores and higher primates that remains unsurpassed....

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

    Directory of Open Access Journals (Sweden)

    Morten A Nielsen

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

  1. Placental baseline conditions modulate the hyperoxic BOLD-MRI response.

    Science.gov (United States)

    Sinding, Marianne; Peters, David A; Poulsen, Sofie S; Frøkjær, Jens B; Christiansen, Ole B; Petersen, Astrid; Uldbjerg, Niels; Sørensen, Anne

    2018-01-01

    Human pregnancies complicated by placental dysfunction may be characterized by a high hyperoxic Blood oxygen level-dependent (BOLD) MRI response. The pathophysiology behind this phenomenon remains to be established. The aim of this study was to evaluate whether it is associated with altered placental baseline conditions, including a lower oxygenation and altered tissue morphology, as estimated by the placental transverse relaxation time (T2*). We included 49 normal pregnancies (controls) and 13 pregnancies complicated by placental dysfunction (cases), defined by a birth weight baseline BOLD)/baseline BOLD) from a dynamic single-echo gradient-recalled echo (GRE) MRI sequence and the absolute ΔT2* (hyperoxic T2*- baseline T2*) from breath-hold multi-echo GRE sequences. In the control group, the relative ΔBOLD response increased during gestation from 5% in gestational week 20 to 20% in week 40. In the case group, the relative ΔBOLD response was significantly higher (mean Z-score 4.94; 95% CI 2.41, 7.47). The absolute ΔT2*, however, did not differ between controls and cases (p = 0.37), whereas the baseline T2* was lower among cases (mean Z-score -3.13; 95% CI -3.94, -2.32). Furthermore, we demonstrated a strong negative linear correlation between the Log 10 ΔBOLD response and the baseline T2* (r = -0.88, p baseline conditions, as the absolute increase in placental oxygenation (ΔT2*) does not differ between groups. Copyright © 2017 Elsevier Ltd. All rights reserved.

  2. Imaging of placental transport mechanisms: a review.

    Science.gov (United States)

    Sölder, Elisabeth; Rohr, Irena; Kremser, Christian; Hutzler, Peter; Debbage, Paul L

    2009-05-01

    Functional analysis of material transfers requires precise statement of residence times in each tissue compartment. For the placenta, neither extractive biochemistry, isotope partitioning, nor mass-based quantitative assays provide adequate spatial resolution to allow the necessary precision. Dual-perfusion assays of material transfer in isolated placental cotyledons provide time-series data for two compartments, the maternal and fetal blood, but fail to distinguish the two cellular compartments (syncytiotrophoblast, fetal endothelium) which actively regulate rates of transfer in each direction for essentially every important molecule type. At present, no definitive technology exists for functional analysis of placental transfer functions. The challenge in developing such a technology lies in the exquisitely small and delicate structures involved, which are scaled at cellular and subcellular sizes (between 50 nm and 50 microm). The only available technologies attaining this high spatial resolution are imaging technologies, primarily light and electron microscopy. To achieve the high-quality images necessary, confocal laser scanning microscopy (CLSM) is required, to provide a uniform optical sectioning plane. In turn, this requires relatively high fluorescence intensities. Design of an adequate technology therefore bases on CLSM imaging fluorochrome-tagged tracers. The temporal resolution necessary to analyse placental material transfers is expected to be of the order of a few seconds, so that conventional wet-fixation protocols are too slow. For adequately rapid fixation, snap-freezing is required. As part of this review we report results obtained from an appropriately designed experimental protocol, analysed by CLSM and transmission electron microscopy (TEM). The images acquired were tested for uniformity of illumination and fluorescence emission strength. Relevant data was encoded in the green channel of the trichrome images obtained, and this was thresholded by

  3. Placental transfer of the actinides and related heavy elements

    International Nuclear Information System (INIS)

    Sikov, M.R.

    1987-01-01

    This manuscript presents a selective review of the literature dealing with prenatal exposure of experimental animals and humans to actinides and related heavy elements, and uses this information to consider comparative aspects of placental transfer and fetoplacental distribution. General patterns have been derived from typical quantitative values, and used to compare similarities and dissimilarities, and to examine factors responsible for observed differences. 37 refs.; 1 figure; 2 tabs

  4. Sources for comparative studies of placentation I. Embryological collections

    DEFF Research Database (Denmark)

    Carter, Anthony Michael

    2008-01-01

    A rich source of material for comparative studies of the placenta is the collections made by pioneers in the field such as H.W. Mossman, A.A.W. Hubrecht and J.P. Hill. This overview gives a brief description of collections known to be available and information on how each can be accessed. Include...... are some of the major series of human and animal embryos, such as the Boyd and Carnegie collections, as these also house placental material....

  5. 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

    The harmful effects of pregnancy-associated malaria (PAM) are engendered by the heavy sequestration of Plasmodium falciparum-parasitized RBCs in the placenta. It is well documented that this process is mediated by interactions of parasite-encoded variant surface antigens and placental receptors...... and adhesion to multiple receptors (IgG/IgM/HA/CSA) rather than the exclusive binding to CSA is a characteristic of fresh Ugandan placental isolates. These findings are of importance for the understanding of the pathogenesis of placental malaria and have implications for the ongoing efforts to develop a global...

  6. Histologic Changes Associated With Placental Separation in Gilts Infected with Porcine Reproductive and Respiratory Syndrome Virus.

    Science.gov (United States)

    Novakovic, Predrag; Detmer, Susan E; Suleman, Muhammad; Malgarin, Carol M; MacPhee, Daniel J; Harding, John C S

    2018-07-01

    The placenta is a vital organ providing the developing fetus with nutrient and gas exchange, thermoregulation, and waste elimination necessary for fetal development, as well as producing hormones to maintain pregnancy. It is hypothesized that fetal pig death in porcine reproductive and respiratory syndrome may be attributed to pathology of the maternal-fetal interface leading to premature placental separation. This study was designed to evaluate the chronologic progression of porcine reproductive and respiratory syndrome virus (PRRSV)-induced lesions at the maternal-fetal interface, with particular focus on placental separation in experimentally challenged third-trimester gilts. Fifteen gilts were inoculated with a virulent strain of PRRSV-2 on gestation day 86 ± 0.4. On multiple days postinoculation, 3 gilts along with 1 sham-inoculated control per time point were euthanized, and uterine and fetal placental tissues corresponding to each fetus were collected for histopathologic evaluation. The presence of any fetal lesion was 23 times more likely in compromised (meconium-stained and decomposed) compared with viable fetuses ( P < .001). In PRRSV-infected gilts, endometritis was more severe than placentitis, and the severity of endometrial inflammation and vasculitis increased progressively from 2 to 14 days postinoculation. Neither placental vasculitis nor a chronologic progression in the severity of placental detachment was observed. Severe placental detachment was more frequently present in PRRSV-infected compared with noninfected samples and was most significantly associated with placental inflammation, compared with other uterine lesions, viral load, or termination day. The results of this study suggest that placental separation by itself is not sufficient to significantly compromise fetal viability in reproductive porcine reproductive and respiratory syndrome.

  7. The Multiple Roles of EG-VEGF/PROK1 in Normal and Pathological Placental Angiogenesis

    Directory of Open Access Journals (Sweden)

    Nadia Alfaidy

    2014-01-01

    Full Text Available Placentation is associated with several steps of vascular adaptations throughout pregnancy. These vascular changes occur both on the maternal and fetal sides, consisting of maternal uterine spiral arteries remodeling and placental vasculogenesis and angiogenesis, respectively. Placental angiogenesis is a pivotal process for efficient fetomaternal exchanges and placental development. This process is finely controlled throughout pregnancy, and it involves ubiquitous and pregnancy-specific angiogenic factors. In the last decade, endocrine gland derived vascular endothelial growth factor (EG-VEGF, also called prokineticin 1 (PROK1, has emerged as specific placental angiogenic factor that controls many aspects of normal and pathological placental angiogenesis such as recurrent pregnancy loss (RPL, gestational trophoblastic diseases (GTD, fetal growth restriction (FGR, and preeclampsia (PE. This review recapitulates EG-VEGF mediated-angiogenesis within the placenta and at the fetomaternal interface and proposes that its deregulation might contribute to the pathogenesis of several placental diseases including FGR and PE. More importantly this paper argues for EG-VEGF clinical relevance as a potential biomarker of the onset of pregnancy pathologies and discusses its potential usefulness for future therapeutic directions.

  8. The multiple roles of EG-VEGF/PROK1 in normal and pathological placental angiogenesis.

    Science.gov (United States)

    Alfaidy, Nadia; Hoffmann, Pascale; Boufettal, Houssine; Samouh, Naima; Aboussaouira, Touria; Benharouga, Mohamed; Feige, Jean-Jacques; Brouillet, Sophie

    2014-01-01

    Placentation is associated with several steps of vascular adaptations throughout pregnancy. These vascular changes occur both on the maternal and fetal sides, consisting of maternal uterine spiral arteries remodeling and placental vasculogenesis and angiogenesis, respectively. Placental angiogenesis is a pivotal process for efficient fetomaternal exchanges and placental development. This process is finely controlled throughout pregnancy, and it involves ubiquitous and pregnancy-specific angiogenic factors. In the last decade, endocrine gland derived vascular endothelial growth factor (EG-VEGF), also called prokineticin 1 (PROK1), has emerged as specific placental angiogenic factor that controls many aspects of normal and pathological placental angiogenesis such as recurrent pregnancy loss (RPL), gestational trophoblastic diseases (GTD), fetal growth restriction (FGR), and preeclampsia (PE). This review recapitulates EG-VEGF mediated-angiogenesis within the placenta and at the fetomaternal interface and proposes that its deregulation might contribute to the pathogenesis of several placental diseases including FGR and PE. More importantly this paper argues for EG-VEGF clinical relevance as a potential biomarker of the onset of pregnancy pathologies and discusses its potential usefulness for future therapeutic directions.

  9. Effects of placental infarctions on the fatal outcome in pregnancies complicated by hypertension

    International Nuclear Information System (INIS)

    Salgado, S.S.; Pathmeswaran, A.

    2008-01-01

    To determine the frequency of placental infarcts and its effects on the fetal outcome in pregnancies complicated by hypertension. Placentae of 150 normotensive women and 200 hypertensive women were studied to detect the number of placentae with infarctions. Apgar score, birth weight and the head circumference of the newborns were measured and analyzed. The frequency of placental infarcts was significantly higher in hypertensive group (30%) compared to normotensive group (18.7%). An association between placental infarction and low Apgar score of the newborn was seen in the hypertensive group (p<0.001). The difference in the birth weight of the newborns in hypertensive and normotensive groups in relation to placental infarction was statistically significant (2.2 vs. 3.1 kg, p<0.001). A highly significant difference was observed in the head circumference of the newborns of hypertensive group compared to normotensive group in relation to placental infarctions (30.7 cm vs. 32.3 cm, p<0.001). The frequency of placental infarcts was higher in hypertensive women when compared to normotensives. Placental infarctions had an adverse effect on growth and development of the newborns. This information can be useful in planning and management of future pregnancies. (author)

  10. Growth charts of human development.

    Science.gov (United States)

    van Buuren, Stef

    2014-08-01

    This article reviews and compares two types of growth charts for tracking human development over age. Both charts assume the existence of a continuous latent variable, but relate to the observed data in different ways. The D-score diagram summarizes developmental indicators into a single aggregate score measuring global development. The relations between the indicators should be consistent with the Rasch model. If true, the D-score is a measure with interval scale properties, and allows for the calculation of meaningful differences both within and across age. The stage line diagram describes the natural development of ordinal indicators. The method models the transition probabilities between successive stages of the indicator as smoothly varying functions of age. The location of each stage is quantified by the mid-P-value. Both types of diagrams assist in identifying early and delayed development, as well as finding differences in tempo. The relevant techniques are illustrated to track global development during infancy and early childhood (0-2 years) and Tanner pubertal stages (8-21 years). New reference values for both applications are provided. © The Author(s) 2013 Reprints and permissions: sagepub.co.uk/journalsPermissions.nav.

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

    African Journals Online (AJOL)

    fetal. Hence, DV provides information about the fetal side of the placenta and, alongside placental ... The study was prospective and conducted in a low-income setting. .... placental tissue (n=10), and some cases were lost to follow-up (n=6).

  12. 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.

  13. [The role of oxidative stress in placental-related diseases of pregnancy].

    Science.gov (United States)

    Jauniaux, E; Burton, G J

    2016-10-01

    In normal pregnancies, the earliest stages of development take place in a low oxygen (O 2 ) environment. This physiological hypoxia of the early gestational sac protects the developing fetus against the deleterious and teratogenic effects of O 2 free radicals. Oxidative stress is manifested at the maternal-fetal interface from early pregnancy onwards. In early pregnancy, a well-controlled oxidative stress plays a role in modulating placental development, functions and remodelling. Focal trophoblastic oxidative damage and progressive villous degeneration trigger the formation of the fetal membranes, which is an essential developmental step enabling vaginal delivery. Our data have demonstrated that the first trimester placenta in humans is histiotrophic and not haemochorial. The development and maintenance of a physiological O 2 gradient between the uterine and fetal circulations is also essential for placental functions, such as transport and hormonal synthesis. Pathological oxidative stress arises when the production of reactive O 2 species overwhelms the intrinsic anti-oxidant defences causing indiscriminate damage to biological molecules, leading to loss of function and cell death. We here review the role of oxidative stress in the pathophysiology of miscarriage, pre-eclampsia and fetal growth restriction. Copyright © 2016 Elsevier Masson SAS. All rights reserved.

  14. Angiogenic proteins, placental weight and perinatal outcomes among pregnant women in Tanzania.

    Science.gov (United States)

    McDonald, Chloe R; Darling, Anne M; Liu, Enju; Tran, Vanessa; Cabrera, Ana; Aboud, Said; Urassa, Willy; Kain, Kevin C; Fawzi, Wafaie W

    2016-01-01

    Placental vascular development, and ultimately placental weight, is essential to healthy fetal development. Here, we examined placental weight in a cohort of Tanzanian women in association with angiogenic proteins known to regulate placental vascular development and perinatal outcomes. A total of n = 6579 women with recorded placental weight were included in this study. The relative risk of adverse perinatal outcomes (Apgar score, death, asphyxia, respiratory distress, seizures, pneumonia and sepsis) was compared between placental weight in the bottom and top 10th percentiles. We quantified angiogenic mediators (Ang-1, Ang-2, VEGF, PGF and sFlt-1) in plasma samples (n = 901) collected between 12 to 27 weeks of pregnancy using ELISA and assessed the relative risk of placental weight in the bottom and top 10th percentiles by protein levels in quartiles. Women with Ang-2 levels in the highest quartile had an increased relative risk of placental weight in the bottom 10th percentile (RR = 1.45 (1.10, 1.91), p = 0.01). Women with VEGF-A (RR = 0.73 (0.56, 0.96), p = 0.05) and PGF (RR = 0.58 (0.44, 0.72), p = 0.002) in the highest quartile had a reduced relative risk of placental weight in the bottom 10th percentile. Low placental weight (in bottom 10th percentile) was associated with an increased relative risk of Apgar score of <7 at 1 minute (RR = 2.31 (1.70, 3.13), p = 0.001), at 5 minutes (RR = 3.53 (2.34, 5.33), p = 0.001), neonatal death (RR = 5.02 (3.61, 7.00), p = 0.001), respiratory distress (RR = 4.80(1.71, 13.45), p = 0.001), and seizures (RR = 4.18 (1.16, 15.02), p = 0.03). The association between low placental weight and risk of adverse perinatal outcomes in this cohort suggests that placental weight could serve as a useful indicator, providing additional insight into high-risk pregnancies and identifying neonates that may require additional monitoring and follow-up.

  15. 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. The avai......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...

  16. The effects of human resource flexibility on human resources development

    Directory of Open Access Journals (Sweden)

    SeidMehdi Veise

    2014-08-01

    Full Text Available Human resources are the primary factor for development of competitiveness and innovation and reaching competitive advantage and they try to improve corporate capabilities through various characteristics such as value creation, scarcity and difficulty of imitation. This paper investigates the effect of human resource flexibility and its dimensions on human resource development and its dimensions. The survey was conducted using descriptive-correlation method that intended to describe how human resource flexibility was effective on human resource development. Questionnaire was tool of data collection. The statistical population included one hundred employees of the Electric Company in Ilam province, thus census method was used. Reliability of the questionnaire was measured via Cronbach's alpha equal to 0.96. The findings revealed that flexibility and its dimensions were effective on human resource development and dimensions of it. As a result, human resource flexibility should be considered for development of human resources and employees with the highest flexibility should be selected.

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

    Science.gov (United States)

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

    2013-06-01

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

  18. Human resource development for decommissioning

    International Nuclear Information System (INIS)

    Yanagihara, Satoshi

    2016-01-01

    This paper summarized the features of decommissioning work and the methods how to develop human resources. The general flow of decommissioning includes the following steps: (1) evaluation of facility characteristics, (2) planning, (3) decontamination and disassembly of equipment and structures contaminated with radioactivity, (4) radioactivity measurement, (5) treatment and disposal of radioactive waste, and (6) release from legal restrictions (termination of decommissioning). For this purpose, techniques in various fields are required. In the evaluation of facility characteristics, radiation measurement and calculation of activation amount in the core part are required. In decontamination and dismantling, cutting technology (mechanical cutting, thermal cutting, etc.), decontamination technology, and remote control technology are required. In the nuclear power education in the past, the fields related to design, construction, operation, and maintenance among the plant life cycle were the main parts. Much attention was not payed to decommissioning and the treatment/disposal of radioactive waste in the second half of life cycle. As university education, Hokkaido University and Fukui University have lectures on decommissioning. Furthermore, the education and research for students are proceeding at seven universities, with a focus on common reactors including those of Fukushima Daiichi Power Station. It is a key for promoting decommissioning, to incorporate project management, risk analysis, cost evaluation, and decision making into education, and to foster human resources heading toward challenging problems including social problems. (A.O.)

  19. Human placental Na/sup +/, K/sup +/-ATPase. cap alpha. subunit: cDNA cloning, tissue expression, DNA polymorphism, and chromosomal localization

    Energy Technology Data Exchange (ETDEWEB)

    Chehab, F.F.; Kan, Y.W.; Law, M.L.; Hartz, J.; Kao, F.T.; Blostein, R.

    1987-11-01

    A 2.2-kilobase clone comprising a major portion of the coding sequence of the Na/sup +/, K/sup +/-ATPase ..cap alpha.. subunit was cloned from human placenta and its sequence was identical to that encoding the ..cap alpha.. subunit of human kidney and HeLa cells. Transfer blot analysis of the mRNA products of the Na/sup +/, K/sup +/-ATPase gene from various human tissues and cell lines revealed only one band (approx. = 4.7 kilobases) under low and high stringency washing conditions. The levels of expression in the tissues were intestine > placenta > liver > pancreas, and in the cell lines the levels were human erythroleukemia > butyrate-induced colon > colon > brain > HeLa cells. mRNA was undetectable in reticulocytes, consistent with the authors failure to detect positive clones in a size-selected ( > 2 kilobases) lambdagt11 reticulocyte cDNA library. DNA analysis revealed by a polymorphic EcoRI band and chromosome localization by flow sorting and in situ hybridization showed that the ..cap alpha.. subunit is on the short is on the short arm (band p11-p13) of chromosome 1.

  20. The effects from placental exposure

    International Nuclear Information System (INIS)

    Kawamoto, Sadahisa

    1975-01-01

    Investigations of the effects on the people who had received placental exposure at either Hiroshima or Nagasaki were discussed. All of the subjects were children who had been born at either Hiroshima or Nagasaki between noon of 31, May, 1946 and the atomic-bomb detornation. Deaths of embryos and neonates were determined by the radiation dosage and the growth phase of embryos. Bifid uvula and a slight decrease of number of lumbar vertebra were observed in 14 males and 3 females at Nagasaki. Mental deficiency occurred in 25% of the children whose mothers had received radiation at Nagasaki, and in 8% at Hiroshima. The occurrence of microcephaly was high at both places in the children who had received placental exposure of more than 150 rad. A significant retardation of growth was observed in those who had had a high radiation dosage. Congenitally abnormal persistence of pupillary membrane was very frequently observed in the group which had received a high dosage of radiation. Concerning progeria, mortality of infants under one year of age was increased in the group which had received a high dosage of radiation, but mortality statistics should continue to be observed. (Kanao, N.)

  1. In vitro placental model optimization for nanoparticle transport studies

    Directory of Open Access Journals (Sweden)

    Cartwright L

    2012-01-01

    Full Text Available Laura Cartwright1, Marie Sønnegaard Poulsen2, Hanne Mørck Nielsen3, Giulio Pojana4, Lisbeth E Knudsen2, Margaret Saunders1, Erik Rytting2,51Bristol Initiative for Research of Child Health (BIRCH, Biophysics Research Unit, St Michael's Hospital, UH Bristol NHS Foundation Trust, Bristol, UK; 2University of Copenhagen, Faculty of Health Sciences, Department of Public Health, 3University of Copenhagen, Faculty of Pharmaceutical Sciences, Department of Pharmaceutics and Analytical Chemistry, Copenhagen, Denmark; 4Department of Environmental Sciences, Informatics and Statistics, University Ca' Foscari Venice, Venice, Italy; 5Department of Obstetrics and Gynecology, University of Texas Medical Branch, Galveston, Texas, USABackground: Advances in biomedical nanotechnology raise hopes in patient populations but may also raise questions regarding biodistribution and biocompatibility, especially during pregnancy. Special consideration must be given to the placenta as a biological barrier because a pregnant woman's exposure to nanoparticles could have significant effects on the fetus developing in the womb. Therefore, the purpose of this study is to optimize an in vitro model for characterizing the transport of nanoparticles across human placental trophoblast cells.Methods: The growth of BeWo (clone b30 human placental choriocarcinoma cells for nanoparticle transport studies was characterized in terms of optimized Transwell® insert type and pore size, the investigation of barrier properties by transmission electron microscopy, tight junction staining, transepithelial electrical resistance, and fluorescein sodium transport. Following the determination of nontoxic concentrations of fluorescent polystyrene nanoparticles, the cellular uptake and transport of 50 nm and 100 nm diameter particles was measured using the in vitro BeWo cell model.Results: Particle size measurements, fluorescence readings, and confocal microscopy indicated both cellular uptake of

  2. Alcohol, Methamphetamine, and Marijuana Exposure Have Distinct Effects on the Human Placenta.

    Science.gov (United States)

    Carter, R Colin; Wainwright, Helen; Molteno, Christopher D; Georgieff, Michael K; Dodge, Neil C; Warton, Fleur; Meintjes, Ernesta M; Jacobson, Joseph L; Jacobson, Sandra W

    2016-04-01

    Animal studies have demonstrated adverse effects of prenatal alcohol exposure on placental development, but few studies have examined these effects in humans. Little is known about effects of prenatal exposure to methamphetamine, marijuana, and cigarette smoking on placental development. Placentas were collected from 103 Cape Coloured (mixed ancestry) pregnant women recruited at their first antenatal clinic visit in Cape Town, South Africa. Sixty-six heavy drinkers and 37 nondrinkers were interviewed about their alcohol, cigarette smoking, and drug use at 3 antenatal visits. A senior pathologist, blinded to exposure status, performed comprehensive pathology examinations on each placenta using a standardized protocol. In multivariable regression models, effects of prenatal exposure were examined on placental size, structure, and presence of infections and meconium. Drinkers reported a binge pattern of heavy drinking, averaging 8.0 drinks/occasion across pregnancy on 1.4 d/wk. 79.6% smoked cigarettes; 22.3% used marijuana; and 17.5% used methamphetamine. Alcohol exposure was related to decreased placental weight and a smaller placenta-to-birthweight ratio. By contrast, methamphetamine was associated with larger placental weight and a larger placenta-to-birthweight ratio. Marijuana was also associated with larger placental weight. Alcohol exposure was associated with increased risk of placental hemorrhage. Prenatal alcohol, drug, and cigarette use were not associated with chorioamnionitis, villitis, deciduitis, or maternal vascular underperfusion. Alcohol and cigarette smoking were associated with a decreased risk of intrauterine passing of meconium, a sign of acute fetal stress and/or hypoxia; methamphetamine, with an increased risk. This is the first human study to show that alcohol, methamphetamine, and marijuana were associated with distinct patterns of pathology, suggesting different mechanisms mediating their effects on placental development. Given the growing

  3. Human Capital Accumulation: The Role of Human Resource Development.

    Science.gov (United States)

    Garavan, Thomas N.; Morley, Michael; Gunnigle, Patrick; Collins, Eammon

    2001-01-01

    Presents definitions of intellectual and human capital. Examines human capital from the individual perspective (employability, performance, career development) and organization perspective (investment, ownership, knowledge management). Reviews papers in the theme issue. (Contains 117 references.) (SK)

  4. Sexual dimorphism in activation of placental autophagy in obese women with evidence for fetal programming from a placenta-specific mouse model.

    Science.gov (United States)

    Muralimanoharan, Sribalasubashini; Gao, Xiaoli; Weintraub, Susan; Myatt, Leslie; Maloyan, Alina

    2016-05-03

    The incidence of maternal obesity and its co-morbidities (diabetes, cardiovascular disease) continues to increase at an alarming rate, with major public health implications. In utero exposure to maternal obesity has been associated with development of cardiovascular and metabolic diseases in the offspring as a result of developmental programming. The placenta regulates maternal-fetal metabolism and shows significant changes in its function with maternal obesity. Autophagy is a cell-survival process, which is responsible for the degradation of damaged organelles and misfolded proteins. Here we show an activation of autophagosomal formation and autophagosome-lysosome fusion in placentas of males but not females from overweight (OW) and obese (OB) women vs. normal weight (NW) women. However, total autophagic activity in these placentas appeared to be decreased as it showed an increase in SQSTM1/p62 and a decrease in lysosomal biogenesis. A mouse model with a targeted deletion of the essential autophagy gene Atg7 in placental tissue showed significant placental abnormalities comparable to those seen in human placenta with maternal obesity. These included a decrease in expression of mitochondrial genes and antioxidants, and decreased lysosomal biogenesis. Strikingly, the knockout mice were developmentally programmed as they showed an increased sensitivity to high-fat diet-induced obesity, hyperglycemia, hyperinsulinemia, increased adiposity, and cardiac remodeling. In summary, our results indicate a sexual dimorphism in placental autophagy in response to maternal obesity. We also show that autophagy plays an important role in placental function and that inhibition of placental autophagy programs the offspring to obesity, and to metabolic and cardiovascular diseases.

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

    OpenAIRE

    Grozdea Jean J; Fournier Didier D; Biasini Ghislaine G; Brisson-Lougarre Andrée A; Denier Colette C

    2002-01-01

    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 pro...

  6. Potential synergistic effects of human placental extract and minoxidil on hair growth-promoting activity in C57BL/6J mice.

    Science.gov (United States)

    Kwon, T-R; Oh, C T; Park, H M; Han, H J; Ji, H J; Kim, B J

    2015-08-01

    Human placenta extract (HPE) has been used to alleviate tiredness and promote wound healing, and for its antiageing functions; however, it has not yet been studied for its effects on hair growth. In the present study, we evaluated the in vitro effect of HPE on hair growth by observing its actions on human dermal papilla cells (DPCs). To define how HPE promotes induction of anagen hair growth during the telogen phase, and to understand the synergistic molecular mechanisms of HPE and minoxidil (MXD) actions on hair growth. We examined the effects of HPE and MXD on C57BL6/J mice using haematoxylin and eosin staining, quantitative histomorphometry, hair growth scoring, immunohistochemistry and immunofluorescence on the dorsal skins of C57BL/6J mice. We found that HPE synergistically augmented the effects of MXD, a promoter of hair growth. In particular, histomorphometric analysis data indicated that subcutaneous injection of HPE induced an earlier anagen phase and prolonged the anagen phase. It also stimulated increases in both the number and size of hair follicles in groups treated with HPE alone and HPE + MXD. From our data, we conclude that HPE increases β-catenin and Wnt3a expression levels. Overall, our findings suggest that HPE in combination with MXD has hair growth-promoting activity and is a potential novel therapeutic treatment for alopecia or baldness in humans. © 2015 British Association of Dermatologists.

  7. Macroeconomics and Human Development, by Deepak Nayyar

    Directory of Open Access Journals (Sweden)

    Cristiana Ioana ŞERBĂNEL

    2013-12-01

    Full Text Available Microeconomics and Human Development pursue to tackle both negative and positive effects of macroeconomics on human development and vice-versa through a series of external and internal factors. The book consists in a series of articles published in a prestigious publication: Journal of Human Development and Capabilities. The authors have a perennial echo in the economic field.

  8. Placental mesenchymal dysplasia: case report with gross and histological findings.

    Science.gov (United States)

    Toscano, Marcello Pecoraro; Schultz, Regina

    2014-01-01

    Placental mesenchymal dysplasia (PMD) is a rare placental disorder characterized by placental enlargement and areas of abnormal, enlarged, grape-like villi. This condition may resemble a partial hydatidiform mole and may occur associated with Beckwith-Wiedemann syndrome (BWS) or in phenotypically normal fetuses. There were 110 cases reported so far. We describe one case with typical gross and microscopic placental lesions.

  9. Placental mesenchymal dysplasia: case report with gross and histological findings

    OpenAIRE

    Marcello Pecoraro Toscano; Regina Schultz

    2014-01-01

    Placental mesenchymal dysplasia (PMD) is a rare placental disorder characterized by placental enlargement and areas of abnormal, enlarged, grape-like villi. This condition may resemble a partial hydatidiform mole and may occur associated with Beckwith?Wiedemann syndrome (BWS) or in phenotypically normal fetuses. There were 110 cases reported so far. We describe one case with typical gross and microscopic placental lesions.

  10. Social touch and human development.

    Science.gov (United States)

    Cascio, Carissa J; Moore, David; McGlone, Francis

    2018-04-24

    Social touch is a powerful force in human development, shaping social reward, attachment, cognitive, communication, and emotional regulation from infancy and throughout life. In this review, we consider the question of how social touch is defined from both bottom-up and top-down perspectives. In the former category, there is a clear role for the C-touch (CT) system, which constitutes a unique submodality that mediates affective touch and contrasts with discriminative touch. Top-down factors such as culture, personal relationships, setting, gender, and other contextual influences are also important in defining and interpreting social touch. The critical role of social touch throughout the lifespan is considered, with special attention to infancy and young childhood, a time during which social touch and its neural, behavioral, and physiological contingencies contribute to reinforcement-based learning and impact a variety of developmental trajectories. Finally, the role of social touch in an example of disordered development -autism spectrum disorder-is reviewed. Copyright © 2018. Published by Elsevier Ltd.

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

    Directory of Open Access Journals (Sweden)

    B. M. Fonseca

    2013-01-01

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

  12. Method for the assessment of placental blood perfusion using /sup 99/Tc pertechnetate

    Energy Technology Data Exchange (ETDEWEB)

    Suonio, S; Olkkonen, H [Kuopio Central Hospital (Finland)

    1977-10-01

    A radioisotope method was developed for the measurement of placental blood flow using /sup 99/Tc pertechnetate as a tracer and a single detector as a measuring device. The results are given as placental perfusion rate (ml/min/ml) calculated from the tracer-appearance curve. The series consisted of 148 healthy pregnant women between the 28th and 42nd week and fifty pregnancies with a hypertensive disease. In healthy subjects the placental perfusion rate increased by about 32% in the period between 28th and 38th week, but there was a large variation. The perfusion rate showed a tendency to diminish at term. In a group of fifty hypertensive pregnancies a highly significant decrease in the perfusion rate was observed when compared with normal subjects. The conclusion drawn is that this method can be used for the quantitative measurement of placental blood supply.

  13. Role of transporters in placental transfer of drugs

    International Nuclear Information System (INIS)

    Ganapathy, Vadivel; Prasad, Puttur D.

    2005-01-01

    Human placenta functions as an important transport organ that mediates the exchange of nutrients and metabolites between maternal and fetal circulations. This function is made possible because of the expression of a multitude of transport proteins in the placental syncytiotrophoblast with differential localization in the maternal-facing brush border membrane versus the fetal-facing basal membrane. Even though the physiological role of most of these transport proteins is to handle nutrients, many of them interact with xenobiotics and pharmacological agents. These transport proteins therefore play a critical role in the disposition of drugs across the maternal-fetal interface, with some transporters facilitating the entry of drugs from maternal circulation into fetal circulation whereas others preventing such entry by actively eliminating drugs from the placenta back into maternal circulation. The net result as to whether the placenta enhances the exposure of the developing fetus to drugs and xenobiotics or functions as a barrier to protect the fetus from such agents depends on the types of transporters expressed in the brush border membrane and basal membrane of the syncytiotrophoblast and on the functional mode of these transporters (influx versus efflux)

  14. Human Resource Management and Human Resource Development: Evolution and Contributions

    Science.gov (United States)

    Richman, Nicole

    2015-01-01

    Research agrees that a high performance organization (HPO) cannot exist without an elevated value placed on human resource management (HRM) and human resource development (HRD). However, a complementary pairing of HRM and HRD has not always existed. The evolution of HRD from its roots in human knowledge transference to HRM and present day HRD…

  15. Placental alterations in structure and function in intra-uterine growth-retarded horses.

    Science.gov (United States)

    Robles, M; Peugnet, P M; Valentino, S A; Dubois, C; Dahirel, M; Aubrière, M-C; Reigner, F; Serteyn, D; Wimel, L; Couturier-Tarrade, A; Chavatte-Palmer, P

    2018-05-01

    Following embryo transfer (ET), the size and breed of the recipient mare can affect fetal development and subsequent post natal growth rate and insulin sensitivity in foals. To investigate placental adaptation in pregnancies where increased or restricted fetal growth was induced through ET between Pony, Saddlebred and Draught horses. In vivo experiment. Control Pony (P, n = 21) and Saddlebred (S, n = 28) pregnancies were obtained by artificial insemination. Increased pregnancies were obtained by transferring Pony (P-D, n = 6) and Saddlebred (S-D, n = 8) embryos into Draught mares. Restricted pregnancies were obtained by transferring Saddlebred embryos into Pony mares (S-P, n = 6). Placental weight and surface were recorded and samples collected for stereology and analysis of expression of genes involved in placental growth, vascularisation and nutrient transport. Data were analysed by linear model. S-P foals were growth retarded when compared with controls despite increased gestational length. Placental weight was reduced but placental surface density and volume fraction were increased. Placental expression of genes involved in growth and development and nutrient transfer was strongly reduced. In contrast, placental size and weight were increased in enhanced growth P-D and S-D foals. The trophoblastic surface density and the allantoic vessels surface density were decreased in P-D and S-D, respectively, both with very few modifications in gene expression. Control embryos were produced by artificial insemination whereas experimental embryos were produced by ET. Placental structure and gene expression are modified after ET into a smaller or larger breed than that of the embryo. These adaptations contribute to the observed phenotype of foal growth restriction or enhanced growth at birth. © 2017 EVJ Ltd.

  16. Development of Humane Interpersonal Relationships

    Science.gov (United States)

    Kleptsova, Elena Yuryevna; Balabanov, Anton Anatolyevich

    2016-01-01

    The article reflects some theoretical aspects of humanization of interpersonal relationships in the sphere of education. The notion "humanization of interpersonal relationships" is being analyzed. The authors offer a characterization of some parameters of relationships: orientation, modality, valence, intensity, awareness,…

  17. Early development of the human pelvic diaphragm

    NARCIS (Netherlands)

    Koch, Wijnandus Franciscus Robertus Maria

    2006-01-01

    The last decade an increasing interest in the pelvic floor can be observed in medical sciences. The lack of data on the development of the human pelvic floor is striking. The early development of the human pelvic diaphragm was studied. Materials and methodsUse was made of 38 human embryos and

  18. Why did humans develop a large brain?

    OpenAIRE

    Muscat Baron, Yves

    2012-01-01

    "Of all animals, man has the largest brain in proportion to his size"- Aristotle. Dr Yves Muscat Baron shares his theory on how humans evolved large brains. The theory outlines how gravity could have helped humans develop a large brain- the author has named the theory 'The Gravitational Vascular Theory'. http://www.um.edu.mt/think/why-did-humans-develop-a-large-brain/

  19. Assisted reproduction causes placental maldevelopment and dysfunction linked to reduced fetal weight in mice.

    Science.gov (United States)

    Chen, Shuqiang; Sun, Fang-zhen; Huang, Xiuying; Wang, Xiaohong; Tang, Na; Zhu, Baoyi; Li, Bo

    2015-06-18

    Compelling evidence indicates that stress in utero, as manifested by low birth weight (LBW), increases the risk of metabolic syndrome in adulthood. Singletons conceived by assisted reproductive technology (ART) display a significant increase in LBW risk and ART offspring have a different metabolic profile starting at birth. Here, used mouse as a model, we found that ART resulted in reduced fetal weight and placental overgrowth at embryonic day 18.5 (E18.5). The ART placentae exhibited histomorphological alterations with defects in placental layer segregation and glycogen cells migration at E18.5. Further, ART treatments resulted in downregulation of a majority of placental nutrient transporters and reduction in placental efficiency. Moreover, the ART placentae were associated with increased methylation levels at imprinting control regions of H19, KvDMR1 and disrupted expression of a majority of imprinted genes important for placental development and function at E18.5. Our results from the mouse model show the first piece of evidence that ART treatment could affect fetal growth by disrupting placental development and function, suggests that perturbation of genomic imprinting resulted from embryo manipulation may contribute to these problems.

  20. Partial separation of platelet and placental adenosine receptors from adenosine A2-like binding protein

    International Nuclear Information System (INIS)

    Zolnierowicz, S.; Work, C.; Hutchison, K.; Fox, I.H.

    1990-01-01

    The ubiquitous adenosine A2-like binding protein obscures the binding properties of adenosine receptors assayed with 5'-N-[ 3 H]ethylcarboxamidoadenosine [( 3 H]NECA). To solve this problem, we developed a rapid and simple method to separate adenosine receptors from the adenosine A2-like binding protein. Human platelet and placental membranes were solubilized with 1% 3-[(3-cholamidopropyl)dimethylammonio]-1-propanesulfonate. The soluble platelet extract was precipitated with polyethylene glycol and the fraction enriched in adenosine receptors was isolated from the precipitate by differential centrifugation. The adenosine A2-like binding protein was removed from the soluble placental extract with hydroxylapatite and adenosine receptors were precipitated with polyethylene glycol. The specificity of the [ 3 H]NECA binding is typical of an adenosine A2 receptor for platelets and an adenosine A1 receptor for placenta. This method leads to enrichment of adenosine A2 receptors for platelets and adenosine A1 receptors for placenta. This provides a useful preparation technique for pharmacologic studies of adenosine receptors

  1. HUMAN CAPITAL DEVELOPMENT: A STRATEGY FOR MOVING ...

    African Journals Online (AJOL)

    economy” but also “Knowledge economy” via human capital development. She has not been serious with her ... economy, Human capital, Strategy. Introduction. The world is now controlled by the revolution of Information and Communication.

  2. 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, t...

  3. 3D Power Doppler ultrasound and computerised placental assessment in normal pregnancy

    International Nuclear Information System (INIS)

    Moran, Mary; Zombori, Gergely; Ryan, John; McAuliffe, Fionnuala M.

    2014-01-01

    Background: In recent years there have been significant developments in the use of 3D Power Doppler (3DPD) imaging and quantitative 3DPD histogram analysis to estimate both placental volume and intra-placental vasculature. This study aims to determine if placental volume, vascularisation and blood flow are correlated with gestational age in normal pregnancy. It also examines whether or not a new software method for analysis of percentage calcification (the ‘placentometer’) correlates well with gestation. Material and method: This was a prospective cohort study of 250 women with normal pregnancies (12 + 6 to 39 + 5 weeks gestation). 3DPD ultrasound was used to evaluate placental volume, vascularisation index (VI), flow index (FI) and vascularisation-flow index (VFI). Placental volume (calculated at 35–40 weeks gestation), was correlated with birth weight. Following each scan the percentage of calcification was also calculated using the placentometer. Results: Placental volume correlated significantly with gestational age: 66.676 + 0.623 × GA (P < 0.001). No significant change with gestation was noted in VI, FI and VFI (VI: P = 0.199, FI: P = 0.299, VFI: P = 0.557). Software analysis of the percentage of calcification, demonstrated the expected increase in calcification as gestation increased: −4.605 + 0.032 × GA (P < 0.001). From 35 to 40 weeks gestation volume was related to birth weight (P < 0.01). Conclusion: This study shows that in normal low-risk pregnancy placental volume increases with gestational age, whereas vascularisation and blood flow are independent of gestation. Placental volume in late pregnancy is related to birth weight. Software analysis of the percentage of calcification demonstrates an increase with advancing gestation

  4. Protein Profiling of Preeclampsia Placental Tissues

    OpenAIRE

    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

    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 expres...

  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......PGH was not correlated to the increase in insulin requirements, nor was any consistent relationship revealed during each gestational period. In conclusion, our study suggests a role for hPGH in the regulation of both IGFs and fetal growth in type 1 diabetes. In contrast, the increase in insulin requirements during...... pregnancy in type 1 diabetic subjects could not be related to hPGH levels....

  6. Placental invasion, preeclampsia risk and adaptive molecular evolution at the origin of the great apes: evidence from genome-wide analyses.

    Science.gov (United States)

    Crosley, E J; Elliot, M G; Christians, J K; Crespi, B J

    2013-02-01

    Recent evidence from chimpanzees and gorillas has raised doubts that preeclampsia is a uniquely human disease. The deep extravillous trophoblast (EVT) invasion and spiral artery remodeling that characterizes our placenta (and is abnormal in preeclampsia) is shared within great apes, setting Homininae apart from Hylobatidae and Old World Monkeys, which show much shallower trophoblast invasion and limited spiral artery remodeling. We hypothesize that the evolution of a more invasive placenta in the lineage ancestral to the great apes involved positive selection on genes crucial to EVT invasion and spiral artery remodeling. Furthermore, identification of placentally-expressed genes under selection in this lineage may identify novel genes involved in placental development. We tested for positive selection in approximately 18,000 genes using the ratio of non-synonymous to synonymous amino acid substitution for protein-coding DNA. DAVID Bioinformatics Resources identified biological processes enriched in positively selected genes, including processes related to EVT invasion and spiral artery remodeling. Analyses revealed 295 and 264 genes under significant positive selection on the branches ancestral to Hominidae (Human, Chimp, Gorilla, Orangutan) and Homininae (Human, Chimp, Gorilla), respectively. Gene ontology analysis of these gene sets demonstrated significant enrichments for several functional gene clusters relevant to preeclampsia risk, and sets of placentally-expressed genes that have been linked with preeclampsia and/or trophoblast invasion in other studies. Our study represents a novel approach to the identification of candidate genes and amino acid residues involved in placental pathologies by implicating them in the evolution of highly-invasive placenta. Copyright © 2012 Elsevier Ltd. All rights reserved.

  7. Placental responses to changes in the maternal environment determine fetal growth

    Directory of Open Access Journals (Sweden)

    Kris Genelyn eDimasuay

    2016-01-01

    Full Text Available Placental responses to maternal perturbations are complex and remain poorly understood. Altered maternal environment during pregnancy such as hypoxia, stress, obesity, diabetes, toxins, altered nutrition, inflammation, and reduced utero-placental blood flow may influence fetal development, which can predispose to diseases later in life. The placenta being a metabolically active tissue responds to these perturbations by regulating the fetal supply of nutrients and oxygen and secretion of hormones into the maternal and fetal circulation. We have proposed that placental nutrient sensing integrates maternal and fetal nutritional cues with information from intrinsic nutrient sensing signaling pathways to balance fetal demand with the ability of the mother to support pregnancy by regulating maternal physiology, placental growth, and placental nutrient transport. Emerging evidence suggests that the nutrient-sensing signaling pathway mechanistic target of rapamycin (mTOR plays a central role in this process. Thus, placental nutrient sensing plays a critical role in modulating maternal-fetal resource allocation, thereby affecting fetal growth and the life-long health of the fetus.

  8. Growth and development of the placenta in the capybara (Hydrochaeris hydrochaeris)

    DEFF Research Database (Denmark)

    Kanashiro, Claudia; Santos, Tatiana C; Miglino, Maria Angelica

    2009-01-01

    BACKGROUND: The guinea pig is an attractive model for human pregnancy and placentation, mainly because of its haemomonochorial placental type, but is rather small in size. Therefore, to better understand the impact of body mass, we studied placental development in the capybara which has a body mass...... around 50 kg and a gestation period of around 150 days. We paid attention to the development of the lobulated arrangement of the placenta, the growth of the labyrinth in the course of gestation, the differentiation of the subplacenta, and the pattern of invasion by extraplacental trophoblast. METHODS...... found in smaller hystricognath rodents including the guinea pig. These features apparently do not dependent on body size. Clearly, placentation in hystricognaths adheres to an extraordinarily stable pattern suggesting they can be used interchangeably as models of human placenta....

  9. Annals of Humanities and Development Studies

    African Journals Online (AJOL)

    The Annals of Humanities and Development Studies publishes papers in all aspects of humanities and rural, social and cultural development, including peace and international cooperation activities related to societal transformation in developing countries. Papers arising from original research and case studies or forming ...

  10. Quality Communication For human development

    Directory of Open Access Journals (Sweden)

    Federico Mayor Zaragoza

    2017-10-01

    Full Text Available In the digital age, the Media are today, fortunately, affordable instruments that progressively allow all human beings –up to now confined and silent– to know what is happening anywhere in the world, being able, in addition, to express their own views and opinions. This article insists on the value of Communication to achieve the equality of the human being in all the senses. “The same dignity –writes the author– as the foundation of the world we long for.”

  11. Maternal and placental melatonin: actions and implication for successful pregnancies.

    Science.gov (United States)

    Sagrillo-Fagundes, L; Soliman, A; Vaillancourt, C

    2014-06-01

    Melatonin is one of the main sources of mitochondrial protection and its protective effects are equal or even better if compared with several consecrated antioxidants. Furthermore, the activation of specific melatonin receptors triggers several cellular pathways that improve the oxidoreduction and inflammatory cellular state. The discovery of the melatoninergic machinery in placental cells was the first step to understand the effects of this indoleamine during pregnancy. In critical points of pregnancy, melatonin has been pointed as a protagonist and its beneficial effects have been shown as essential for the control of trophoblastic function and development. On the contrary of the plasmatic melatonin (produced in pineal gland), placental melatonin does not vary according to the circadian cycle and acts as an autocrine, paracrine, intracrine, and endocrine hormone. The important effects of melatonin in placenta have been demonstrated in the physiopathology of pre-eclampsia with alterations in the levels of melatonin and in the expression of its receptors and synthetizing enzymes. Some authors suggested melatonin as a biomarker of pre-eclampsia and as a possible treatment for this disease and other obstetric pathologies associated with placental defect and increases in oxidative stress. This review will approach the beneficial effects of melatonin on placenta homeostasis and consequently on pregnancy and fetal health.

  12. Do macromorphological features of the human placenta influence somatic and psychomotor development of the newborn and early infant? A historic question revisited.

    Science.gov (United States)

    Westhof, Gregor; Deerberg, Jost C; Schad, Wolfgang; Zimmermann, Ralf C; Hatzmann, Hendrike

    2010-01-01

    We examined the meaning of placental weight, form (massive and thick or extended and flat) and circumference for early somatic and psychomotor childhood development. In this prospective study, fresh placentas (n = 265) were measured for weight and circumference and correlated with neonatal data. A subset of placentas statistically defined as 'massive' (circumference 90th percentile) was correlated with somatic and basic psychomotor variables during the first 4 years of life. A 'medium' category (circumference 45-55th percentile) served as control. Placental weight correlated with birth weight (r = 0.53, p psychomotor development (first sitting, crawling, running, one- and two-word sentences) were not related with placental weight or circumference nor with extremes of placental morphology. Placental weight and circumference seem to influence very early somatic but not psychomotor development. Copyright (c) 2010 S. Karger AG, Basel.

  13. Deoxynivalenol transport across the human placental barrier

    DEFF Research Database (Denmark)

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

    2011-01-01

    Deoxynivalenol (DON) is the most commonly detected mycotoxin contaminant of cereal crops and cereal based food products in temperate regions of the world. DON causes adverse health effects in animals, passes through to the foetus and causes foetal abnormalities in animals. Biomonitoring for DON has...

  14. Placental dysfunction in Suramin-treated rats: impact of maternal diabetes and effects of antioxidative treatment.

    Science.gov (United States)

    Nash, Peppi; Olovsson, Matts; Eriksson, Ulf J

    2005-04-01

    The aim of the present study was to evaluate a rat model of placental dysfunction/preeclampsia in pregnancies complicated by maternal diabetes. A second objective was to evaluate the effects of vitamin E treatment in this model. Normal and streptozotocin-induced diabetic rats of two different strains (U and H) were given intraperitoneal (IP) injections of the angiogenesis inhibitor Suramin (Sigma Chemical Co, St Louis, MO) or saline in early pregnancy, and fed standard or vitamin E-enriched food. The outcome of pregnancy was evaluated on gestational day 20. In both rat strains Suramin caused fetal growth retardation, decreased placental blood flow, and increased placental concentration of the isoprostane 8-iso-PGF(2alpha). In the U rats Suramin also caused increased fetal resorption rate, increased maternal blood pressure, decreased renal blood flow, and diminished maternal growth. Diabetes caused severe maternal and fetal growth retardation, increased resorption rate, and increased placental 8-iso-PGF(2alpha) concentration independent of Suramin administration. The maternal and fetal effects of Suramin and diabetes were more pronounced in the U strain than in the H strain. Vitamin E treatment improved the status of Suramin-injected diabetic rats: in U rats the blood pressure increase was normalized; and in both U and H rats the decreased placental blood flow was marginally enhanced, and the increase in placental 8-iso-PGF(2alpha) was partly normalized by vitamin E. Suramin injections to pregnant rats cause a state of placental insufficiency, which in U rats resembles human preeclampsia. The induction of this condition is at least partly mediated by oxidative stress, and antagonized by antioxidative treatment. Maternal diabetes involves increased oxidative stress, and causes both maternal and fetal morbidity, which are only marginally affected by additional Suramin treatment.

  15. Placental transfer of other radionuclides

    International Nuclear Information System (INIS)

    Stieve, F.-E.

    1987-01-01

    This paper comments upon some basic principles of the transfer of radioactive substances in human beings to the embryo and fetus and their age-dependence. These principles may apply to the main effects currently known from the uptake, accumulation, retention and excretion of those radioactive substances, which may be of special interest in assessing the dose and therefore the risk of exposure in nuclear medicine, in connection with environmental problems of nuclear power production as well as nuclear explosions. As an example the age-dependence of several typical radionuclides and their age-dependence during the development of the human embryo and fetus and its correlation to observations on several animal species are presented. 30 refs.; 5 figs

  16. Learning Human Aspects of Collaborative Software Development

    Science.gov (United States)

    Hadar, Irit; Sherman, Sofia; Hazzan, Orit

    2008-01-01

    Collaboration has become increasingly widespread in the software industry as systems have become larger and more complex, adding human complexity to the technological complexity already involved in developing software systems. To deal with this complexity, human-centric software development methods, such as Extreme Programming and other agile…

  17. Virtual reality imaging techniques in the study of embryonic and early placental health.

    Science.gov (United States)

    Rousian, Melek; Koster, Maria P H; Mulders, Annemarie G M G J; Koning, Anton H J; Steegers-Theunissen, Régine P M; Steegers, Eric A P

    2018-04-01

    Embryonic and placental growth and development in the first trimester of pregnancy have impact on the health of the fetus, newborn, child and even the adult. This emphasizes the importance of this often neglected period in life. The development of three-dimensional transvaginal ultrasonography in combination with virtual reality (VR) opens the possibility of accurate and reliable visualization of embryonic and placental structures with real depth perception. These techniques enable new biometry and volumetry measurements that contribute to the knowledge of the (patho)physiology of embryonic and early placental health. Examples of such measurements are the length of complex structures like the umbilical cord, vitelline duct, limbs and cerebellum or the volume of the whole embryo and brain cavities. Moreover, for the first time, embryos can now be staged in vivo (Carnegie stages) and vasculature volumes of both the embryo and the early placenta can be measured when VR is combined with power Doppler signals. These innovative developments have already been used to study associations between periconceptional maternal factors, such as age, smoking, alcohol use, diet and vitamin status, and embryonic and early placental growth and development. Future studies will also focus on the identification of abnormal embryonic and early placental development already in the earliest weeks of pregnancy, which provides opportunities for early prevention of pregnancy complications. Copyright © 2018 IFPA, Elsevier Ltd. Published by Elsevier Ltd.. All rights reserved.

  18. Placental IGF-1 and IGFBP-3 expression correlate with umbilical cord blood PAH and PBDE levels from prenatal exposure to electronic waste

    International Nuclear Information System (INIS)

    Xu, Xijin; Yekeen, Taofeek Akangbe; Xiao, Qiongna; Wang, Yuangping; Lu, Fangfang; Huo, Xia

    2013-01-01

    Electronic waste recycling produces Polycyclic Aromatic Hydrocarbons (PAHs) and Polybrominated Diphenyl Ethers (PBDEs) which may affect fetal growth and development by altering the insulin-like-growth factor (IGF) system. Questionnaires were administered to pregnant women (Guiyu, an e-waste site, n = 101; control, n = 53), and umbilical cord blood (UCB) and placentas were collected upon delivery. PBDEs and PAHs in UCB and placental IGF-1 and IGFBP-3 mRNA levels were analyzed using GC–MS and real-time PCR, respectively. Infant birth length and Apgar scores were lower in Guiyu. All PAHs (except Fl, Chr, IP, BbF and BP), total 16-PAHs, total/individual PBDEs, placental IGF-1 (median 0.23 vs 0.19; P < 0.05) and IGFBP-3 (median 1.91 vs 0.68; P < 0.001) levels were significantly higher in Guiyu. Spearman correlation showed that BDE-154, BDE-209 and ∑5ring-PAHs positively correlate with IGF-1 while PBDEs, 4 rings and total PAHs correlate with IGFBP-3 expression. Increased placental IGF-1 level might indirectly affect fetal growth and development. -- Highlights: •PAHs and PBDEs from e-waste may affect fetal growth via alteration of IGF system. •Infant birth length and Apgar scores were lower in Guiyu compared to Chaoan. •Most PAHs, all PBDEs, IGF-1 and IGFBP-3 levels were significantly higher in Guiyu. •IGF-1 positively correlates with BDE-154, BDE-209 and ∑5ring-PAHs. •The observed increase in IGF-1 might indirectly affect fetal growth and development. -- The correlation between POPs and placental IGF-1 and IGFBP-3 assessed provides more information on the human health risk associated with electronic waste

  19. Artificial intelligence and human development

    International Development Research Centre (IDRC) Digital Library (Canada)

    Job and tax revenue loss through automation: With the growing use of machine .... practices that support the development of inclusive AI applications. What ..... been tested in Malaysia and in Queen Elizabeth National Park in Uganda.25 ...... We need to develop global and local values and principles for AI that prioritize.

  20. Human Resources in Geothermal Development

    Energy Technology Data Exchange (ETDEWEB)

    Fridleifsson, I.B.

    1995-01-01

    Some 80 countries are potentially interested in geothermal energy development, and about 50 have quantifiable geothermal utilization at present. Electricity is produced from geothermal in 21 countries (total 38 TWh/a) and direct application is recorded in 35 countries (34 TWh/a). Geothermal electricity production is equally common in industrialized and developing countries, but plays a more important role in the developing countries. Apart from China, direct use is mainly in the industrialized countries and Central and East Europe. There is a surplus of trained geothermal manpower in many industrialized countries. Most of the developing countries as well as Central and East Europe countries still lack trained manpower. The Philippines (PNOC) have demonstrated how a nation can build up a strong geothermal workforce in an exemplary way. Data from Iceland shows how the geothermal manpower needs of a country gradually change from the exploration and field development to monitoring and operations.

  1. Protecting the fetus against HIV infection: a systematic review of placental transfer of antiretrovirals.

    Science.gov (United States)

    McCormack, Shelley A; Best, Brookie M

    2014-11-01

    Maternal-to-fetal transfer of antiretroviral drugs contributes to prevention of vertical transmission of HIV. This systematic review discusses published studies containing data pertaining to the pharmacokinetics of placental transfer of antiretrovirals in humans, including paired cord and maternal plasma samples collected at the time of delivery as well as ex vivo placental perfusion models. Articles pertaining to placental transfer of antiretrovirals were identified from PubMed, from references of included articles, and from US Department of Health and Human Services Panel on Treatment of HIV-infected Pregnant Women and Prevention of Perinatal Transmission guidelines. Articles from non-human animal models or that had no original maternal-to-fetal transfer data were excluded. PRISMA guidelines were followed. A total of 103 published studies were identified. Data across studies appeared relatively consistent for the nucleoside reverse transcriptase inhibitors (NRTIs) and the non-nucleotide reverse transcriptase inhibitors (NNRTIs), with cord to maternal ratios approaching 1 for many of these agents. The protease inhibitors atazanavir and lopinavir exhibited consistent maternal-to-fetal transfer across studies, although the transfer may be influenced by variations in drug-binding proteins. The protease inhibitors indinavir, nelfinavir, and saquinavir exhibited unreliable placental transport, with cord blood concentrations that were frequently undetectable. Limited data, primarily from case reports, indicate that darunavir and raltegravir provide detectable placental transfer. These findings appear consistent with current guidelines of using two NRTIs plus an NNRTI, atazanavir/ritonavir, or lopinavir/ritonavir to maximize placental transfer as well as to optimally suppress maternal viral load. Darunavir/ritonavir and raltegravir may reasonably serve as second-line agents.

  2. The SK3 channel promotes placental vascularization by enhancing secretion of angiogenic factors.

    Science.gov (United States)

    Rada, Cara C; Murray, Grace; England, Sarah K

    2014-11-15

    Proper placental perfusion is essential for fetal exchange of oxygen, nutrients, and waste with the maternal circulation. Impairment of uteroplacental vascular function can lead to pregnancy complications, including preeclampsia and intrauterine growth restriction (IUGR). Potassium channels have been recognized as regulators of vascular proliferation, angiogenesis, and secretion of vasoactive factors, and their dysfunction may underlie pregnancy-related vascular diseases. Overexpression of one channel in particular, the small-conductance calcium-activated potassium channel 3 (SK3), is known to increase vascularization in mice, and mice overexpressing the SK3 channel (SK3(T/T) mice) have a high rate of fetal demise and IUGR. Here, we show that overexpression of SK3 causes fetal loss through abnormal placental vascularization. We previously reported that, at pregnancy day 14, placentas isolated from SK3(T/T) mice are smaller than those obtained from wild-type mice. In this study, histological analysis reveals that SK3(T/-) placentas at this stage have abnormal placental morphology, and microcomputed tomography shows that these placentas have significantly larger and more blood vessels than those from wild-type mice. To identify the mechanism by which these vascularization defects occur, we measured levels of vascular endothelial growth factor (VEGF), placental growth factor, and the soluble form of VEGF receptor 1 (sFlt-1), which must be tightly regulated to ensure proper placental development. Our data reveal that overexpression of SK3 alters systemic and placental ratios of the angiogenic factor VEGF to antiangiogenic factor sFlt-1 throughout pregnancy. Additionally, we observe increased expression of hypoxia-inducing factor 2α in SK3(T/-) placentas. We conclude that the SK3 channel modulates placental vascular development and fetal health by altering VEGF signaling. Copyright © 2014 the American Physiological Society.

  3. Effects of exposure to pesticides during pregnancy on placental maturity and weight of newborns: a cross-sectional pilot study in women from the Chihuahua State, Mexico.

    Science.gov (United States)

    Acosta-Maldonado, Brenda; Sánchez-Ramírez, Blanca; Reza-López, Sandra; Levario-Carrillo, Margarita

    2009-08-01

    It is known that pesticides cross the placental barrier and can cause alterations in the development of placental structures resulting in adverse effects in reproduction. The objectives of this study were to investigate the effects of pesticide exposure during pregnancy on placental maturity and to evaluate the relationship between placental maturity, gestational age and birth weight. We collected the placentas from singleton pregnancies from women exposed (n = 9) and non-exposed (n = 45 full-term and n = 31 preterm) to pesticides as evaluated geographically, by questionnaire and by acetylcholinesterase levels. Placental morphometry from the central and peripheral regions was examined by microscopy and staining with hematoxylin and eosin. The placental maturity index (PMI) was estimated by dividing the number of epithelial plates in terminal villi to their thickness in 1 mm(2) of the placental parenchyma. Gestational age, birth weight and the following characteristics of the mother were also recorded: pre-pregnancy body mass index, weight gain during pregnancy and hemoglobin concentrations. Birth weight and the gestational age were correlated with PMI (r = .54 and r = .44, respectively; p Pesticide exposure was associated with a higher PMI (beta = 7.38, p = .01) after adjusting by variables related to placental maturity. In conclusion, the results suggest a relationship between prenatal exposure to pesticides and placental maturity and may potentially affect the nutrient transport from the mother to the fetus.

  4. Assessment of placental volume and vascularization at 11-14 weeks of gestation in a Taiwanese population using three-dimensional power Doppler ultrasound.

    Science.gov (United States)

    Wang, Hsing-I; Yang, Ming-Jie; Wang, Peng-Hui; Wu, Yi-Cheng; Chen, Chih-Yao

    2014-12-01

    The placental volume and vascular indices are crucial in helping doctors to evaluate early fetal growth and development. Inadequate placental volume or vascularity might indicate poor fetal growth or gestational complications. This study aimed to evaluate the placental volume and vascular indices during the period of 11-14 weeks of gestation in a Taiwanese population. From June 2006 to September 2009, three-dimensional power Doppler ultrasound was performed in 222 normal pregnancies from 11-14 weeks of gestation. Power Doppler ultrasound was applied to the placenta and the placental volume was obtained by a rotational technique (VOCAL). The three-dimensional power histogram was used to assess the placental vascular indices, including the mean gray value, the vascularization index, the flow index, and the vascularization flow index. The placental vascular indices were then plotted against gestational age (GA) and placental volume. Our results showed that the linear regression equation for placental volume using gestational week as the independent variable was placental volume = 18.852 × GA - 180.89 (r = 0.481, p power Doppler ultrasonography showed a constant distribution throughout gestation. Copyright © 2014. Published by Elsevier Taiwan.

  5. Ecological Factors in Human Development.

    Science.gov (United States)

    Cross, William E

    2017-05-01

    Urie Bronfenbrenner (1992) helped developmental psychologists comprehend and define "context" as a rich, thick multidimensional construct. His ecological systems theory consists of five layers, and within each layer are developmental processes unique to each layer. The four articles in this section limit the exploration of context to the three innermost systems: the individual plus micro- and macrolayers. Rather than examine both the physical features and processes, the articles tend to focus solely on processes associated with a niche. Processes explored include social identity development, social network dynamics, peer influences, and school-based friendship patterns. The works tend to extend the generalization of extant theory to the developmental experience of various minority group experiences. © 2017 The Authors. Child Development © 2017 Society for Research in Child Development, Inc.

  6. Sustainable development, human and endogenous

    Directory of Open Access Journals (Sweden)

    Ignasi Brunet Icart

    2015-05-01

    Full Text Available This article aims to analyze the dispersion of the conceptualizations of development linked to the “Second Development Decade”. This dispersion took place within a context of knowledge-based economy, which is shaped by learning and powered by innovation. A context dominated by neoclassical economics, which marked the globalized and financial capitalism of the late twentieth century and the early twenty first century. This neoclassical hegemony results from Keynesian analysis’ discredit, the Latin-American structuralism crisis and the decadence of the critical views —de-velopment neo-Marxists.

  7. Neoliberalism, Pedagogy and Human Development

    NARCIS (Netherlands)

    Kontopodis, M.

    2012-01-01

    In most Western developed countries, adult life is increasingly organized on the basis of short-term work contracts and reduced social security funds. In this context it seems that producing efficient job-seekers and employees becomes the main aim of educational programs for the next generation.

  8. Placental mesenchymal dysplasia: case report with gross and histological findings

    Directory of Open Access Journals (Sweden)

    Marcello Pecoraro Toscano

    2014-12-01

    Full Text Available Placental mesenchymal dysplasia (PMD is a rare placental disorder characterized by placental enlargement and areas of abnormal, enlarged, grape-like villi. This condition may resemble a partial hydatidiform mole and may occur associated with Beckwith–Wiedemann syndrome (BWS or in phenotypically normal fetuses. There were 110 cases reported so far. We describe one case with typical gross and microscopic placental lesions.

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

    DEFF Research Database (Denmark)

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

    2017-01-01

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

  10. Educating the Human Brain. Human Brain Development Series

    Science.gov (United States)

    Posner, Michael I.; Rothbart, Mary K.

    2006-01-01

    "Educating the Human Brain" is the product of a quarter century of research. This book provides an empirical account of the early development of attention and self regulation in infants and young children. It examines the brain areas involved in regulatory networks, their connectivity, and how their development is influenced by genes and…

  11. Human placenta secretes apolipoprotein B-100-containing lipoproteins

    DEFF Research Database (Denmark)

    Munk-Madsen, Eva; Lindegaard, Marie Louise Skakkebæk; Andersen, Claus B

    2004-01-01

    Supply of lipids from the mother is essential for fetal growth and development. In mice, disruption of yolk sac cell secretion of apolipoprotein (apo) B-containing lipoproteins results in embryonic lethality. In humans, the yolk sac is vestigial. Nutritional functions are instead established very...... lipoproteins secreted from placental tissue showed spherical particles with a diameter of 47 +/- 10 nm. These results demonstrate that human placenta expresses both apoB and MTP and consequently synthesize and secrete apoB-100-containing lipoproteins. Placental lipoprotein formation constitutes a novel pathway...

  12. Evolution of factors affecting placental oxygen transfer

    DEFF Research Database (Denmark)

    Carter, A M

    2009-01-01

    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 sta......, 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...

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

    Science.gov (United States)

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

    2017-12-01

    Background: Little is known about placental vitamin D metabolism and its impact on maternal circulating vitamin D concentrations in humans. Objective: This study sought to advance the current understanding of placental vitamin D metabolism and its role in modulating maternal circulating vitamin D metabolites during pregnancy. Design: Nested within a feeding study, 24 healthy pregnant women (26-29 wk of gestation) consumed a single amount of vitamin D (511 IU/d from diet and a cholecalciferol supplement) for 10 wk. Concentrations of placental and blood vitamin D metabolites and placental messenger RNA (mRNA) abundance of vitamin D metabolic pathway components were quantified. In addition, cultured human trophoblasts were incubated with 13 C-cholecalciferol to examine the intracellular generation and secretion of vitamin D metabolites along with the regulation of target genes. Results: In placental tissue, 25-hydroxyvitamin D 3 [25(OH)D 3 ] was strongly correlated ( r = 0.83, P D 3 Moreover, these placental metabolites were strongly correlated ( r ≤ 0.85, P ≤ 0.04) with their respective metabolites in maternal circulation. Positive associations ( P ≤ 0.045) were also observed between placental mRNA abundance of 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

  14. Pakistan's Water Challenges: A Human Development Perspective

    NARCIS (Netherlands)

    S. Shezad (Shafqat); K.A. Siegmann (Karin Astrid)

    2006-01-01

    textabstractAbstract This paper gives an overview of the human and social dimensions of Pakistan’s water policies to provide the basis for water-related policy interventions that contribute to the country’s human development, with special attention being given to the concerns of women and the

  15. Human Resource Development in Changing Organizations.

    Science.gov (United States)

    London, Manuel; Wueste, Richard A.

    This book is intended to help managers and human resource professionals understand organizational change and manage its effects on their own development and that of their subordinates. The following topics are covered in 11 chapters: organizational change, employee motivation, new managerial roles, human performance systems, upward and peer…

  16. Instructor's Guide for Human Development Student Modules.

    Science.gov (United States)

    South Carolina State Dept. of Education, Columbia. Office of Vocational Education.

    This instructor's guide is designed for use with an accompanying set of 61 student learning modules on human development. Included among the topics covered in the individual modules are the following: consumer and homemaking education (health and nutrition, personal appearance and grooming, puberty, menstruation, the human reproductive system,…

  17. Human Capital Development: Comparative Analysis of BRICs

    Science.gov (United States)

    Ardichvili, Alexandre; Zavyalova, Elena; Minina, Vera

    2012-01-01

    Purpose: The goal of this article is to conduct macro-level analysis of human capital (HC) development strategies, pursued by four countries commonly referred to as BRICs (Brazil, Russia, India, and China). Design/methodology/approach: This analysis is based on comparisons of macro indices of human capital and innovativeness of the economy and a…

  18. A double antibody radioimmunoassay specific for placental alkaline phosphatase

    International Nuclear Information System (INIS)

    Dass, S.; Bagshawe, K.D.

    1984-01-01

    Placental alkaline phosphatase (PLAP) is normally found in enzymically measurable amounts in second and third trimester pregnancy serum. Its occurrence in sera and tumours from patients with malignant disease has led to the development of methods to specifically identify and quantitate the enzyme. Recently immunological techniques have been used, employing antibodies raised to purified PLAP; these include solid phase radioimmunoassays and enzyme-immunoassay. The development of a sensitive, specific, automated double-antibody radioimmunoassay for the measurement of PLAP in serum is reported. (Auth.)

  19. Development of the Human Placenta and Fetal Heart: Synergic or Independent?

    Directory of Open Access Journals (Sweden)

    Graham J. Burton

    2018-04-01

    Full Text Available The placenta is the largest fetal organ, and toward the end of pregnancy the umbilical circulation receives at least 40% of the biventricular cardiac output. It is not surprising, therefore, that there are likely to be close haemodynamic links between the development of the placenta and the fetal heart. Development of the placenta is precocious, and in advance of that of the fetus. The placenta undergoes considerable remodeling at the end of the first trimester of pregnancy, and its vasculature is capable of adapting to environmental conditions and to variations in the blood supply received from the mother. There are two components to the placental membranes to consider, the secondary yolk sac and the chorioallantoic placenta. The yolk sac is the first of the extraembryonic membranes to be vascularized, and condensations in the mesenchyme at ~17 days post-conception (p.c. give rise to endothelial and erythroid precursors. A network of blood vessels is established ~24 days p.c., with the vitelline vein draining through the region of the developing liver into the sinus venosus. Gestational sacs of early pregnancy failures often display aberrant development of the yolk sac, which is likely to be secondary to abnormal fetal development. Vasculogenesis occurs in the villous mesenchyme of the chorioallantoic placenta at a similarly early stage. Nucleated erythrocytes occupy the lumens of the placental capillaries and end-diastolic flow is absent in the umbilical arterial circulation throughout most of the first trimester, indicating a high resistance to blood flow. Resistance begins to fall in the umbilico-placental circulation around 12–14 weeks. During normal early pregnancy the placental capillary network is plastic, and considerable remodeling occurs in response to the local oxygen concentration, and in particular to oxidative stress. In pregnancies complicated by preeclampsia and/or fetal growth restriction, utero-placental malperfusion induces

  20. Human Resources Development Programmes in Nigerian Academic ...

    African Journals Online (AJOL)

    Samaru Journal of Information Studies ... The purpose of this study was to assess Human Resources Development (HRD) programmes of librarians ... It was suggested that for effective HRD, each university library should have a written staff

  1. 67 Philosophy and Human Development: Nigerian Context ...

    African Journals Online (AJOL)

    Philosophy and Human Development: Nigerian Context. Purissima Egbekpalu ... confronting man and his existence and the environment in which he lives. ... mind it is a very powerful medium through which necessary skills can be acquired to ...

  2. Human Resources Development in the 70s

    Science.gov (United States)

    Ludeman, Bart L.

    1977-01-01

    Discusses five major objectives (put forth by the behavioral scientist, Dr. Gordon Lippitt) for human resource development which focus on the need for teamwork among future leaders, company management, and top educators. (LAS)

  3. Resource efficiency in agricultural development: human capital ...

    African Journals Online (AJOL)

    Resource efficiency in agricultural development: human capital development perspective and poverty challenges in developing countries. ... in Nigeria and contributed about 23.9% of the Gross National Domestic product in 2016. ... Equally, the new focus on agriculture involves training on new technologies and evolving ...

  4. Placental melatonin system is present throughout pregnancy and regulates villous trophoblast differentiation.

    Science.gov (United States)

    Soliman, Ahmed; Lacasse, Andrée-Anne; Lanoix, Dave; Sagrillo-Fagundes, Lucas; Boulard, Véronique; Vaillancourt, Cathy

    2015-08-01

    Melatonin is highly produced in the placenta where it protects against molecular damage and cellular dysfunction arising from hypoxia/re-oxygenation-induced oxidative stress as observed in primary cultures of syncytiotrophoblast. However, little is known about melatonin and its receptors in the human placenta throughout pregnancy and their role in villous trophoblast development. The purpose of this study was to determine melatonin-synthesizing enzymes, arylalkylamine N-acetyltransferase (AANAT) and hydroxyindole O-methyltransferase (HIOMT), and melatonin receptors (MT1 and MT2) expression throughout pregnancy as well as the role of melatonin and its receptors in villous trophoblast syncytialization. Our data show that the melatonin generating system is expressed throughout pregnancy (from week 7 to term) in placental tissues. AANAT and HIOMT show maximal expression at the 3rd trimester of pregnancy. MT1 receptor expression is maximal at the 1st trimester compared to the 2nd and 3rd trimesters, while MT2 receptor expression does not change significantly during pregnancy. Moreover, during primary villous cytotrophoblast syncytialization, MT1 receptor expression increases, while MT2 receptor expression decreases. Treatment of primary villous cytotrophoblast with an increasing concentration of melatonin (10 pM-1 mM) increases the fusion index (syncytium formation; 21% augmentation at 1 mM melatonin vs. vehicle) and β-hCG secretion (121% augmentation at 1 mM melatonin vs. vehicle). This effect of melatonin appears to be mediated via its MT1 and MT2 receptors. In sum, melatonin machinery (synthetizing enzymes and receptors) is expressed in human placenta throughout pregnancy and promotes syncytium formation, suggesting an essential role of this indolamine in placental function and pregnancy well-being. © 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  5. Placental determinants of fetal growth: identification of key factors in the insulin-like growth factor and cytokine systems using artificial neural networks

    Directory of Open Access Journals (Sweden)

    Faleschini Elena

    2008-06-01

    Full Text Available Abstract Background Changes and relationships of components of the cytokine and IGF systems have been shown in placenta and cord serum of fetal growth restricted (FGR compared with normal newborns (AGA. This study aimed to analyse a data set of clinical and biochemical data in FGR and AGA newborns to assess if a mathematical model existed and was capable of identifying these two different conditions in order to identify the variables which had a mathematically consistent biological relevance to fetal growth. Methods Whole villous tissue was collected at birth from FGR (N = 20 and AGA neonates (N = 28. Total RNA was extracted, reverse transcribed and then real-time quantitative (TaqMan RT-PCR was performed to quantify cDNA for IGF-I, IGF-II, IGFBP-1, IGFBP-2 and IL-6. The corresponding proteins with TNF-α in addition were assayed in placental lysates using specific kits. The data were analysed using Artificial Neural Networks (supervised networks, and principal component analysis and connectivity map. Results The IGF system and IL-6 allowed to predict FGR in approximately 92% of the cases and AGA in 85% of the cases with a low number of errors. IGF-II, IGFBP-2, and IL-6 content in the placental lysates were the most important factors connected with FGR. The condition of being FGR was connected mainly with the IGF-II placental content, and the latter with IL-6 and IGFBP-2 concentrations in placental lysates. Conclusion These results suggest that further research in humans should focus on these biochemical data. Furthermore, this study offered a critical revision of previous studies. The understanding of this system biology is relevant to the development of future therapeutical interventions possibly aiming at reducing IL-6 and IGFBP-2 concentrations preserving IGF bioactivity in both placenta and fetus.

  6. Ionising radiation and the developing human brain

    International Nuclear Information System (INIS)

    Schull, W.J.

    1991-01-01

    This article reviews the effects of radiation exposure of the developing human brain. Much of the evidence has come from the prenatally exposed in Hiroshima and Nagasaki. The effects on development age, mental retardation, head size, neuromuscular performance, intelligence tests, school performance and the occurrence of convulsions are discussed. Other topics covered include the biological nature of the damage to the brain, risk estimates in human and problems in radiation protection. (UK)

  7. The development of human behaviour analysis techniques -The development of human factors technologies-

    International Nuclear Information System (INIS)

    Lee, Jung Woon; Cheon, Se Woo; Shu, Sang Moon; Park, Geun Ok; Lee, Yong Hee; Lee, Han Yeong; Park, Jae Chang; Lee, Eu Jin; Lee, Seung Hee

    1994-04-01

    This project has two major areas ; one is the development of an operator task simulation software and another is the development of human error analysis and application technologies. In this year project, the second year, for the development of an operator task simulation software, we studied the followings: - analysis of the characteristics of operator tasks, - development of operator task structures : Macro Structures, - development of an operator task simulation analyzes, - analysis of performance measures. And the followings for the development of human error analysis and application technologies : - analysis of human error mechanisms, - analysis of human error characteristics in tasks, - analysis of human error occurrence in Korean Nuclear Power Plants, - establishment of an experimental environment for human error data collection with Compact Nuclear Simulator, - basic design of a Multimedia-based Human Error Representing System. (Author)

  8. The physiologic and therapeutic role of heparin in implantation and placentation

    Directory of Open Access Journals (Sweden)

    Michela Quaranta

    2015-01-01

    Full Text Available Implantation, trophoblast development and placentation are crucial processes in the establishment and development of normal pregnancy. Abnormalities of these processes can lead to pregnancy complications known as the great obstetrical syndromes: preeclampsia, intrauterine growth restriction, fetal demise, premature prelabor rupture of membranes, preterm labor, and recurrent pregnancy loss. There is mounting evidence regarding the physiological and therapeutic role of heparins in the establishment of normal gestation and as a modality for treatment and prevention of pregnancy complications. In this review, we will summarize the properties and the physiological contributions of heparins to the success of implantation, placentation and normal pregnancy.

  9. Differential Spatiotemporal Patterns of Galectin Expression are a Hallmark of Endotheliochorial Placentation.

    Science.gov (United States)

    Conrad, Melanie L; Freitag, Nancy; Diessler, Mónica E; Hernandez, Rocío; Barrientos, Gabriela; Rose, Matthias; Casas, Luciano A; Barbeito, Claudio G; Blois, Sandra M

    2016-03-01

    Galectins influence the progress of pregnancy by regulating key processes associated with embryo-maternal cross talk, including angiogenesis and placentation. Galectin family members exert multiple roles in the context of hemochorial and epitheliochorial placentation; however, the galectin prolife in endotheliochorial placenta remains to be investigated. Here, we used immunohistochemistry to analyze galectin (gal)-1, gal-3 and gal-9 expression during early and late endotheliochorial placentation in two different species (dogs and cats). We found that during early feline gestation, all three galectin members were more strongly expressed on trophoblast and maternal vessels compared to the decidua. This was accompanied by an overall decrease of gal-1, gal-3 and gal-9 expressions in late feline gestation. In canine early pregnancy, we observed that gal-1 and gal-9 were expressed strongly in cytotrophoblast (CTB) cells compared to gal-3, and no galectin expression was observed in syncytiotrophoblast (STB) cells. Progression of canine gestation was accompanied by increased gal-1 and gal-3 expressions on STB cells, whereas gal-9 expression remained similar in CTB and STB. These data suggest that both the maternal and fetal compartments are characterized by a spatiotemporal regulation of galectin expression during endotheliochorial placentation. This strongly suggests the involvement of the galectin family in important developmental processes during gestation including immunemodulation, trophoblast invasion and angiogenesis. A conserved functional role for galectins during mammalian placental development emerges from these studies. © 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  10. Gender development and the human brain.

    Science.gov (United States)

    Hines, Melissa

    2011-01-01

    Convincing evidence indicates that prenatal exposure to the gonadal hormone, testosterone, influences the development of children's sex-typical toy and activity interests. In addition, growing evidence shows that testosterone exposure contributes similarly to the development of other human behaviors that show sex differences, including sexual orientation, core gender identity, and some, though not all, sex-related cognitive and personality characteristics. In addition to these prenatal hormonal influences, early infancy and puberty may provide additional critical periods when hormones influence human neurobehavioral organization. Sex-linked genes could also contribute to human gender development, and most sex-related characteristics are influenced by socialization and other aspects of postnatal experience, as well. Neural mechanisms underlying the influences of gonadal hormones on human behavior are beginning to be identified. Although the neural mechanisms underlying experiential influences remain largely uninvestigated, they could involve the same neural circuitry as that affected by hormones.

  11. Development of human factors design review guidelines

    Energy Technology Data Exchange (ETDEWEB)

    Lee, Jung Woon; Oh, In Suk; Suh, Sang Moon; Lee, Hyun Chul [Korea Atomic Energy Research Institute, Taejon (Korea)

    1997-10-01

    The objective of this study is to develop human factors engineering program review guidelines and alarm system review guidelines in order to resolve the two major technical issues: 25. Human Factors Engineering Program Review Model and 26. Review Criteria for Human Factors Aspects of Advanced Controls and Instrumentation, which are related to the development of human factors safety regulation guides being performed by KINS. For the development of human factors program review guidelines, we made a Korean version of NUREG-0711 and added our comments by considering Korean regulatory situation and reviewing the reference documents of NUREG-0711. We also computerized the Korean version of NUREG-0711, additional comments, and selected portion of the reference documents for the developer of safety regulation guides in KINS to see the contents comparatively at a glance and use them easily. For the development of alarm system review guidelines, we made a Korean version of NUREG/CR-6105, which was published by NRC in 1994 as a guideline document for the human factors review of alarm systems. Then we will update the guidelines by reviewing the literature related to alarm design published after 1994. (author). 12 refs., 5 figs., 2 tabs.

  12. Development of human factors design review guidelines

    International Nuclear Information System (INIS)

    Lee, Jung Woon; Oh, In Suk; Suh, Sang Moon; Lee, Hyun Chul

    1997-10-01

    The Objective of this study is to develop human factors engineering program review guidelines and alarm system review guidelines in order to resolve the two major technical issues: '25, Human factors engineering program review model' and '26, Review criteria for human actors aspects of advanced controls and instrumentation', which are related to the development of human factors safety regulation guides be ing performed by KINS. For the development of human factors program review guidelines, we made a Korean version of NUREG-0711 and added our comments by considering Korean regulatory situation and reviewing the reference documents of NUREG-0711. We also computerized the Korean version of NUREG-0711, additional comments, and selected portion of the reference documents for the developer of safety regulation guides in KINS to see the contents comparatively at a glance and use them easily. For the development of alarm system review guidelines, we made a Korean version of NUREG/CR-6105, which was published by NRC in 1994 as a guideline document for the human factors review of alarm systems. Then we well update the guidelines by reviewing the literature related to alarm design published after 1994

  13. Quality assessment of a placental perfusion protocol

    DEFF Research Database (Denmark)

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

    2010-01-01

    mlh(-1) from the fetal reservoir) when adding 2 (n=7) and 20mg (n=9) FITC-dextran/100ml fetal perfusion media. Success rate of the Copenhagen placental perfusions is provided in this study, including considerations and quality control parameters. Three checkpoints suggested to determine success rate...

  14. 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%

  15. Placental transfer of plutonium and other actinides

    International Nuclear Information System (INIS)

    Griessl, I.; Stieve, F.E.

    1988-10-01

    The report is based on an extensive literature search. All data available from studies on placental transfer of plutonium and other actinides in man and animals have been collected and analysed, and the report presents the significant results as well as unresolved questions and knowledge gaps which may serve as a waypost to future research work. (orig./MG) [de

  16. 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.

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

    African Journals Online (AJOL)

    The study was prospective and conducted in a low-income setting. A total of 130 non-anomalous singleton FGR pregnancies (≥24 weeks) were included in the study. All pregnancies were confirmed to be small for gestational age (SGA) after the birth of the neonate. The placental lesions and neonatal outcomes were ...

  18. 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...

  19. Nitric oxide synthase and oxidative-nitrosative stress play a key role in placental infection by Trypanosoma cruzi.

    Science.gov (United States)

    Triquell, María Fernanda; Díaz-Luján, Cintia; Romanini, María Cristina; Ramirez, Juan Carlos; Paglini-Oliva, Patricia; Schijman, Alejandro Gabriel; Fretes, Ricardo Emilio

    2018-03-25

    The innate immune response of the placenta may participate in the congenital transmission of Chagas disease through releasing reactive oxygen and nitrogen intermediates. Placental explants were cultured with 1 × 10 6 and 1 × 10 5 trypomastigotes of Tulahuen and Lucky strains and controls without parasites, and with the addition of nitric oxide synthase inhibitor Nω-Nitro-l-arginine methyl ester (l-NAME) and N-acetyl cysteine (NAC) as the reactive oxygen species (ROS) scavenger. Detachment of the syncytiotrophoblast (STB) was examined by histological analysis, and the nitric oxide synthase, endothelial (eNOS), and nitrotyrosine expressions were analyzed by immunohistochemistry, as well as the human chorionic gonadotrophin (hCG) levels in the culture supernatant through ELISA assays. Parasite load with qPCR using Taqman primers was quantified. The higher number of T. cruzi (10 6 ) increased placental infection, eNOS expression, nitrosative stress, and STB detachment, with the placental barrier being injured by oxidative stress. The higher number of parasites caused deleterious consequences to the placental barrier, and the inhibitors (l-NAME and NAC) prevented the damage caused by trypomastigotes in placental villi but not that of the infection. Moreover, trophoblast eNOS played a key role in placental infection with the highest inoculum of Lucky, demonstrating the importance of the enzyme and nitrosative-oxidative stress in Chagas congenital transmission. © 2018 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  20. Differential proteomic expression of human placenta and fetal development following e-waste lead and cadmium exposure in utero

    Energy Technology Data Exchange (ETDEWEB)

    Xu, Long; Ge, Jingjing; Huo, Xia; Zhang, Yuling [Laboratory of Environmental Medicine and Developmental Toxicology, Shantou University Medical College, Shantou 515041 (China); Lau, Andy T.Y. [Laboratory of Cancer Biology and Epigenetics, Shantou University Medical College, Shantou 515041 (China); Department of Cell Biology and Genetics, Shantou University Medical College, Shantou 515041 (China); Xu, Xijin, E-mail: xuxj@stu.edu.cn [Laboratory of Environmental Medicine and Developmental Toxicology, Shantou University Medical College, Shantou 515041 (China); Department of Cell Biology and Genetics, Shantou University Medical College, Shantou 515041 (China)

    2016-04-15

    ABSTRACT: Prenatal exposure to lead (Pb) and cadmium (Cd) has been associated with a series of physiological problems resulting in fetal growth restriction. We aimed to investigate the effects of Pb and Cd exposure on placental function and the potential mechanisms involved in fetal development. Placental specimens and questionnaires were collected from an e-waste area and a reference area in China. Two-dimensional electrophoresis combined with MALDI-TOF-MS/MS and molecular network relationship were performed to analyze differentially expressed proteins using a compositing sample pool. Compared with the reference group, the exposed group exhibited significantly higher levels of placental Pb and Cd (p < 0.01), shorter body length and higher gestational age (p < 0.01). After bivariate adjustment in a linear regression model, decreases of 205.05 g in weight and 0.44 cm in body length were associated with a 10 ng/g wt increase in placental Cd. Pb showed a negative trend but lacked statistical significance. Proteomic analysis showed 32 differentially-expressed proteins and were predominantly involved in protein translocation, cytoskeletal structure, and energy metabolism. Fumarate hydratase was down-regulated in the exposed placenta tissues and validated by ELISA. Alterations in placental proteome suggest that imbalances in placental mitochondria respiration might be a vital pathway targeting fetal growth restriction induced by exposure to Cd. - Highlights: • The placental Pb and Cd levels were higher in the e-waste polluted area. • Proteome in placenta tissues was performed by two-dimensional gel electrophoresis. • Cd exposure in the placenta was associated with the reduced fetal development. • 32 proteins covered in translocation, energy metabolism and cytoskeletal structure. • Dysregulated mitochondrial respiration may act in the Cd-reduced fetal development.

  1. Differential proteomic expression of human placenta and fetal development following e-waste lead and cadmium exposure in utero

    International Nuclear Information System (INIS)

    Xu, Long; Ge, Jingjing; Huo, Xia; Zhang, Yuling; Lau, Andy T.Y.; Xu, Xijin

    2016-01-01

    ABSTRACT: Prenatal exposure to lead (Pb) and cadmium (Cd) has been associated with a series of physiological problems resulting in fetal growth restriction. We aimed to investigate the effects of Pb and Cd exposure on placental function and the potential mechanisms involved in fetal development. Placental specimens and questionnaires were collected from an e-waste area and a reference area in China. Two-dimensional electrophoresis combined with MALDI-TOF-MS/MS and molecular network relationship were performed to analyze differentially expressed proteins using a compositing sample pool. Compared with the reference group, the exposed group exhibited significantly higher levels of placental Pb and Cd (p < 0.01), shorter body length and higher gestational age (p < 0.01). After bivariate adjustment in a linear regression model, decreases of 205.05 g in weight and 0.44 cm in body length were associated with a 10 ng/g wt increase in placental Cd. Pb showed a negative trend but lacked statistical significance. Proteomic analysis showed 32 differentially-expressed proteins and were predominantly involved in protein translocation, cytoskeletal structure, and energy metabolism. Fumarate hydratase was down-regulated in the exposed placenta tissues and validated by ELISA. Alterations in placental proteome suggest that imbalances in placental mitochondria respiration might be a vital pathway targeting fetal growth restriction induced by exposure to Cd. - Highlights: • The placental Pb and Cd levels were higher in the e-waste polluted area. • Proteome in placenta tissues was performed by two-dimensional gel electrophoresis. • Cd exposure in the placenta was associated with the reduced fetal development. • 32 proteins covered in translocation, energy metabolism and cytoskeletal structure. • Dysregulated mitochondrial respiration may act in the Cd-reduced fetal development.

  2. DNA Methylation Landscapes of Human Fetal Development

    NARCIS (Netherlands)

    Slieker, Roderick C.; Roost, Matthias S.; van Iperen, Liesbeth; Suchiman, H. Eka D; Tobi, Elmar W.; Carlotti, Françoise; de Koning, Eelco J P; Slagboom, P. Eline; Heijmans, Bastiaan T.; Chuva de Sousa Lopes, Susana M.

    2015-01-01

    Remodelling the methylome is a hallmark of mammalian development and cell differentiation. However, current knowledge of DNA methylation dynamics in human tissue specification and organ development largely stems from the extrapolation of studies in vitro and animal models. Here, we report on the DNA

  3. Signaling hierarchy regulating human endothelial cell development

    Science.gov (United States)

    Our present knowledge of the regulation of mammalian endothelial cell differentiation has been largely derived from studies of mouse embryonic development. However, unique mechanisms and hierarchy of signals that govern human endothelial cell development are unknown and, thus, explored in these stud...

  4. Human Resource Development in the Knowledge Economy

    DEFF Research Database (Denmark)

    Jørgensen, Sanne Lehmann

    . In this line of thinking, the aim is to propose a model for analysing the progress of knowledge improvements in developing countries as an outcome of the management of human, social and organisational capital. In this regard, the paper considers relevant practices and strategies in the context of developing...

  5. [Experimental validation of the efficacy of laser-magnetic therapy for chronic placental insufficiency].

    Science.gov (United States)

    Ordzhonikidze, N V; Filimonov, V G; Klimenko, P A; Kondrikov, N I; Akin'shina, V S; Berlin, Iu V

    1994-01-01

    A new pathogenetically based non-medicamentous method for correction of uteroplacental bloodflow disturbances has been developed on the model of chronic placental insufficiency in rats. A single 5 min laser-magnetic exposure on day 21 of normal pregnancy resulted in a vasodilating effect with reduction of the peripheral resistance in the uterine horn vessels and with improvement of their blood supply. A new LAMA laser magneto-therapeutic device was employed. Daily 5 min sessions of laser magnetic therapy administered to rats with chronic placental insufficiency from pregnancy days 15-16 to 21 normalized uterine horn contractility and resulted in positive morphofunctional changes in the components of the uterine horns and placenta, being associated with a noticeable improvement of fetal functions. Hence, laser magnetic therapy may be regarded as an effective non-drug method for therapy of chronic placental insufficiency.

  6. Fetal liver blood flow distribution: role in human developmental strategy to prioritize fat deposition versus brain development.

    Directory of Open Access Journals (Sweden)

    Keith M Godfrey

    Full Text Available Among primates, human neonates have the largest brains but also the highest proportion of body fat. If placental nutrient supply is limited, the fetus faces a dilemma: should resources be allocated to brain growth, or to fat deposition for use as a potential postnatal energy reserve? We hypothesised that resolving this dilemma operates at the level of umbilical blood distribution entering the fetal liver. In 381 uncomplicated pregnancies in third trimester, we measured blood flow perfusing the fetal liver, or bypassing it via the ductus venosus to supply the brain and heart using ultrasound techniques. Across the range of fetal growth and independent of the mother's adiposity and parity, greater liver blood flow was associated with greater offspring fat mass measured by dual-energy X-ray absorptiometry, both in the infant at birth (r = 0.43, P<0.001 and at age 4 years (r = 0.16, P = 0.02. In contrast, smaller placentas less able to meet fetal demand for essential nutrients were associated with a brain-sparing flow pattern (r = 0.17, p = 0.02. This flow pattern was also associated with a higher degree of shunting through ductus venosus (P = 0.04. We propose that humans evolved a developmental strategy to prioritize nutrient allocation for prenatal fat deposition when the supply of conditionally essential nutrients requiring hepatic inter-conversion is limited, switching resource allocation to favour the brain if the supply of essential nutrients is limited. Facilitated placental transfer mechanisms for glucose and other nutrients evolved in environments less affluent than those now prevalent in developed populations, and we propose that in circumstances of maternal adiposity and nutrient excess these mechanisms now also lead to prenatal fat deposition. Prenatal developmental influences play important roles in the human propensity to deposit fat.

  7. Glucosamine supplementation affects placental development in swine

    Science.gov (United States)

    Previous studies indicated that the depth of the folds of the endometrial epithelial-fetal trophoblast bilayer of the pig placenta is increased in the placenta of small fetuses during late gestation, and that hyaluronan metabolism plays a role in the process. Given this, we hypothesized that glucosa...

  8. Signaling hierarchy regulating human endothelial cell development.

    Science.gov (United States)

    Kelly, Melissa A; Hirschi, Karen K

    2009-05-01

    Our present knowledge of the regulation of mammalian endothelial cell differentiation has been largely derived from studies of mouse embryonic development. However, unique mechanisms and hierarchy of signals that govern human endothelial cell development are unknown and, thus, explored in these studies. Using human embryonic stem cells as a model system, we were able to reproducibly and robustly generate differentiated endothelial cells via coculture on OP9 marrow stromal cells. We found that, in contrast to studies in the mouse, bFGF and VEGF had no specific effects on the initiation of human vasculogenesis. However, exogenous Ihh promoted endothelial cell differentiation, as evidenced by increased production of cells with cobblestone morphology that coexpress multiple endothelial-specific genes and proteins, form lumens, and exhibit DiI-AcLDL uptake. Inhibition of BMP signaling using Noggin or BMP4, specifically, using neutralizing antibodies suppressed endothelial cell formation; whereas, addition of rhBMP4 to cells treated with the hedgehog inhibitor cyclopamine rescued endothelial cell development. Our studies revealed that Ihh promoted human endothelial cell differentiation from pluripotent hES cells via BMP signaling, providing novel insights applicable to modulating human endothelial cell formation and vascular regeneration for human clinical therapies.

  9. The Institutional Paradigm of Human Capital Development

    Directory of Open Access Journals (Sweden)

    Kolomiiets Viktoriia М.

    2018-03-01

    Full Text Available The formation of the modern conception of human capital is connected with the development of post-industrial information society, knowledge economy and digital economy. The main role in analyzing of the content and role of human capital can play a new institutional economic theory. It is determined that the methodology of research of paradigm change in economic science remains the subject of discussion. The conception of institutional paradigm of human capital development can be attributed to the new economy, the development of which is carried out on the condition that the employee is not always alienated from the relationships of ownership: he himself becomes the owner of the «new» economic resources. The factors of education along with the factors of health care which are determining in the development of human capital are researched. Special attention is paid to education, as it acts as an intellectual capital of the new economy, where knowledge and skills become the «intellectual 5D printer», producing the modern human capital. The transition to a new, post-industrial economy is characterized by a major long-term tendency: the progress of knowledge and the increasing complexity of the socio-economic life; created by powerful factors of information and computer technologies and leading to expansion of global economic space.

  10. The development of human behavior analysis techniques

    International Nuclear Information System (INIS)

    Lee, Jung Woon; Lee, Yong Hee; Park, Geun Ok; Cheon, Se Woo; Suh, Sang Moon; Oh, In Suk; Lee, Hyun Chul; Park, Jae Chang.

    1997-07-01

    In this project, which is to study on man-machine interaction in Korean nuclear power plants, we developed SACOM (Simulation Analyzer with a Cognitive Operator Model), a tool for the assessment of task performance in the control rooms using software simulation, and also develop human error analysis and application techniques. SACOM was developed to assess operator's physical workload, workload in information navigation at VDU workstations, and cognitive workload in procedural tasks. We developed trip analysis system including a procedure based on man-machine interaction analysis system including a procedure based on man-machine interaction analysis and a classification system. We analyzed a total of 277 trips occurred from 1978 to 1994 to produce trip summary information, and for 79 cases induced by human errors time-lined man-machine interactions. The INSTEC, a database system of our analysis results, was developed. The MARSTEC, a multimedia authoring and representation system for trip information, was also developed, and techniques for human error detection in human factors experiments were established. (author). 121 refs., 38 tabs., 52 figs

  11. The development of human behavior analysis techniques

    Energy Technology Data Exchange (ETDEWEB)

    Lee, Jung Woon; Lee, Yong Hee; Park, Geun Ok; Cheon, Se Woo; Suh, Sang Moon; Oh, In Suk; Lee, Hyun Chul; Park, Jae Chang

    1997-07-01

    In this project, which is to study on man-machine interaction in Korean nuclear power plants, we developed SACOM (Simulation Analyzer with a Cognitive Operator Model), a tool for the assessment of task performance in the control rooms using software simulation, and also develop human error analysis and application techniques. SACOM was developed to assess operator`s physical workload, workload in information navigation at VDU workstations, and cognitive workload in procedural tasks. We developed trip analysis system including a procedure based on man-machine interaction analysis system including a procedure based on man-machine interaction analysis and a classification system. We analyzed a total of 277 trips occurred from 1978 to 1994 to produce trip summary information, and for 79 cases induced by human errors time-lined man-machine interactions. The INSTEC, a database system of our analysis results, was developed. The MARSTEC, a multimedia authoring and representation system for trip information, was also developed, and techniques for human error detection in human factors experiments were established. (author). 121 refs., 38 tabs., 52 figs.

  12. Placental Expression of Glucose Transporter Proteins in Pregnancies Complicated by Gestational and Pregestational Diabetes Mellitus.

    Science.gov (United States)

    Stanirowski, Paweł Jan; Szukiewicz, Dariusz; Pazura-Turowska, Monika; Sawicki, Włodzimierz; Cendrowski, Krzysztof

    2018-04-01

    Gestational diabetes mellitus and pregestational diabetes mellitus constitute carbohydrate metabolism disorders, which, if not diagnosed and adequately treated, lead to serious and often life-threatening pregnancy complications. According to a recently formulated hypothesis, some diabetes-related complications, such as fetal macrosomia, may be the result of disturbances in the transplacental transport of nutrients-in particular, excessive maternal-fetal glucose transfer. Throughout pregnancy, glucose flux across the placenta is mediated by the group of facilitative glucose transporters (GLUT), the expression of which in different placental compartments is the precondition for effective glucose uptake from maternal blood and its subsequent transfer to the fetal circulation. In diabetes-complicated pregnancies, the location, expression and activity of glucose transporters are modified to an extent that results in alterations in the maternal-fetal glucose exchange, potentially leading to an excessive supply of energy substrates to the fetus. This paper reviews the literature on the expression and activity of glucose transporter proteins-GLUT-1, GLUT-3, GLUT-4, GLUT-8, GLUT-9 and GLUT-12-in the human placenta, with a special focus on diabetes-complicated pregnancy. The characteristics of transporters in conditions of maternal normoglycemia and modifications occurring in the diabetic placenta are summarized, and the factors responsible for the regulation of the expression of selected isoforms are described. Finally, the impact of alterations in the placental expression of the aforementioned members of the GLUT family on intrauterine fetal development in pregnancies complicated by diabetes mellitus is discussed. Copyright © 2017 Diabetes Canada. Published by Elsevier Inc. All rights reserved.

  13. Hallmarks of Human Small Antral Follicle Development

    DEFF Research Database (Denmark)

    Kristensen, Stine G; Mamsen, Linn S; Jeppesen, Janni V

    2018-01-01

    Regulation of human ovarian steroidogenesis differs from other species and precise knowledge on how human small antral follicles (hSAF) develop and acquire competence for continued growth and steroid output is still incomplete. The present study has characterized almost 1,000 normal hSAF collected...... increased steroid output profoundly. Furthermore, the highly significant association between FSHR and AR mRNA gene expression enforces important functions of androgens in follicular development. Collectively, these data reintroduce the understanding of the follicular phase as two parted in which regulation...

  14. The human brain. Prenatal development and structure

    International Nuclear Information System (INIS)

    Marin-Padilla, Miguel

    2011-01-01

    This book is unique among the current literature in that it systematically documents the prenatal structural development of the human brain. It is based on lifelong study using essentially a single staining procedure, the classic rapid Golgi procedure, which ensures an unusual and desirable uniformity in the observations. The book is amply illustrated with 81 large, high-quality color photomicrographs never previously reproduced. These photomicrographs, obtained at 6, 7, 11, 15, 18, 20, 25, 30, 35, and 40 weeks of gestation, offer a fascinating insight into the sequential prenatal development of neurons, blood vessels, and glia in the human brain. (orig.)

  15. The human brain. Prenatal development and structure

    Energy Technology Data Exchange (ETDEWEB)

    Marin-Padilla, Miguel

    2011-07-01

    This book is unique among the current literature in that it systematically documents the prenatal structural development of the human brain. It is based on lifelong study using essentially a single staining procedure, the classic rapid Golgi procedure, which ensures an unusual and desirable uniformity in the observations. The book is amply illustrated with 81 large, high-quality color photomicrographs never previously reproduced. These photomicrographs, obtained at 6, 7, 11, 15, 18, 20, 25, 30, 35, and 40 weeks of gestation, offer a fascinating insight into the sequential prenatal development of neurons, blood vessels, and glia in the human brain. (orig.)

  16. Developing Entrepreneurial Resilience: Implications for Human Resource Development

    Science.gov (United States)

    Lee, Jin; Wang, Jia

    2017-01-01

    Purpose: Leadership development has attracted much research attention within the human resource development (HRD) community. However, little scholarly effort has been made to study a special group of leaders--entrepreneurs. This paper aims to fill in this knowledge gap by taking a close look at entrepreneurial resilience, a key ability of…

  17. The development of human factors technologies -The development of human behaviour analysis techniques-

    International Nuclear Information System (INIS)

    Lee, Jung Woon; Lee, Yong Heui; Park, Keun Ok; Chun, Se Woo; Suh, Sang Moon; Park, Jae Chang

    1995-07-01

    In order to contribute to human error reduction through the studies on human-machine interaction in nuclear power plants, this project has objectives to develop SACOM(Simulation Analyzer with a Cognitive Operator Model) and techniques for human error analysis and application. In this year, we studied the followings: 1) Site investigation of operator tasks, 2) Development of operator task micro structure and revision of micro structure, 3) Development of knowledge representation software and SACOM prototype, 4) Development of performance assessment methodologies in task simulation and analysis of the effects of performance shaping factors. 1) Classification of error shaping factors(ESFs) and development of software for ESF evaluation, 2) Analysis of human error occurrences and revision of analysis procedure, 3) Experiment for human error data collection using a compact nuclear simulator, 4) Development of a prototype data base system of the analyzed information on trip cases. 55 figs, 23 tabs, 33 refs. (Author)

  18. A STUDY ON PLACENTAL MORPHOLOGY IN GESTATIONAL DIABETES

    Directory of Open Access Journals (Sweden)

    Katadi Venkata Sudha Madhuri

    2017-01-01

    Full Text Available BACKGROUND Gestational Diabetes Mellitus (GDM refers to any degree of glucose intolerance with onset or first recognition during pregnancy. Maternal diabetes constitutes an unfavourable environment for embryonic and foetoplacental development. The histomorphological changes in the placenta are associated with increased perinatal morbidity, increased risk of diabetes in the offspring and the mother in the ensuing years of life. Present study aims to study the morphological changes in the placenta along with maternal and foetal outcomes in pregnancies complicated by GDM. MATERIALS AND METHODS A descriptive observational case-controlled study was conducted from January 2013 to November 2016 in King George Hospital, Visakhapatnam. Hundred and sixty four women diagnosed with GDM and hundred women with normal gestation were enrolled in the study. Foetal surveillance was done by Doppler ultrasound and kick count technique during the gestation. Foetal and maternal outcome was evaluated and compared to the outcome of normal gestation. Placental specimens from term gestations (38-42 weeks diagnosed with GDM and normal full-term gestations were studied to assess the morphological parameters. Statistical analysis was done using descriptive statistical measures. RESULTS In the present study, 62.19% of the GDM cases terminated as normal gestations. Recurrent UTI was the most common complication (14.02% during the antenatal period. 17.68% of the foetuses from GDM mothers presented with macrosomia, however, there were no cases of congenital anomalies or shoulder dystocia. Placental tissue from the GDM cases was larger, heavier and more cotyledonous as compared to placenta from normal subjects. The umbilical cord showed eccentric and central attachment in all the controls and most of the cases and 5.48% of the cases showed marginal attachment of the umbilical cord. CONCLUSION The study describes the various maternal, foetal and placental outcomes in pregnancies

  19. A gestational profile of placental exosomes in maternal plasma and their effects on endothelial cell migration.

    Directory of Open Access Journals (Sweden)

    Carlos Salomon

    Full Text Available Studies completed to date provide persuasive evidence that placental cell-derived exosomes play a significant role in intercellular communication pathways that potentially contribute to placentation and development of materno-fetal vascular circulation. The aim of this study was to establish the gestational-age release profile and bioactivity of placental cell-derived exosome in maternal plasma. Plasma samples (n = 20 per pregnant group were obtained from non-pregnant and pregnant women in the first (FT, 6-12 weeks, second (ST, 22-24 weeks and third (TT, 32-38 weeks trimester. The number of exosomes and placental exosome contribution were determined by quantifying immunoreactive exosomal CD63 and placenta-specific marker (PLAP, respectively. The effect of exosomes isolated from FT, ST and TT on endothelial cell migration were established using a real-time, live-cell imaging system (Incucyte. Exosome plasma concentration was more than 50-fold greater in pregnant women than in non-pregnant women (p<0.001. During normal healthy pregnancy, the number of exosomes present in maternal plasma increased significantly with gestational age by more that two-fold (p<0.001. Exosomes isolated from FT, ST and TT increased endothelial cell migration by 1.9±0.1, 1.6±0.2 and 1.3±0.1-fold, respectively compared to the control. Pregnancy is associated with a dramatic increase in the number of exosomes present in plasma and maternal plasma exosomes are bioactive. While the role of placental cell-derived exosome in regulating maternal and/or fetal vascular responses remains to be elucidated, changes in exosome profile may be of clinical utility in the diagnosis of placental dysfunction.

  20. In vivo placental MRI shape and textural features predict fetal growth restriction and postnatal outcome.

    Science.gov (United States)

    Dahdouh, Sonia; Andescavage, Nickie; Yewale, Sayali; Yarish, Alexa; Lanham, Diane; Bulas, Dorothy; du Plessis, Adre J; Limperopoulos, Catherine

    2018-02-01

    To investigate the ability of three-dimensional (3D) MRI placental shape and textural features to predict fetal growth restriction (FGR) and birth weight (BW) for both healthy and FGR fetuses. We recruited two groups of pregnant volunteers between 18 and 39 weeks of gestation; 46 healthy subjects and 34 FGR. Both groups underwent fetal MR imaging on a 1.5 Tesla GE scanner using an eight-channel receiver coil. We acquired T2-weighted images on either the coronal or the axial plane to obtain MR volumes with a slice thickness of either 4 or 8 mm covering the full placenta. Placental shape features (volume, thickness, elongation) were combined with textural features; first order textural features (mean, variance, kurtosis, and skewness of placental gray levels), as well as, textural features computed on the gray level co-occurrence and run-length matrices characterizing placental homogeneity, symmetry, and coarseness. The features were used in two machine learning frameworks to predict FGR and BW. The proposed machine-learning based method using shape and textural features identified FGR pregnancies with 86% accuracy, 77% precision and 86% recall. BW estimations were 0.3 ± 13.4% (mean percentage error ± standard error) for healthy fetuses and -2.6 ± 15.9% for FGR. The proposed FGR identification and BW estimation methods using in utero placental shape and textural features computed on 3D MR images demonstrated high accuracy in our healthy and high-risk cohorts. Future studies to assess the evolution of each feature with regard to placental development are currently underway. 2 Technical Efficacy: Stage 2 J. Magn. Reson. Imaging 2018;47:449-458. © 2017 International Society for Magnetic Resonance in Medicine.

  1. Development and application of Human Genome Epidemiology

    Science.gov (United States)

    Xu, Jingwen

    2017-12-01

    Epidemiology is a science that studies distribution of diseases and health in population and its influencing factors, it also studies how to prevent and cure disease and promote health strategies and measures. Epidemiology has developed rapidly in recent years and it is an intercross subject with various other disciplines to form a series of branch disciplines such as Genetic epidemiology, molecular epidemiology, drug epidemiology and tumor epidemiology. With the implementation and completion of Human Genome Project (HGP), Human Genome Epidemiology (HuGE) has emerged at this historic moment. In this review, the development of Human Genome Epidemiology, research content, the construction and structure of relevant network, research standards, as well as the existing results and problems are briefly outlined.

  2. Puberty and structural brain development in humans.

    Science.gov (United States)

    Herting, Megan M; Sowell, Elizabeth R

    2017-01-01

    Adolescence is a transitional period of physical and behavioral development between childhood and adulthood. Puberty is a distinct period of sexual maturation that occurs during adolescence. Since the advent of magnetic resonance imaging (MRI), human studies have largely examined neurodevelopment in the context of age. A breadth of animal findings suggest that sex hormones continue to influence the brain beyond the prenatal period, with both organizational and activational effects occurring during puberty. Given the animal evidence, human MRI research has also set out to determine how puberty may influence otherwise known patterns of age-related neurodevelopment. Here we review structural-based MRI studies and show that pubertal maturation is a key variable to consider in elucidating sex- and individual- based differences in patterns of human brain development. We also highlight the continuing challenges faced, as well as future considerations, for this vital avenue of research. Copyright © 2016. Published by Elsevier Inc.

  3. Development and the evolvability of human limbs.

    Science.gov (United States)

    Young, Nathan M; Wagner, Günter P; Hallgrímsson, Benedikt

    2010-02-23

    The long legs and short arms of humans are distinctive for a primate, the result of selection acting in opposite directions on each limb at different points in our evolutionary history. This mosaic pattern challenges our understanding of the relationship of development and evolvability because limbs are serially homologous and genetic correlations should act as a significant constraint on their independent evolution. Here we test a developmental model of limb covariation in anthropoid primates and demonstrate that both humans and apes exhibit significantly reduced integration between limbs when compared to quadrupedal monkeys. This result indicates that fossil hominins likely escaped constraints on independent limb variation via reductions to genetic pleiotropy in an ape-like last common ancestor (LCA). This critical change in integration among hominoids, which is reflected in macroevolutionary differences in the disparity between limb lengths, facilitated selection for modern human limb proportions and demonstrates how development helps shape evolutionary change.

  4. Developing Human Performance Measures (PSAM8)

    International Nuclear Information System (INIS)

    Jeffrey C. Joe

    2006-01-01

    Through the reactor oversight process (ROP), the U.S. Nuclear Regulatory Commission (NRC) monitors the performance of utilities licensed to operate nuclear power plants. The process is designed to assure public health and safety by providing reasonable assurance that licensees are meeting the cornerstones of safety and designated crosscutting elements. The reactor inspection program, together with performance indicators (PIs), and enforcement activities form the basis for the NRC's risk-informed, performance based regulatory framework. While human performance is a key component in the safe operation of nuclear power plants and is a designated cross-cutting element of the ROP, there is currently no direct inspection or performance indicator for assessing human performance. Rather, when human performance is identified as a substantive cross cutting element in any 1 of 3 categories (resources, organizational or personnel), it is then evaluated for common themes to determine if follow-up actions are warranted. However, variability in human performance occurs from day to day, across activities that vary in complexity, and workgroups, contributing to the uncertainty in the outcomes of performance. While some variability in human performance may be random, much of the variability may be attributed to factors that are not currently assessed. There is a need to identify and assess aspects of human performance that relate to plant safety and to develop measures that can be used to successfully assure licensee performance and indicate when additional investigation may be required. This paper presents research that establishes a technical basis for developing human performance measures. In particular, we discuss: (1) how historical data already gives some indication of connection between human performance and overall plant performance, (2) how industry led efforts to measure and model human performance and organizational factors could serve as a data source and basis for a

  5. Teaching and Technologies for Human Development.

    Science.gov (United States)

    Chickering, Arthur W.; Payne, Carla; Poitras, Gail

    2001-01-01

    Discusses the potential of emerging communication and information technologies in terms of human development. Topics include distinctions between training and education, instrumental and developmental purposes, and differentiation and integration; developmental stages theory; a leadership seminar based on developmental stages; and uses of…

  6. Cultural Implications of Human Resource Development.

    Science.gov (United States)

    Hiranpruk, Chaiskran

    A discussion of the cultural effects of economic and, by extension, human resource development in Southeast Asia looks at short- and long-term implications. It is suggested that in the short term, increased competition will affect distribution of wealth, which can promote materialism and corruption. The introduction of labor-saving technology may…

  7. Philosophy and Human Development: Nigerian Context | Egbekpalu ...

    African Journals Online (AJOL)

    ... confronting man and his existence and the environment in which he lives. ... With philosophy, one develops a rational outlook on life that interrogates the basic ... their culture about the problems on ground and seeks to proffer humane solutions. ... To this effect, Philosophers believe that knowledge is power (scientia est ...

  8. Human Capital Development Policies: Enhancing Employees Satisfaction

    Science.gov (United States)

    Wan, Hooi Lan

    2007-01-01

    Purpose--The aim of this article is to gain insight into some of the human capital development (HCD) policies that enhance employee satisfaction. A salient focus of the study is to assess whether employees in globalised foreign-owned MNCs are likely to be more satisfied with the HCD policies than with the practices employed by locally owned MNCs.…

  9. Governance and Human Development: Empirical Evidence from ...

    African Journals Online (AJOL)

    This study empirically investigates the effects of governance on human development in Nigeria. Using annual time series data covering the period 1998 to 2010, obtained from various sources, and employing the classical least squares estimation technique, the study finds that corruption, foreign aid and government ...

  10. Life after placental dysfunction : the mother's renal function and her child's health

    NARCIS (Netherlands)

    Paauw, N.D.

    2018-01-01

    Introduction: over the last decades it has become apparent that implications of pregnancy complications are not limited to the pregnancy itself, but extend to later life, not only for the exposed mother, but also for the exposed child. After placental dysfunction, characterized by the development of

  11. Using genomic data to unravel the root of the placental mammal phylogeny.

    Science.gov (United States)

    Murphy, William J; Pringle, Thomas H; Crider, Tess A; Springer, Mark S; Miller, Webb

    2007-04-01

    The phylogeny of placental mammals is a critical framework for choosing future genome sequencing targets and for resolving the ancestral mammalian genome at the nucleotide level. Despite considerable recent progress defining superordinal relationships, several branches remain poorly resolved, including the root of the placental tree. Here we analyzed the genome sequence assemblies of human, armadillo, elephant, and opossum to identify informative coding indels that would serve as rare genomic changes to infer early events in placental mammal phylogeny. We also expanded our species sampling by including sequence data from >30 ongoing genome projects, followed by PCR and sequencing validation of each indel in additional taxa. Our data provide support for a sister-group relationship between Afrotheria and Xenarthra (the Atlantogenata hypothesis), which is in turn the sister-taxon to Boreoeutheria. We failed to recover any indels in support of a basal position for Xenarthra (Epitheria), which is suggested by morphology and a recent retroposon analysis, or a hypothesis with Afrotheria basal (Exafricoplacentalia), which is favored by phylogenetic analysis of large nuclear gene data sets. In addition, we identified two retroposon insertions that also support Atlantogenata and none for the alternative hypotheses. A revised molecular timescale based on these phylogenetic inferences suggests Afrotheria and Xenarthra diverged from other placental mammals approximately 103 (95-114) million years ago. We discuss the impacts of this topology on earlier phylogenetic reconstructions and repeat-based inferences of phylogeny.

  12. Ancient origin of placental expression in the growth hormone genes of anthropoid primates.

    Science.gov (United States)

    Papper, Zack; Jameson, Natalie M; Romero, Roberto; Weckle, Amy L; Mittal, Pooja; Benirschke, Kurt; Santolaya-Forgas, Joaquin; Uddin, Monica; Haig, David; Goodman, Morris; Wildman, Derek E

    2009-10-06

    In anthropoid primates, growth hormone (GH) genes have undergone at least 2 independent locus expansions, one in platyrrhines (New World monkeys) and another in catarrhines (Old World monkeys and apes). In catarrhines, the GH cluster has a pituitary-expressed gene called GH1; the remaining GH genes include placental GHs and placental lactogens. Here, we provide cDNA sequence evidence that the platyrrhine GH cluster also includes at least 3 placenta expressed genes and phylogenetic evidence that placenta expressed anthropoid GH genes have undergone strong adaptive evolution, whereas pituitary-expressed GH genes have faced strict functional constraint. Our phylogenetic evidence also points to lineage-specific gene gain and loss in early placental mammalian evolution, with at least three copies of the GH gene present at the time of the last common ancestor (LCA) of primates, rodents, and laurasiatherians. Anthropoid primates and laurasiatherians share gene descendants of one of these three copies, whereas rodents and strepsirrhine primates each maintain a separate copy. Eight of the amino-acid replacements that occurred on the lineage leading to the LCA of extant anthropoids have been implicated in GH signaling at the maternal-fetal interface. Thus, placental expression of GH may have preceded the separate series of GH gene duplications that occurred in catarrhines and platyrrhines (i.e., the roles played by placenta-expressed GHs in human pregnancy may have a longer evolutionary history than previously appreciated).

  13. Placental perfusion in 3rd trimester pregnancy

    Science.gov (United States)

    Sitepu, M.; Syahriza, A.; Sibuea, D.; Hanafiah, T. M.

    2018-03-01

    The placenta is an organ for transmitting nutrition and oxygen to thefetus; it means if there is a defect in the placenta could make growth restriction to the fetus, even death. Uterine artery flow escalated since the halfway point of the pregnancy or the complete trophoblast invasion of spiralis artery, and keep going in every week. 3D power Doppler examination on placenta could show the uterineplacenta circulation and fetoplacental at once so could give themore accurate result. A cross-sectional study in RSUP HAM and theprivate specialist clinic was conducted in 100 pregnant samples with 28-40 week gestational age, exact last menstrual period date, and no underlying disease to examine the alteration of placental perfusion by gestationalage and placental location. There was a correlation between VI and VFI in placenta toward umbilical artery flow, but no correlation in FI. The placental location also plays a role in interval blood flow, especially FI and VFI, it means the VFI hold the strongest correlation in both ways.

  14. Placental transfer of selected radiopharmaceuticals

    International Nuclear Information System (INIS)

    Wegst, A.V.

    1992-01-01

    This paper reviews animal experiments carried out to determine the transfer of radiopharmaceuticals from mother to fetus. Animal data are compared to any human data available. The radiopharmaceuticals included in the discussion are Tc-99m pertechnetate, Tc-99m DTPA, Ga-67 citrate and Tl-201 chloride. (6 tab., 5 refs.)

  15. Human work interaction design meets international development

    DEFF Research Database (Denmark)

    Campos, P.; Clemmensen, T.; Barricelli, B.R.

    2017-01-01

    opportunity to observe technology-mediated innovative work practices in informal settings that may be related to the notion of International Development. In this unique context, this workshop proposes to analyze findings related to opportunities for design research in this type of work domains: a) human......Over the last decade, empirical relationships between work domain analysis and HCI design have been identified by much research in the field of Human Work Interaction Design (HWID) across five continents. Since this workshop takes place at the Interact Conference in Mumbai, there is a unique...

  16. Radiation effects on the developing human brain

    International Nuclear Information System (INIS)

    1993-01-01

    The developing human brain has been shown to be especially sensitive to ionizing radiation. Mental retardation has been observed in the survivors of the atomic bombings in Japan exposed in utero during sensitive periods, and clinical studies of pelvically irradiated pregnant women have demonstrated damaging effects on the fetus. In this annex the emphasis is on reviewing the results of the study of the survivors of the atomic bombings in Japan, although the results of other human epidemiological investigations and of pertinent experimental studies are also considered. Refs, 3 figs, 10 tabs

  17. Human resource development for management of decommissioning

    International Nuclear Information System (INIS)

    Tanaka, Kenichi

    2017-01-01

    This paper described the contents of 'Human resource development for the planning and implementation of safe and reasonable nuclear power plant decommissioning' as the nuclear human resource development project by the Ministry of Education, Culture, Sports, Science and Technology. The decommissioning of a nuclear power plant takes 30 to 40 years for its implementation, costing tens of billions of yen. As the period of decommissioning is almost the same as the operation period, it is necessary to provide a systematic and continuous supply of engineers who understand the essence of the decommissioning project. The engineers required here should have project management ability to take charge of preparation, implementation, and termination of decommissioning, and have the ability to perform not only technology, but also factor management, cost management, and the like. As the preconditions of these abilities, it is important to develop human resources who possess qualities that can oversee decommissioning in the future. The contents of human resource education are as follows; (1) desk training (teaching materials: facilities of nuclear power plants, management of nuclear fuels, related laws, decommissioning work, decontamination, dismantling, disposal of waste, etc.), (2) field training (simulators, inspection of power station under decommissioning, etc.), (3) practical training (radiation inventory evaluation, and safety assessment), and (4) inspection of overseas decommissioning, etc. (A.O.)

  18. Education positive approach: contributions to human development

    Directory of Open Access Journals (Sweden)

    Clara ROMERO PÉREZ

    2012-02-01

    Full Text Available This article analizes the current theoretical perspectives underlying educational proposals aimed at promoting the positive development of the people. Firstly we show the most important characteristics of the positive approach. Then, we focus on the positive concept of the inner and its relation to eudaimonia, self-care and emotional selfgovernance. Thirdly, with reference to the contributions of Positive Psychology and Prevention Science we examine the two points of view –hedonic and eudaemonic– from which different pedagogical approaches are based and focus towards education for the welfare, social-emotional development and educational character. We conclude that, despite the lack of practical knowledge about happiness and the art of living, a positive education oriented to the human construction processes must promote both emotional and social skills such as feelings and moral responsibilities for the optimal development of human being.

  19. Impact of placental insufficiency on fetal skeletal muscle growth

    Science.gov (United States)

    Hay, William W.

    2016-01-01

    Intrauterine growth restriction (IUGR) caused by placental insufficiency is one of the most common and complex problems in perinatology, with no known cure. In pregnancies affected by placental insufficiency, a poorly functioning placenta restricts nutrient supply to the fetus and prevents normal fetal growth. Among other significant deficits in organ development, the IUGR fetus characteristically has less lean body and skeletal muscle mass than their appropriately-grown counterparts. Reduced skeletal muscle growth is not fully compensated after birth, as individuals who were born small for gestational age (SGA) from IUGR have persistent reductions in muscle mass and strength into adulthood. The consequences of restricted muscle growth and accelerated postnatal “catch-up” growth in the form of adiposity may contribute to the increased later life risk for visceral adiposity, peripheral insulin resistance, diabetes, and cardiovascular disease in individuals who were formerly IUGR. This review will discuss how an insufficient placenta results in impaired fetal skeletal muscle growth and how lifelong reductions in muscle mass might contribute to increased metabolic disease risk in this vulnerable population. PMID:26994511

  20. Challenges of Research and Human Capital Development in Nigeria

    Science.gov (United States)

    Chikwe, Christian K.; Ogidi, Reuben C.; Nwachukwu, K.

    2015-01-01

    The paper discussed the challenges of research and human capital development in Nigeria. Research and human capital development are critical to the development of any nation. Research facilitates human capital development. A high rating in human capital development indices places a country among the leading countries of the world. The paper…

  1. Genital Mycoplasmas in Placental Infections

    Directory of Open Access Journals (Sweden)

    Andreas Stein

    1994-01-01

    Full Text Available Objective: The involvement of the genital mycoplasmas Ureaplasma urealyticum and Mycoplasma hominis in complications of pregnancy has remained controversial especially because these microorganisms are frequent colonizers of the lower genital tract. Recovery of bacteria from the placenta appears to be the sole technique to represent a true infection and not vaginal contamination. Therefore, we investigated the presence of genital mycoplasmas, aerobic and anaerobic bacteria, and fungi in human placentas and evaluated their association with morbidity and mortality of pregnancy.

  2. Placental transfer of antidepressant medications: implications for postnatal adaptation syndrome.

    Science.gov (United States)

    Ewing, Grace; Tatarchuk, Yekaterina; Appleby, Dina; Schwartz, Nadav; Kim, Deborah

    2015-04-01

    Seven to thirteen percent of women are either prescribed or taking (depending on the study) an antidepressant during pregnancy. Because antidepressants freely cross into the intrauterine environment, we aim to summarize the current findings on placental transfer of antidepressants. Although generally low risk, antidepressants have been associated with postnatal adaptation syndrome (PNAS). Specifically, we explore whether the antidepressants most closely associated with PNAS (paroxetine, fluoxetine, venlafaxine) cross the placenta to a greater extent than other antidepressants. We review research on antidepressants in the context of placental anatomy, placental transport mechanisms, placental metabolism, pharmacokinetics, as well as non-placental maternal and fetal factors. This provides insight into the complexity involved in understanding how placental transfer of antidepressants may relate to adverse perinatal outcomes. Ultimately, from this data there is no pattern in which PNAS is related to placental transfer of antidepressant medications. In general, there is large interindividual variability for each type of antidepressant. To make the most clinically informed decisions about the use of antidepressants in pregnancy, studies that link maternal, placental and fetal genetic polymorphisms, placental transfer rates and infant outcomes are needed.

  3. IAEA Nuclear Security Human Resource Development Program

    International Nuclear Information System (INIS)

    Braunegger-Guelich, A.

    2009-01-01

    The IAEA is at the forefront of international efforts to strengthen the world's nuclear security framework. The current Nuclear Security Plan for 2006-2009 was approved by the IAEA Board of Governors in September 2005. This Plan has three main points of focus: needs assessment, prevention, detection and response. Its overall objective is to achieve improved worldwide security of nuclear and other radioactive material in use, storage and transport, and of their associated facilities. This will be achieved, in particular, through the provision of guidelines and recommendations, human resource development, nuclear security advisory services and assistance for the implementation of the framework in States, upon request. The presentation provides an overview of the IAEA nuclear security human resource development program that is divided into two parts: training and education. Whereas the training program focuses on filling gaps between the actual performance of personnel working in the area of nuclear security and the required competencies and skills needed to meet the international requirements and recommendations described in UN and IAEA documents relating to nuclear security, the Educational Program in Nuclear Security aims at developing nuclear security experts and specialists, at fostering a nuclear security culture and at establishing in this way sustainable knowledge in this field within a State. The presentation also elaborates on the nuclear security computer based learning component and provides insights into the use of human resource development as a tool in achieving the IAEA's long term goal of improving sustainable nuclear security in States. (author)

  4. The development of human factors technologies -The development of human factors experimental evaluation techniques-

    International Nuclear Information System (INIS)

    Shim, Bong Sik; Oh, In Suk; Cha, Kyung Hoh; Lee, Hyun Chul

    1995-07-01

    In this year, we studied the followings: 1) Development of operator mental workload evaluation techniques, 2) Development of a prototype for preliminary human factors experiment, 3) Suitability test of information display on a large scale display panel, 4) Development of guidelines for VDU-based control room design, 5) Development of integrated test facility (ITF). 6) Establishment of an eye tracking system, and we got the following results: 1) Mental workload evaluation techniques for MMI evaluation, 2) PROTOPEX (PROTOtype for preliminary human factors experiment) for preliminary human factors experiments, 3) Usage methods of APTEA (Analysis-Prototyping-Training-Experiment-Analysis) experiment design, 4) Design guidelines for human factors verification, 5) Detail design requirements and development plan of ITF, 6) Eye movement measurement system. 38 figs, 20 tabs, 54 refs. (Author)

  5. The development of human factors technologies -The development of human behaviour analysis techniques-

    Energy Technology Data Exchange (ETDEWEB)

    Lee, Jung Woon; Lee, Yong Heui; Park, Keun Ok; Chun, Se Woo; Suh, Sang Moon; Park, Jae Chang [Korea Atomic Energy Research Institute, Taejon (Korea, Republic of)

    1995-07-01

    In order to contribute to human error reduction through the studies on human-machine interaction in nuclear power plants, this project has objectives to develop SACOM(Simulation Analyzer with a Cognitive Operator Model) and techniques for human error analysis and application. In this year, we studied the followings: development of SACOM> (1) Site investigation of operator tasks, (2) Development of operator task micro structure and revision of micro structure, (3) Development of knowledge representation software and SACOM prototype, (4) Development of performance assessment methodologies in task simulation and analysis of the effects of performance shaping factors. development of human error analysis and application techniques> (1) Classification of error shaping factors(ESFs) and development of software for ESF evaluation, (2) Analysis of human error occurrences and revision of analysis procedure, (3) Experiment for human error data collection using a compact nuclear simulator, (4) Development of a prototype data base system of the analyzed information on trip cases. 55 figs, 23 tabs, 33 refs. (Author).

  6. Development and the evolvability of human limbs

    OpenAIRE

    Young, Nathan M.; Wagner, Günter P.; Hallgrímsson, Benedikt

    2010-01-01

    The long legs and short arms of humans are distinctive for a primate, the result of selection acting in opposite directions on each limb at different points in our evolutionary history. This mosaic pattern challenges our understanding of the relationship of development and evolvability because limbs are serially homologous and genetic correlations should act as a significant constraint on their independent evolution. Here we test a developmental model of limb covariation in anthropoid primate...

  7. Human Resource Development in Hybrid Libraries

    OpenAIRE

    Prakasan, E. R.; Swarna, T.; Vijai Kumar, *

    2000-01-01

    This paper explores the human resources and development implications in hybrid libraries. Due to technological changes in libraries, which is a result of the proliferation of electronic resources, there has been a shift in workloads and workflow, requiring staff with different skills and educational backgrounds. Training of staff at all levels in information technology is the key to manage change, alleviate anxiety in the workplace and assure quality service in the libraries. Staff developmen...

  8. Entrepreneurship and human capital development in children

    DEFF Research Database (Denmark)

    Brandt, Kasper; Rutasitara, Longinus; Selejio, Onesmo

    2017-01-01

    This paper explores the link between entrepreneurship and child human capital development. We specifically examine how operating a non-farm enterprise (NFE) as opposed to working in agriculture relates to child labour and schooling outcomes. Accounting for timeinvariant unobservable characteristics...... for girls. Given these findings, it appears that household entrepreneurship may contribute to decreasing the severe child labour problem in Tanzania, but resolving the problem of low school attendance rates will require a different strategy....

  9. Credit Market Development and Human Capital Accumulation

    OpenAIRE

    Ho, Wai-Hong

    2008-01-01

    In a two period overlapping generations economy with asymmetric information, we investigate the interaction between credit market development and human capital accumulation. As is typical, young borrowers supply their endowed unit of labor time to earn wage income which is used as internal funds. In contrast to conventional setups, young lenders distribute theirs between acquiring education and working for earnings. Through identifying the risk types of borrowers by a costly screening tech...

  10. Maternal psychological distress and placental circulation in pregnancies after a previous offspring with congenital malformation.

    Directory of Open Access Journals (Sweden)

    Anne Helbig

    Full Text Available INTRODUCTION: Antenatal maternal psychological distress may be associated with reduced placental circulation, which could lead to lower birthweight. Studies investigating this in humans show mixed results, which may be partially due to type, strength and timing of distress. In addition, the arterial vascular resistance measures often used as outcome measures do not detect smaller changes in placental volume blood flow. We aimed to investigate the effect of a specific stressor, with increased levels of stress early in pregnancy, on the fetoplacental volume blood flow in third trimester. METHODS: This was a prospective observational study of 74 pregnant women with a congenital malformation in a previous fetus or child. Psychological distress was assessed twice, around 16 and 30 weeks' gestation. Psychometric measures were the General Health Questionnaire-28 (subscales anxiety and depression, Edinburgh Postnatal Depression Scale, and Impact of Event Scale-22 (subscales intrusion, avoidance, and arousal. Placental circulation was examined at 30 weeks, using Doppler ultrasonography, primarily as fetoplacental volume blood flow in the umbilical vein, normalized for abdominal circumference; secondarily as vascular resistance measures, obtained from the umbilical and the uterine arteries. RESULTS: Maternal distress in second but not third trimester was associated with increased normalized fetoplacental blood flow (P-values 0.006 and 0.013 for score > mean for depression and intrusion, respectively. Post-hoc explorations suggested that a reduced birthweight/placental weight ratio may mediate this association. Psychological distress did not affect vascular resistance measures in the umbilical and uterine arteries, regardless of adjustment for confounders. CONCLUSIONS: In pregnant women with a previous fetus or child with a congenital malformation, higher distress levels in second trimester were associated with third trimester fetoplacental blood flow that

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

    Science.gov (United States)

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

    2015-01-01

    transporter and metabolic genes and maternal smoking, physical activity and diet raises the possibility that their effects are mediated in part through alterations in placental function. The observed changes in placental gene expression in relation to modifiable maternal factors are important as they could form part of interventions aimed at maintaining a healthy lifestyle for the mother and for optimal fetal development. PMID:26657885

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

    Directory of Open Access Journals (Sweden)

    Pricilla E Day

    , physical activity and diet raises the possibility that their effects are mediated in part through alterations in placental function. The observed changes in placental gene expression in relation to modifiable maternal factors are important as they could form part of interventions aimed at maintaining a healthy lifestyle for the mother and for optimal fetal development.

  13. Caspase dependent and independent mechanisms of apoptosis across gestation in a sheep model of placental insufficiency and intrauterine growth restriction.

    Science.gov (United States)

    Monson, Troy; Wright, Tanner; Galan, Henry L; Reynolds, Paul R; Arroyo, Juan A

    2017-05-01

    Increased placental apoptosis is a hallmark of intrauterine growth restricted (IUGR). Several molecules have been shown to be involved in the control of apoptosis during this disease. Our objective was to determine the expression of Bcl2, Bax, phospho XIAP, AIF, caspase 3 and 9, and telomerase activity across gestation in an ovine hyperthermia-induced model of IUGR. Pregnant sheep were placed in hyperthermic (HT) conditions to induce IUGR along with age-matched controls. Placental tissues were collected at 55 (early), 95 (mid-gestation) and 130 (near-term) days of gestational age (dGA) to determine the expression of apoptotic molecules during the development of IUGR. Compared to the control placenta, IGUR pregnancies showed: significantly reduced placental Bcl2 in early gestation (55 dGA) with a significant increase observed at mid gestation (95 dGA); decreased placental pXIAP at both mid and near term gestational days (95 and 130 dGA); placental AIF increased only at 55 dGA (early gestation); active caspase 3 increased at both mid and near term gestational days (95 and 130 dGA); caspase 9 only increased at mid gestation (95 dGA) and decreased Telomerase activity near term. Placental apoptosis, mediated in part by the apoptosis related molecule, participates in the development of IUGR. Findings from this study suggest a caspase-independent apoptotic pathway during early gestation and caspase-dependent apoptosis at mid and near term gestation. The data also implicate decreased activation of XIAP as a plausible factor involved in the control of placental apoptosis during IUGR.

  14. Vinorelbine Potently Induces Placental Cell Death, Does Not Harm Fertility and is a Potential Treatment for Ectopic Pregnancy

    Directory of Open Access Journals (Sweden)

    Roxanne Hastie

    2018-03-01

    Full Text Available Ectopic pregnancies complicate 1–2 pregnancies and are a leading cause of maternal death. An effective oral drug therapy that replaces surgery might make its treatment safer, cheaper, simpler and therefore more widely accessible. The only current medical treatment offered to women is intramuscular methotrexate, but this only reliably resolves smaller ectopic pregnancies. As such, many ectopic pregnancies require surgical excision. We show that vinorelbine, an orally available chemotherapeutic agent, potently induced placental cell death but did not harm fertility in mice. Vinorelbine was 100–1000 times more potent than methotrexate in inducing placental cell death in vitro, and more potent than combination methotrexate and gefitinib (another proposed treatment for ectopic pregnancy being evaluated in phase III trials. Mechanistically, it caused microtubule condensation, blocked mitosis and activated the apoptosis cascade in placental cells. Vinorelbine was more efficacious than methotrexate ± gefitinib in reducing the volume of placental cell tumors xenografted subcutaneously in SCID mice. Mice exposed to vinorelbine and allowed to breed, following a four week washout period, displayed normal fertility, however long-term fertility was not assessed. Human Fallopian tubes treated with vinorelbine did not exhibit up-regulation of apoptosis molecules. Our findings show that placental cells appear sensitive to vinorelbine and it has potential as a tablet-only approach to treat ectopic pregnancy. Keywords: Ectopic pregnancy, Vinorelbine, Methotrexate, Placenta, Treatment

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

    Directory of Open Access Journals (Sweden)

    O. I. Stepanova

    2013-01-01

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

  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. Human development: from conception to maturity

    Directory of Open Access Journals (Sweden)

    Valdemiro Carlos Sgarbieri

    2017-05-01

    Full Text Available Abstract The main objective of this review was to describe and emphasize the care that a woman must have in the period prior to pregnancy, as well as throughout pregnancy and after the birth of the baby, cares and duties that should continue to be followed by mother and child throughout the first years of the child’s life. Such cares are of nutritional, behavioral and lifestyle natures, and also involve the father and the whole family. Human development, from conception to maturity, consists of a critical and important period due to the multitude of intrinsic genetic and environmental factors that influence, positively or negatively, the person's entire life. The human being, who originated and passed his/her first phase of development in the womb, receives influence from different factors: a of parental origin (father and mother, including health and lifestyle of the father and mother, genetic inheritance, nutrition of the mother prior to and during pregnancy; b events that affected the mother and hence the child under development in intrauterine life, at birth (delivery, during perinatal period, and throughout the early years of life. The fragility of development continues throughout the preschool, school and adolescent periods during which proper nutrition with a balanced lifestyle is essential and depends on guidance from the parents, caregivers and teachers.

  18. 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.

  19. Epigenetic Placental Programming of Preeclampsia

    Science.gov (United States)

    Preeclampsia (PE) affects 8-10% of women in the US and long-term consequences include subsequent development of maternal hypertension and hypertension in offspring. As methylation patterns are established during fetal life, we focused on epigenetic alterations in DNA methylation as a plausible expla...

  20. Placental morphology at different maternal hemoglobin levels: a histopathological study

    International Nuclear Information System (INIS)

    Kiran, N.; Zubair, A.; Malik, T.M.

    2015-01-01

    To evaluate the histopathological parameters of the placenta like weight, infarct and syncytial knots, at different maternal hemoglobin levels, in both qualitative and quantitative manner. Study design: Descriptive study Place and Duration of Study: Army Medical College, National University of Sciences and Technology in collaboration with Department of Obstetrics and Gynecology, Military Hospital, Rawalpindi, Pakistan, from December 2011 to November 2012. Patients and Methods: A total of 75 placentas were included, that were collected from full term mothers at the time of childbirth. Placental weight was taken without umbilical cord and gross placental infarcts were noted. Samples of placental tissue were taken and stained by haematoxylin and eosin (H and E). Microscopic study was done to evaluate placental infarcts and syncytial knots. Results: Mean placental weight at normal and low maternal hemoglobin was 581.67 ± 83.97g and 482.58 ± 104.74g respectively. Gross placental infarcts were found in all cases having low maternal hemoglobin concentration (60% cases). Syncytial knots were found in all placentas but they were considerably more at decreasing levels of maternal hemoglobin (19.79 ± 5.22). Conclusion: The present study showed decrease in placental weight, increase in placental infarcts and syncytial knot hyperplasia at low maternal hemoglobin concentration, displaying adaptive alterations. (author)

  1. 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

  2. Associations between intrapartum death and piglet, placental, and umbilical characteristics.

    Science.gov (United States)

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

    2012-12-01

    Intrapartum death in multiparous gestations in sows (Sus scrofa) is often caused by hypoxia. There is little information in the literature on the assessment of the placenta in relation to intrapartum death in piglets. The aim of this study was to evaluate the impact of the placental area and weight upon piglet birth characteristics and intrapartum death. Litters from 26 Landrace-Yorkshire sows were monitored during farrowing and the status of each piglet was recorded, including blood parameters of piglets and their umbilical veins. Of 413 piglets born, 6.5% were stillborn. Blood concentrations of glucose, lactate, and CO(2) partial pressure were increased in the stillborn piglets (P birth was increased for piglets born dead vs. live (P birth weight for piglets born dead was not different from live-born piglets (P = 0.631), whereas mean body mass index was reduced (P 0.2). Piglet BW was positively correlated with placental area and placental weight (P birth order group, and broken umbilical cords explained 71% of the stillbirths (P = 0.001). We conclude that placental area and placental weight are both positively associated with piglet birth weight, but not with the probability of being born dead. Placental area was a better predictor of piglet vitality than placental weight. Because umbilical cord rupture and prolonged birth time were associated with being born dead, umbilical cord rupture and placental detachment seem to be probable causes of intrapartum death.

  3. Placental transfer of 14C-hexoprenaline

    International Nuclear Information System (INIS)

    Lipshitz, J.; Broyles, K.; Whybrew, W.D.; Ahokas, R.A.; Anderson, G.D.

    1982-01-01

    The placental transfer of a single intravenous injection of 14 C-hexoprenaline was studied in eight pregnant New Zealand white rabbits. Maternal and fetal blood was sampled intermittently for 60 minutes after the injection. An initial rapid decrease in the levels of 14 C-hexoprenaline in maternal blood was followed by a second slower phase, whereas fetal heart rate after the administration of a single maternal intravenous injection of hexoprenaline in the treatment of fetal distress is due to the action on the uterus and/or on maternal cardiovascular function, and not to direct stimulation of the fetus

  4. The first trimester human placenta is a site for terminal maturation of primitive erythroid cells.

    Science.gov (United States)

    Van Handel, Ben; Prashad, Sacha L; Hassanzadeh-Kiabi, Nargess; Huang, Andy; Magnusson, Mattias; Atanassova, Boriana; Chen, Angela; Hamalainen, Eija I; Mikkola, Hanna K A

    2010-10-28

    Embryonic hematopoiesis starts via the generation of primitive red blood cells (RBCs) that satisfy the embryo's immediate oxygen needs. Although primitive RBCs were thought to retain their nuclei, recent studies have shown that primitive RBCs in mice enucleate in the fetal liver. It has been unknown whether human primitive RBCs enucleate, and what hematopoietic site might support this process. Our data indicate that the terminal maturation and enucleation of human primitive RBCs occurs in first trimester placental villi. Extravascular ζ-globin(+) primitive erythroid cells were found in placental villi between 5-7 weeks of development, at which time the frequency of enucleated RBCs was higher in the villous stroma than in circulation. RBC enucleation was further evidenced by the presence of primitive reticulocytes and pyrenocytes (ejected RBC nuclei) in the placenta. Extravascular RBCs were found to associate with placental macrophages, which contained ingested nuclei. Clonogenic macrophage progenitors of fetal origin were present in the chorionic plate of the placenta before the onset of fetoplacental circulation, after which macrophages had migrated to the villi. These findings indicate that placental macrophages may assist the enucleation process of primitive RBCs in placental villi, implying an unexpectedly broad role for the placenta in embryonic hematopoiesis.

  5. Next Generation Safeguards Initiative: Human Capital Development

    International Nuclear Information System (INIS)

    Scholz, M.; Irola, G.; Glynn, K.

    2015-01-01

    Since 2008, the Human Capital Development (HCD) subprogramme of the U.S. National Nuclear Security Administration's (NNSA) Next Generation Safeguards Initiative (NGSI) has supported the recruitment, education, training, and retention of the next generation of international safeguards professionals to meet the needs of both the International Atomic Energy Agency (IAEA) and the United States. Specifically, HCD's efforts respond to data indicating that 82% of safeguards experts at U.S. Laboratories will have left the workforce within 15 years. This paper provides an update on the status of the subprogramme since its last presentation at the IAEA Safeguards Symposium in 2010. It highlights strengthened, integrated efforts in the areas of graduate and post-doctoral fellowships, young and midcareer professional support, short safeguards courses, and university engagement. It also discusses lessons learned from the U.S. experience in safeguards education and training as well as the importance of long-range strategies to develop a cohesive, effective, and efficient human capital development approach. (author)

  6. Full Human Development And School Psychology

    DEFF Research Database (Denmark)

    Chaiklin, Seth

    The aim of this keynote address is to show how theoretical ideas from the cultural-historical tradition have been used to address issues that fall within the scope of interest for Brazilian school psychologists. The first part of the conference discusses the idea of radical-local teaching...... which explains how this perspective was used with lower secondary school boys in Denmark who had been expelled from several schools. These two parts will be used to illustrate a perspective about full human development, expressed through cultural-historical theoretical concepts, as an orientation...... for all professional approaches to school psychology....

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

    Science.gov (United States)

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

    2016-12-01

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

  8. Physical biology of human brain development

    Directory of Open Access Journals (Sweden)

    Silvia eBudday

    2015-07-01

    Full Text Available Neurodevelopment is a complex, dynamic process that involves a precisely orchestrated sequence of genetic, environmental, biochemical, and physical events. Developmental biology and genetics have shaped our understanding of the molecular and cellular mechanisms during neurodevelopment. Recent studies suggest that physical forces play a central role in translating these cellular mechanisms into the complex surface morphology of the human brain. However, the precise impact of neuronal differentiation, migration, and connection on the physical forces during cortical folding remains unknown. Here we review the cellular mechanisms of neurodevelopment with a view towards surface morphogenesis, pattern selection, and evolution of shape. We revisit cortical folding as the instability problem of constrained differential growth in a multi-layered system. To identify the contributing factors of differential growth, we map out the timeline of neurodevelopment in humans and highlight the cellular events associated with extreme radial and tangential expansion. We demonstrate how computational modeling of differential growth can bridge the scales-from phenomena on the cellular level towards form and function on the organ level-to make quantitative, personalized predictions. Physics-based models can quantify cortical stresses, identify critical folding conditions, rationalize pattern selection, and predict gyral wavelengths and gyrification indices. We illustrate that physical forces can explain cortical malformations as emergent properties of developmental disorders. Combining biology and physics holds promise to advance our understanding of human brain development and enable early diagnostics of cortical malformations with the ultimate goal to improve treatment of neurodevelopmental disorders including epilepsy, autism spectrum disorders, and schizophrenia.

  9. A 3D co-culture microtissue model of the human placenta for nanotoxicity assessment

    DEFF Research Database (Denmark)

    Muoth, Carina; Wichser, Adrian; Monopoli, Marco

    2016-01-01

    and functionality of the placental tissue. The effects of NPs on the human placenta are not well studied or understood, and predictive in vitro placenta models to achieve mechanistic insights on NP-placenta interactions are essentially lacking. Using the scaffold-free hanging drop technology, we developed a well...

  10. Development of the human infant intestinal microbiota.

    Science.gov (United States)

    Palmer, Chana; Bik, Elisabeth M; DiGiulio, Daniel B; Relman, David A; Brown, Patrick O

    2007-07-01

    Almost immediately after a human being is born, so too is a new microbial ecosystem, one that resides in that person's gastrointestinal tract. Although it is a universal and integral part of human biology, the temporal progression of this process, the sources of the microbes that make up the ecosystem, how and why it varies from one infant to another, and how the composition of this ecosystem influences human physiology, development, and disease are still poorly understood. As a step toward systematically investigating these questions, we designed a microarray to detect and quantitate the small subunit ribosomal RNA (SSU rRNA) gene sequences of most currently recognized species and taxonomic groups of bacteria. We used this microarray, along with sequencing of cloned libraries of PCR-amplified SSU rDNA, to profile the microbial communities in an average of 26 stool samples each from 14 healthy, full-term human infants, including a pair of dizygotic twins, beginning with the first stool after birth and continuing at defined intervals throughout the first year of life. To investigate possible origins of the infant microbiota, we also profiled vaginal and milk samples from most of the mothers, and stool samples from all of the mothers, most of the fathers, and two siblings. The composition and temporal patterns of the microbial communities varied widely from baby to baby. Despite considerable temporal variation, the distinct features of each baby's microbial community were recognizable for intervals of weeks to months. The strikingly parallel temporal patterns of the twins suggested that incidental environmental exposures play a major role in determining the distinctive characteristics of the microbial community in each baby. By the end of the first year of life, the idiosyncratic microbial ecosystems in each baby, although still distinct, had converged toward a profile characteristic of the adult gastrointestinal tract.

  11. Development of the human infant intestinal microbiota.

    Directory of Open Access Journals (Sweden)

    Chana Palmer

    2007-07-01

    Full Text Available Almost immediately after a human being is born, so too is a new microbial ecosystem, one that resides in that person's gastrointestinal tract. Although it is a universal and integral part of human biology, the temporal progression of this process, the sources of the microbes that make up the ecosystem, how and why it varies from one infant to another, and how the composition of this ecosystem influences human physiology, development, and disease are still poorly understood. As a step toward systematically investigating these questions, we designed a microarray to detect and quantitate the small subunit ribosomal RNA (SSU rRNA gene sequences of most currently recognized species and taxonomic groups of bacteria. We used this microarray, along with sequencing of cloned libraries of PCR-amplified SSU rDNA, to profile the microbial communities in an average of 26 stool samples each from 14 healthy, full-term human infants, including a pair of dizygotic twins, beginning with the first stool after birth and continuing at defined intervals throughout the first year of life. To investigate possible origins of the infant microbiota, we also profiled vaginal and milk samples from most of the mothers, and stool samples from all of the mothers, most of the fathers, and two siblings. The composition and temporal patterns of the microbial communities varied widely from baby to baby. Despite considerable temporal variation, the distinct features of each baby's microbial community were recognizable for intervals of weeks to months. The strikingly parallel temporal patterns of the twins suggested that incidental environmental exposures play a major role in determining the distinctive characteristics of the microbial community in each baby. By the end of the first year of life, the idiosyncratic microbial ecosystems in each baby, although still distinct, had converged toward a profile characteristic of the adult gastrointestinal tract.

  12. Association between Placental Lesions, Cytokines and Angiogenic Factors in Pregnant Women with Preeclampsia.

    Directory of Open Access Journals (Sweden)

    Ingrid C Weel

    Full Text Available Preeclampsia (PE is considered the leading cause of maternal and perinatal morbidity and mortality. The placenta seems to play an essential role in this disease, probably due to factors involved in its formation and development. The present study aimed to investigate the association between placental lesions, cytokines and angiogenic factors in pregnant women with preeclampsia (PE. We evaluated 20 normotensive pregnant women, 40 with early-onset PE and 80 with late-onset PE. Placental samples were analyzed for histopathology, immunohistochemistry and determination of granulocyte-macrophage colony-stimulating factor (GM-CSF, interleukin-10 (IL-10, transforming growth factor-beta 1 (TGF-β1, tumor necrosis factor-alpha (TNF-α, placental growth factor (PlGF, vascular endothelial growth factor (VEGF, fms-like tyrosine-kinase-1 (Flt-1 and endoglin (Eng levels. Higher percentages of increased syncytial knots and increased perivillous fibrin deposits, and greater levels of TNF-α, TGF-β1and Flt-1 were detected in placentas from early-onset PE. Levels of IL-10, VEGF and PlGF were decreased in PE versus normotensive placentas. Both the TNF-α/IL-10 and sFlt-1/PlGF ratios were higher in placental homogenate of early-onset PE than late-onset PE and control groups. The more severe lesions and the imbalance between TNF-α/IL-10 and PlGF/sFlt-1 in placentas from early-onset PE allows differentiation of early and late-onset PE and suggests higher placental impairment in early-onset PE.

  13. Placental protein-13 (PP13) in combination with PAPP-A and free leptin index (fLI) in first trimester maternal serum screening for severe and early preeclampsia

    DEFF Research Database (Denmark)

    Villiers, Carin P.De; Hedley, Paula L.; Placing, Sophie

    2017-01-01

    Placental protein-13 (PP13) is involved in placental invasion and has been suggested as a maternal serum marker of preeclampsia (PE) development. However, the discriminatory ability of PP13 in first trimester has not been completely clarified. PP13 was measured in first trimester (week 10...

  14. Pathologic evaluation of normal and perfused term placental tissue

    DEFF Research Database (Denmark)

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

    2014-01-01

    This study reports for the 1st time the incidence and interobserver variation of morphologic findings in a series of 34 term placentas from pregnancies with normal outcome used for perfusion studies. Histologic evaluation of placental tissue is challenging, especially when it comes to defining...... "normal tissue" versus "pathologic lesions." A scoring system for registration of abnormal morphologic findings was developed. Light microscopic examination was performed independently by 2 pathologists, and interobserver variation was analyzed. Findings in normal and perfused tissue were compared...... and selected findings were tested against success parameters from the perfusions. Finally, the criteria for frequent lesions with fair to poor interobserver variation in the nonperfused tissue were revised and reanalyzed. In the perfused tissue, the perfusion artefact "trophoblastic vacuolization," which...

  15. PLACENTAL GROWTH FACTOR AND CORONARY NEOANGIOGENESIS IN CORONARY HEART DISEASE

    Directory of Open Access Journals (Sweden)

    M. V. Tulikov

    2013-01-01

    Full Text Available Neoangiogenesis in coronary heart disease is a protective reaction aimed to improve ischemic myocardial perfusion, by increasing the number and size of arterial collaterals. Placental growth factor (PlGF is one of the key peptides regulating angiogenic processes in atherosclerosis. In particular, a number of investigators have shown that injection of recombinant PlGF into the system or regional blood flow can stimulate neoangiogenesis. On the other hand, there is evidence confirming the involvement of PlGF in the progression of atherosclerosis and in the development of acute coronary syndrome. In this connection, the problem of investigating the efficiency and safety of possible use of PlGF preparations, as well as its place in the diagnosis of coronary heart disease and acute coronary syndrome remains urgent

  16. Establishing operational stability--developing human infrastructure.

    Science.gov (United States)

    Gomez, Max A; Byers, Ernest J; Stingley, Preston; Sheridan, Robert M; Hirsch, Joshua A

    2010-12-01

    Over the past year, Toyota has come under harsh scrutiny as a result of several recalls. These well publicized mishaps have not only done damage to Toyota's otherwise sterling reputation for quality but have also called into question the assertions from a phalanx of followers that Toyota's production system (generically referred to as TPS or Lean) is the best method by which to structure one's systems of operation. In this article, we discuss how Toyota, faced with the pressure to grow its business, did not appropriately cadence this growth with the continued development and maintenance of the process capabilities (vis a vis the development of human infrastructure) needed to adequately support that growth. We draw parallels between the pressure Toyota faced to grow its business and the pressure neurointerventional practices face to grow theirs, and offer a methodology to support that growth without sacrificing quality.

  17. DETERMINANTS OF GLOBAL DEVELOPMENT IN HUMAN MOTIVATION

    Directory of Open Access Journals (Sweden)

    ŢÂMPU DIANA LARISA

    2015-06-01

    Full Text Available We live in a world were manner of use of information is crucial in determining the level of performance. Each country around the globe uses a proper way of spreading information and communication. Studies present the Information and Communication Technology (ICT indicator the proper tool to provide an objective evaluation of the countries performance. The question that this research wants to answer is what are the main ways of motivation (extrinsic and intrinsic in countries where ICT Development Index reaches the highest values in the last 2 years. In this way, we want to verify if ICT has different predictors and different possible consequence that depend on human motivation. Thus relying on calculations made by the International Telecommunication Union for ICT and key factors of motivation this paper will present if there is any relationship between citizens motivation and ICT. This hypothesized model will be illustrated with data from thirty developed countries.

  18. 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.

  19. Placental effects of lead in mice.

    Science.gov (United States)

    Fuentes, M; Torregrosa, A; Mora, R; Götzens, V; Corbellla, J; Domingo, J L

    1996-01-01

    Although a number of studies in animal models have shown embryolethal and teratogenic lead effects when this element is administered by a parenteral route, the mechanism of the embryonary changes is well not established. In this study, the embryonic effects of parenteral lead exposure on day 9 of gestation were assessed in the Swiss mouse. Lead acetate trihydrate was injected intraperitoneally at 14, 28, 56 and 112 mg/kg. There was no maternal toxicity evidenced by death, reduced body weight gain or reduced food consumption. However, absolute placental weight at 112 mg/kg and relative placental weight at 14, 56 and 112 mg/kg were diminished significantly. The number of total implants, live and dead fetuses, sex ratio and fetal body weight were unaffected by lead exposure. Most sections of placenta showed vascular congestion, an increase of intracellular spaces and deposits of hyaline material of perivascular predominance. Trophoblast hyperplasia was also observed, whereas there was a reinforcement of the fibrovascular network in the labyrinth. It is concluded that the trophoblast hyperplasia observed in the placenta of pregnant mice after parenteral lead exposure at doses that are not toxic for the dam could act as a repairing mechanism of the extraembryonary tissues.

  20. Protein profiling of preeclampsia placental tissues.

    Directory of Open Access Journals (Sweden)

    Chang Shu

    Full Text Available 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.

  1. 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

  2. Placental Chorangiosis: Increased Risk for Cesarean Section

    Directory of Open Access Journals (Sweden)

    Shariska S. Petersen

    2017-01-01

    Full Text Available We describe a patient with Class C diabetes who presented for nonstress testing at 36 weeks and 4 days of gestation with nonreassuring fetal heart tones (NRFHT and oligohydramnios. Upon delivery, thrombosis of the umbilical cord was grossly noted. Pathological analysis of the placenta revealed chorangiosis, vascular congestion, and 40% occlusion of the umbilical vein. Chorangiosis is a vascular change of the placenta that involves the terminal chorionic villi. It has been proposed to result from longstanding, low-grade hypoxia in the placental tissue and has been associated with such conditions such as diabetes, intrauterine growth restriction (IUGR, and hypertensive conditions in pregnancy. To characterize chorangiosis and its associated obstetric outcomes we identified 61 cases of “chorangiosis” on placental pathology at Henry Ford Hospital from 2010 to 2015. Five of these cases were omitted due to lack of complete records. Among the 56 cases, the cesarean section rate was 51%, indicated in most cases for nonreassuring fetal status. Thus, we suggest that chorangiosis, a marker of chronic hypoxia, is associated with increased rates of cesarean sections for nonreassuring fetal status because of long standing hypoxia coupled with the stress of labor.

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

    Directory of Open Access Journals (Sweden)

    Jaime Eduardo Bernal Villegas

    2012-08-01

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

  4. Early androgen exposure and human gender development.

    Science.gov (United States)

    Hines, Melissa; Constantinescu, Mihaela; Spencer, Debra

    2015-01-01

    During early development, testosterone plays an important role in sexual differentiation of the mammalian brain and has enduring influences on behavior. Testosterone exerts these influences at times when the testes are active, as evidenced by higher concentrations of testosterone in developing male than in developing female animals. This article critically reviews the available evidence regarding influences of testosterone on human gender-related development. In humans, testosterone is elevated in males from about weeks 8 to 24 of gestation and then again during early postnatal development. Individuals exposed to atypical concentrations of testosterone or other androgenic hormones prenatally, for example, because of genetic conditions or because their mothers were prescribed hormones during pregnancy, have been consistently found to show increased male-typical juvenile play behavior, alterations in sexual orientation and gender identity (the sense of self as male or female), and increased tendencies to engage in physically aggressive behavior. Studies of other behavioral outcomes following dramatic androgen abnormality prenatally are either too small in their numbers or too inconsistent in their results, to provide similarly conclusive evidence. Studies relating normal variability in testosterone prenatally to subsequent gender-related behavior have produced largely inconsistent results or have yet to be independently replicated. For studies of prenatal exposures in typically developing individuals, testosterone has been measured in single samples of maternal blood or amniotic fluid. These techniques may not be sufficiently powerful to consistently detect influences of testosterone on behavior, particularly in the relatively small samples that have generally been studied. The postnatal surge in testosterone in male infants, sometimes called mini-puberty, may provide a more accessible opportunity for measuring early androgen exposure during typical development. This

  5. Current View on Osteogenic Differentiation Potential of Mesenchymal Stromal Cells Derived from Placental Tissues.

    Science.gov (United States)

    Kmiecik, Gabriela; Spoldi, Valentina; Silini, Antonietta; Parolini, Ornella

    2015-08-01

    Mesenchymal stromal cells (MSC) isolated from human term placental tissues possess unique characteristics, including their peculiar immunomodulatory properties and their multilineage differentiation potential. The osteogenic differentiation capacity of placental MSC has been widely disputed, and continues to be an issue of debate. This review will briefly discuss the different MSC populations which can be obtained from different regions of human term placenta, along with their unique properties, focusing specifically on their osteogenic differentiation potential. We will present the strategies used to enhance osteogenic differentiation potential in vitro, such as through the selection of subpopulations more prone to differentiate, the modification of the components of osteo-inductive medium, and even mechanical stimulation. Accordingly, the applications of three-dimensional environments in vitro and in vivo, such as non-synthetic, polymer-based, and ceramic scaffolds, will also be discussed, along with results obtained from pre-clinical studies of placental MSC for the regeneration of bone defects and treatment of bone-related diseases.

  6. 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...... in the chimpanzee, we postulated the occurrence of deep invasion in gorilla pregnancy. Tissues were processed for histology (PAS, orcein), lectin staining (Ulex europaeus agglutinin 1) and immunohistochemistry (cytokeratin 7/17, α-actin). A specimen of young but undetermined gestational age included deep placental...... no definite conclusions about the origin of the intramural trophoblast and the time-course of spiral artery invasion. A different late second trimester placenta specimen showed scattered extravillous trophoblast in the basal plate and underlying decidua, as well as a remodelled spiral artery containing...

  7. Alpha-Fetoprotein, Identified as a Novel Marker for the Antioxidant Effect of Placental Extract, Exhibits Synergistic Antioxidant Activity in the Presence of Estradiol

    Science.gov (United States)

    Choi, Hye Yeon; Kim, Seung Woo; Kim, BongWoo; Lee, Hae Na; Kim, Su-Jeong; Song, Minjung; Kim, Sol; Kim, Jungho; Kim, Young Bong; Kim, Jin-Hoi; Cho, Ssang-Goo

    2014-01-01

    Placenta, as a reservoir of nutrients, has been widely used in medical and cosmetic materials. Here, we focused on the antioxidant properties of placental extract and attempted to isolate and identify the main antioxidant factors. Porcine placental extracts were prepared through homogenization or acid hydrolysis, and their antioxidant activity was investigated in the human keratinocyte HaCaT cell line. Treatment with homogenized placental extract (H-PE) increased the cell viability of H2O2-treated HaCaT cells more than two-fold. H-PE treatment suppressed H2O2-induced apoptotic and necrotic cell death and decreased intracellular ROS levels in H2O2-treated HaCaT cells. The antioxidant factors in H-PE were found to be thermo-unstable and were thus expected to include proteins. The candidate antioxidant proteins were fractionated with cation-exchange, anion-exchange, and size-exclusion chromatography, and the antioxidant properties of the chromatographic fractions were investigated. We obtained specific antioxidant fractions that suppressed ROS generation and ROS-induced DNA strand breaks. From silver staining and MALDI-TOF analyses, alpha-fetoprotein (AFP) precursor was identified as a main marker for the antioxidant effect of H-PE. Purified AFP or ectopically expressed AFP exhibited synergistic antioxidant activity in the presence of estradiol. Taken together, our data suggest that AFP, a serum glycoprotein produced at high levels during fetal development, is a novel marker protein for the antioxidant effect of the placenta that exhibits synergistic antioxidant activity in the presence of estradiol. PMID:24922551

  8. Alpha-fetoprotein, identified as a novel marker for the antioxidant effect of placental extract, exhibits synergistic antioxidant activity in the presence of estradiol.

    Directory of Open Access Journals (Sweden)

    Hye Yeon Choi

    Full Text Available Placenta, as a reservoir of nutrients, has been widely used in medical and cosmetic materials. Here, we focused on the antioxidant properties of placental extract and attempted to isolate and identify the main antioxidant factors. Porcine placental extracts were prepared through homogenization or acid hydrolysis, and their antioxidant activity was investigated in the human keratinocyte HaCaT cell line. Treatment with homogenized placental extract (H-PE increased the cell viability of H2O2-treated HaCaT cells more than two-fold. H-PE treatment suppressed H2O2-induced apoptotic and necrotic cell death and decreased intracellular ROS levels in H2O2-treated HaCaT cells. The antioxidant factors in H-PE were found to be thermo-unstable and were thus expected to include proteins. The candidate antioxidant proteins were fractionated with cation-exchange, anion-exchange, and size-exclusion chromatography, and the antioxidant properties of the chromatographic fractions were investigated. We obtained specific antioxidant fractions that suppressed ROS generation and ROS-induced DNA strand breaks. From silver staining and MALDI-TOF analyses, alpha-fetoprotein (AFP precursor was identified as a main marker for the antioxidant effect of H-PE. Purified AFP or ectopically expressed AFP exhibited synergistic antioxidant activity in the presence of estradiol. Taken together, our data suggest that AFP, a serum glycoprotein produced at high levels during fetal development, is a novel marker protein for the antioxidant effect of the placenta that exhibits synergistic antioxidant activity in the presence of estradiol.

  9. HUMAN POTENTIAL AS A STRATEGIC FACTOR OF REGIONAL DEVELOPMENT

    Directory of Open Access Journals (Sweden)

    A.M. Korobeynikov

    2008-12-01

    Full Text Available The article gives an insight of human potential as the strategic factor of regional development. The matter of human potential and its role in regional reproducing process is considered; regional intellectual potential as an integral part of human potential is analysed. The author outlines major directions of active social policy, aimed to develop regional human potential.

  10. MONOAMINE OXIDASE: RADIOTRACER DEVELOPMENT AND HUMAN STUDIES.

    Energy Technology Data Exchange (ETDEWEB)

    FOWLER,J.S.; LOGAN,J.; VOLKOW,N.D.; WANG,G.J.; MACGREGOR,R.R.; DING,Y.S.

    2000-09-28

    PET is uniquely capable of providing information on biochemical transformations in the living human body. Although most of the studies of monoamine oxidase (MAO) have focused on measurements in the brain, the role of peripheral MAO as a phase 1 enzyme for the metabolism of drugs and xenobiotics is gaining attention (Strolin Benedetti and Tipton, 1998; Castagnoli et al., 1997.). MAO is well suited for this role because its concentration in organs such as kidneys, liver and digestive organs is high sometimes exceeding that in the brain. Knowledge of the distribution of the MAO subtypes within different organs and different cells is important in determining which substrates (and which drugs and xenobiotics) have access to which MAO subtypes. The highly variable subtype distribution with different species makes human studies even more important. In addition, the deleterious side effects of combining MAO inhibitors with other drugs and with foodstuffs makes it important to know the MAO inhibitory potency of different drugs both in the brain and in peripheral organs (Ulus et al., 2000). Clearly PET can play a role in answering these questions, in drug research and development and in discovering some of the factors which contribute to the highly variable MAO levels in different individuals.

  11. [Clinical efficacy and safety of uterine artery chemoembolization in abnormal placental implantation complicated with postpartum hemorrhage].

    Science.gov (United States)

    Chen, Yao-ting; Xu, Lin-feng; Sun, Hong-liang; Li, Hui-qing; Hu, Ren-mei; Tan, Qi-yin

    2010-04-01

    To investigate the safety and clinical efficacy of uterime artery chemoembolization in postpartum hemorrhage (PPH) caused by abnormal placental implantation. Between December 2006 and September 2009, there were 23 cases of abnormal placental implantation with PPH in our hospital, among which 9 presented with continuous small amount of vaginal bleeding and 14 with acute excessive bleeding. The average bleeding time was (8+/-6) d and the mean blood loss was (980+/-660) ml. Abnormal placental implantation was confirmed by color Doppler ultrasound (CD-US) in all cases, the internal iliac artery angiography was performed to identify the uterine artery and bilateral uterine artery chemoembolization (UACE) with methotrexate (MTX) and gelfoam particles to the distal end of uterine artery was conducted after. CD-US rechecked all patients within 48 h after UACE and those patients with blurred margins between placenta and uterus and abnormal blood flow (>1 cmx1 cm) received ultrasonic-guided per vagina MTX multipoint injections. All cases were followed up for 3-26 months (average 12 months) to observe vaginal bleeding, placenta tissue discharge, serum human chorionic gonadotropin (hCG), uterine involution, menses, and side-effects or complications. (1) Curative effect: These 23 cases underwent 24 procedures of UACE successfully and vaginal bleeding ceased at an average of (3.5+/-1.3) min after UACE. Reduced blood flow in the placental implantation area was detected under CD-US after UACE. Among the 23 patients, wterine curettage was required in 16 cases due to retained placenta tissues with the mean blood loss of (40+/-28) ml during the operation, 2 underwent subtotal hysterectomy and confirmed to be placenta percreta by pathology examination, and placenta tissues were spontaneously discharged completely in 5 cases. Totally, 91% of the patients (21/23) reserved their uterus. (2) FOLLOW-UP: the serum hCG reduced to normal within 1-13 d after the placenta tissue were evacuated

  12. Infant feeding, poverty and human development

    Directory of Open Access Journals (Sweden)

    Amir Lisa H

    2007-10-01

    Full Text Available Abstract The relationship between poverty and human development touches on a central aim of the International Breastfeeding Journal's editorial policy which is to support and protect the health and wellbeing of all infants through the promotion of breastfeeding. It is proposed that exclusive breastfeeding for 6 months, followed by continued breastfeeding to 12 months, could prevent 1,301,000 deaths or 13% of all child deaths under 5 years in a hypothetical year. Although there is a conventional wisdom that poverty 'protects' breastfeeding in developing countries, poverty actually threatens breastfeeding, both directly and indirectly. In the light of increasingly aggressive marketing behaviour of the infant formula manufacturers and the need to protect the breastfeeding rights of working women, urgent action is required to ensure the principles and aim of the International Code of Breastmilk Substitutes, and subsequent relevant resolutions of the World Health Assembly, are implemented. If global disparities in infant health and development are to be significantly reduced, gender inequities associated with reduced access to education and inadequate nutrition for girls need to be addressed. Improving women's physical and mental health will lead to better developmental outcomes for their children.

  13. Sustainable human development: an educational commitment

    Directory of Open Access Journals (Sweden)

    Pilar AZNAR MÍNGUET

    2017-06-01

    Full Text Available Sustainable Human Development (hereafter SHD is taking shape as a proposal for progress in the face of a crisis in civilization so complex and far-reaching that it is considered quite difficult to solve. The aim of this article is to offer a reasoned justification of the evolution of the concept of development and of the need for an educational commitment to be able to make progress towards it. Although it is still polemical and the object of criticism, SHD has become consolidated as a strongly ethical proposal to lead the change in the course of development, transversally affecting its multiple dimensions and advocating interdisciplinary and intercultural cooperation and dialogue. The article analyses the challenges posed by SHD to today’s global society, as well as some ways to respond to them from the field of educational action and research. It concludes with a reasoned structuring of the contents of the monograph and an analytical description of the contents of the different contributions.

  14. Activities of nuclear human resource development in nuclear industry

    International Nuclear Information System (INIS)

    Tsujikura, Yonezo

    2010-01-01

    Since 2007, the JAIF (Japan Atomic Industrial Forum) had established the nuclear energy human resource development council to make analysis of the issue on nuclear human resource development. The author mainly contributed to develop its road map as a chairman of working group. Questionnaire survey to relevant parties on issues of nuclear human resource development had been conducted and the council identified the six relevant issues and ten recommendations. Both aspects for career design and skill-up program are necessary to develop nuclear human resource at each developing step and four respective central coordinating hubs should be linked to each sector participating in human resource development. (T. Tanaka)

  15. 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.

  16. 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.

  17. Development and function of human innate immune cells in a humanized mouse model.

    Science.gov (United States)

    Rongvaux, Anthony; Willinger, Tim; Martinek, Jan; Strowig, Till; Gearty, Sofia V; Teichmann, Lino L; Saito, Yasuyuki; Marches, Florentina; Halene, Stephanie; Palucka, A Karolina; Manz, Markus G; Flavell, Richard A

    2014-04-01

    Mice repopulated with human hematopoietic cells are a powerful tool for the study of human hematopoiesis and immune function in vivo. However, existing humanized mouse models cannot support development of human innate immune cells, including myeloid cells and natural killer (NK) cells. Here we describe two mouse strains called MITRG and MISTRG, in which human versions of four genes encoding cytokines important for innate immune cell development are knocked into their respective mouse loci. The human cytokines support the development and function of monocytes, macrophages and NK cells derived from human fetal liver or adult CD34(+) progenitor cells injected into the mice. Human macrophages infiltrated a human tumor xenograft in MITRG and MISTRG mice in a manner resembling that observed in tumors obtained from human patients. This humanized mouse model may be used to model the human immune system in scenarios of health and pathology, and may enable evaluation of therapeutic candidates in an in vivo setting relevant to human physiology.

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

    DEFF Research Database (Denmark)

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

    2017-01-01

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

  19. A 3D co-culture microtissue model of the human placenta for nanotoxicity assessment.

    Science.gov (United States)

    Muoth, Carina; Wichser, Adrian; Monopoli, Marco; Correia, Manuel; Ehrlich, Nicky; Loeschner, Katrin; Gallud, Audrey; Kucki, Melanie; Diener, Liliane; Manser, Pius; Jochum, Wolfram; Wick, Peter; Buerki-Thurnherr, Tina

    2016-10-06

    There is increasing evidence that certain nanoparticles (NPs) can overcome the placental barrier, raising concerns on potential adverse effects on the growing fetus. But even in the absence of placental transfer, NPs may pose a risk to proper fetal development if they interfere with the viability and functionality of the placental tissue. The effects of NPs on the human placenta are not well studied or understood, and predictive in vitro placenta models to achieve mechanistic insights on NP-placenta interactions are essentially lacking. Using the scaffold-free hanging drop technology, we developed a well-organized and highly reproducible 3D co-culture microtissue (MT) model consisting of a core of placental fibroblasts surrounded by a trophoblast cell layer, which resembles the structure of the in vivo placental tissue. We could show that secretion levels of human chorionic gonadotropin (hCG) were significantly higher in 3D than in 2D cell cultures, which indicates an enhanced differentiation of trophoblasts grown on 3D MTs. NP toxicity assessment revealed that cadmium telluride (CdTe) and copper oxide (CuO) NPs but not titanium dioxide (TiO 2 ) NPs decreased MT viability and reduced the release of hCG. NP acute toxicity was significantly reduced in 3D co-culture MTs compared to 2D monocultures. Taken together, 3D placental MTs provide a new and promising model for the fast generation of tissue-relevant acute NP toxicity data, which are indispensable for the safe development of NPs for industrial, commercial and medical applications.

  20. Perspectives of Nuclear Energy for Human Development

    International Nuclear Information System (INIS)

    Rouyer, Jean-Loup

    2002-01-01

    In this period of expectation and short term viewing, everyone has difficulties to draw long term perspectives. A positive global world vision of sustainable development gives confidence in the preparation of energy future in a moving international context. This presentation proposes to share such a long term vision inside which energy scenarios for nuclear development take their right place. It is founded on a specific analysis of an index of countries global development which is representative of a country efficiency. Human Development Index (HDI) is a composite international index recommended and calculated every year since 1990 by the United Nations Development Program (UNDP). This index is still very dependent of GNP, which ignores the disparities of revenues inside the country. That is why a Country Efficiency Index (CEI) has been defined to better represent the capacity of a country to utilize its resources for welfare of its inhabitants. CEI is a ratio of health and education levels to the capacity of the country to satisfy this welfare. CEI has been calculated for the 70 more populated countries of the world for the year 1997. CEI calculation has been also performed for European Countries, the United States, China and India on the period from 1965 to 1997. It is observed a growth of CEI. for France from 0.6 to 0.78, and from 0.7 to 0.85 for USA. In 1997, CEI of China was 0.46, and 0.38 for India. This index is a good tool to measure the progression of development of the countries and the related energy needs. Comparison of the evolutions of CEI of these different countries shows a similar positive trend with some delay between OECD countries and China or India. A positive scenario for the future is based on a similar curve for these developing countries with learning effect which produces development with less energy consumption. This simulation results however in energy needs that exceed fossil fuel today available resources in 2070. Ultimate fossil

  1. Standard development at the Human Variome Project.

    Science.gov (United States)

    Smith, Timothy D; Vihinen, Mauno

    2015-01-01

    The Human Variome Project (HVP) is a world organization working towards facilitating the collection, curation, interpretation and free and open sharing of genetic variation information. A key component of HVP activities is the development of standards and guidelines. HVP Standards are systems, procedures and technologies that the HVP Consortium has determined must be used by HVP-affiliated data sharing infrastructure and should be used by the broader community. HVP guidelines are considered to be beneficial for HVP affiliated data sharing infrastructure and the broader community to adopt. The HVP also maintains a process for assessing systems, processes and tools that implement HVP Standards and Guidelines. Recommended System Status is an accreditation process designed to encourage the adoption of HVP Standards and Guidelines. Here, we describe the HVP standards development process and discuss the accepted standards, guidelines and recommended systems as well as those under acceptance. Certain HVP Standards and Guidelines are already widely adopted by the community and there are committed users for the others. © The Author(s) 2015. Published by Oxford University Press.

  2. Development of a realistic human airway model.

    Science.gov (United States)

    Lizal, Frantisek; Elcner, Jakub; Hopke, Philip K; Jedelsky, Jan; Jicha, Miroslav

    2012-03-01

    Numerous models of human lungs with various levels of idealization have been reported in the literature; consequently, results acquired using these models are difficult to compare to in vivo measurements. We have developed a set of model components based on realistic geometries, which permits the analysis of the effects of subsequent model simplification. A realistic digital upper airway geometry except for the lack of an oral cavity has been created which proved suitable both for computational fluid dynamics (CFD) simulations and for the fabrication of physical models. Subsequently, an oral cavity was added to the tracheobronchial geometry. The airway geometry including the oral cavity was adjusted to enable fabrication of a semi-realistic model. Five physical models were created based on these three digital geometries. Two optically transparent models, one with and one without the oral cavity, were constructed for flow velocity measurements, two realistic segmented models, one with and one without the oral cavity, were constructed for particle deposition measurements, and a semi-realistic model with glass cylindrical airways was developed for optical measurements of flow velocity and in situ particle size measurements. One-dimensional phase doppler anemometry measurements were made and compared to the CFD calculations for this model and good agreement was obtained.

  3. Cell-free placental mRNA in maternal plasma to predict placental invasion in patients with placenta accreta.

    Science.gov (United States)

    El Behery, Manal M; Rasha L, Etewa; El Alfy, Yehya

    2010-04-01

    To evaluate whether measuring cell-free placental mRNA in maternal plasma improves the diagnostic accuracy of ultrasound and color Doppler in detecting placental invasion in patients at risk for placenta accreta. Thirty-five singleton pregnant women of more than 28 weeks of gestation and at risk for placenta accreta underwent ultrasound and color Doppler assessment. Cell-free placental mRNA in maternal plasma was measured using real-time reverse-transcription polymerase chain reaction. Patients were classified into 2 groups based on the findings at cesarean delivery and histological