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Sample records for abnormal placental development

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

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

    2015-08-14

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

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

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    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.

  3. Placental loctogen levels associated with gross fetal abnormality.

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    Gau, G S; Cadle, G

    1977-02-01

    Four cases of severe congenital abnormality associated with persistently low maternal serum human placental lactogen levels are described. It is thought that this pattern might act as a warning of severe fetal abnormality.

  4. 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.

  5. Abnormal placentation, angiogenic factors, and the pathogenesis of preeclampsia.

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    Silasi, Michelle; Cohen, Bruce; Karumanchi, S Ananth; Rana, Sarosh

    2010-06-01

    Preeclampsia is a common complication of pregnancy with potentially devastating consequences to both the mother and the baby.It is the leading cause of maternal deaths in developing countries. In developed countries it is the major cause of iatrogenic premature delivery and contributes significantly to increasing health care cost associated with prematurity. There is currently no known treatment for preeclampsia; ultimate treatment involves delivery of the placenta. Although there are several risk factors (such as multiple gestation or chronic hypertension), most patients present with no obvious risk factors. The molecular pathogenesis of preeclampsia is just now being elucidated. It has been proposed that abnormal placentation and an imbalance in angiogenic factors lead to the clinical findings and complications seen in preeclampsia. Preeclampsia is characterized by high levels of circulating antiangiogenic factors such as soluble fms-like tyrosine kinase-1 and soluble endoglin, which induce maternal endothelial dysfunction. These soluble factors are altered not only at the time of clinical disease but also several weeks before the onset of clinical signs and symptoms. Many methods of prediction and surveillance have been proposed to identify women who will develop preeclampsia, but studies have been inconclusive. With the recent discovery of the role of angiogenic factors in preeclampsia, novel methods of prediction and diagnosis are being developed to aid obstetricians and midwives in clinical practice. This article discusses the role of angiogenic factors in the pathogenesis, prediction, diagnosis, and possible treatment of preeclampsia.

  6. Imaging of activated complement using ultrasmall superparamagnetic iron oxide particles (USPIO) - conjugated vectors: an in vivo in utero non-invasive method to predict placental insufficiency and abnormal fetal brain development

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    Girardi, G; Fraser, J; Lennen, R; Vontell, R; Jansen, M; Hutchison, G

    2015-01-01

    In the current study, we have developed a magnetic resonance imaging-based method for non-invasive detection of complement activation in placenta and foetal brain in vivo in utero. Using this method, we found that anti-complement C3-targeted ultrasmall superparamagnetic iron oxide (USPIO) nanoparticles bind within the inflamed placenta and foetal brain cortical tissue, causing a shortening of the T2* relaxation time. We used two mouse models of pregnancy complications: a mouse model of obstetrics antiphospholipid syndrome (APS) and a mouse model of preterm birth (PTB). We found that detection of C3 deposition in the placenta in the APS model was associated with placental insufficiency characterised by increased oxidative stress, decreased vascular endothelial growth factor and placental growth factor levels and intrauterine growth restriction. We also found that foetal brain C3 deposition was associated with cortical axonal cytoarchitecture disruption and increased neurodegeneration in the mouse model of APS and in the PTB model. In the APS model, foetuses that showed increased C3 in their brains additionally expressed anxiety-related behaviour after birth. Importantly, USPIO did not affect pregnancy outcomes and liver function in the mother and the offspring, suggesting that this method may be useful for detecting complement activation in vivo in utero and predicting placental insufficiency and abnormal foetal neurodevelopment that leads to neuropsychiatric disorders. PMID:25245499

  7. Maternal risk factors for abnormal placental growth: The national collaborative perinatal project

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    Nicholson Wanda K

    2008-09-01

    Full Text Available Abstract Background Previous studies of maternal risk factors for abnormal placental growth have focused on placental weight and placental ratio as measures of placental growth. We sought to identify maternal risk factors for placental weight and two neglected dimensions of placental growth: placental thickness and chorionic plate area. Methods We conducted an analysis of 24,135 mother-placenta pairs enrolled in the National Collaborative Perinatal Project, a prospective cohort study of pregnancy and child health. We defined growth restriction as th percentile and hypertrophy as > 90th percentile for three placental growth dimensions: placental weight, placental thickness and chorionic plate area. We constructed parallel multinomial logistic regression analyses to identify (a predictors of restricted growth (vs. normal and (b predictors of hypertrophic growth (vs. normal. Results Black race was associated with an increased likelihood of growth restriction for placental weight, thickness and chorionic plate area, but was associated with a reduced likelihood of hypertrophy for these three placental growth dimensions. We observed an increased likelihood of growth restriction for placental weight and chorionic plate area among mothers with hypertensive disease at 24 weeks or beyond. Anemia was associated with a reduced likelihood of growth restriction for placental weight and chorionic plate area. Pre-pregnancy BMI and pregnancy weight gain were associated with a reduced likelihood of growth restriction and an increased likelihood of hypertrophy for all three dimensions of placental growth. Conclusion Maternal risk factors are either associated with placental growth restriction or placental hypertrophy not both. Our findings suggest that the placenta may have compensatory responses to certain maternal risk factors suggesting different underlying biological mechanisms.

  8. HSPC117 deficiency in cloned embryos causes placental abnormality and fetal death

    Energy Technology Data Exchange (ETDEWEB)

    Wang, Yingying [Department of Reproduction and Development, Kunming Institute of Zoology and Kunming Primate Research Center, Chinese Academy of Sciences, Kunming 650223 (China); State Key Laboratory of Reproductive Biology, Institute of Zoology, Chinese Academy of Sciences, Beijing 100080 (China); Graduate University of Chinese Academy of Sciences, Beijing 100049 (China); Hai, Tang; Liu, Zichuan; Zhou, Shuya; Lv, Zhuo [State Key Laboratory of Reproductive Biology, Institute of Zoology, Chinese Academy of Sciences, Beijing 100080 (China); Graduate University of Chinese Academy of Sciences, Beijing 100049 (China); Ding, Chenhui; Liu, Lei [State Key Laboratory of Reproductive Biology, Institute of Zoology, Chinese Academy of Sciences, Beijing 100080 (China); Niu, Yuyu [Department of Reproduction and Development, Kunming Institute of Zoology and Kunming Primate Research Center, Chinese Academy of Sciences, Kunming 650223 (China); Zhao, Xiaoyang; Tong, Man [State Key Laboratory of Reproductive Biology, Institute of Zoology, Chinese Academy of Sciences, Beijing 100080 (China); Graduate University of Chinese Academy of Sciences, Beijing 100049 (China); Wang, Liu [State Key Laboratory of Reproductive Biology, Institute of Zoology, Chinese Academy of Sciences, Beijing 100080 (China); Jouneau, Alice [INRA, UMR 1198, ENVA, CNRS, FRE 2857, Biologie du Developpement et Reproduction, Jouy en Josas F-78350 (France); Zhang, Xun [Neuroendocrine Unit, Massachusetts General Hospital and Harvard Medical School, Boston, MA 02114 (United States); Ji, Weizhi, E-mail: wji@mail.kiz.ac.cn [Department of Reproduction and Development, Kunming Institute of Zoology and Kunming Primate Research Center, Chinese Academy of Sciences, Kunming 650223 (China); Zhou, Qi, E-mail: qzhou@ioz.ac.cn [State Key Laboratory of Reproductive Biology, Institute of Zoology, Chinese Academy of Sciences, Beijing 100080 (China)

    2010-07-02

    Somatic cell nuclear transfer (SCNT) has been successfully used in many species to produce live cloned offspring, albeit with low efficiency. The low frequency of successful development has usually been ascribed to incomplete or inappropriate reprogramming of the transferred nuclear genome. Elucidating the genetic differences between normal fertilized and cloned embryos is key to understand the low efficiency of SCNT. Here, we show that expression of HSPC117, which encodes a hypothetical protein of unknown function, was absent or very low in cloned mouse blastocysts. To investigate the role of HSPC117 in embryo development, we knocked-down this gene in normal fertilized embryos using RNA interference. We assessed the post-implantation survival of HSPC117 knock-down embryos at 3 stages: E9 (prior to placenta formation); E12 (after the placenta was fully functional) and E19 (post-natal). Our results show that, although siRNA-treated in vivo fertilized/produced (IVP) embryos could develop to the blastocyst stage and implanted without any difference from control embryos, the knock-down embryos showed substantial fetal death, accompanied by placental blood clotting, at E12. Furthermore, comparison of HSPC117 expression in placentas of nuclear transfer (NT), intracytoplasmic sperm injection (ICSI) and IVP embryos confirmed that HSPC117 deficiency correlates well with failures in embryo development: all NT embryos with a fetus, as well as IVP and ICSI embryos, had normal placental HSPC117 expression while those NT embryos showing reduced or no expression of HSPC117 failed to form a fetus. In conclusion, we show that HSPC117 is an important gene for post-implantation development of embryos, and that HSPC117 deficiency leads to fetal abnormalities after implantation, especially following placental formation. We suggest that defects in HSPC117 expression may be an important contributing factor to loss of cloned NT embryos in vivo.

  9. Notch signalling in placental development and gestational diseases.

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    Haider, S; Pollheimer, J; Knöfler, M

    2017-01-16

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

  10. Intrauterine Growth Restriction Associated with Hematologic Abnormalities: Probable Manifestations of Placental Mesenchymal Dysplasia

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    Martinez-Payo, Cristina; Bernabeu, Rocio Alvarez; Villar, Isabel Salas; Goy, Enrique Iglesias

    2015-01-01

    Introduction Placental mesenchymal dysplasia is a rare vascular disease associated with intrauterine growth restriction, fetal demise as well as Beckwith–Wiedemann syndrome. Some neonates present hematologic abnormalities possibly related to consumptive coagulopathy and hemolytic anemia in the placental circulation. Case report We present a case of placental mesenchymal dysplasia in a fetus with intrauterine growth restriction and cerebellar hemorrhagic injury diagnosed in the 20th week of pregnancy. During 26th week, our patient had an intrauterine fetal demise in the context of gestational hypertension. We have detailed the ultrasound findings that made us suspect the presence of hematologic disorders during 20th week. Discussion We believe that the cerebellar hematoma could be the consequence of thrombocytopenia accompanied by anemia. If hemorrhagic damage during fetal life is found, above all associates with an anomalous placental appearance and with intrauterine growth restriction, PMD should be suspected along other etiologies. PMID:26495159

  11. Placental abnormalities associated with post-natal mortality in sheep somatic cell clones.

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    Loi, Pasqualino; Clinton, Michael; Vackova, Irena; Fulka, Josef; Feil, Robert; Palmieri, Chiara; Della Salda, Leonardo; Ptak, Grazyna

    2006-04-01

    We report on cloning experiments designed to explore the causes of peri- and post-natal mortality of cloned lambs. A total of 93 blastocysts obtained by nuclear transfer of somatic cells (granulosa cells) were transferred into 41 recipient ewes, and pregnancies were monitored by ultrasound scanning. In vitro derived, fertilized embryos (IVF, n=123) were also transferred to assess oocyte competence, and naturally mated ewes (n=120) were analysed as well. Cloned embryos developed to the blastocyst stage and implanted at the same rate as IVF embryos. After day 30 of gestation, however, dramatic losses occurred, and only 12 out of 93 (13%) clones reached full-term development, compared to 51 out of 123 (41.6%) lambs born from the IVF control embryos. Three full-term lamb clones were delivered stillborn, as a result of placental degeneration. A further five clone recipients developed hydroallantois. Their lambs died within 24h following delivery by caesarian section, and displayed degenerative lesions in liver and kidney resulting from the severe hydroallantois. One set of twins was delivered by assisted parturition at day 150, but died 24h later due to respiratory distress syndrome. The remaining two clone recipients underwent caesarian section, and the corresponding two lambs displayed signs of respiratory dysfunction and died at approximately 1 month of age due to a bacterial complication. Blood samples collected from the cloned lambs after birth revealed a wide range of abnormalities indicative of kidney and liver dysfunction. Macroscopical and histopathological examination of the placentae revealed a marked reduction in vascularization, particularly at the apex of the villous processes, as well as a loss of differentiation of the trophoblastic epithelium. Our results strongly suggest that post-mortality in cloned lambs is mainly caused by placental abnormalities.

  12. Abnormal Placentation: Placenta Previa, Vasa Previa, and Placenta Accreta.

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    Silver, Robert M

    2015-09-01

    Placental disorders such as placenta previa, placenta accreta, and vasa previa are all associated with vaginal bleeding in the second half of pregnancy. They are also important causes of serious fetal and maternal morbidity and even mortality. Moreover, the rates of previa and accreta are increasing, probably as a result of increasing rates of cesarean delivery, maternal age, and assisted reproductive technology. The routine use of obstetric ultrasonography as well as improving ultrasonographic technology allows for the antenatal diagnosis of these conditions. In turn, antenatal diagnosis facilitates optimal obstetric management. This review emphasizes an evidence-based approach to the clinical management of pregnancies with these conditions as well as highlights important knowledge gaps.

  13. Neurotrophins: Role in Placental Growth and Development.

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

    2017-01-01

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

  14. The placental problem: Linking abnormal cytotrophoblast differentiation to the maternal symptoms of preeclampsia

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    Fisher Susan J

    2004-07-01

    Full Text Available Abstract The placenta is a remarkable organ. In normal pregnancy its specialized cells (termed cytotrophoblasts differentiate into various specialized subpopulations that play pivotal roles in governing fetal growth and development. One cytotrophoblast subset acquires tumor-like properties that allow the cells to invade the decidua and myometrium, a process that attaches the placenta to the uterus. The same subset also adopts a vascular phenotype that allows these fetal cells to breach and subsequently line uterine blood vessels, a process that channels maternal blood to the rest of the placenta. In the pregnancy complication preeclampsia, which is characterized by the sudden onset of maternal hypertension, proteinuria and edema, cytotrophoblast invasion is shallow and vascular transformation incomplete. These findings, together with very recent evidence from animal models, suggest that preeclampsia is associated with abnormal placental production of vasculogenic/angiogenic substances that reach the maternal circulation with the potential to produce at least a subset of the clinical signs of this syndrome. The current challenge is to build on this knowledge to design clinically useful tests for predicting, diagnosing and treating this dangerous disorder.

  15. Clinical development of placental malaria vaccines and immunoassays harmonization

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    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...

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

    NARCIS (Netherlands)

    Roescher, Annemiek

    2014-01-01

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

  17. Immunoinformatics of Placental Malaria Vaccine Development

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    Jessen, Leon Eyrich

    for the pathogenesis of PM was identified as the P. falciparum Erythrocyte Membrane Protein 1 (Pf EMP1) variant VAR2CSA. VAR2CSA is the leading candidate for a vaccine against PM. The thesis is divided into 4 parts, where part I provide the reader with an introduction and background for the subjects covered......CSA-DBL5ε sequences each with associated phenotypes. Immunity towards PM is gradually acquired, therefore if a given sequence motif can be phenotype-correlated then the motif may be involved in VAR2CSA immunogenecity. Motifs defining VAR2CSA immunogenecity are naturally interesting in vaccine...... and development in the field of placental malaria vaccine development....

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

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    Robert Klepacz

    2010-06-01

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

  19. 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...

  20. Comparative aspects of trophoblast development and placentation

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    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

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

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

    2015-12-15

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

  2. Value of ultrasonography in diagnosis of placental abnormalities%胎盘异常的超声诊断

    Institute of Scientific and Technical Information of China (English)

    秦胜亚

    2013-01-01

    Objective To evaluate the diagnostic value of ultrasound in placental abnormalities by postnatal confirmation through retrospective analysis of placenta ultrsound images in recent years.Methods Two-dimensional color Doppler was used in routine examination of late pregnant women.Suspicious abnormal placental pregnant women after childbirth were followed-up and compared.Results Of 96 confirmed cases of placental abnormalities after birth or cesarean,prenatal ultrasound diagnosis was precise in 81 cases,and the diagnosis coincidence rate was 84.4%.Conclusion Ultrasound is the preferred and important inspection method in the prenatal diagnosis of placental abnormalities,which has a higher diagnostic yield with little trauma and pain,and has repeatable advantages for clinical obstetrics so that it can provide reliable basis for the correct processing of placental abnormalities and has important significance in reducing perinatal mortality.%目的 评价超声对胎盘异常的诊断价值.近年来被产后证实的胎盘异常的声像图改变. 方法 回顾性分析采用二维彩色多普勒对中晚期孕妇行常规检查,对可疑胎盘异常的孕妇追踪观察并与分娩后进行对比.结果 经分娩或剖宫产证实的96例胎盘异常中,产前超声正确诊断81例,诊断符合率为84.4%.结论 超声是产前诊断胎盘异常的首选而又重要的检查方法,有较高的诊断率而且具有无创伤、无痛苦、可重复的优点,为产科临床正确处理胎盘异常提供可靠的依据.

  3. 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

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

    Directory of Open Access Journals (Sweden)

    Miguel A Garcia-Gonzalez

    Full Text Available BACKGROUND: 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. METHODOLOGY/PRINCIPAL FINDINGS: 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. CONCLUSIONS/SIGNIFICANCE: 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.

  5. Analysis of homeobox gene action may reveal novel angiogenic pathways in normal placental vasculature and in clinical pregnancy disorders associated with abnormal placental angiogenesis.

    Directory of Open Access Journals (Sweden)

    Padma eMurthi

    2014-06-01

    Full Text Available Homeobox genes are essential for both the development of the blood and lymphatic vascular systems, as well as for their maintenance in the adult. Homeobox genes comprise an important family of transcription factors, which are characterised by a well conserved DNA binding motif; the homeodomain. The specificity of the homeodomain allows the transcription factor to bind to the promoter regions of batteries of target genes and thereby regulates their expression. Target genes identified for homeodomain proteins have been shown to control fundamental cell processes such as proliferation, differentiation and apoptosis. We and others have reported that homeobox genes are expressed in the placental vasculature, but our knowledge of their downstream target genes is limited. This review highlights the importance of studying the cellular and molecular mechanisms by which homeobox genes and their downstream targets may regulate important vascular cellular processes such as proliferation, migration, and endothelial tube formation, which are essential for placental vasculogenesis and angiogenesis. A better understanding of the molecular targets of homeobox genes may lead to new therapies for aberrant angiogenesis associated with clinically important pregnancy pathologies, including fetal growth restriction and preeclampsia.

  6. 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.

  7. Placental Pathology, Perinatal Death, Neonatal Outcome, and Neurological Development : A Systematic Review

    NARCIS (Netherlands)

    Roescher, Annemiek M.; Timmer, Albert; Erwich, Jan Jaap H. M.; Bos, Arend F.

    2014-01-01

    Background: The placenta plays a crucial role during pregnancy for growth and development of the fetus. Less than optimal placental performance may result in morbidity or even mortality of both mother and fetus. Awareness among pediatricians, however, of the benefit of placental findings for neonata

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

    Science.gov (United States)

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

    2014-09-26

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

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

    Science.gov (United States)

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

    2015-08-01

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

  10. The Human Placenta Project: Placental Structure, Development, and Function in Real Time

    Science.gov (United States)

    Guttmacher, Alan E.; Maddox, Yvonne T.; Spong, Catherine Y.

    2014-01-01

    Despite its crucial role in the health of both the fetus and the pregnant woman, the placenta is the least understood human organ. Since a growing body of evidence also underscores the importance of placental development in the lifelong health of both mother and offspring, this lack of knowledge about placental structure and function is particularly concerning. Given modern approaches and technologies and the ability to develop new methods, we propose a coordinated “Human Placenta Project,” with the ultimate goal of understanding human placental structure, development, and function in real time. PMID:24661567

  11. The Human Placenta Project: placental structure, development, and function in real time.

    Science.gov (United States)

    Guttmacher, A E; Maddox, Y T; Spong, C Y

    2014-05-01

    Despite its crucial role in the health of both the fetus and the pregnant woman, the placenta is the least understood human organ. Since a growing body of evidence also underscores the importance of placental development in the lifelong health of both mother and offspring, this lack of knowledge about placental structure and function is particularly concerning. Given modern approaches and technologies and the ability to develop new methods, we propose a coordinated "Human Placenta Project", with the ultimate goal of understanding human placental structure, development, and function in real time.

  12. 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

  13. IFPA meeting 2016 workshop report II: Placental imaging, placenta and development of other organs, sexual dimorphism in placental function and trophoblast cell lines.

    Science.gov (United States)

    Adibi, Jennifer; Burton, Graham J; Clifton, Vicki; Collins, Sally; Frias, Antonio E; Gierman, Lobke; Grigsby, Peta; Jones, Helen; Lee, Cheryl; Maloyan, Alina; Markert, Udo R; Morales-Prieto, Diana M; Murthi, Padma; Myatt, Leslie; Pollheimer, Jurgen; Roberts, Victoria; Robinson, Wendy; Salafia, Carolyn; Schabel, Matthias; Shah, Dinesh; Sled, John; Vaillancourt, Cathy; Weber, Maja; O'Tierney-Ginn, Perrie F

    2017-03-06

    Workshops are an important part of the IFPA annual meeting as they allow for discussion of specialized topics. At IFPA meeting 2016 there were twelve themed workshops, four of which are summarized in this report. These workshops addressed challenges, strengths and limitations of techniques and model systems for studying the placenta, as well as future directions for the following areas of placental research: 1) placental imaging; 2) sexual dimorphism; 3) placenta and development of other organs; 4) trophoblast cell lines.

  14. Embryonic rather than extraembryonic tissues have more impact on the development of placental hyperplasia in cloned mice.

    Science.gov (United States)

    Miki, H; Wakisaka, N; Inoue, K; Ogonuki, N; Mori, M; Kim, J-M; Ohta, A; Ogura, A

    2009-06-01

    Somatic cell cloning by nuclear transfer (NT) in mice is associated with hyperplastic placentas at term. To dissect the effects of embryonic and extraembryonic tissues on this clone-associated phenotype, we constructed diploid (2n) fused with () tetraploid (4n) chimeras from NT- and fertilization-derived (FD) embryos. Generally, the 4n cells contributed efficiently to all the extraembryonic tissues but not to the embryo itself. Embryos constructed by 2n NT4n FD aggregation developed hyperplastic placentas (0.33+/-0.22 g) with a predominant contribution by NT-derived cells. Even when the population of FD-derived cells in placentas was increased using multiple FD embryos (up to four) for aggregation, most placentas remained hyperplastic (0.36+/-0.13 g). By contrast, placentas of the reciprocal combination, 2n FD4n NT, were less hyperplastic (0.15+/-0.02 g). These nearly normal-looking placentas had a large proportion of NT-derived cells. Thus, embryonic rather than extraembryonic tissues had more impact on the onset of placental hyperplasia, and that the abnormal placentation in clones occurs in a noncell-autonomous manner. These findings suggest that for improvement of cloning efficiency we should understand the mechanisms regulating placentation, especially those of embryonic origin that might control the proliferation of trophoblastic lineage cells.

  15. Knockout of ERK5 causes multiple defects in placental and embryonic development

    Directory of Open Access Journals (Sweden)

    Murry-Tait Victoria

    2003-12-01

    Full Text Available Abstract Backgroud ERK5 is a member of the mitogen activated protein kinase family activated by certain mitogenic or stressful stimuli in cells, but whose physiological role is largely unclear. Results To help determine the function of ERK5 we have used gene targeting to inactivate this gene in mice. Here we report that ERK5 knockout mice die at approximately E10.5. In situ hybridisation for ERK5, and its upstream activator MKK5, showed strong expression in the head and trunk of the embryo at this stage of development. Between E9.5 and E10.5, multiple developmental problems are seen in the ERK5-/- embryos, including an increase in apoptosis in the cephalic mesenchyme tissue, abnormalities in the hind gut, as well as problems in vascular remodelling, cardiac development and placental defects. Conclusion Erk5 is essential for early embryonic development, and is required for normal development of the vascular system and cell survival.

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

    Science.gov (United States)

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

    2014-01-01

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

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

    DEFF Research Database (Denmark)

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

    2017-01-01

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

  18. 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

    The implantation of the blastocyst and early development of the placenta are crucial for the success of implantation and pregnancy. However, the formative stages of human placental development are largely unknown because of their existence in a 'black box' where access to samples is extremely...

  19. 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...

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

    Science.gov (United States)

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

    2016-01-01

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

  1. 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 (P0.05) in both NCG- and RP-Arg-treated underfed ewes. A supplement of RP-Arg and NCG reduced (P<0.05) the concentrations of progesterone, cortisol, and estradiol-17β; had no effect on T4/T3; and improved (P<0.05) the concentrations of leptin, insulin-like growth factor 1, tri-iodothyronine (T3), and thyroxine (T4) in serum from underfed ewes. 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.

  2. Altered cytokine network in gestational diabetes mellitus affects maternal insulin and placental-fetal development.

    Science.gov (United States)

    Wedekind, Lauren; Belkacemi, Louiza

    2016-01-01

    Pregnancy is characterized by an altered inflammatory profile, compared to the non-pregnant state with an adequate balance between pro-and anti-inflammatory cytokines needed for normal development. Cytokines are small secreted proteins expressed mainly in immunocompetent cells in the reproductive system. From early developmental stages onward, the secretory activity of placenta cells clearly contributes to increase local as well as systemic levels of cytokines. The placental production of cytokines may affect mother and fetus independently. In turn because of this unique position at the maternal fetal interface, the placenta is also exposed to the regulatory influence of cytokines from maternal and fetal circulations, and hence, may be affected by changes in any of these. Gestational diabetes mellitus (GDM) is associated with an overall alteration of the cytokine network. This review discusses the changes that occur in cytokines post GDM and their negative effects on maternal insulin and placental-fetal development.

  3. Forkhead factor FoxO1 is essential for placental morphogenesis in the developing embryo

    Science.gov (United States)

    Ferdous, Anwarul; Morris, Jesse; Abedin, Mohammad Joynal; Collins, Shandon; Richardson, James A.; Hill, Joseph A.

    2011-01-01

    Forkhead box O1 (FoxO1), a member of the Forkhead box-containing O family of transcription factors, is a key regulator of numerous genes that govern a wide array of cellular functions, including differentiation, homeostasis, and survival. However, the role of FoxO1 in development remains elusive. Here, we describe an essential and previously undefined role for FoxO1 in placental development. We demonstrate that FoxO1-null embryos up to embryonic day 9.0 (E9.0) are indistinguishable, including their morphology, cardiovascular structure, and vascular gene expression, from wild-type (WT) littermates. However, FoxO1-nulls manifested a profoundly swollen/hydropic allantois, which failed to fuse with the chorion, a phenotype that leads to subsequent cardiovascular malformation, progressive apoptotic cell death, and embryonic lethality at E10.5. Quantitative RT-PCR analysis of genes involved in placental development revealed significant attenuation of VCAM1 expression in FoxO1-null embryos. Using immunohistochemical, transcriptional, and chromatin immunoprecipitation assays, we further discovered that FoxO1 is an essential upstream regulator of the VCAM1 gene. Collectively, our findings provide critical molecular insight into a unique FoxO1–VCAM1 axis that governs placental morphogenesis, a process that is essential for subsequent normal cardiovascular development and fetal life. PMID:21930913

  4. 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

  5. Mammalian Placentation

    DEFF Research Database (Denmark)

    Carter, Anthony Michael; Mess, A. M.

    2014-01-01

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

  6. Requirement of the mouse I-mfa gene for placental development and skeletal patterning.

    Science.gov (United States)

    Kraut, N; Snider, L; Chen, C M; Tapscott, S J; Groudine, M

    1998-11-02

    The bHLH-repressor protein I-mfa binds to MyoD family members, inhibits their activity, and blocks their nuclear import and binding to DNA. In situ hybridization analysis demonstrated that mouse I-mfa was highly expressed in extraembryonic lineages, in the sclerotome, and subsequently within mesenchymal precursors of the axial and appendicular skeleton, before chondrogenesis occurs. Targeted deletion of I-mfa in a C57Bl/6 background resulted in embryonic lethality around E10.5, associated with a placental defect and a markedly reduced number of trophoblast giant cells. Overexpression of I-mfa in rat trophoblast (Rcho-1) stem cells induced differentiation into trophoblast giant cells. I-mfa interacted with the bHLH protein Mash2, a negative regulator of trophoblast giant cell formation, and inhibited its transcriptional activity in cell culture. In contrast, I-mfa did not interfere with the activity of the bHLH protein Hand1, a positive regulator of giant cell differentiation. Interestingly, I-mfa-null embryos on a 129/Sv background had no placental defect, generally survived to adulthood, and exhibited delayed caudal neural tube closure and skeletal patterning defects that included fusions of ribs, vertebral bodies and abnormal formation of spinous processes. Our results indicate that I-mfa plays an important role in trophoblast and chondrogenic differentiation by negatively regulating a subset of lineage-restricted bHLH proteins.

  7. The Role of Placental Homeobox Genes in Human Fetal Growth Restriction

    Directory of Open Access Journals (Sweden)

    Padma Murthi

    2011-01-01

    Full Text Available Fetal growth restriction (FGR is an adverse pregnancy outcome associated with significant perinatal and paediatric morbidity and mortality, and an increased risk of chronic disease later in adult life. One of the key causes of adverse pregnancy outcome is fetal growth restriction (FGR. While a number of maternal, fetal, and environmental factors are known causes of FGR, the majority of FGR cases remain idiopathic. These idiopathic FGR pregnancies are frequently associated with placental insufficiency, possibly as a result of placental maldevelopment. Understanding the molecular mechanisms of abnormal placental development in idiopathic FGR is, therefore, of increasing importance. Here, we review our understanding of transcriptional control of normal placental development and abnormal placental development associated with human idiopathic FGR. We also assess the potential for understanding transcriptional control as a means for revealing new molecular targets for the detection, diagnosis, and clinical management of idiopathic FGR.

  8. Longitudinal determination of serum placental protein 13 during development of preeclampsia

    OpenAIRE

    Huppertz, Berthold; Sammar, Marei; Chefetz, Ilana; Neumaier-Wagner, Peruka; Bartz, Clemens; Meiri, Hamutal

    2008-01-01

    Objective: To determine maternal serum placental protein 13 (PP13) in normal pregnancy and preeclampsia. Methods: A prospective, longitudinal study with 41 normal pregnant women, 18 cases with preterm delivery or cervix insufficiency and 4 with developing late-onset preeclampsia. Six hundred and sixty-six maternal blood samples were obtained every 2-4 weeks starting at 5-8 weeks gestation (10-12 samples/patient) and tested for serum PP13 by ELISA. Results: In normal pregnant women delivering ...

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

    Science.gov (United States)

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

    2014-02-01

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

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

    Science.gov (United States)

    Longtine, Mark S; Nelson, D Michael

    2011-05-01

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

  11. Effects of Placental Isoferritin on the Mouse Embryo Development in vitro

    Institute of Scientific and Technical Information of China (English)

    ZHU Ying; WU Chaoying; SUN Yongyu

    2007-01-01

    To investigate the effect of placental isoferritin (PLF) on mouse embryo development in vitro, mice 2-cell embryos were co-cultured with human first trimester decidual cells at different concentrations of PLF in vitro. The following changes of the above system were observed under an invert microscope and the number of embryos were recorded and the embryos were classified. The results showed there was no significant difference in the percentage of embryos development to 4-cell,8-cell and morula (P>0.05). PLF at the doses of 10 and 100 U/mL significantly enhanced more em-bryos development to the blastocyst and hatching blastocyst (P0.05). It was concluded that PLF at the concentration of 10--100 U/mL had no significant effects on the early development of mice embryos, however, PLF could promote the growth, differentiation, and hatching of preimplantion blastocysts.

  12. Important aspects of placental-specific gene transfer.

    Science.gov (United States)

    Kaufman, Melissa R; Albers, Renee E; Keoni, Chanel; Kulkarni-Datar, Kashmira; Natale, David R; Brown, Thomas L

    2014-10-15

    The placenta is a unique and highly complex organ that develops only during pregnancy and is essential for growth and survival of the developing fetus. The placenta provides the vital exchange of gases and wastes, the necessary nutrients for fetal development, acts as immune barrier that protects against maternal rejection, and produces numerous hormones and growth factors that promote fetal maturity to regulate pregnancy until parturition. Abnormal placental development is a major underlying cause of pregnancy-associated disorders that often result in preterm birth. Defects in placental stem cell propagation, growth, and differentiation are the major factors that affect embryonic and fetal well-being and dramatically increase the risk of pregnancy complications. Understanding the processes that regulate placentation is important in determining the underlying factors behind abnormal placental development. The ability to manipulate genes in a placenta-specific manner provides a unique tool to analyze development and eliminates potentially confounding results that can occur with traditional gene knockouts. Trophoblast stem cells and mouse embryos are not overly amenable to traditional gene transfer techniques. Most viral vectors, however, have a low infection rate and often lead to mosaic transgenesis. Although the traditional method of embryo transfer is intrauterine surgical implantation, the methodology reported here, combining lentiviral blastocyst infection and nonsurgical embryo transfer, leads to highly efficient and placental-specific gene transfer. Numerous advantages of our optimized procedures include increased investigator safety, a reduction in animal stress, rapid and noninvasive embryo transfer, and higher a rate of pregnancy and live birth.

  13. 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.

  14. Nik-related kinase regulates trophoblast proliferation and placental development by modulating AKT phosphorylation

    Science.gov (United States)

    Morioka, Yuka; Nam, Jin-Min; Ohashi, Takashi

    2017-01-01

    Nik-related kinase (Nrk) is a Ser/Thr kinase and was initially discovered as a molecule that was predominantly detected in skeletal muscles during development. A recent study using Nrk-null mice suggested the importance of Nrk in proper placental development; however, the molecular mechanism remains unknown. In this study, we demonstrated that differentiated trophoblasts from murine embryonic stem cells (ESCs) endogenously expressed Nrk and that Nrk disruption led to the enhanced proliferation of differentiated trophoblasts. This phenomenon may reflect the overproliferation of trophoblasts that has been reported in enlarged placentas of Nrk-null mice. Furthermore, we demonstrated that AKT phosphorylation at Ser473 was upregulated in Nrk-null trophoblasts and that inhibition of AKT phosphorylation cancelled the enhanced proliferation observed in differentiated Nrk-null trophoblasts. These results indicated that the upregulation of AKT phosphorylation was the possible cause of enhanced proliferation observed in Nrk-null trophoblasts. The upregulation of AKT phosphorylation was also confirmed in enlarged Nrk-null placentas in vivo, suggesting that proper regulation of AKT by Nrk was important for normal placental development. In addition, our detailed analysis on phosphorylation status of AKT isoforms in newly established trophoblast stem cells (TSCs) revealed that different levels of upregulation of AKT phosphorylation were occurred in Nrk-null TSCs depending on AKT isoforms. These results further support the importance of Nrk in proper development of trophoblast lineage cells and indicate the possible application of TSCs for the analysis of differently regulated activation mechanisms of AKT isoforms. PMID:28152035

  15. Role of mouse Wdr13 in placental growth; a genetic evidence for lifetime body weight determination by placenta during development.

    Science.gov (United States)

    Singh, Vijay Pratap; Alex, Jomini Liza; Lakshmi, B Jyothi; Sailasree, S Purnima; Raj, T Avinash; Kumar, Satish

    2015-08-26

    Placental development is essential for implantation and growth of foetus in the uterus of eutherian mammals. Numerous growth factors are responsible for placental development and cell lineage differentiation. Gene knockout mice have shown role of various genes in the placenta. Here using Wdr13 knockout mice, we show that this gene is important for proper placental development. Wdr13, a X-linked gene, expresses in multiple trophoblast cell types of placenta and the mutant placenta had reduced size after 17.5 dpc due to reduction of junctional zone (JZ) and labyrinth zone (LZ). We observed reduction in levels of angiopoietin-2 and cd44 mRNA in Wdr13 mutant placenta as compared to that in the wild type. Our findings show that Wdr13 is required for normal placental development and cell differentiation. Wdr13 heterozygous female placenta when the mutant allele was of maternal origin showed similar defects as those in case of Wdr13 null placenta. Using two types of heterozygous females carrying either maternally and paternally derived mutant Wdr13 allele we provide genetic evidence that development of placenta determines body weight of mice for the entire life.

  16. Altered development and function of the placental regions in preeclampsia and its association with long-chain polyunsaturated fatty acids.

    Science.gov (United States)

    Rani, Alka; Wadhwani, Nisha; Chavan-Gautam, Preeti; Joshi, Sadhana

    2016-09-01

    The placenta is an essential organ formed during pregnancy that mainly transfers nutrients from the mother to the fetus. Nutrients taken up by the placenta are required for its own growth and development and to optimize fetal growth. Hence, placental function is an important determinant of pregnancy outcome. Among various nutrients, fatty acids, especially long-chain polyunsaturated fatty acids (LCPUFAs), including omega 3 and omega 6 fatty acids, are essential for placental development from the time of implantation. Studies have associated these LCPUFAs with placental development through their roles in regulating oxidative stress, angiogenesis, and inflammation, which may in turn influence their transfer to the fetus. The placenta has a heterogeneous morphology with variable regional vasculature, oxidative stress, and LCPUFA levels in healthy pregnancies depending upon the location within the placenta. However, these regional structural and functional parameters are found to be disturbed in pathological conditions, such as preeclampsia (PE), thereby affecting pregnancy outcome. Hence, the alterations in LCPUFA metabolism and transport in different regions of the PE placenta as compared with normal placenta could potentially be contributing to the pathological features of PE. The regional variations in development and function of the placenta and its possible association with placental LCPUFA metabolism and transport in normal and PE pregnancies are discussed in this review. WIREs Dev Biol 2016, 5:582-597. doi: 10.1002/wdev.238 For further resources related to this article, please visit the WIREs website.

  17. Possible roles for folic acid in the regulation of trophoblast invasion and placental development in normal early human pregnancy.

    Science.gov (United States)

    Williams, Paula J; Bulmer, Judith N; Innes, Barbara A; Broughton Pipkin, Fiona

    2011-06-01

    In addition to its role in the prevention of neural tube defects, folic acid has many other physiological functions, including cell proliferation, DNA replication, and antioxidant protection. The aim of this study was to determine the role that folic acid has in regulating placental trophoblast development. Placental explants from placentae at gestational age 7 wk (n = 3) were cultured in folic acid at concentrations of 10(-6) M, 10(-8) M, and 10(-10) M. Extravillous trophoblast (EVT) invasion was assessed following 6-day culture, and explants were used for immunohistochemical evaluation of proliferation (MKI67) and apoptosis (active caspase 3). In addition, an array was performed on cell culture supernatants to examine a range of matrix metalloproteinases (MMPs) and tissue inhibitors of MMPs (TIMPs). Folic acid increased the invasion of EVT cells in this explant model by between 83% and 19% (P = 0.005), and this was associated with increased MKI67 positivity and decreased active caspase 3 positivity; this effect was concentration dependent and showed a biphasic response. In addition, culture in folic acid increased vascular density, as determined by anti-CD31 immunostaining (P = 0.05). The increase in EVT invasion correlated with increased placental explant secretion of MMP2 (P = 0.01), MMP3 (P = 0.01), and MMP9 (P = 0.02). This study demonstrates that folic acid is potentially important in a number of crucial early stages of placental development, including EVT invasion, angiogenesis, and secretion of MMPs, and highlights the need for further studies to address the benefit of longer-term folic acid supplementation throughout pregnancy to prevent pregnancy disorders associated with deficient placental development, including preeclampsia.

  18. 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.

  19. 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.

  20. Clinical study in diagnosis placental implantation abnormality with Transvaginal Doppler ul-trasound%经腹彩超诊断胎盘植入的临床研究

    Institute of Scientific and Technical Information of China (English)

    卜凡文; 沈树娜

    2015-01-01

    Objective To evaluate the ultra sonographic charateristics and the diagnostic value in placental implanta-tion abnormality ( PIA) with transvaginal Doppler ultrasound, improve the rate of diagnosis accuracy in the prenatal and postnatal of PIA with transvaginal Doppler ultrasound, for early diagnosis and treatment,to avoid hysterectomy beacuse of fatally and heavy bleeding. Method There were 61 cases complicated with PIA by operation and patho-logically confirmed in our hospital. 33 cases were Prenatal PIA, 28 cases were postnatal PIA. To discuss sonograph-ic charateristics, and analysis the Sensitivity and missed diagnosis of transvaginal Doppler ultrasound contrasted with surgery pathology. Result Muscular layer of the placenta has abundant signals of blood flow, this was major sono-graphic performance in prenatal PIA, incidence rate was 85. 7%, followed by whirlpool in placenta and plancental invasion;placental remnants was major sonographic performance in postpartum PIA, incidence rate was 100%, fol-lowed by abundant signals of blood flow in muscular layer of the placenta and boundary was disappear between mus-cular layer and placenta. There were 14 cases by transvaginal Doppler ultrasound diagnosed prenatal PIA accurate-ly, sensitivity was 42. 4%, false negative rate was 57. 6%. There were 21 cases by transvaginal Doppler ultrasound diagnosed postnatal PIA accurately, sensitivity was 75. 0%, false negative rate was 25. 0%. Conclusion Specificity is low in Prenatal PIA by transvaginal Doppler ultrasound, false negative rate is higher. if necessary,to improve the diagnostic accuracy combination with MRI. Specificity is higher in postnatal PIA, false negative rate is low. The Ul-trasonography of PIA has certain characteristics, strengthen the consciousness of the diagnosis in PIA, especially in the prenatal, To do a good job of auxiliary diagnosis in PIA.%目的:探讨经腹彩超诊断胎盘植入的声像图特点和诊断价值,提高经腹彩超在产前

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

    OpenAIRE

    Erickson, Anders C; Laura Arbour

    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...

  2. Correlation study of uterine spiral artery blood flow characteristics with placental development and hypoxia in patients with preeclampsia

    Institute of Scientific and Technical Information of China (English)

    Rong Ma

    2016-01-01

    Objective:To study the correlation of uterine spiral artery blood flow characteristics with placental development and hypoxia in patients with preeclampsia.Methods:A total of 66 patients diagnosed with preeclampsia in our hospital between June 2013 and May 2016 were selected as the preeclampsia group (PE group) of the study and healthy women who gave birth in our hospital during the same period were selected as control group. At 32-37 weeks of gestation, uterine spiral artery ultrasonography was conducted to determine blood flow parameters PI, RI and S/D, and peripheral blood was collected to separate mononuclear cells and then determine CTLA-4 and CD28 mRNA level; after childbirth, placenta tissue was collect to determine the levels of placental development-related cytokines and apoptotic molecules.Results: Uterine spiral artery RI, PI and S/D of PE group were significantly higher than those of control group; PLGF, NGF, EGF, IGF-I, VEGF, Xiap, Survivin, bcl-2 and CD28 content in placenta tissue of PE group were significantly lower than those of control group and negatively correlated with uterine spiral artery PI, RI and S/D while GDF-15, caspase-3, caspase-9 and CTLA-4 content were significantly higher than those of control group and positively correlated with uterine spiral artery PI, RI and S/D; CTLA-4 mRNA level in peripheral blood mononuclear cells of PE group was significantly higher than that of control group and positively correlated with uterine spiral artery were PI, RI and S/D while CD28 mRNA level was significantly lower than that of control group and negatively correlated with uterine spiral artery PI, RI and S/D.Conclusion:Uterine spiral artery blood flow resistance increases and blood flow volume decreases in patients with preeclampsia, and the above blood flow characteristics will hinder the placental development, induce cell apoptosis and aggravate the placental hypoxia.

  3. Abnormalities Occurring during Female Gametophyte Development Result in the Diversity of Abnormal Embryo Sacs and Leads to Abnormal Fertilization in indicaljaponica Hybrids in Rice

    Institute of Scientific and Technical Information of China (English)

    Yu-Xiang Zeng; Chao-Yue Hu; Yong-Gen Lu; Jin-Quan Li; Xiang-Dong Liu

    2009-01-01

    Embryo sac abortion is one of the major masons for sterility in indicaljaponica hybrids In rice. To clarify the causal mechanism of embryo sac abortion, we studied the female gametophyte development in two indicaljaponica hybrids via an eosin B staining procedure for embryo sac scanning using confocal laser scanning microscope. Different types of abnormalities occurred during megasporogenesis and megagamatogenesis were demonstrated. The earliest abnormality was observed in the megasporocyte. A lot of the chalazal-most megaspores were degenerated before the mono-nucleate embryo sac stage. Disordered positioning of nucleus and abnormal nucallus tissue were characteristics of the abnormal female gametes from the mono-nucleate to four-nucleate embryo sac stages. The abnormalities that occurred from the early stage of the eight-nucleate embryo sac development to the mature embryo sac stage were characterized by smaller sizes and wrinkled antipodals. Asynchronous nuclear migration, abnormal positioning of nucleus, and degeneration of egg apparatus were also found at the eight-nucleate embryo sac stage. The abnormalities that occurred during female gametophyte development resulted in five major types of abnormal embryo sacs. These abnormal embryo sacs led to abnormal fertilization. Hand pollination using normal pollens on the spikelets during anthesis showed that normal pollens could not exclude the effect of abnormal embryo sac on seed setting.

  4. Placental Malaria is associated with reduced early life weight development of affected children independent of low birth weight

    Directory of Open Access Journals (Sweden)

    Palmero Melba S

    2010-01-01

    Full Text Available Abstract Background Infection with Plasmodium falciparum during pregnancy contributes substantially to the disease burden in both mothers and offspring. Placental malaria may lead to intrauterine growth restriction or preterm delivery resulting in low birth weight (LBW, which, in general, is associated with increased infant morbidity and mortality. However, little is known about the possible direct impact of the specific disease processes occurring in PM on longer term outcomes such as subsequent retarded growth development independent of LBW. Methods In an existing West-African cohort, 783 healthy infants with a birth weight of at least 2,000 g were followed up during their first year of life. The aim of the study was to investigate if Plasmodium falciparum infection of the placenta, assessed by placental histology, has an impact on several anthropometric parameters, measured at birth and after three, six and 12 months using generalized estimating equations models adjusting for moderate low birth weight. Results Independent of LBW, first to third born infants who were exposed to either past, chronic or acute placental malaria during pregnancy had significantly lower weight-for-age (-0.43, 95% CI: -0.80;-0.07, weight-for-length (-0.47, 95% CI: -0.84; -0.10 and BMI-for-age z-scores (-0.57, 95% CI: -0.84; -0.10 compared to infants born to mothers who were not diagnosed with placental malaria (p = 0.019, 0.013, and 0.012, respectively. Interestingly, the longitudinal data on histology-based diagnosis of PM also document a sharp decline of PM prevalence in the Sukuta cohort from 16.5% in 2002 to 5.4% in 2004. Conclusions It was demonstrated that PM has a negative impact on the infant's subsequent weight development that is independent of LBW, suggesting that the longer term effects of PM have been underestimated, even in areas where malaria transmission is declining.

  5. Gross Motor Development, Movement Abnormalities, and Early Identification of Autism

    Science.gov (United States)

    Ozonoff, Sally; Young, Gregory S.; Goldring, Stacy; Greiss-Hess, Laura; Herrera, Adriana M.; Steele, Joel; Macari, Suzanne; Hepburn, Susan; Rogers, Sally J.

    2008-01-01

    Gross motor development (supine, prone, rolling, sitting, crawling, walking) and movement abnormalities were examined in the home videos of infants later diagnosed with autism (regression and no regression subgroups), developmental delays (DD), or typical development. Group differences in maturity were found for walking, prone, and supine, with…

  6. 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.

  7. Placental economies

    DEFF Research Database (Denmark)

    Lee, Jieun

    2016-01-01

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

  8. A murine model for the assessment of placental and fetal development in teratogenicity studies.

    Science.gov (United States)

    Hau, J; Basse, A; Wolstrup, C

    1987-01-01

    During normal pregnancy in the mouse, maternal serum levels of the analogues to human schwangerschaftsprotein-1 and alpha-fetoprotein correlate significantly with the growth of the placenta and fetus respectively. This relationship has been utilized in the analysis of the effect of sodium selenite on placental and fetal growth in mice. Moderate doses of sodium selenite did not affect the growth of the placenta and fetus significantly, whereas high doses of selenite resulted in a large percentage of abortions. The protein markers were found to be useful in the prediction of placental and fetal growth, and they are suggested to be of general use in the study of the impact of teratogenic substances, since they reflect the status of the fetoplacental mass during gestation.

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

    Science.gov (United States)

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

    2007-01-01

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

  10. MyD88 Signaling Is Directly Involved in the Development of Murine Placental Malaria

    Science.gov (United States)

    Barboza, Renato; Reis, Aramys Silva; da Silva, Leandro Gustavo; Hasenkamp, Lutero; Pereira, Keitty Raquel Benevides; Câmara, Niels Olsen Saraiva; Costa, Fabio Trindade Maranhão; Lima, Maria Regina D'Império; Alvarez, José Maria; Boscardin, Silvia Beatriz; Epiphanio, Sabrina

    2014-01-01

    Malaria is a widespread infectious disease caused by the parasite Plasmodium. During pregnancy, malaria infection leads to a range of complications that can affect both the mother and fetus, including stillbirth, infant mortality, and low birth weight. In this study, we utilized a mouse model of placental malaria (PM) infection to determine the importance of the protein MyD88 in the host immune response to Plasmodium during pregnancy. Initially, we demonstrated that Plasmodium berghei NK65GFP adhered to placental tissue via chondroitin sulfate A and induced PM in mice with a C57BL/6 genetic background. To evaluate the involvement of MyD88 in the pathology of PM, we performed a histopathological analysis of placentas obtained from MyD88−/− and wild-type (WT) mice following infection on the 19th gestational day. Our data demonstrated that the detrimental placental alterations observed in the infected mice were correlated with the expression of MyD88. Moreover, in the absence of this protein, production of interleukin 6 (IL-6) and tumor necrosis factor alpha (TNF-α) was significantly reduced in the infected mice. More importantly, in contrast to fetuses from infected WT mice, which exhibited a reduction in body weight, the fetuses from infected MyD88−/− mice did not display significant weight loss compared to their noninfected littermates. In addition, we observed a decrement of maternal care associated with malaria infection, which was attenuated in the MyD88-deficient mice. Collectively, the results of this study illustrate the pivotal importance of the MyD88 signaling pathway in the pathogenesis of placental malaria, thus presenting new possibilities for targeting MyD88 in therapeutic interventions. PMID:24478096

  11. 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.

  12. Abnormal retinal development associated with FRMD7 mutations.

    Science.gov (United States)

    Thomas, Mervyn G; Crosier, Moira; Lindsay, Susan; Kumar, Anil; Araki, Masasuke; Leroy, Bart P; McLean, Rebecca J; Sheth, Viral; Maconachie, Gail; Thomas, Shery; Moore, Anthony T; Gottlob, Irene

    2014-08-01

    Idiopathic infantile nystagmus (IIN) is a genetically heterogeneous disorder, often associated with FRMD7 mutations. As the appearance of the retina is reported to be normal based on conventional fundus photography, IIN is postulated to arise from abnormal cortical development. To determine whether the afferent visual system is involved in FRMD7 mutations, we performed in situ hybridization studies in human embryonic and fetal stages (35 days post-ovulation to 9 weeks post-conception). We show a dynamic retinal expression pattern of FRMD7 during development. We observe expression within the outer neuroblastic layer, then in the inner neuroblastic layer and at 9 weeks post-conception a bilaminar expression pattern. Expression was also noted within the developing optic stalk and optic disk. We identified a large cohort of IIN patients (n = 100), and performed sequence analysis which revealed 45 patients with FRMD7 mutations. Patients with FRMD7 mutations underwent detailed retinal imaging studies using ultrahigh-resolution optical coherence tomography. The tomograms were compared with a control cohort (n = 60). The foveal pit was significantly shallower in FRMD7 patients (P < 0.0001). The optic nerve head morphology was abnormal with significantly decreased optic disk area, retinal nerve fiber layer thickness, cup area and cup depth in FRMD7 patients (P < 0.0001). This study shows for the first time that abnormal afferent system development is associated with FRMD7 mutations and could be an important etiological factor in the development of nystagmus.

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

    Science.gov (United States)

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

    2006-10-01

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

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

    Science.gov (United States)

    Lakisic, Goran; Wendling, Olivia; Libertini, Emanuele; Radford, Elizabeth J.; Le Guillou, Morwenna; Champy, Marie-France; Wattenhofer-Donzé, Marie; Soubigou, Guillaume; Ait-Si-Ali, Slimane; Feunteun, Jean; Sorg, Tania; Coppée, Jean-Yves; Ferguson-Smith, Anne C.; Cossart, Pascale; Bierne, Hélène

    2016-01-01

    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. PMID:26938916

  15. Energy status and HIF signalling in chorionic villi show no evidence of hypoxic stress during human early placental development.

    Science.gov (United States)

    Cindrova-Davies, T; van Patot, M Tissot; Gardner, L; Jauniaux, E; Burton, G J; Charnock-Jones, D S

    2015-03-01

    Early human placental and embryonic development occurs in a physiologically low oxygen environment supported by histiotrophic secretions from endometrial glands. In this study, we compare the placental metabolomic profile in the first, second and third trimesters to determine whether the energy demands are adequately met in the first trimester. We investigated whether hypoxia-inducible factors, HIF-1α and/or HIF-2α, might regulate transcription during the first trimester. First and second trimester tissue was collected using a chorionic villus sampling-like (CVS) technique. Part of each villus sample was frozen immediately and the remainder cultured under 2 or 21% O2 ± 1 mM H2O2, and ±the p38 MAPK pathway inhibitor, PD169316. Levels of HIF-1α were assessed by western blotting and VEGFA, PlGF and GLUT3 transcripts were quantified by RT-PCR. Term samples were collected from normal elective Caesarean deliveries. There were no significant differences in concentrations of ADP, NAD(+), lactate, and glucose, and in the ATP/ADP ratio, across gestational age. Neither HIF-1α nor HIF-2α could be detected in time-zero CVS samples. However, culture under any condition (2 or 21% O2 ± 1 mM H2O2) increased HIF-1α and HIF-2α. HIF-1α and HIF-2α were additionally detected in specimens retrieved after curettage. HIF-1α stabilization was accompanied by significant increases in VEGFA and GLUT3 and a decrease in PlGF mRNAs. These effects were suppressed by PD169316. In conclusion, our data suggest that first trimester placental tissues are not energetically compromised, and that HIF-1α is unlikely to play an appreciable role in regulating transcriptional activity under steady-state conditions in vivo. However, the pathway may be activated by stress conditions.

  16. PLACENTAL PATHOLOGY IN INTRA UTERINE GROWTH RETARDATION

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    Vijaya Sheela

    2015-04-01

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

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

    Science.gov (United States)

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

    2016-12-01

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

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

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    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

  19. The shared pathoetiological effects of particulate air pollution and the social environment on fetal-placental development.

    Science.gov (United States)

    Erickson, Anders C; Arbour, Laura

    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.

  20. 流产对再次妊娠分娩产程及胎盘异常的影响%Effect of induced aborion on stage of labor and placental abnormality of primiparous women during parturition

    Institute of Scientific and Technical Information of China (English)

    王志强; 杨希娟

    2010-01-01

    目的 探讨人工流产后对未生育妇女再次妊娠产程及胎盘异常的影响.方法 对176例妊娠有人工流产史74例(观察组)和无人工流产史102例(对照组)的初产妇进行回顾性调查,分析其产程、胎盘异常的发生情况.结果 观察组产妇的第三产程时间(10.75±2.64)min长于对照组(8.12±3.26)min,差异有统计学意义(P<0.05).观察组胎盘粘连、胎盘残留、低置胎盘的发生率分别为13.52%、10.81%、8.11%,明显高于对照组2.95%、1.96%、0.98%,差异有统计学意义(P<0.05).观察组胎盘置入率(2.71%)高于对照组(0.98%),但差异无统计学意义(P>0.05).结论 人工流产可使未生育妇女妊娠分娩第三产程延长并增加胎盘异常的发生率,应尽可能杜绝产前人工流产.%Objective To investigate the effect of induced aborion on stage of labor and placental abnormality of primiparous women during parturition. Methods Birth process and abnormal placenta during labor for 74 women with a history of induced abortion (observation group) and 102 women without a history of induced abortion ( control group) in their first parities were collected and compared. Results The third stage of labor of the observation group was (10.75 ±2.64) min,longer than (8.12 ±3.26)min of the control group,the difference had statistical significance(P <0.05). The rate of placenta adhesion,placental remnants and low lying placenta of the observation group were 13.52%, 10.81% and 8.11% respectively, significantly higher than 2.95 %, 1.96% and 0.98% in the control group(P <0. 05). Conclusion It was demonstrated that induced aborion had obvious untoward effect on pregnancy such as prolonged third stage of labor and increased incidence of placental abnormalities. So, it was necessary to prevent induced aborion for primiparous women.

  1. High resolution ultrasound-guided microinjection for interventional studies of early embryonic and placental development in vivo in mice

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    Sunn Nana

    2006-02-01

    Full Text Available Abstract Background In utero microinjection has proven valuable for exploring the developmental consequences of altering gene expression, and for studying cell lineage or migration during the latter half of embryonic mouse development (from embryonic day 9.5 of gestation (E9.5. In the current study, we use ultrasound guidance to accurately target microinjections in the conceptus at E6.5–E7.5, which is prior to cardiovascular or placental dependence. This method may be useful for determining the developmental effects of targeted genetic or cellular interventions at critical stages of placentation, gastrulation, axis formation, and neural tube closure. Results In 40 MHz ultrasound images at E6.5, the ectoplacental cone region and proamniotic cavity could be visualized. The ectoplacental cone region was successfully targeted with 13.8 nL of a fluorescent bead suspension with few or no beads off-target in 51% of concepti microinjected at E6.5 (28/55 injected. Seventy eight percent of the embryos survived 2 to 12 days post injection (93/119, 73% (41/56 survived to term of which 68% (38/56 survived and appeared normal one week after birth. At E7.5, the amniotic and exocoelomic cavities, and ectoplacental cone region were discernable. Our success at targeting with few or no beads off-target was 90% (36/40 for the ectoplacental cone region and 81% (35/43 for the exocoelomic cavity but tended to be less, 68% (34/50, for the smaller amniotic cavity. At E11.5, beads microinjected at E7.5 into the ectoplacental cone region were found in the placental spongiotrophoblast layer, those injected into the exocoelomic cavity were found on the surface or within the placental labyrinth, and those injected into the amniotic cavity were found on the surface or within the embryo. Following microinjection at E7.5, survival one week after birth was 60% (26/43 when the amniotic cavity was the target and 66% (19/29 when the target was the ectoplacental cone region. The

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

    Science.gov (United States)

    Elliot, Michael G; Crespi, Bernard J

    2015-03-05

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

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

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    Babu JJ Geddam

    2012-07-01

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

  4. {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.

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

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    Nagesh

    2016-03-01

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

  6. Uterine activin receptor-like kinase 5 is crucial for blastocyst implantation and placental development

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    Peng, Jia; Monsivais, Diana; You, Ran; Zhong, Hua; Pangas, Stephanie A.; Matzuk, Martin M.

    2015-01-01

    Members of the transforming growth factor β (TGF-β) superfamily are key regulators in most developmental and physiological processes. However, the in vivo roles of TGF-β signaling in female reproduction remain uncertain. Activin receptor-like kinase 5 (ALK5) is the major type 1 receptor for the TGF-β subfamily. Absence of ALK5 leads to early embryonic lethality because of severe defects in vascular development. In this study, we conditionally ablated uterine ALK5 using progesterone receptor-cre mice to define the physiological roles of ALK5 in female reproduction. Despite normal ovarian functions and artificial decidualization in conditional knockout (cKO) mice, absence of uterine ALK5 resulted in substantially reduced female reproduction due to abnormalities observed at different stages of pregnancy, including implantation defects, disorganization of trophoblast cells, fewer uterine natural killer (uNK) cells, and impairment of spiral artery remodeling. In our microarray analysis, genes encoding proteins involved in cytokine–cytokine receptor interactions and NK cell-mediated cytotoxicity were down-regulated in cKO decidua compared with control decidua. Flow cytometry confirmed a 10-fold decrease in uNK cells in cKO versus control decidua. According to these data, we hypothesize that TGF-β acts on decidual cells via ALK5 to induce expression of other growth factors and cytokines, which are key regulators in luminal epithelium proliferation, trophoblast development, and uNK maturation during pregnancy. Our findings not only generate a mouse model to study TGF-β signaling in female reproduction but also shed light on the pathogenesis of many pregnancy complications in human, such as recurrent spontaneous abortion, preeclampsia, and intrauterine growth restriction. PMID:26305969

  7. 被动吸烟诱导的胎儿生长受限大鼠胎盘血管结构异常及其机制%Abnormal Placental Vascular Structure in Smoking-induced FGR and the Mechanism

    Institute of Scientific and Technical Information of China (English)

    陈镇燕; 李静; 黄光英

    2012-01-01

    目的 研究被动吸烟诱导的胎儿生长受限(fetal growth retardation,FGR)大鼠胎盘血管结构的异常及其分子机制.方法 采用被动吸烟法建立大鼠FGR模型,将12只孕鼠随机分为正常组(n=6)和FGR组(n=6),每只孕鼠取3个胎盘检测(即每组n=18).运用凝集素标记血管内皮细胞以观察胎盘血管形态,体视学方法分析胎盘血管密度,实时荧光PCR检测胎盘血管因子VEGF-A、VEGFR1、VEGFR2、Tie2、Angpt1、Angpt2 mRNA的表达,免疫组化及Western blot检测VEGF-A、VEGFR2、Tie2、Angpt2蛋白的表达.结果 FGR组胎盘胎儿血管总体积为(45±21)mm3,显著小于正常组(70±19)mm3(P<0.05).FGR组胎盘血液交换屏障厚度为(5.839±0.205)μm显著高于正常组(1.967±0.543)μm(P<0.05).FGR组胎盘血管体积密度为(0.100±0.450)(0.032~0.158),正常组胎盘血管体积密度为(0.113±0.018)(0.086~0.135),两组间差异无统计学意义.与正常组相比,FGR组的VEGF-A mRNA 表达显著下降(P<0.05),其它因子的mRNA表达较正常组微升高,但差异无统计学意义.FGR组的VEGF-A、VEGFR2、Tie2、Angpt2蛋白表达有增加趋势,但差异无统计学意义.结论 被动吸烟可使胎盘血管总体积显著减少、胎盘血液交换屏障厚度显著增加,导致胎盘营养交换功能不足,从而引发胎儿生长受限.但部分被动吸烟所诱导的FGR胎盘血管密度发生代偿性增加,以致FGR胎盘血管密度及血管因子mRNA、蛋白表达的改变不显著.%Objective To investigate the placental vascular abnormalities associated with fetal growth retardation(FGR) induced by passive smoking and the mechanism. Methods The animal FGR model was established by passive smoking. Twelve pregnant rats were randomly divided into normal group and FGR group. Three placentas were selected from each pregnant rat, so there were 18 samples in each group. The vessel was labeled with lectin and analyzed by stereological techniques. Real-time PCR was used

  8. PLACENTAL SIZE AND PERINATAL OUTCOMES

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    Nagamani

    2015-03-01

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

  9. Placental ischemia-induced increases in brain water content and cerebrovascular permeability: role of TNF-α.

    Science.gov (United States)

    Warrington, Junie P; Drummond, Heather A; Granger, Joey P; Ryan, Michael J

    2015-12-01

    Cerebrovascular complications and increased risk of encephalopathies are characteristic of preeclampsia and contribute to 40% of preeclampsia/eclampsia-related deaths. Circulating tumor necrosis factor-α (TNF-α) is elevated in preeclamptic women, and infusion of TNF-α into pregnant rats mimics characteristics of preeclampsia. While this suggests that TNF-α has a mechanistic role to promote preeclampsia, the impact of TNF-α on the cerebral vasculature during pregnancy remains unclear. We tested the hypothesis that TNF-α contributes to cerebrovascular abnormalities during placental ischemia by first infusing TNF-α in pregnant rats (200 ng/day ip, from gestational day 14 to 19) at levels to mimic those reported in preeclamptic women. TNF-α increased mean arterial pressure (MAP, P blood-brain barrier (BBB) permeability in the anterior cerebrum or posterior cerebrum. We then assessed the role of endogenous TNF-α in mediating these abnormalities in a model of placental ischemia induced by reducing uterine perfusion pressure followed by treatment with the soluble TNF-α receptor (etanercept, 0.8 mg/kg sc) on gestational day 18. Etanercept reduced placental ischemia-mediated increases in MAP, anterior brain water content (P permeability (202 ± 44% in placental ischemic rats to 101 ± 28% of normal pregnant rats). Our results indicate that TNF-α mechanistically contributes to cerebral edema by increasing BBB permeability and is an underlying factor in the development of cerebrovascular abnormalities associated with preeclampsia complicated by placental ischemia.

  10. 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.

  11. Placental iron uptake and its regulation

    NARCIS (Netherlands)

    M. Bierings (Marc)

    1989-01-01

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

  12. 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...

  13. Cytomegalovirus induces abnormal chondrogenesis and osteogenesis during embryonic mandibular development

    Directory of Open Access Journals (Sweden)

    Bringas Pablo

    2008-03-01

    Full Text Available Abstract Background Human clinical studies and mouse models clearly demonstrate that cytomegalovirus (CMV disrupts normal organ and tissue development. Although CMV is one of the most common causes of major birth defects in humans, little is presently known about the mechanism(s underlying CMV-induced congenital malformations. Our prior studies have demonstrated that CMV infection of first branchial arch derivatives (salivary glands and teeth induced severely abnormal phenotypes and that CMV has a particular tropism for neural crest-derived mesenchyme (NCM. Since early embryos are barely susceptible to CMV infection, and the extant evidence suggests that the differentiation program needs to be well underway for embryonic tissues to be susceptible to viral infection and viral-induced pathology, the aim of this study was to determine if first branchial arch NCM cells are susceptible to mCMV infection prior to differentiation of NCM derivatives. Results E11 mouse mandibular processes (MANs were infected with mouse CMV (mCMV for up to 16 days in vitro. mCMV infection of undifferentiated embryonic mouse MANs induced micrognathia consequent to decreased Meckel's cartilage chondrogenesis and mandibular osteogenesis. Specifically, mCMV infection resulted in aberrant stromal cellularity, a smaller, misshapen Meckel's cartilage, and mandibular bone and condylar dysmorphogenesis. Analysis of viral distribution indicates that mCMV primarily infects NCM cells and derivatives. Initial localization studies indicate that mCMV infection changed the cell-specific expression of FN, NF-κB2, RelA, RelB, and Shh and Smad7 proteins. Conclusion Our results indicate that mCMV dysregulation of key signaling pathways in primarily NCM cells and their derivatives severely disrupts mandibular morphogenesis and skeletogenesis. The pathogenesis appears to be centered around the canonical and noncanonical NF-κB pathways, and there is unusual juxtaposition of abnormal stromal

  14. 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

    2016-07-01

    Although much progress is being made in understanding the molecular pathways in the placenta that are involved in the pathophysiology of pregnancy-related disorders, a significant gap exists in the utilization of this information for the development of 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 2-day workshop titled Placental Origins of Adverse Pregnancy Outcomes: Potential Molecular Targets to begin to address this gap. Particular emphasis was given to 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 that workshop. A broad number of topics were covered that ranged 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 noninfectious agents. Research findings in these areas will be critical for the formulation of the development of future treatments and the development of therapies for the prevention of a number of pregnancy disorders of placental origin that include preeclampsia, fetal growth restriction, and uterine inflammation. Research was also presented that summarized ongoing clinical efforts in the United States and in Europe that has tested novel interventions for preeclampsia and fetal growth restriction, including agents such as oral arginine supplementation, sildenafil, pravastatin, gene therapy with virally delivered vascular endothelial growth factor, and oxygen supplementation therapy. Strategies were also proposed to improve fetal growth by the enhancement of nutrient transport to the fetus by modulation of their placental transporters and the targeting of placental

  15. Modulation of serotonin transporter function during fetal development causes dilated heart cardiomyopathy and lifelong behavioral abnormalities.

    Directory of Open Access Journals (Sweden)

    Cornelle W Noorlander

    Full Text Available BACKGROUND: Women are at great risk for mood and anxiety disorders during their childbearing years and may become pregnant while taking antidepressant drugs. In the treatment of depression and anxiety disorders, selective serotonin reuptake inhibitors (SSRIs are the most frequently prescribed drugs, while it is largely unknown whether this medication affects the development of the central nervous system of the fetus. The possible effects are the product of placental transfer efficiency, time of administration and dose of the respective SSRI. METHODOLOGY/PRINCIPAL FINDINGS: In order to attain this information we have setup a study in which these parameters were measured and the consequences in terms of physiology and behavior are mapped. The placental transfer of fluoxetine and fluvoxamine, two commonly used SSRIs, was similar between mouse and human, indicating that the fetal exposure of these SSRIs in mice is comparable with the human situation. Fluvoxamine displayed a relatively low placental transfer, while fluoxetine showed a relatively high placental transfer. Using clinical doses of fluoxetine the mortality of the offspring increased dramatically, whereas the mortality was unaffected after fluvoxamine exposure. The majority of the fluoxetine-exposed offspring died postnatally of severe heart failure caused by dilated cardiomyopathy. Molecular analysis of fluoxetine-exposed offspring showed long-term alterations in serotonin transporter levels in the raphe nucleus. Furthermore, prenatal fluoxetine exposure resulted in depressive- and anxiety-related behavior in adult mice. In contrast, fluvoxamine-exposed mice did not show alterations in behavior and serotonin transporter levels. Decreasing the dose of fluoxetine resulted in higher survival rates and less dramatic effects on the long-term behavior in the offspring. CONCLUSIONS: These results indicate that prenatal fluoxetine exposure affects fetal development, resulting in cardiomyopathy

  16. Development of fetal and placental innate immune responses during establishment of persistent infection with bovine viral diarrhea virus.

    Science.gov (United States)

    Smirnova, Natalia P; Webb, Brett T; Bielefeldt-Ohmann, Helle; Van Campen, Hana; Antoniazzi, Alfredo Q; Morarie, Susan E; Hansen, Thomas R

    2012-08-01

    Transplacental viral infections are dependent upon complex interactions between feto-placental and maternal immune responses and the stage of fetal development at which the infection occurs. Bovine viral diarrhea virus (BVDV) has the ability to cross the placenta and infect the fetus. Infection early in gestation with non-cytopathic (ncp) BVDV leads to persistent infection. Establishment of fetal persistent infection results in life-long viremia, virus-specific immunotolerance, and may have detrimental developmental consequences. We have previously shown that heifers infected experimentally with ncp BVDV type 2 on d. 75 of gestation had transient robust up-regulation of the type I interferon (IFN) stimulated genes (ISGs) 3-15 days after viral inoculation. Blood from persistently infected (PI) fetuses, collected 115 days post maternal infection, demonstrated moderate chronic up-regulation of ISGs. This infection model was used to delineate timing of the development of innate immune responses in the fetus and placenta during establishment of persistent infection. It was hypothesized that: (i) chronic stimulation of innate immune responses occurs following infection of the fetus and (ii) placental production of the type I IFN contributes to up-regulation of ISGs in PI fetuses. PI fetuses, generated by intranasal inoculation of pregnant heifers with ncp BVDV, and control fetuses from uninfected heifers, were collected via Cesarean sections on d. 82, 89, 97, 192, and 245 of gestation. Fetal viremia was confirmed starting on d. 89. Significant up-regulation of mRNA encoding cytosolic dsRNA sensors -RIG-I and MDA5 - was detected on d. 82-192. Detection of viral dsRNA by cytosolic sensors leads to the stimulation of ISGs, which was reflected in significant up-regulation of ISG15 mRNA in fetal blood on d. 89, 97, and 192. No difference in IFN-α and IFN-β mRNA concentration was found in fetal blood or caruncular tissue, while a significant increase in both IFN-α and IFN

  17. Modeling abnormal early development with induced pluripotent stem cells from aneuploid syndromes.

    Science.gov (United States)

    Li, Wen; Wang, Xianming; Fan, Wenxia; Zhao, Ping; Chan, Yau-Chi; Chen, Shen; Zhang, Shiqiang; Guo, Xiangpeng; Zhang, Ya; Li, Yanhua; Cai, Jinglei; Qin, Dajiang; Li, Xingyan; Yang, Jiayin; Peng, Tianran; Zychlinski, Daniela; Hoffmann, Dirk; Zhang, Ruosi; Deng, Kang; Ng, Kwong-Man; Menten, Bjorn; Zhong, Mei; Wu, Jiayan; Li, Zhiyuan; Chen, Yonglong; Schambach, Axel; Tse, Hung-Fat; Pei, Duanqing; Esteban, Miguel A

    2012-01-01

    Many human diseases share a developmental origin that manifests during childhood or maturity. Aneuploid syndromes are caused by supernumerary or reduced number of chromosomes and represent an extreme example of developmental disease, as they have devastating consequences before and after birth. Investigating how alterations in gene dosage drive these conditions is relevant because it might help treat some clinical aspects. It may also provide explanations as to how quantitative differences in gene expression determine phenotypic diversity and disease susceptibility among natural populations. Here, we aimed to produce induced pluripotent stem cell (iPSC) lines that can be used to improve our understanding of aneuploid syndromes. We have generated iPSCs from monosomy X [Turner syndrome (TS)], trisomy 8 (Warkany syndrome 2), trisomy 13 (Patau syndrome) and partial trisomy 11;22 (Emanuel syndrome), using either skin fibroblasts from affected individuals or amniocytes from antenatal diagnostic tests. These cell lines stably maintain the karyotype of the donors and behave like embryonic stem cells in all tested assays. TS iPSCs were used for further studies including global gene expression analysis and tissue-specific directed differentiation. Multiple clones displayed lower levels of the pseudoautosomal genes ASMTL and PPP2R3B than the controls. Moreover, they could be transformed into neural-like, hepatocyte-like and heart-like cells, but displayed insufficient up-regulation of the pseudoautosomal placental gene CSF2RA during embryoid body formation. These data support that abnormal organogenesis and early lethality in TS are not caused by a tissue-specific differentiation blockade, but rather involves other abnormalities including impaired placentation.

  18. Prenatal craniofacial development: new insights on normal and abnormal mechanisms.

    Science.gov (United States)

    Johnston, M C; Bronsky, P T

    1995-01-01

    Technical advances are radically altering our concepts of normal prenatal craniofacial development. These include concepts of germ layer formation, the establishment of the initial head plan in the neural plate, and the manner in which head segmentation is controlled by regulatory (homeobox) gene activity in neuromeres and their derived neural crest cells. There is also a much better appreciation of ways in which new cell associations are established. For example, the associations are achieved by neural crest cells primarily through cell migration and subsequent cell interactions that regulate induction, growth, programmed cell death, etc. These interactions are mediated primarily by two groups of regulatory molecules: "growth factors" (e.g., FGF and TGF alpha) and the so-called steroid/thyroid/retinoic acid superfamily. Considerable advances have been made with respect to our understanding of the mechanisms involved in primary and secondary palate formation, such as growth, morphogenetic movements, and the fusion/merging phenomenon. Much progress has been made on the mechanisms involved in the final differentiation of skeletal tissues. Molecular genetics and animal models for human malformations are providing many insights into abnormal development. A mouse model for the fetal alcohol syndrome (FAS), a mild form of holoprosencephaly, demonstrates a mid-line anterior neural plate deficiency which leads to olfactory placodes being positioned too close to the mid-line, and other secondary changes. Work on animal models for the retinoic acid syndrome (RAS) shows that there is major involvement of neural crest cells. There is also major crest cell involvement in similar syndromes, apparently including hemifacial microsomia. Later administration of retinoic acid prematurely and excessively kills ganglionic placodal cells and leads to a malformation complex virtually identical to the Treacher Collins syndrome. Most clefts of the lip and/or palate appear to have a

  19. Chronic tempol prevents hypertension, proteinuria, and poor feto-placental outcomes in BPH/5 mouse model of preeclampsia.

    Science.gov (United States)

    Hoffmann, Darren S; Weydert, Christine J; Lazartigues, Eric; Kutschke, William J; Kienzle, Martha F; Leach, Jenny E; Sharma, Jennifer A; Sharma, Ram V; Davisson, Robin L

    2008-04-01

    Recently we described a mouse model, BPH/5, that spontaneously develops the hallmark clinical features of preeclampsia. BPH/5 exhibit impaired placentation before the onset of hypertension and proteinuria, supporting a causal role for the placenta in the pathogenesis of preeclampsia. Here we tested the hypothesis that an increase in reactive oxygen species (ROS) early in pregnancy results in placental abnormalities leading to the maternal symptoms of preeclampsia. We further hypothesized that chronic antioxidant therapy would ameliorate both feto-placental abnormalities and maternal symptoms. ROS levels measured by dihydroethidium revealed significant increases in oxidative stress in BPH/5 placentas at midgestation compared with C57 controls. This increase in ROS was correlated with reduced expression and activity of cytoplasmic superoxide dismutase in early and midgestation BPH/5 placentas. These abnormalities in placental oxidant factors occurred before the onset of maternal symptoms, suggesting a possible causal link between increased ROS and maternal and feto-placental pathology in this model. In support of this, chronic treatment of BPH/5 with the superoxide dismutase-mimetic Tempol throughout gestation significantly improved fetal growth and survival. Furthermore, Tempol ameliorated pregnancy-induced increases in blood pressure and proteinuria in BPH/5 mothers. We confirmed that Tempol radical was present in plasma, and it normalized ROS levels in all placental zones in BPH/5. These data for the first time demonstrate an important causative role for increased ROS in the placenta in the pathogenesis of preeclampsia in a model that spontaneously develops the disease. The results also strongly suggest the potential utility of antioxidant therapy in treating preeclampsia.

  20. 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.

  1. 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.

  2. Huntingtin interacting proteins 14 and 14-like are required for chorioallantoic fusion during early placental development.

    Science.gov (United States)

    Sanders, Shaun S; Hou, Juan; Sutton, Liza M; Garside, Victoria C; Mui, Katherine K N; Singaraja, Roshni R; Hayden, Michael R; Hoodless, Pamela A

    2015-01-15

    Huntington disease (HD) is an adult-onset neurodegenerative disease characterized by motor, cognitive, and psychiatric symptoms that is caused by a CAG expansion in the HTT gene. Palmitoylation is the addition of saturated fatty acids to proteins by DHHC palmitoylacyl transferases. HTT is palmitoylated by huntingtin interacting proteins 14 and 14-like (HIP14 and HIP14L or ZDHHC17 and 13 respectively). Mutant HTT is less palmitoylated and this reduction of palmitoylation accelerates its aggregation and increases cellular toxicity. Mouse models deficient in either Hip14 (Hip14(-/-)) or Hip14l (Hip14l(-/-)) develop HD-like phenotypes. The biological function of HTT palmitoylation and the role that loss of HTT palmitoylation plays in the pathogenesis of HD are unknown. To address these questions mice deficient for both genes were created. Loss of Hip14 and Hip14l leads to early embryonic lethality at day embryonic day 10-11 due to failed chorioallantoic fusion. The chorion is thickened and disorganized and the allantois does not fuse correctly with the chorion and forms a balloon-like shape compared to Hip14l(-/-); Hip14(+/+) littermate control embryos. Interestingly, the Hip14(-/-) ; Hip14(-/-) embryos share many features with the Htt(-/-) embryos, including folding of the yolk sac, a bulb shaped allantois, and a thickened and disorganized chorion. This may be due to a decrease in HTT palmitoylation. In Hip14(-/-); Hip14l(-/-) mouse embryonic fibroblasts show a 25% decrease in HTT palmitoylation compared to wild type cells. This is the first description of a double PAT deficient mouse model where loss of a PAT or multiple PATs results in embryonic lethality in mammals. These results reinforce the physiological importance of palmitoylation during embryogenesis.

  3. Measurement of Second-trimester Placental Volume by Ultrasound: Prediction of Fetal Intrauterine Growth%超声测量中孕期胎盘容积预测胎儿发育

    Institute of Scientific and Technical Information of China (English)

    王慧芳; 李慰玑; 黄幼珍; 王新房

    1993-01-01

    本文对中孕期胎盘容积的增长和胎盘循环进行了纵向性监测,发现中孕期胎盘容积增长较快,且有二个加速期,即15~17孕周,19~21孕周.胎盘容积发育不良或胎盘循环功能受损,均能影响胎儿宫内生长发育.中孕期胎盘发育的超声监测对预测胎儿宫内生长发育迟缓有价值,而中孕期胎儿生物学测量对胎儿宫内生长发育迟缓预测价值不大.%Placental volume includes the placental cellular mass and placental circulating blood volume.The development of placental volume was not even during pregnancy.A longitudinal ultrasonic study of placental volume and placental circulation were performed.The results were that placental vol-nme developed rapidly during second-trimester and has two quickened phases at 15~17 weeks and 19 ~21 weeks of gestation respectively.Both abnormal placental volume and placental circulation could in-fluence the fetal growth.The developmentof second-trimester placental volome monitored by ultra-sound Was proved to be valuable in predicting fetal intrauterine growth retardation(IUGR).Fetal biom-etry during second-trimester has little value in predicting IUGR.

  4. Abnormal ventricular development in preterm neonates with visually normal MRIs

    Science.gov (United States)

    Shi, Jie; Wang, Yalin; Lao, Yi; Ceschin, Rafael; Mi, Liang; Nelson, Marvin D.; Panigrahy, Ashok; Leporé, Natasha

    2015-12-01

    Children born preterm are at risk for a wide range of neurocognitive and neurobehavioral disorders. Some of these may stem from early brain abnormalities at the neonatal age. Hence, a precise characterization of neonatal neuroanatomy may help inform treatment strategies. In particular, the ventricles are often enlarged in neurocognitive disorders, due to atrophy of surrounding tissues. Here we present a new pipeline for the detection of morphological and relative pose differences in the ventricles of premature neonates compared to controls. To this end, we use a new hyperbolic Ricci flow based mapping of the ventricular surfaces of each subjects to the Poincaré disk. Resulting surfaces are then registered to a template, and a between group comparison is performed using multivariate tensor-based morphometry. We also statistically compare the relative pose of the ventricles within the brain between the two groups, by performing a Procrustes alignment between each subject's ventricles and an average shape. For both types of analyses, differences were found in the left ventricles between the two groups.

  5. 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.

  6. Regional placental blood oxygen level dependent (BOLD) changes with gestational age in normally developing pregnancies using long duration R2* mapping in utero

    Science.gov (United States)

    Dighe, Manjiri; Kim, Yun Jung; Seshamani, Sharmishtaa; Blazejewska, Ania I.; Mckown, Susan; Caucutt, Jason; Gatenby, Christopher; Studholme, Colin

    2016-03-01

    The aim of this study was to examine the use of R2* mapping in maternal and fetal sub-regions of the placenta with the aim of providing a reference for blood oxygenation levels during normative development. There have been a number of MR relaxation studies of placental tissues in-utero, but none have reported R2* value changes with age, or examined differences in sub-regions of the placenta. Here specialized long-duration Multi-frame R2* imaging was used to create a stable estimate for R2* values in different placental regions in healthy pregnant volunteers not imaged for clinical reasons. 27 subjects were recruited and scanned up to 3 times during their pregnancy. A multi-slice dual echo EPI based BOLD acquisition was employed and repeated between 90 and 150 times over 3 to 5 minutes to provide a high accuracy estimate of the R2* signal level. Acquisitions were also repeated in 13 cases within a visit to evaluate reproducibility of the method in a given subject. Experimental results showed R2* measurements were highly repeatable within a visit with standard deviation of (0.76). Plots of all visits against gestational age indicated clear correlations showing decreases in R2* with age. This increase was consistent was also consistent over time in multiple visits of the same volunteer during their pregnancy. Maternal and fetal regional changes with gestational age followed the same trend with increase in R2* over the gestational age.

  7. Environmental Enteropathy: Elusive but Significant Subclinical Abnormalities in Developing Countries.

    Science.gov (United States)

    Watanabe, Koji; Petri, William A

    2016-08-01

    Environmental enteropathy/Environmental enteric dysfunction (EE/EED) is a chronic disease of small intestine characterized by gut inflammation and barrier disruption, malabsorption and systemic inflammation in the absence of diarrhea. It is predominantly diseases of children in low income countries and is hypothesized to be caused by continuous exposure to fecally contaminated food, water and fomites. It had not been recognized as a priority health issue because it does not cause overt symptoms and was seen in apparently healthy individuals. However, there is a growing concern of EE/EED because of its impact on longitudinal public health issues, such as growth faltering, oral vaccine low efficacy and poor neurocognitive development. Recent works have provided important clues to unravel its complex pathogenesis, and suggest possible strategies for controlling EE/EED. However, effective diagnostic methods and interventions remain unsettled. Here, we review the existing literature, especially about its pathogenesis, and discuss a solution for children living in the developing world.

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

    Directory of Open Access Journals (Sweden)

    Higgins Michael J

    2010-05-01

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

  9. 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.

  10. Risk factors of placental abruption

    OpenAIRE

    2013-01-01

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

  11. Visualized gene network reveals the novel target transcripts Sox2 and Pax6 of neuronal development in trans-placental exposure to bisphenol A.

    Directory of Open Access Journals (Sweden)

    Chung-Wei Yang

    Full Text Available Bisphenol A (BPA is a ubiquitous endocrine disrupting chemical in our daily life, and its health effect in response to prenatal exposure is still controversial. Early-life BPA exposure may impact brain development and contribute to childhood neurological disorders. The aim of the present study was to investigate molecular target genes of neuronal development in trans-placental exposure to BPA.A meta-analysis of three public microarray datasets was performed to screen for differentially expressed genes (DEGs in exposure to BPA. The candidate genes of neuronal development were identified from gene ontology analysis in a reconstructed neuronal sub-network, and their gene expressions were determined using real-time PCR in 20 umbilical cord blood samples dichotomized into high and low BPA level groups upon the median 16.8 nM.Among 36 neuronal transcripts sorted from DAVID ontology clusters of 457 DEGs using the analysis of Bioconductor limma package, we found two neuronal genes, sex determining region Y-box 2 (Sox2 and paired box 6 (Pax6, had preferentially down-regulated expression (Bonferroni correction p-value <10(-4 and log2-transformed fold change ≤-1.2 in response to BPA exposure. Fetal cord blood samples had the obviously attenuated gene expression of Sox2 and Pax6 in high BPA group referred to low BPA group. Visualized gene network of Cytoscape analysis showed that Sox2 and Pax6 which were contributed to neural precursor cell proliferation and neuronal differentiation might be down-regulated through sonic hedgehog (Shh, vascular endothelial growth factor A (VEGFA and Notch signaling.These results indicated that trans-placental BPA exposure down-regulated gene expression of Sox2 and Pax6 potentially underlying the adverse effect on childhood neuronal development.

  12. A Brief History of the Development of Abnormal Psychology: A Training Guide. Final Report.

    Science.gov (United States)

    Phelps, William R.

    Presented for practitioners is a history of the development of abnormal psychology. Areas covered include the following: Early medical concepts, ideas carried over from literature, early treatment of the mentally ill, development of the psychological viewpoint, Freud's psychoanalytic theory, Jung's analytic theory, the individual psychology of…

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

  14. Placental histology and neutrophil extracellular traps in lupus and pre-eclampsia pregnancies

    Science.gov (United States)

    Marder, Wendy; Knight, Jason S; Kaplan, Mariana J; Somers, Emily C; Zhang, Xu; O'Dell, Alexander A; Padmanabhan, Vasantha; Lieberman, Richard W

    2016-01-01

    Objective Systemic lupus erythematosus (SLE) is associated with increased risk of adverse pregnancy outcomes, including pre-eclampsia, particularly in association with antiphospholipid antibody syndrome (APS). While significant placental abnormalities are expected in pre-eclampsia, less is known about how lupus activity and APS in pregnancy affect the placenta. We describe placental pathology from a population of lupus pregnancies, several of which were complicated by APS-related thromboses, in which pre-eclampsia and other complications developed. We performed standard histopathological placental review and quantified neutrophils and neutrophil extracellular traps (NETs) in the intervillous space, given the recognised association of NETs with lupus, APS and pre-eclampsia. Methods Pre-eclampsia, SLE and control placentas were scored for histological features, and neutrophils were quantified on H&E and immunohistochemical staining for the granular protein myeloperoxidase. NETs were identified by extracellular myeloperoxidase staining in the setting of decondensed nuclei. Non-parametric analysis was used to evaluate differences in netting and intact neutrophils between groups, with Kruskal–Wallis testing for associations between histological findings and neutrophils. Results Placentas were evaluated from 35 pregnancies: 10 controls, 11 pre-eclampsia, 4 SLE+pre-eclampsia and 10 SLE, including one complicated by catastrophic APS and one complicated by hepatic and splenic vein thromboses during pregnancy. Intrauterine growth restriction and oligohydramnios were observed in lupus cases but not controls. Significantly more NETs were found infiltrating placental intervillous spaces in pre-eclampsia, SLE+pre-eclampsia and all 10 SLE non-pre-eclampsia cases. The ratio of NETs to total neutrophils was significantly increased in all case groups compared with controls. When present, NETs were associated with maternal vasculitis, laminar decidual necrosis, maternal

  15. Overexpression of Fyn tyrosine kinase causes abnormal development of primary sensory neurons in Xenopus laevis embryos.

    Science.gov (United States)

    Saito, R; Fujita, N; Nagata, S

    2001-06-01

    The expression and function of the Src family protein tyrosine kinase Fyn in Xenopus laevis embryos have been examined. In situ hybridization analysis demonstrated nervous system-specific expression of Fyn mRNA in tail-bud embryos. However, a class of primary sensory neurons; that is, Rohon-Beard (RB) neurons, which is positive for immunoglobulin superfamily cell adhesion molecules (CAM), neural cell adhesion molecule (N-CAM) and contactin, is devoid of Fyn expression. Injection of Fyn mRNA into one of the blastomeres at the 2-cell stage led to overexpression of Fyn in the injected half of the tail-bud embryos. Immunolabeling of the embryos with anti-HNK-1 antibody revealed that the peripheral axons of RB neurons were partially misguided and bound to each other to form abnormal subcutaneous fascicles. Similar abnormality was induced by injection of the Fyn overexpression vector. The incidence of abnormality appeared dose-dependent, being 68-92% of the injected embryos at 50-400 pg of mRNA. Co-injection of the contactin antisense vector depleted contactin mRNA accumulation without affecting Fyn overexpression and reduced the incidence of the abnormal RB-cell phenotype. However, the N-CAM antisense was ineffective in reducing this abnormality. These results suggest that Fyn can modify signals regulating axonal guidance or fasciculation in the developing X. laevis nervous system and that contactin may affect this action of Fyn.

  16. Abnormal development of the lesser wing of the sphenoid with microphthalmos and microcephaly

    Energy Technology Data Exchange (ETDEWEB)

    Jacquemin, C. [King Khaled Eye Specialist Hospital, Riyadh (Saudi Arabia). Radiology Dept.; Mullaney, P. [Paediatric Ophthalmology Div., King Khaled Eye Specialist Hospital, Riyadh (Saudi Arabia); Bosley, T.M. [Neuro-Ophthalmology Div., King Khaled Eye Specialist Hospital, Riyadh (Saudi Arabia)

    2001-02-01

    We report two patients with abnormal development of the lesser wing of the sphenoid bone, globe, optic nerve and cerebral hemisphere without stigmata of neurofibromatosis type 1. The lesser wing of the sphenoid bone was abnormally formed and was not ossified ipsilateral to the dysmorphic eye and underdeveloped cerebral hemisphere. Maldevelopment of the sphenoid wing may interfere with the normal closure of the optic vesicle and normal growth of encephalic structures, possibly by disturbing developmental tissue interactions. These patients may exhibit a type of restricted primary sphenoid dysplasia, while the sphenoid dysplasia of neurofibromatosis type 1 may be secondary to orbital or ocular neurofibromas and other factors associated with that disease. (orig.)

  17. Abnormal development of the lesser wing of the sphenoid with microphthalmos and microcephaly.

    Science.gov (United States)

    Jacquemin, C; Mullaney, P; Bosley, T M

    2001-02-01

    We report two patients with abnormal development of the lesser wing of the sphenoid bone, globe, optic nerve and cerebral hemisphere without stigmata of neurofibromatosis type 1. The lesser wing of the sphenoid bone was abnormally formed and was not ossified ipsilateral to the dysmorphic eye and underdeveloped cerebral hemisphere. Maldevelopment of the sphenoid wing may interfere with the normal closure of the optic vesicle and normal growth of encephalic structures, possibly by disturbing developmental tissue interactions. These patients may exhibit a type of restricted primary sphenoid dysplasia, while the sphenoid dysplasia of neurofibromatosis type 1 may be secondary to orbital or ocular neurofibromas and other factors associated with that disease.

  18. Disturbance in Maternal Environment Leads to Abnormal Synaptic Instability during Neuronal Circuitry Development

    Science.gov (United States)

    Hatanaka, Yusuke; Kabuta, Tomohiro; Wada, Keiji

    2017-01-01

    Adverse maternal environment during gestation and lactation can have negative effects on the developing brain that persist into adulthood and result in behavioral impairment. Recent studies of human and animal models suggest epidemiological and experimental association between disturbances in maternal environments during brain development and the occurrence of neuropsychiatric disorders, including autism spectrum disorder, attention deficit hyperactivity disorder, schizophrenia, anxiety, depression, and neurodegenerative diseases. In this review, we summarize recent advances in understanding the effects of maternal metabolic and hormonal abnormalities on the developing brain by focusing on the dynamics of dendritic spine, an excitatory postsynaptic structure. We discuss the abnormal instability of dendritic spines that is common to developmental disorders and neurological diseases. We also introduce our recent studies that demonstrate how maternal obesity and hyperandrogenism leads to abnormal development of neuronal circuitry and persistent synaptic instability, which results in the loss of synapses. The aim of this review is to highlight the links between abnormal maternal environment, behavioral impairment in offspring, and the dendiric spine pathology of neuropsychiatric disorders.

  19. Maternal Outcomes According to Placental Position in Placental Previa

    Directory of Open Access Journals (Sweden)

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

    2011-01-01

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

  20. pitx2 Deficiency results in abnormal ocular and craniofacial development in zebrafish.

    Directory of Open Access Journals (Sweden)

    Yi Liu

    Full Text Available Human PITX2 mutations are associated with Axenfeld-Rieger syndrome, an autosomal-dominant developmental disorder that involves ocular anterior segment defects, dental hypoplasia, craniofacial dysmorphism and umbilical abnormalities. Characterization of the PITX2 pathway and identification of the mechanisms underlying the anomalies associated with PITX2 deficiency is important for better understanding of normal development and disease; studies of pitx2 function in animal models can facilitate these analyses. A knockdown of pitx2 in zebrafish was generated using a morpholino that targeted all known alternative transcripts of the pitx2 gene; morphant embryos generated with the pitx2(ex4/5 splicing-blocking oligomer produced abnormal transcripts predicted to encode truncated pitx2 proteins lacking the third (recognition helix of the DNA-binding homeodomain. The morphological phenotype of pitx2(ex4/5 morphants included small head and eyes, jaw abnormalities and pericardial edema; lethality was observed at ∼6-8-dpf. Cartilage staining revealed a reduction in size and an abnormal shape/position of the elements of the mandibular and hyoid pharyngeal arches; the ceratobranchial arches were also decreased in size. Histological and marker analyses of the misshapen eyes of the pitx2(ex4/5 morphants identified anterior segment dysgenesis and disordered hyaloid vasculature. In summary, we demonstrate that pitx2 is essential for proper eye and craniofacial development in zebrafish and, therefore, that PITX2/pitx2 function is conserved in vertebrates.

  1. pitx2 Deficiency results in abnormal ocular and craniofacial development in zebrafish.

    Science.gov (United States)

    Liu, Yi; Semina, Elena V

    2012-01-01

    Human PITX2 mutations are associated with Axenfeld-Rieger syndrome, an autosomal-dominant developmental disorder that involves ocular anterior segment defects, dental hypoplasia, craniofacial dysmorphism and umbilical abnormalities. Characterization of the PITX2 pathway and identification of the mechanisms underlying the anomalies associated with PITX2 deficiency is important for better understanding of normal development and disease; studies of pitx2 function in animal models can facilitate these analyses. A knockdown of pitx2 in zebrafish was generated using a morpholino that targeted all known alternative transcripts of the pitx2 gene; morphant embryos generated with the pitx2(ex4/5) splicing-blocking oligomer produced abnormal transcripts predicted to encode truncated pitx2 proteins lacking the third (recognition) helix of the DNA-binding homeodomain. The morphological phenotype of pitx2(ex4/5) morphants included small head and eyes, jaw abnormalities and pericardial edema; lethality was observed at ∼6-8-dpf. Cartilage staining revealed a reduction in size and an abnormal shape/position of the elements of the mandibular and hyoid pharyngeal arches; the ceratobranchial arches were also decreased in size. Histological and marker analyses of the misshapen eyes of the pitx2(ex4/5) morphants identified anterior segment dysgenesis and disordered hyaloid vasculature. In summary, we demonstrate that pitx2 is essential for proper eye and craniofacial development in zebrafish and, therefore, that PITX2/pitx2 function is conserved in vertebrates.

  2. A RADIOIMMUNOASSAY FOR PLACENTAL PROTEIN PP5

    Institute of Scientific and Technical Information of China (English)

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

    1989-01-01

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

  3. mTOR signaling and its roles in normal and abnormal brain development.

    Science.gov (United States)

    Takei, Nobuyuki; Nawa, Hiroyuki

    2014-01-01

    Target of rapamycin (TOR) was first identified in yeast as a target molecule of rapamycin, an anti-fugal and immunosuppressant macrolide compound. In mammals, its orthologue is called mammalian TOR (mTOR). mTOR is a serine/threonine kinase that converges different extracellular stimuli, such as nutrients and growth factors, and diverges into several biochemical reactions, including translation, autophagy, transcription, and lipid synthesis among others. These biochemical reactions govern cell growth and cause cells to attain an anabolic state. Thus, the disruption of mTOR signaling is implicated in a wide array of diseases such as cancer, diabetes, and obesity. In the central nervous system, the mTOR signaling cascade is activated by nutrients, neurotrophic factors, and neurotransmitters that enhances protein (and possibly lipid) synthesis and suppresses autophagy. These processes contribute to normal neuronal growth by promoting their differentiation, neurite elongation and branching, and synaptic formation during development. Therefore, disruption of mTOR signaling may cause neuronal degeneration and abnormal neural development. While reduced mTOR signaling is associated with neurodegeneration, excess activation of mTOR signaling causes abnormal development of neurons and glia, leading to brain malformation. In this review, we first introduce the current state of molecular knowledge of mTOR complexes and signaling in general. We then describe mTOR activation in neurons, which leads to translational enhancement, and finally discuss the link between mTOR and normal/abnormal neuronal growth during development.

  4. mTOR signaling and its roles in normal and abnormal brain development.

    Directory of Open Access Journals (Sweden)

    Nobuyuki eTakei

    2014-04-01

    Full Text Available Target of rapamycin (TOR was first identified in yeast as a target molecule of rapamycin, an anti-fugal and immunosuppressant macrolide compound. In mammals, its orthologue is called mTOR (mammalian TOR. mTOR is a serine/threonine kinase that converges different extracellular stimuli, such as nutrients and growth factors, and diverges into several biochemical reactions, including translation, autophagy, transcription, and lipid synthesis among others. These biochemical reactions govern cell growth and cause cells to attain an anabolic state. Thus, the disruption of mTOR signaling is implicated in a wide array of diseases such as cancer, diabetes, and obesity. In the central nervous system (CNS, the mTOR signaling cascade is activated by nutrients, neurotrophic factors, and neurotransmitters that enhances protein (and possibly lipid synthesis and suppresses autophagy. These processes contribute to normal neuronal growth by promoting their differentiation, neurite elongation and branching, and synaptic formation during development. Therefore, disruption of mTOR signaling may cause neuronal degeneration and abnormal neural development. While reduced mTOR signaling is associated with neurodegeneration, excess activation of mTOR signaling causes abnormal development of neurons and glia, leading to brain malformation. In this review, we first introduce the current state of molecular knowledge of mTOR complexes and signaling in general. We then describe mTOR activation in neurons, which leads to translational enhancement, and finally discuss the link between mTOR and normal/abnormal neuronal growth during development.

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

    Directory of Open Access Journals (Sweden)

    Konje Justin C

    2009-10-01

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

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

    Science.gov (United States)

    Redman, Christopher W G; Staff, Anne Cathrine

    2015-10-01

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

  7. Placental specializations in lecithotrophic viviparous squamate reptiles.

    Science.gov (United States)

    Stewart, James R

    2015-09-01

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

  8. Bioactive factors in uteroplacental and systemic circulation link placental ischemia to generalized vascular dysfunction in hypertensive pregnancy and preeclampsia.

    Science.gov (United States)

    Shah, Dania A; Khalil, Raouf A

    2015-06-15

    Preeclampsia is a pregnancy-associated disorder characterized by hypertension, and could lead to maternal and fetal morbidity and mortality; however, the pathophysiological mechanisms involved are unclear. Predisposing demographic, genetic and environmental risk factors could cause localized abnormalities in uteroplacental cytoactive factors such as integrins, matrix metalloproteinases, cytokines and major histocompatibility complex molecules leading to decreased vascular remodeling, uteroplacental vasoconstriction, trophoblast cells apoptosis, and abnormal development of the placenta. Defective placentation and decreased trophoblast invasion of the myometrium cause reduction in uteroplacental perfusion pressure (RUPP) and placental ischemia/hypoxia, an important event in preeclampsia. RUPP could stimulate the release of circulating bioactive factors such as the anti-angiogenic factors soluble fms-like tyrosine kinase-1 and soluble endoglin that cause imbalance with the pro-angiogenic factors vascular endothelial growth factor and placental growth factor, or cause the release of inflammatory cytokines, reactive oxygen species, hypoxia-induced factor-1 and AT1 angiotensin receptor agonistic autoantibodies. The circulating bioactive factors target endothelial cells causing generalized endotheliosis, endothelial dysfunction, decreased vasodilators such as nitric oxide and prostacyclin and increased vasoconstrictors such as endothelin-1 and thromboxane A2, leading to increased vasoconstriction. The bioactive factors also stimulate the mechanisms of VSM contraction including Ca(2+), protein kinase C, and Rho-kinase and induce extracellular matrix remodeling leading to further vasoconstriction and hypertension. While therapeutic options are currently limited, understanding the underlying mechanisms could help design new interventions for management of preeclampsia.

  9. Cytogenetic studies of 1232 patients with different sexual development abnormalities from the Sultanate of Oman.

    Science.gov (United States)

    Al-Alawi, Intisar; Goud, Tadakal Mallana; Al-Harasi, Salma; Rajab, Anna

    2016-02-01

    The aim of this study was to evaluate cytogenetic findings in Omani patients who had been referred for suspicion of sex chromosome abnormalities that resulted in different clinical disorders. Furthermore, it sought to examine the frequency of chromosomal anomalies in these patients and to compare the obtained results with those reported elsewhere. Cytogenetic analysis was performed on 1232 cases with variant characteristics of sexual development disorders who had been referred to the cytogenetic department, National Genetic Centre, Ministry of Health, from different hospitals in the Sultanate of Oman between 1999 and 2014. The karyotype results demonstrated chromosomal anomalies in 24.2% of the cases, where 67.5% of abnormalities were identified in referral females, whereas only 32.6% were in referral males. Of all sex chromosome anomalies detected, Turner syndrome was the most frequent (38.2%) followed by Klinefelter syndrome (24.9%) and XY phenotypic females (16%). XXX syndrome and XX phenotypic males represented 6.8% and 3.8% of all sex chromosome anomalies, respectively. Cytogenetic analysis of patients referred with various clinical suspicions of chromosomal abnormalities revealed a high rate of chromosomal anomalies. This is the first broad cytogenetic study reporting combined frequencies of sex chromosome anomalies in sex development disorders in Oman.

  10. Familial liability, obstetric complications and childhood development abnormalities in early onset schizophrenia: a case control study

    Directory of Open Access Journals (Sweden)

    Lucarelli Elisabetta

    2011-04-01

    Full Text Available Abstract Background Genetic and environmental risk factors and gene-environment interactions are linked to higher likelihood of developing schizophrenia in accordance with the neurodevelopmental model of disease; little is known about risk factors and early development in early-onset schizophrenia (EOS and very early-onset schizophrenia (VEOS. Methods We present a case-control study of a sample of 21 patients with EOS/VEOS and a control group of 21 patients with migraine, recruited from the Child Neuropsychiatry Unit, Department of Neurologic and Psychiatric Science, University of Bari, Italy. The aim was to assess the statistical association between VEOS/EOS and family history for psychiatric disorders, obstetric complications and childhood developmental abnormalities using 2 × 2 tables and a Chi Squared or Fisher test. Results The results show a statistical association between EOS/VEOS and schizophrenia and related disorders (P = 0.02 and personality disorders (P = 0.003 in relatives, and between EOS/VEOS and developmental abnormalities of early relational skills (P = 0.008 and learning (P = 0.04; there is not a statistically relevant difference between cases and controls (P > 0.05 for any obstetric complications (pre, peri and postpartum. Conclusions This study confirms the significant role of familial liability but not of obstetric complications in the pathogenesis of VEOS/EOS; the association between childhood developmental abnormalities and EOS/VEOS supports the neurodevelopmental model of disease.

  11. Human placental lactogen and unconjugated estriol concentrations in twin pregnancy: monitoring of fetal development in intrauterine growth retardation and single intrauterine fetal death.

    Science.gov (United States)

    Trapp, M; Kato, K; Bohnet, H G; Gerhard, I; Weise, H C; Leidenberger, F

    1986-11-01

    Human placental lactogen and unconjugated estriol concentrations in maternal serum were evaluated in 100 uneventful twin pregnancies, and these values were compared with those observed in 16 twin pregnancies associated with intrauterine growth retardation or single intrauterine fetal death. In pregnancies associated with intrauterine growth retardation (n = 8), human placental lactogen levels were at the lower limit of normal range for singleton pregnancies, whereas estriol levels were normal in most cases. When one of the fetuses had died before week 33 of pregnancy (n = 5), both human placental lactogen and estriol levels were low and they were almost at the levels in singleton pregnancy. When intrauterine fetal death occurred after week 36 of pregnancy (n = 3), both hormone levels remained normal until term. Thus human placental lactogen rather than estriol is a good indicator of intrauterine growth retardation in twin pregnancy. Both human placental lactogen and estriol are useful for the monitoring of the surviving fetus in the case of single intrauterine fetal death.

  12. Clinical use of placental hormones in pregnancy management.

    Science.gov (United States)

    De Bonis, M; Vellucci, F L; Di Tommaso, M; Voltolini, C; Torricelli, M; Petraglia, F

    2012-09-01

    Across human pregnancy, placenta represents a transit of oxygen and nutrients from the mother to the fetus and actively produces a large number of hormones that serve to regulate and balance maternal and fetal physiology. An abnormal secretion of placental hormones may be part of the pathogenesis of the main obstetric syndrome, from early to late pregnancy, in particular chromosomopathies, miscarriage, gestational trophoblastic diseases, preeclampsia, gestational diabetes, and pre-term delivery. The possibility to measure placental hormones represents an important tool not only for the diagnosis and management of gestational disorders, but it is also fundamental in the early identification of women at risk for these pregnancy complications. In the last decades, the use of ultrasound examination has provided additional biophysical markers, improving the early diagnosis of gestational diseases. In conclusion, while few placental hormones have sufficient sensitivity for clinical application, there are promising new biochemical and biophysical markers that, if used in combination, may provide a valid screening tool.

  13. Non-placental causes of intrauterine growth restriction.

    Science.gov (United States)

    Hendrix, Nancy; Berghella, Vincenzo

    2008-06-01

    Placental insufficiency, in some form or fashion, is associated with the majority of cases of intrauterine growth restriction (IUGR). There are numerous causes of IUGR which are not caused primarily by placental insufficiency, but indirectly lead to it. The causes of IUGR can be subdivided into fetal and maternal etiologies. The fetal etiologies consist of genetic diseases, congenital malformations, infections, multiple gestations, and placental/cord abnormalities. The maternal etiologies are categorized as follows: (1) decreased uteroplacental blood flow, (2) reduced blood volume, (3) decreased oxygen carrying capacity, (4) nutrition status, (5) teratogens, and (6) miscellaneous causes such as short interpregnancy intervals, race, maternal age, and low socioeconomic status. Knowledge of the etiologies of fetal growth restriction is essential, so that future care can be targeted at prevention. There are several primary and secondary prevention strategies that can be adopted.

  14. [Fetal circulation in normal pregnancy and in placental insufficiency].

    Science.gov (United States)

    Ivanov, B; Malinova, M

    2010-01-01

    The fetal circulation is different from the adult circulation. One of the quite common conditions that are challenging to the developing fetus is placental hypoxia. Regardless of its cause, placental vascular insufficiency is commonly assumed to be an important factor in the development of intrauterine growth retardation. Several mechanisms are involved in the fetal adaptation to the decompensation during hypoxemia. Doppler Ultrasound technologies can help to evaluate of the fetal wellbeing.

  15. Genetic analysis of abnormal male sexual development in Aedes aegypti and Ae. mascarensis backcross progeny.

    Science.gov (United States)

    Hilburn, L R; Rai, K S

    1982-01-01

    When male hybrids of Aedes aegypti females and A. mascarensis males were backcrossed to A. aegypti females, 32.8 percent of the male progeny exhibited abnormal sexual development, including failure of the terminalia to rotate, a split sternite of the eighth abdominal segment with partially duplicated telomeres, or feminization that gives rise to sterile intersexes. Observations made on three morphological marker loci and five isozyme loci with characteristic electromorphs in the two parental species suggested that when the sex-determining M locus is derived from A. mascarensis and the chromosome regions including s, LDH, and lDH2 on chromosome 2 and blt and 6PGD on chromosome 3 are homozygous for genes from A. aegypti, the frequency of abnormal sexual development is increased. An even greater percentage of males suffer aberrant development if recombination also occurs between the M and re locus of chromosome 1. The data suggest that genes on chromosome 2 control normal development of the male terminalia, genes on chromosome 3 control sexual differentiation, and the entire process is controlled by genes on chromosome 1 that are linked to, but not identical with, the M locus.

  16. A mechanical model predicts morphological abnormalities in the developing human brain

    Science.gov (United States)

    Budday, Silvia; Raybaud, Charles; Kuhl, Ellen

    2014-07-01

    The developing human brain remains one of the few unsolved mysteries of science. Advancements in developmental biology, neuroscience, and medical imaging have brought us closer than ever to understand brain development in health and disease. However, the precise role of mechanics throughout this process remains underestimated and poorly understood. Here we show that mechanical stretch plays a crucial role in brain development. Using the nonlinear field theories of mechanics supplemented by the theory of finite growth, we model the human brain as a living system with a morphogenetically growing outer surface and a stretch-driven growing inner core. This approach seamlessly integrates the two popular but competing hypotheses for cortical folding: axonal tension and differential growth. We calibrate our model using magnetic resonance images from very preterm neonates. Our model predicts that deviations in cortical growth and thickness induce morphological abnormalities. Using the gyrification index, the ratio between the total and exposed surface area, we demonstrate that these abnormalities agree with the classical pathologies of lissencephaly and polymicrogyria. Understanding the mechanisms of cortical folding in the developing human brain has direct implications in the diagnostics and treatment of neurological disorders, including epilepsy, schizophrenia, and autism.

  17. 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

  18. Risk factors of placental abruption

    Directory of Open Access Journals (Sweden)

    Hooria Seyedhosseini Ghaheh

    2013-01-01

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

  19. Risk factors of placental abruption

    Science.gov (United States)

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

    2013-01-01

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

  20. Subinvolution of placental bed vessels: case report and review of the literature.

    Science.gov (United States)

    Kavalar, Rajko; Arko, Darja; Fokter Dovnik, Nina; Takač, Iztok

    2012-10-01

    Subinvolution of placental bed vessels, a well-recognized cause of postpartum and postabortal hemorrhage, is defined with prolonged or excessive uterine hemorrhage beginning after the delivery or abortion. Although physiological changes in uteroplacental parts of spiral arteries are well known, the sequence of events in involution of these vessels is not yet clearly understood. In this article we present two cases of subinvolution of placental bed vessels in which we were able to demonstrate the presence of extravillous trophoblast in and around the placental bed vessels. The disease is supposed to be the result of abnormal interaction between maternal uterine cells and fetal trophoblast.

  1. Transcriptome Analysis for Abnormal Spike Development of the Wheat Mutant dms.

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    Xin-Xin Zhu

    Full Text Available Wheat (Triticum aestivum L. spike development is the foundation for grain yield. We obtained a novel wheat mutant, dms, characterized as dwarf, multi-pistil and sterility. Although the genetic changes are not clear, the heredity of traits suggests that a recessive gene locus controls the two traits of multi-pistil and sterility in self-pollinating populations of the medium plants (M, such that the dwarf genotype (D and tall genotype (T in the progeny of the mutant are ideal lines for studies regarding wheat spike development. The objective of this study was to explore the molecular basis for spike abnormalities of dwarf genotype.Four unigene libraries were assembled by sequencing the mRNAs of the super-bulked differentiating spikes and stem tips of the D and T plants. Using integrative analysis, we identified 419 genes highly expressed in spikes, including nine typical homeotic genes of the MADS-box family and the genes TaAP2, TaFL and TaDL. We also identified 143 genes that were significantly different between young spikes of T and D, and 26 genes that were putatively involved in spike differentiation. The result showed that the expression levels of TaAP1-2, TaAP2, and other genes involved in the majority of biological processes such as transcription, translation, cell division, photosynthesis, carbohydrate transport and metabolism, and energy production and conversion were significantly lower in D than in T.We identified a set of genes related to wheat floral organ differentiation, including typical homeotic genes. Our results showed that the major causal factors resulting in the spike abnormalities of dms were the lower expression homeotic genes, hormonal imbalance, repressed biological processes, and deficiency of construction materials and energy. We performed a series of studies on the homeotic genes, however the other three causal factors for spike abnormal phenotype of dms need further study.

  2. What do placental function tests predict? Observations on placental lactogen levels in growth retardation and fetal distress.

    Science.gov (United States)

    Obiekwe, B C; Chard, T

    1982-11-01

    Single blood samples were obtained from an unselected population of 527 women between 36 and 40 wk gestation. Serum placental lactogen levels were lower than normal in patients whose infants were growth retarded or developed fetal distress in labor. These associations were independent; the fetal distress group did not contain an excess of subjects with growth retardation. Thus, the results of a biochemical test reflect dynamic aspects of placental function and not simply the overall growth of fetus and placenta.

  3. Changes in the metabolic footprint of placental explant-conditioned medium cultured in different oxygen tensions from placentas of small for gestational age and normal pregnancies.

    LENUS (Irish Health Repository)

    Horgan, R P

    2012-01-31

    Being born small for gestational age (SGA) confers significantly increased risks of perinatal morbidity and mortality. Accumulating evidence suggests that an SGA fetus results from a poorly perfused and abnormally developed placenta. Some of the placental features seen in SGA, such as abnormal cell turnover and impaired nutrient transport, can be reproduced by culture of placental explants in hypoxic conditions. Metabolic footprinting offers a hypothesis-generating strategy to investigate factors absorbed by and released from this tissue in vitro. Previously, metabolic footprinting of the conditioned culture media has identified differences in placental explants cultured under normoxic and hypoxic conditions and between normal pregnancies and those complicated by pre-eclampsia. In this study we aimed to examine the differences in the metabolic footprint of placental villous explants cultured at different oxygen (O(2)) tensions between women who deliver an SGA baby (n = 9) and those from normal controls (n = 8). Placental villous explants from cases and controls were cultured for 96 h in 1% (hypoxic), 6% (normoxic) and 20% (hyperoxic) O(2). Metabolic footprints were analysed by Ultra Performance Liquid Chromatography coupled to an electrospray hybrid LTQ-Orbitrap Mass Spectrometry (UPLC-MS). 574 metabolite features showed significant difference between SGA and normal at one or more of the oxygen tensions. SGA explant media cultured under hypoxic conditions was observed, on a univariate level, to exhibit the same metabolic signature as controls cultured under normoxic conditions in 49% of the metabolites of interest, suggesting that SGA tissue is acclimatised to hypoxic conditions in vivo. No such behaviour was observed under hyperoxic culture conditions. Glycerophospholipid and tryptophan metabolism were highlighted as areas of particular interest.

  4. Loss of DNMT1o disrupts imprinted X chromosome inactivation and accentuates placental defects in females.

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    Serge McGraw

    2013-11-01

    Full Text Available The maintenance of key germline derived DNA methylation patterns during preimplantation development depends on stores of DNA cytosine methyltransferase-1o (DNMT1o provided by the oocyte. Dnmt1o(mat-/- mouse embryos born to Dnmt1(Δ1o/Δ1o female mice lack DNMT1o protein and have disrupted genomic imprinting and associated phenotypic abnormalities. Here, we describe additional female-specific morphological abnormalities and DNA hypomethylation defects outside imprinted loci, restricted to extraembryonic tissue. Compared to male offspring, the placentae of female offspring of Dnmt1(Δ1o/Δ1o mothers displayed a higher incidence of genic and intergenic hypomethylation and more frequent and extreme placental dysmorphology. The majority of the affected loci were concentrated on the X chromosome and associated with aberrant biallelic expression, indicating that imprinted X-inactivation was perturbed. Hypomethylation of a key regulatory region of Xite within the X-inactivation center was present in female blastocysts shortly after the absence of methylation maintenance by DNMT1o at the 8-cell stage. The female preponderance of placental DNA hypomethylation associated with maternal DNMT1o deficiency provides evidence of additional roles beyond the maintenance of genomic imprints for DNA methylation events in the preimplantation embryo, including a role in imprinted X chromosome inactivation.

  5. Fetal alcohol exposure leads to abnormal olfactory bulb development and impaired odor discrimination in adult mice

    NARCIS (Netherlands)

    K.G. Akers (Katherine); S.A. Kushner (Steven); A.T. Leslie (Ana); L. Clarke (Laura); D. van der Kooy (Derek); J.P. Lerch (Jason); P.W. Frankland (Paul)

    2011-01-01

    textabstractBackground: Children whose mothers consumed alcohol during pregnancy exhibit widespread brain abnormalities and a complex array of behavioral disturbances. Here, we used a mouse model of fetal alcohol exposure to investigate relationships between brain abnormalities and specific behavior

  6. Placental Transmogrification of the lung

    Energy Technology Data Exchange (ETDEWEB)

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

    2013-12-15

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

  7. The character of abnormalities found in eye development of quail embruos exposed under space flight conditions

    Science.gov (United States)

    Grigoryan, E.; Dadheva, O.; Polinskaya, V.; Guryeva, T.

    The avian embryonic eye is used as a model system for studies on the environmental effects on central nervous system development. Here we present results of qualitative investigation of the eye development in quail embryos incubated in micro-"g" environment. In this study we used eyes of Japanese quail (Coturnix coturnix Japonica) embryos "flown" onboard biosatellite Kosmos-1129 and on Mir station within the framework of Mir-NASA Program. Eyes obtained from embryos ranging in age from 3-12 days (E3-E12) were prepared histologically and compared with those of the synchronous and laboratory gound controls. Ther most careful consideration was given to finding and analysis of eye developmental abnormalities. Then they were compared with those already described by experimental teratology for birds and mammals. At the stage of the "eye cup" (E3) we found the case of invalid formation of the inner retina. The latter was represented by disorganized neuroblasts occupying whole posterior chamber of the eye. On the 7th day of quail eye development, at the period of cellular growth activation some cases of small eyes with many folds of overgrowing neural and pigmented retinal layers were detected. In retinal folds of these eyes the normal layering was disturbed as well as the formation of aqueous body and pecten oculi. At this time point the changes were also found in the anterior part of the eye. The peculiarities came out of the bigger width of the cornea and separation of its layers, but were found in synchronous control as well. Few embryos of E10 had also eyes with the abnormities described for E7 but this time they were more vivid because of the completion of eye tissue differentiation. At the stage E12 we found the case evaluated as microphthalmia attending by overgrowth of anterior pigmented tissues - iris and ciliary body attached with the cornea. Most, but not all, of abnormalities we found in eye morphogeneses belonged to the birds "flown" aboard Kosmos- 1129 and

  8. Placental abruption: a persisting killer

    Directory of Open Access Journals (Sweden)

    Shakuntala Amirchand Chhabra

    2014-06-01

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

  9. Epigenetic regulation of the placental HSD11B2 barrier and its role as a critical regulator of fetal development

    OpenAIRE

    2014-01-01

    “Fetal programming” is a term used to describe how early-life experience influences fetal development and later disease risk. In humans, prenatal stress-induced fetal programming is associated with increased risk of preterm birth, and a heightened risk of metabolic and neurological diseases later in life. A critical determinant of this is the regulation of fetal exposure to glucocorticoids by the placenta. Glucocorticoids are the mediators through which maternal stress influences fetal develo...

  10. Placental activin A is required for follicular development during the second half of pregnancy in the golden hamster (Mesocricetus auratus).

    Science.gov (United States)

    Furuta, Chie; Arakawa, Sayoko; Shi, Zhanquan; Watanabe, Gen; Taya, Kazuyoshi

    2008-04-01

    Numerous antral follicles develop during the second half of pregnancy in the golden hamster even though LH and FSH are maintained at basal levels. To investigate the possible hormone actions of activin A associated with follicular development, pregnant golden hamsters were placentectomized on day 6 of pregnancy and animals were sacrificed at day 8, 10, 12, or 14 of pregnancy. There was a drastic decrease in the plasma concentrations of activin A from day 10 of pregnancy in the operated group compared to the controls. Positive immunohistochemical staining of inhibin/activin subunits betaA and betaB in the syncytiotrophoblast of the placenta revealed the source of activin A, AB, or B. The number of healthy follicles did not change until day 12 between the operated and the control groups, but decreased in numbers in the operated groups thereafter. The decreased concentrations of inhibin A, B, and estradiol-17beta in the operated groups at day 10 and 12 correlated well with the number of mature follicles in response to hCG treatment. In conclusion, we revealed that activin A secreted from the placenta induces folliculogenesis to maintain the high levels of estradiol-17beta needed to induce uterine dilatation for fetus growth and impending parturition.

  11. Abnormal Mammary Development in 129:STAT1-Null Mice is Stroma-Dependent.

    Science.gov (United States)

    Chen, Jane Q; Mori, Hidetoshi; Cardiff, Robert D; Trott, Josephine F; Hovey, Russell C; Hubbard, Neil E; Engelberg, Jesse A; Tepper, Clifford G; Willis, Brandon J; Khan, Imran H; Ravindran, Resmi K; Chan, Szeman R; Schreiber, Robert D; Borowsky, Alexander D

    2015-01-01

    Female 129:Stat1-null mice (129S6/SvEvTac-Stat1(tm1Rds) homozygous) uniquely develop estrogen-receptor (ER)-positive mammary tumors. Herein we report that the mammary glands (MG) of these mice have altered growth and development with abnormal terminal end buds alongside defective branching morphogenesis and ductal elongation. We also find that the 129:Stat1-null mammary fat pad (MFP) fails to sustain the growth of 129S6/SvEv wild-type and Stat1-null epithelium. These abnormalities are partially reversed by elevated serum progesterone and prolactin whereas transplantation of wild-type bone marrow into 129:Stat1-null mice does not reverse the MG developmental defects. Medium conditioned by 129:Stat1-null epithelium-cleared MFP does not stimulate epithelial proliferation, whereas it is stimulated by medium conditioned by epithelium-cleared MFP from either wild-type or 129:Stat1-null females having elevated progesterone and prolactin. Microarrays and multiplexed cytokine assays reveal that the MG of 129:Stat1-null mice has lower levels of growth factors that have been implicated in normal MG growth and development. Transplanted 129:Stat1-null tumors and their isolated cells also grow slower in 129:Stat1-null MG compared to wild-type recipient MG. These studies demonstrate that growth of normal and neoplastic 129:Stat1-null epithelium is dependent on the hormonal milieu and on factors from the mammary stroma such as cytokines. While the individual or combined effects of these factors remains to be resolved, our data supports the role of STAT1 in maintaining a tumor-suppressive MG microenvironment.

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

    Science.gov (United States)

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

    2016-04-01

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

  13. Apert and Crouzon syndromes-Cognitive development, brain abnormalities, and molecular aspects.

    Science.gov (United States)

    Fernandes, Marilyse B L; Maximino, Luciana P; Perosa, Gimol B; Abramides, Dagma V M; Passos-Bueno, Maria Rita; Yacubian-Fernandes, Adriano

    2016-06-01

    Apert and Crouzon are the most common craniosynostosis syndromes associated with mutations in the fibroblast growth factor receptor 2 (FGFR2) gene. We conducted a study to examine the molecular biology, brain abnormalities, and cognitive development of individuals with these syndromes. A retrospective longitudinal review of 14 patients with Apert and Crouzon syndromes seen at the outpatient Craniofacial Surgery Hospital for Rehabilitation of Craniofacial Anomalies in Brazil from January 1999 through August 2010 was performed. Patients between 11 and 36 years of age (mean 18.29 ± 5.80), received cognitive evaluations, cerebral magnetic resonance imaging, and molecular DNA analyses. Eight patients with Apert syndrome (AS) had full scale intelligence quotients (FSIQs) that ranged from 47 to 108 (mean 76.9 ± 20.2), and structural brain abnormalities were identified in five of eight patients. Six patients presented with a gain-of-function mutation (p.Ser252Trp) in FGFR2 and FSIQs in those patients ranged from 47 to78 (mean 67.2 ± 10.7). One patient with a gain-of-function mutation (p.Pro253Arg) had a FSIQ of 108 and another patient with an atypical splice mutation (940-2A →G) had a FSIQ of 104. Six patients with Crouzon syndrome had with mutations in exons IIIa and IIIc of FGFR2 and their FSIQs ranged from 82 to 102 (mean 93.5 ± 6.7). These reveal that molecular aspects are another factor that can be considered in studies of global and cognitive development of patients with Apert and Crouzon syndrome (CS). © 2016 Wiley Periodicals, Inc.

  14. 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

  15. Congenital hydrocephalus and abnormal subcommissural organ development in Sox3 transgenic mice.

    Directory of Open Access Journals (Sweden)

    Kristie Lee

    Full Text Available Congenital hydrocephalus (CH is a life-threatening medical condition in which excessive accumulation of CSF leads to ventricular expansion and increased intracranial pressure. Stenosis (blockage of the Sylvian aqueduct (Aq; the narrow passageway that connects the third and fourth ventricles is a common form of CH in humans, although the genetic basis of this condition is unknown. Mouse models of CH indicate that Aq stenosis is associated with abnormal development of the subcommmissural organ (SCO a small secretory organ located at the dorsal midline of the caudal diencephalon. Glycoproteins secreted by the SCO generate Reissner's fibre (RF, a thread-like structure that descends into the Aq and is thought to maintain its patency. However, despite the importance of SCO function in CSF homeostasis, the genetic program that controls SCO development is poorly understood. Here, we show that the X-linked transcription factor SOX3 is expressed in the murine SCO throughout its development and in the mature organ. Importantly, overexpression of Sox3 in the dorsal diencephalic midline of transgenic mice induces CH via a dose-dependent mechanism. Histological, gene expression and cellular proliferation studies indicate that Sox3 overexpression disrupts the development of the SCO primordium through inhibition of diencephalic roof plate identity without inducing programmed cell death. This study provides further evidence that SCO function is essential for the prevention of hydrocephalus and indicates that overexpression of Sox3 in the dorsal midline alters progenitor cell differentiation in a dose-dependent manner.

  16. Incidence of abnormal offspring from cloning and other assisted reproductive technologies.

    Science.gov (United States)

    Hill, Jonathan R

    2014-02-01

    In animals produced by assisted reproductive technologies, two abnormal phenotypes have been characterized. Large offspring syndrome (LOS) occurs in offspring derived from in vitro cultured embryos, and the abnormal clone phenotype includes placental and fetal changes. LOS is readily apparent in ruminants, where a large calf or lamb derived from in vitro embryo production or cloning may weigh up to twice the expected body weight. The incidence of LOS varies widely between species. When similar embryo culture conditions are applied to nonruminant species, LOS either is not as dramatic or may even be unapparent. Coculture with serum and somatic cells was identified in the 1990s as a risk factor for abnormal development of ruminant pregnancies. Animals cloned from somatic cells may display a combination of fetal and placental abnormalities that are manifested at different stages of pregnancy and postnatally. In highly interventional technologies, such as nuclear transfer (cloning), the incidence of abnormal offspring continues to be a limiting factor to broader application of the technique. This review details the breadth of phenotypes found in nonviable pregnancies, together with the phenotypes of animals that survive the transition to extrauterine life. The focus is on animals produced using in vitro embryo culture and nuclear transfer in comparison to naturally occurring phenotypes.

  17. Abnormal arterial flows by a distributed model of the fetal circulation.

    Science.gov (United States)

    van den Wijngaard, Jeroen P H M; Westerhof, Berend E; Faber, Dirk J; Ramsay, Margaret M; Westerhof, Nico; van Gemert, Martin J C

    2006-11-01

    Modeling the propagation of blood pressure and flow along the fetoplacental arterial tree may improve interpretation of abnormal flow velocity waveforms in fetuses. The current models, however, either do not include a wide range of gestational ages or do not account for variation in anatomical, vascular, or rheological parameters. We developed a mathematical model of the pulsating fetoumbilical arterial circulation using Womersley's oscillatory flow theory and viscoelastic arterial wall properties. Arterial flow waves are calculated at different arterial locations from which the pulsatility index (PI) can be determined. We varied blood viscosity, placental and brain resistances, placental compliance, heart rate, stiffness of the arterial wall, and length of the umbilical arteries. The PI increases in the umbilical artery and decreases in the cerebral arteries, as a result of increasing placental resistance or decreasing brain resistance. Both changes in resistance decrease the flow through the placenta. An increased arterial stiffness increases the PIs in the entire fetoplacental circulation. Blood viscosity and peripheral bed compliance have limited influence on the flow profiles. Bradycardia and tachycardia increase and decrease the PI in all arteries, respectively. Umbilical arterial length has limited influence on the PI but affects the mean arterial pressure at the placental cord insertion. The model may improve the interpretation of arterial flow pulsations and thus may advance both the understanding of pathophysiological processes and clinical management.

  18. Docosahexaenoic Acid Supplementation Early in Pregnancy May Prevent Deep Placentation Disorders

    Directory of Open Access Journals (Sweden)

    Jorge A. Carvajal

    2014-01-01

    Full Text Available Uteroplacental ischemia may cause preterm birth, either due to preterm labor, preterm premature rupture of membranes, or medical indication (in the presence of preeclampsia or fetal growth restriction. Uteroplacental ischemia is the product of defective deep placentation, a failure of invasion, and transformation of the spiral arteries by the trophoblast. The failure of normal placentation generates a series of clinical abnormalities nowadays called “deep placentation disorders”; they include preeclampsia, fetal growth restriction, preterm labor, preterm premature rupture of membranes, in utero fetal death, and placental abruption. Early reports suggested that a LC-PUFAs (long chain polyunsaturated fatty acids rich diet reduces the incidence of deep placentation disorders. Recent randomized controlled trials are inconsistent to show the benefit of docosahexaenoic acid (DHA supplementation during pregnancy to prevent deep placentation disorders, but most of them showed that DHA supplementation was associated with lower risk of early preterm birth. We postulate that DHA supplementation, early in pregnancy, may reduce the incidence of deep placentation disorders. If our hypothesis is correct, DHA supplementation, early in pregnancy, will become a safe and effective strategy for primary prevention of highly relevant pregnancy diseases, such as preterm birth, preeclampsia, and fetal growth restriction.

  19. Abnormal development of tapetum and microspores induced by chemical hybridization agent SQ-1 in wheat.

    Science.gov (United States)

    Wang, Shuping; Zhang, Gaisheng; Song, Qilu; Zhang, Yingxin; Li, Zheng; Guo, Jialin; Niu, Na; Ma, Shoucai; Wang, Junwei

    2015-01-01

    Chemical hybridization agent (CHA)-induced male sterility is an important tool in crop heterosis. To demonstrate that CHA-SQ-1-induced male sterility is associated with abnormal tapetal and microspore development, the cytology of CHA-SQ-1-treated plant anthers at various developmental stages was studied by light microscopy, scanning and transmission electron microscopy, in situ terminal deoxynucleotidyl transferasemediated dUTP nick end-labelling (TUNEL) assay and DAPI staining. The results indicated that the SQ-1-treated plants underwent premature tapetal programmed cell death (PCD), which was initiated at the early-uninucleate stage of microspore development and continued until the tapetal cells were completely degraded; the process of microspore development was then blocked. Microspores with low-viability (fluorescein diacetate staining) were aborted. The study suggests that premature tapetal PCD is the main cause of pollen abortion. Furthermore, it determines the starting period and a key factor in CHA-SQ-1-induced male sterility at the cell level, and provides cytological evidence to further study the mechanism between PCD and male sterility.

  20. Abnormal development of tapetum and microspores induced by chemical hybridization agent SQ-1 in wheat.

    Directory of Open Access Journals (Sweden)

    Shuping Wang

    Full Text Available Chemical hybridization agent (CHA-induced male sterility is an important tool in crop heterosis. To demonstrate that CHA-SQ-1-induced male sterility is associated with abnormal tapetal and microspore development, the cytology of CHA-SQ-1-treated plant anthers at various developmental stages was studied by light microscopy, scanning and transmission electron microscopy, in situ terminal deoxynucleotidyl transferasemediated dUTP nick end-labelling (TUNEL assay and DAPI staining. The results indicated that the SQ-1-treated plants underwent premature tapetal programmed cell death (PCD, which was initiated at the early-uninucleate stage of microspore development and continued until the tapetal cells were completely degraded; the process of microspore development was then blocked. Microspores with low-viability (fluorescein diacetate staining were aborted. The study suggests that premature tapetal PCD is the main cause of pollen abortion. Furthermore, it determines the starting period and a key factor in CHA-SQ-1-induced male sterility at the cell level, and provides cytological evidence to further study the mechanism between PCD and male sterility.

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

    Institute of Scientific and Technical Information of China (English)

    高咏梅; 仵妍

    2010-01-01

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

  2. Molecules consolidate the placental mammal tree

    NARCIS (Netherlands)

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

    2004-01-01

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

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

    Science.gov (United States)

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

    2015-08-01

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

  4. Over-expression of thymosin beta 4 promotes abnormal tooth development and stimulation of hair growth.

    Science.gov (United States)

    Cha, Hee-Jae; Philp, Deborah; Lee, Soo-Hyun; Moon, Hye-Sung; Kleinman, Hynda K; Nakamura, Takashi

    2010-01-01

    Thymosin beta 4 has multi-functional roles in cell physiology. It accelerates wound healing, hair growth and angiogenesis, and increases laminin-5 expression in corneal epithelium. Furthermore, thymosin beta 4 stimulates tumor growth and metastasis by induction of cell migration and vascular endothelial growth factor-mediated angiogenesis. Using a construct on the skin-specific keratin-5 promoter, we have developed thymosin beta 4 over-expressing transgenic mice to further study its functional roles. Thymosin beta 4 in adult skin and in embryonic stages of the transgenic mouse was analyzed by both Western blot and immunohistochemistry. The over-expression of thymosin beta 4 was observed especially around hair follicles and in the teeth in the transgenic mice. We examined the phenotype of the thymosin beta 4 over-expressing mice. Hair growth was accelerated. In addition, the transgenic mice had abnormally-shaped white teeth and dull incisors. We found that the expression of laminin-5 was up-regulated in the skin of the transgenic mice. We conclude that thymosin beta 4 has an important physiological role in hair growth and in tooth development.

  5. Development of spent fuel remote handling technology - Kinematic analysis of bilateral arms for abnormal spent fuels

    Energy Technology Data Exchange (ETDEWEB)

    Jeong, Kyu Won; Yoo, Ju Sang; Kim, Jong Yoon [Chungbuk National University, Chongju (Korea)

    2000-03-01

    In the project of 'Development of Spent Fuel Remote Handling Technology', Preprocessing technique, mechanism and teleoperation technique are being developed. One of the mechanisms is a device for disassembling of the spent fuel bundle. However, there may be abnormal fuel bar among the fuel bundle, In this case the unpacking task will be difficult and dangerous. So, in that case, a force reflected teleoperation manipulator is desirable. The system is composed of a anthropomorphic input device at control site, power manipulator at remote site and control system. In this research, the forward and inverse kinematic equations of input device and manipulators has been solved, respectively. In addition, the mapping algorithm is proposed and shown using computer simulation. The reaction force of the telemanipulator with the environmental object is reflected through control system. The reaction force is decomposed into joint torque of the input device based on the jacobian equation. The obtained theoretical relations are verified through computer simulation and they will be used effectively in the spent fuel remote handling technology. 6 refs., 26 figs., 7 tabs. (Author)

  6. A curious abnormally developed embryo of the pill millipede Glomeris marginata (Villers, 1789

    Directory of Open Access Journals (Sweden)

    Ralf Janssen

    2013-03-01

    Full Text Available This paper reports on an abnormally developed embryo (ADE of the common pill millipede Glomeris marginata. This ADE represents a modified case of Duplicitas posterior, in which two posterior ends are present, but only one anterior end. While the major posterior germ band of the embryo appears almost normally developed, the minor posterior germ band is heavily malformed, has no clear correlation to the single head, little or no ventral tissue, and a minute amount of yolk. The anterior end of the minor germ band is fused to the ventral side of the major germ band between the first and second trunk segment. At least one appendage of the second trunk segment appears to be shared by the two germ bands. Morphology and position of the minor germ band suggest that the ADE may be the result of an incorrectly established single cumulus [the later posterior segment addition zone (SAZ]. This differs from earlier reports on D. posterior type ADEs in G. marginata that are likely the result of the early formation of two separate cumuli.

  7. Placental lactogen levels in diabetic pregnancy.

    Science.gov (United States)

    Ursell, W; Brudenell, M; Chard, T

    1973-04-14

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

  8. Plasma placental lactogen in pregnancy.

    Science.gov (United States)

    Raghuramulu, N

    1978-01-01

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

  9. 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....

  10. Bidirectional Transfer Study of Polystyrene Nanoparticles across the Placental Barrier in an ex Vivo Human Placental Perfusion Model

    Science.gov (United States)

    Grafmueller, Stefanie; Manser, Pius; Diener, Liliane; Diener, Pierre-André; Maeder-Althaus, Xenia; Maurizi, Lionel; Jochum, Wolfram; Krug, Harald F.; Buerki-Thurnherr, Tina; von Mandach, Ursula

    2015-01-01

    Background Nanoparticle exposure in utero might not be a major concern yet, but it could become more important with the increasing application of nanomaterials in consumer and medical products. Several epidemiologic and in vitro studies have shown that nanoparticles can have potential toxic effects. However, nanoparticles also offer the opportunity to develop new therapeutic strategies to treat specifically either the pregnant mother or the fetus. Previous studies mainly addressed whether nanoparticles are able to cross the placental barrier. However, the transport mechanisms underlying nanoparticle translocation across the placenta are still unknown. Objectives In this study we examined which transport mechanisms underlie the placental transfer of nanoparticles. Methods We used the ex vivo human placental perfusion model to analyze the bidirectional transfer of plain and carboxylate modified polystyrene particles in a size range between 50 and 300 nm. Results We observed that the transport of polystyrene particles in the fetal to maternal direction was significantly higher than for the maternal to fetal direction. Regardless of their ability to cross the placental barrier and the direction of perfusion, all polystyrene particles accumulated in the syncytiotrophoblast of the placental tissue. Conclusions Our results indicate that the syncytiotrophoblast is the key player in regulating nanoparticle transport across the human placenta. The main mechanism underlying this translocation is not based on passive diffusion, but is likely to involve an active, energy-dependent transport pathway. These findings will be important for reproductive toxicology as well as for pharmaceutical engineering of new drug carriers. Citation Grafmueller S, Manser P, Diener L, Diener PA, Maeder-Althaus X, Maurizi L, Jochum W, Krug HF, Buerki-Thurnherr T, von Mandach U, Wick P. 2015. Bidirectional transfer study of polystyrene nanoparticles across the placental barrier in an ex vivo human

  11. Reduction of mitoferrin results in abnormal development and extended lifespan in Caenorhabditis elegans.

    Science.gov (United States)

    Ren, Yaguang; Yang, Su; Tan, Guoqiang; Ye, Wei; Liu, Danhui; Qian, Xu; Ding, Zhongying; Zhong, Yuhong; Zhang, Jingrui; Jiang, Dandan; Zhao, Yuhong; Lu, Jianxin

    2012-01-01

    Iron is essential for organisms. It is mainly utilized in mitochondria for biosynthesis of iron-sulfur clusters, hemes and other cofactors. Mitoferrin 1 and mitoferrin 2, two homologues proteins belonging to the mitochondrial solute carrier family, are required for iron delivery into mitochondria. Mitoferrin 1 is highly expressed in developing erythrocytes which consume a large amount of iron during hemoglobinization. Mitoferrin 2 is ubiquitously expressed, whose functions are less known. Zebrafish with mitoferrin 1 mutation show profound hypochromic anaemia and erythroid maturation arrests, and yeast with defects in MRS3/4, the counterparts of mitoferrin 1/2, has low mitochondrial iron levels and grows poorly by iron depletion. Mitoferrin 1 expression is up-regulated in yeast and mouse models of Fiedreich's ataxia disease and in human cell culture models of Parkinson disease, suggesting its involvement in the pathogenesis of diseases with mitochondrial iron accumulation. In this study we found that reduced mitoferrin levels in C. elegans by RNAi treatment causes pleiotropic phenotypes such as small body size, reduced fecundity, slow movement and increased sensitivity to paraquat. Despite these abnormities, lifespan was increased by 50% to 80% in N2 wild type strain, and in further studies using the RNAi sensitive strain eri-1, more than doubled lifespan was observed. The pathways or mechanisms responsible for the lifespan extension and other phenotypes of mitoferrin RNAi worms are worth further study, which may contribute to our understanding of aging mechanisms and the pathogenesis of iron disorder related diseases.

  12. The potential significance of binovular follicles and binucleate giant oocytes for the development of genetic abnormalities

    Indian Academy of Sciences (India)

    Bernd Rosenbusch

    2012-12-01

    Normal development of a fertilizable female gamete emanates from a follicle containing only one oocyte that becomes haploid after first meiotic division. Binovular follicles including two oocytes and binucleate giant oocytes that are diploid after first meiosis constitute notable exceptions from this rule. Data provided by programmes of human-assisted reproduction on the occurrence of both phenomena have been reviewed to evaluate possible implications for the formation of genetic abnormalities. To exclude confusion with oocytes aspirated from two adjacent individual follicles, true binovularity has been defined as inclusion of two oocytes within a common zona pellucida or their fusion in the zonal region. A total of 18 conjoined oocytes have been reported and one of the oocyte was normally fertilized in seven cases. Simultaneous fertilization of both female gametes occurred only once. No pregnancy was achieved after transfer of an embryo from a binovular follicle. Binucleate giant oocytes have been observed sporadically but a few reports suggest an incidence of up to 0.3% of all gametes retrieved. Extensive studies performed by two independent centres demonstrated that giant oocytes are diploid at metaphase II, can undergo fertilization in vitro with formation of two or three pronuclei and develop into triploid zygotes and triploid or triploid/mosaic embryos. In summary, giant binucleate oocytes may be responsible for the development of digynic triploidy whereas the currently available data do not support a role of conjoined oocytes in producing dizygotic twins, mosaicism, chimaeras or tetraploidy. However, more information on the maturity and fertilizability of oocytes from binovular follicles is needed. Future studies should also evaluate a possible impact of pharmaceutical and environmental oestrogens on the formation of multiovular follicles.

  13. Folic acid and homocyst(e)ine metabolic defects and the risk of placental abruption, pre-eclampsia and spontaneous pregnancy loss: A systematic review.

    Science.gov (United States)

    Ray, J G; Laskin, C A

    1999-09-01

    Placental infarction or abruption, recurrent pregnancy loss and pre-eclampsia are thought to arise due to defects within the placental vascular bed. Deficiencies of vitamin B12 and folate, or other abnormalities within the methionine-homocyst(e)ine pathway have been implicated in the development of such placental diseases. We conducted a systematic literature review to quantify the risk of placental disease in the presence of these metabolic defects. Studies were identified through OVID Medline between 1966 and February 1999. Terms relating to the measurement of vitamin B12, folic acid, methylenetetrahydrofolate reductase or homocyst(e)ine were combined with those of pre-eclampsia, placental abruption/infarction or spontaneous and habitual abortion. Human studies comprising both cases and controls and published in the English language were accepted. Their references were explored for other publications. Data were abstracted on the matching of cases with controls, the mean levels of folate, B12 or homocyst(e)ine in each group or the frequency of the homozygous state for the thermolabile variant of methylenetetrahydrofolate reductase. The definition of 'abnormal' for each exposure was noted and the presence or absence of the exposure of interest for each outcome was calculated as an absolute rate with a 95 per cent confidence interval. The crude odds ratios were calculated for each study and then pooled using a random effects model. Eighteen studies were finally included. Eight studies examined the risk of placental abruption/infarction in the presence of vitamin B12 or folate deficiency, or hyperhomocyst(e)inaemia. Folate deficiency was a prominent risk factor for placental abruption/infarction among four studies, though not statistically significant (pooled odds ratio 25.9, 95 per cent CI 0.9-736.3). Hyperhomocyst(e)inaemia was also associated with placental abruption/infarction both without (pooled odds ratio 5.3, 95 per cent CI 1.8-15.9) and with methionine

  14. Developmental genes during placentation: insights from mouse mutants

    Institute of Scientific and Technical Information of China (English)

    Jinhu a LU; Qiang WANG; Bingyan WANG; Fengchao WANG; Haibin WANG

    2011-01-01

    Placenta,a temporary organ first formed during the development of a new life is essential for the survival and growth of the fetus in eutherian mammals.It serves as an interface for the exchange of nutrients,gases and wastes between the maternal and fetal compartments.During the past decades,studies employing gene-engineered mouse mutants have revealed a wide range of signaling molecules governing the trophoblast development and function during placentation under various pathophysiological conditions.Here,we summarize the recent progress with particular respect to the involvement of developmental genes during placentation.

  15. The Importance of a Late First Trimester Placental Sonogram in Patients at Risk of Abnormal Placentation

    Directory of Open Access Journals (Sweden)

    Felipe Moretti

    2014-01-01

    Full Text Available Background. Placenta accreta is a potentially life-threatening obstetrical condition and is responsible for many emergency Caesarean hysterectomies. Early prenatal diagnosis may help minimize maternal morbidity and mortality. This report highlights risk factors, early diagnostic findings and complications associated with placenta accreta, and the role of first trimester sonography in diagnosis. Case. A 38-year-old pregnant woman, G2P1L1 with history of one previous Caesarean section, presented with vaginal bleeding at 13 weeks’ gestation. Ultrasound examination was highly suspicious of placenta previa with accreta. During an earlier 12-week scan for nuchal translucency measurement, the placenta was suboptimally visualized. She was counselled regarding potential maternal and fetal complications as well as management options. At 33 weeks’ gestation Caesarean hysterectomy was performed due to vaginal bleeding. Conclusion. Early ultrasound screening in high-risk patients may be advantageous in order to identify placenta accreta and conduct appropriate patient counseling regarding risks and management options.

  16. Placental diversity in malagasy tenrecs

    DEFF Research Database (Denmark)

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

    2007-01-01

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

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

    Science.gov (United States)

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

    2017-03-14

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

  18. The role of the second heart field in pulmonary vein development : new insights in the origin of clinical abnormalities

    NARCIS (Netherlands)

    Douglas, Yvonne Louise

    2010-01-01

    In this thesis we describe normal and abnormal pulmonary vein development in human and mouse hearts, and focus on the histo(patho)logy of the pulmonary venous and left atrial dorsal wall, in order to elucidate the role of the posterior heart field in the formation and differentiation of the pulmonar

  19. Genetically induced oxidative stress in mice causes thrombocytosis, splenomegaly and placental angiodysplasia that leads to recurrent abortion

    Directory of Open Access Journals (Sweden)

    Takamasa Ishii

    2014-01-01

    Full Text Available Historical data in the 1950s suggests that 7%, 11%, 33%, and 87% of couples were infertile by ages 30, 35, 40 and 45, respectively. Up to 22.3% of infertile couples have unexplained infertility. Oxidative stress is associated with male and female infertility. However, there is insufficient evidence relating to the influence of oxidative stress on the maintenance of a viable pregnancy, including pregnancy complications and fetal development. Recently, we have established Tet-mev-1 conditional transgenic mice, which can express the doxycycline-induced mutant SDHCV69E transgene and experience mitochondrial respiratory chain dysfunction leading to intracellular oxidative stress. In this report, we demonstrate that this kind of abnormal mitochondrial respiratory chain-induced chronic oxidative stress affects fertility, pregnancy and delivery rates as well as causes recurrent abortions, occasionally resulting in maternal death. Despite this, spermatogenesis and early embryogenesis are completely normal, indicating the mutation's effects to be rather subtle. Female Tet-mev-1 mice exhibit thrombocytosis and splenomegaly in both non-pregnant and pregnant mice as well as placental angiodysplasia with reduced Flt-1 protein leading to hypoxic conditions, which could contribute to placental inflammation and fetal abnormal angiogenesis. Collectively these data strongly suggest that chronic oxidative stress caused by mitochondrial mutations provokes spontaneous abortions and recurrent miscarriage resulting in age-related female infertility.

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

    DEFF Research Database (Denmark)

    Brøgger, Torbjørn; Forman, Axel; Aalkjær, Christian;

    2014-01-01

    Background: The placenta is the base for the exchange of nutrients, oxygen and waste products for the fetus. The placental vessels hold a crucial role in regulation of blood flow, and compromised function may lead to complications like growth retardation and preeclampsia where no specific treatment...... 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...

  1. Placental mesenchymal dysplasia associated with hepatic and pulmonary hamartoma.

    Science.gov (United States)

    Tortoledo, Maria; Galindo, A; Ibarrola, C

    2010-01-01

    This report describes a 31-week stillborn female infant with placental mesenchymal dysplasia (PMD) in association with hepatic mesenchymal hamartoma (HMH) and pulmonary hamartoma. Placental mesenchymal dysplasia was initially misdiagnosed as a partial mole. However, histologically, no trophoblastic proliferation or inclusions were observed. Differential diagnosis of the hepatic mass with similar tumors is discussed. To our knowledge, this is the first case of lung hamartoma reported in a fetus and the first case related to PMD and HMH. A common anomalous development of the mesoderm, a reparative post-injury process and a genetic mechanism, have been proposed to explain their pathogenesis.

  2. Study of placentation and maternal and fetal outcomes in cases of 2 or more caesarean sections

    Directory of Open Access Journals (Sweden)

    Supriya Poonia

    2016-07-01

    Conclusions: The incidences of abnormal placentation have increased with the rise in previous two CS Also the maternal and perinatal morbidity and mortality increases with history of previous two CS. [Int J Reprod Contracept Obstet Gynecol 2016; 5(7.000: 2402-2406

  3. Studying placental transfer of highly purified non-dioxin-like PCBs in two models of the placental barrier

    DEFF Research Database (Denmark)

    Correia Carreira, S; Cartwright, L; Mathiesen, L;

    2011-01-01

    Currently, toxicology and toxicokinetics of purified non-dioxin-like polychlorinated biphenyls (NDL-PCBs) are poorly characterised. Transplacental kinetics of NDL-PCBs can be studied in a variety of models, but careful validation of each model is crucial. We aimed to develop a standard operating...... procedure for establishing an in vitro model of the human placental barrier. Using this model, we sought to investigate placental transport kinetics of two NDL-PCB congeners. Firstly, we compared the BeWo cell line of the American Type Culture Collection with the BeWo b30 clone and determined parameters...... for monolayer formation. Secondly, we performed placental perfusions to validate the in vitro model. To that end, the transport of radiolabelled PCB52 and 180 was investigated in both models. We were not able to grow the ATCC cell line to confluency, but determined monolayer formation using BeWo b30...

  4. Long-Term Effects of Placental Growth on Overweight and Body Composition

    Science.gov (United States)

    Eriksson, Johan G.; Gelow, Jill; Thornburg, Kent L.; Osmond, Clive; Laakso, Markku; Uusitupa, Matti; Lindi, Virpi; Kajantie, Eero; Barker, David J. P.

    2012-01-01

    Obesity is programmed in utero and small babies generally have small placentas. In some circumstances, an undernourished fetus can expand its placental surface to extract more nutrients. We hypothesize that this results in an imbalanced nutrient supply to the fetus leading to obesity. To determine whether placental size determines overweight and body composition, we studied 2003 subjects in adult life. Associations between placental surface area and indices of overweight were restricted to people who carried the Pro12Pro genotype of the PPARγ2 gene. For every 1 SD increase in placental surface area, the odds ratio for overweight was 1.37 (95% CI 1.10 to 1.71; P = 0.005). Expansion of the placental surface in compensation for fetal undernutrition increases the risk of overweight and a higher body fat percentage in people carrying the Pro12Pro genotype. We suggest that similar underlying multifactorial mechanisms affect the development of obesity in general. PMID:22570665

  5. Long-Term Effects of Placental Growth on Overweight and Body Composition

    Directory of Open Access Journals (Sweden)

    Johan G. Eriksson

    2012-01-01

    Full Text Available Obesity is programmed in utero and small babies generally have small placentas. In some circumstances, an undernourished fetus can expand its placental surface to extract more nutrients. We hypothesize that this results in an imbalanced nutrient supply to the fetus leading to obesity. To determine whether placental size determines overweight and body composition, we studied 2003 subjects in adult life. Associations between placental surface area and indices of overweight were restricted to people who carried the Pro12Pro genotype of the PPARγ2 gene. For every 1 SD increase in placental surface area, the odds ratio for overweight was 1.37 (95% CI 1.10 to 1.71; P=0.005. Expansion of the placental surface in compensation for fetal undernutrition increases the risk of overweight and a higher body fat percentage in people carrying the Pro12Pro genotype. We suggest that similar underlying multifactorial mechanisms affect the development of obesity in general.

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

    DEFF Research Database (Denmark)

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

    2015-01-01

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

  7. Amniotic fluid deficiency and congenital abnormalities both influence fluctuating asymmetry in developing limbs of human deceased fetuses.

    Directory of Open Access Journals (Sweden)

    Clara Mariquita Antoinette ten Broek

    Full Text Available Fluctuating asymmetry (FA, as an indirect measure of developmental instability (DI, has been intensively studied for associations with stress and fitness. Patterns, however, appear heterogeneous and the underlying causes remain largely unknown. One aspect that has received relatively little attention in the literature is the consequence of direct mechanical effects on asymmetries. The crucial prerequisite for FA to reflect DI is that environmental conditions on both sides should be identical. This condition may be violated during early human development if amniotic fluid volume is deficient, as the resulting mechanical pressures may increase asymmetries. Indeed, we showed that limb bones of deceased human fetuses exhibited increased asymmetry, when there was not sufficient amniotic fluid (and, thus, space in the uterine cavity. As amniotic fluid deficiency is known to cause substantial asymmetries and abnormal limb development, these subtle asymmetries are probably at least in part caused by the mechanical pressures. On the other hand, deficiencies in amniotic fluid volume are known to be associated with other congenital abnormalities that may disturb DI. More specifically, urogenital abnormalities can directly affect/reduce amniotic fluid volume. We disentangled the direct mechanical effects on FA from the indirect effects of urogenital abnormalities, the latter presumably representing DI. We discovered that both factors contributed significantly to the increase in FA. However, the direct mechanical effect of uterine pressure, albeit statistically significant, appeared less important than the effects of urogenital abnormalities, with an effect size only two-third as large. We, thus, conclude that correcting for the relevant direct factors allowed for a representative test of the association between DI and stress, and confirmed that fetuses form a suitable model system to increase our understanding in patterns of FA and symmetry development.

  8. Prolonged endoplasmic reticulum stress alters placental morphology and causes low birth weight

    Energy Technology Data Exchange (ETDEWEB)

    Kawakami, Takashige, E-mail: tkawakami@ph.bunri-u.ac.jp; Yoshimi, Masaki; Kadota, Yoshito; Inoue, Masahisa; Sato, Masao; Suzuki, Shinya

    2014-03-01

    The role of endoplasmic reticulum (ER) stress in pregnancy remains largely unknown. Pregnant mice were subcutaneously administered tunicamycin (Tun), an ER stressor, as a single dose [0, 50, and 100 μg Tun/kg/body weight (BW)] on gestation days (GDs) 8.5, 12.5, and 15.5. A high incidence (75%) of preterm delivery was observed only in the group treated with Tun 100 μg/kg BW at GD 15.5, indicating that pregnant mice during late gestation are more susceptible to ER stress on preterm delivery. We further examined whether prolonged in utero exposure to ER stress affects fetal development. Pregnant mice were subcutaneously administered a dose of 0, 20, 40, and 60 μg Tun/kg from GD 12.5 to 16.5. Tun treatment decreased the placental and fetal weights in a dose-dependent manner. Histological evaluation showed the formation of a cluster of spongiotrophoblast cells in the labyrinth zone of the placenta of Tun-treated mice. The glycogen content of the fetal liver and placenta from Tun-treated mice was lower than that from control mice. Tun treatment decreased mRNA expression of Slc2a1/glucose transporter 1 (GLUT1), which is a major transporter for glucose, but increased placental mRNA levels of Slc2a3/GLUT3. Moreover, maternal exposure to Tun resulted in a decrease in vascular endothelial growth factor receptor-1 (VEGFR-1), VEGFR-2, and placental growth factor. These results suggest that excessive and exogenous ER stress may induce functional abnormalities in the placenta, at least in part, with altered GLUT and vascular-related gene expression, resulting in low infant birth weight. - Highlights: • Maternal exposure to excessive ER stress induced preterm birth and IUGR. • Prolonged excessive ER stress altered the formation of the placental labyrinth. • ER stress decreased GLUT1 mRNA expression in the placenta, but increased GLUT3. • ER stress-induced IUGR causes decreased glycogen and altered glucose transport.

  9. 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

  10. Review paper: a review of the pathology of abnormal placentae of somatic cell nuclear transfer clone pregnancies in cattle, sheep, and mice.

    Science.gov (United States)

    Palmieri, C; Loi, P; Ptak, G; Della Salda, L

    2008-11-01

    Cloning of cattle, sheep, and mice by somatic cell nuclear transfer (SCNT) can result in apparently healthy offspring, but the probability of a successful and complete pregnancy is less than 5%. Failures of SCNT pregnancy are associated with placental abnormalities, such as placentomegaly, reduced vascularisation, hypoplasia of trophoblastic epithelium, and altered basement membrane. The pathogenesis of these changes is poorly understood, but current evidence implicates aberrant reprogramming of donor nuclei by the recipient oocyte cytoplast, resulting in epigenetic modifications of key regulatory genes essential for normal placental development. The purpose of this review is to provide an overview of the anatomic pathology of abnormal placentae of SCNT clones and to summarize current knowledge concerning underlying pathogenetic mechanisms.

  11. Impact of maternal metabolic abnormalities in pregnancy on human milk and subsequent infant metabolic development: methodology and design

    Directory of Open Access Journals (Sweden)

    Hamilton Jill K

    2010-10-01

    Full Text Available Abstract Background Childhood obesity is on the rise and is a major risk factor for type 2 diabetes later in life. Recent evidence indicates that abnormalities that increase risk for diabetes may be initiated early in infancy. Since the offspring of women with diabetes have an increased long-term risk for obesity and type 2 diabetes, the impact of maternal metabolic abnormalities on early nutrition and infant metabolic trajectories is of considerable interest. Human breast milk, the preferred food during infancy, contains not only nutrients but also an array of bioactive substances including metabolic hormones. Nonetheless, only a few studies have reported concentrations of metabolic hormones in human milk specifically from women with metabolic abnormalities. We aim to investigate the impact of maternal metabolic abnormalities in pregnancy on human milk hormones and subsequently on infant development over the first year of life. The objective of this report is to present the methodology and design of this study. Methods/Design The current investigation is a prospective study conducted within ongoing cohort studies of women and their offspring. Pregnant women attending outpatient obstetrics clinics in Toronto, Canada were recruited. Between April 2009 and July 2010, a total of 216 pregnant women underwent a baseline oral glucose tolerance test and provided medical and lifestyle history. Follow-up visits and telephone interviews are conducted and expected to be completed in October 2011. Upon delivery, infant birth anthropometry measurements and human breast milk samples are collected. At 3 and 12 months postpartum, mothers and infants are invited for follow-up assessments. Interim telephone interviews are conducted during the first year of offspring life to characterize infant feeding and supplementation behaviors. Discussion An improved understanding of the link between maternal metabolic abnormalities in pregnancy and early infant nutrition may

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

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    Rodrigo M Souza

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

  13. Placental chimerism in early human pregnancy

    Directory of Open Access Journals (Sweden)

    Ashutosh Halder

    2005-01-01

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

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

    Science.gov (United States)

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

  15. 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

  16. Clinical Analysis of 122 Cases of Placental Abruption%胎盘早剥122例临床分析

    Institute of Scientific and Technical Information of China (English)

    倪琴; 孙彦华; 宣冬梅; 蒙占松

    2015-01-01

    Objective:To explore the causes of placental abruption and clinical manifestations and its effect on the mothers and their infants.Method:The clinical data of 122 patients with placental abruption in our hospital from January 2012 to December 2013 were analyzed retrospectively.Result:84 mild placental abruption patients and 38 severe placental abruption patients were included in this study.The main incentive of placental abruption was hypertensive disorders complicating pregnancy.Abdominal pain,abnormal fetal heart,uterus plate hard with tenderness in patients with severe placental abruption were significantly higher than those of mild placental abruption patients(P0.05).Prenatal ultrasound examination suggested 98 cases(80.33%) of placental abruption.The incidences of cesarean section,sever neonatalasphyxia,dead fetus,postpartum hemorrhage and uteroplacental apoplexy of sever placental abruption were higher than those of mild placental abruption,the differences were statistically significant(P0.05);产前行超声检查提示胎盘早剥98例(80.33%);重型胎盘早剥剖宫产、重度新生儿窒息、死胎、产后出血、子宫胎盘卒中发生率高于轻型胎盘早剥,差异均有统计学意义(P<0.05)。结论:提高对胎盘早剥的认识,及时发现胎盘早剥的诱因,及时产前诊断及处理,以降低孕产妇及围产儿患病率和死亡率。

  17. Disruption of Ah Receptor Signaling during Mouse Development Leads to Abnormal Cardiac Structure and Function in the Adult.

    Directory of Open Access Journals (Sweden)

    Vinicius S Carreira

    Full Text Available The Developmental Origins of Health and Disease (DOHaD Theory proposes that the environment encountered during fetal life and infancy permanently shapes tissue physiology and homeostasis such that damage resulting from maternal stress, poor nutrition or exposure to environmental agents may be at the heart of adult onset disease. Interference with endogenous developmental functions of the aryl hydrocarbon receptor (AHR, either by gene ablation or by exposure in utero to 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD, a potent AHR ligand, causes structural, molecular and functional cardiac abnormalities and altered heart physiology in mouse embryos. To test if embryonic effects progress into an adult phenotype, we investigated whether Ahr ablation or TCDD exposure in utero resulted in cardiac abnormalities in adult mice long after removal of the agent. Ten-months old adult Ahr-/- and in utero TCDD-exposed Ahr+/+ mice showed sexually dimorphic abnormal cardiovascular phenotypes characterized by echocardiographic findings of hypertrophy, ventricular dilation and increased heart weight, resting heart rate and systolic and mean blood pressure, and decreased exercise tolerance. Underlying these effects, genes in signaling networks related to cardiac hypertrophy and mitochondrial function were differentially expressed. Cardiac dysfunction in mouse embryos resulting from AHR signaling disruption seems to progress into abnormal cardiac structure and function that predispose adults to cardiac disease, but while embryonic dysfunction is equally robust in males and females, the adult abnormalities are more prevalent in females, with the highest severity in Ahr-/- females. The findings reported here underscore the conclusion that AHR signaling in the developing heart is one potential target of environmental factors associated with cardiovascular disease.

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

    DEFF Research Database (Denmark)

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

    2015-01-01

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

  19. The pleiotropic ABNORMAL FLOWER AND DWARF1 affects plant height, floral development and grain yield in rice

    Science.gov (United States)

    Ren, Deyong; Rao, Yuchun; Wu, Liwen; Xu, Qiankun; Li, Zizhuang; Yu, Haiping; Zhang, Yu; Leng, Yujia; Hu, Jiang; Zhu, Li; Gao, Zhenyu; Dong, Guojun; Zhang, Guangheng; Guo, Longbiao

    2016-01-01

    Abstract Moderate plant height and successful establishment of reproductive organs play pivotal roles in rice grain production. The molecular mechanism that controls the two aspects remains unclear in rice. In the present study, we characterized a rice gene, ABNORMAL FLOWER AND DWARF1 (AFD1) that determined plant height, floral development and grain yield. The afd1 mutant showed variable defects including the dwarfism, long panicle, low seed setting and reduced grain yield. In addition, abnormal floral organs were also observed in the afd1 mutant including slender and thick hulls, and hull‐like lodicules. AFD1 encoded a DUF640 domain protein and was expressed in all tested tissues and organs. Subcellular localization showed AFD1‐green fluorescent fusion protein (GFP) was localized in the nucleus. Meantime, our results suggested that AFD1 regulated the expression of cell division and expansion related genes. PMID:26486996

  20. The pleiotropic ABNORMAL FLOWER AND DWARF1 affects plant height, floral development and grain yield in rice

    Institute of Scientific and Technical Information of China (English)

    Deyong Ren; Li Zhu; Zhenyu Gao; Guojun Dong; Guangheng Zhang; Longbiao Guo; Dali Zeng; and Qian Qian; Yuchun Rao; Liwen Wu; Qiankun Xu; Zizhuang Li; Haiping Yu; Yu Zhang; Yujia Leng; Jiang Hu

    2016-01-01

    Moderate plant height and successful establish-ment of reproductive organs play pivotal roles in rice grain production. The molecular mechanism that controls the two aspects remains unclear in rice. In the present study, we characterized a rice gene, ABNORMAL FLOWER AND DWARF1 (AFD1) that determined plant height, floral development and grain yield. The afd1 mutant showed variable defects including the dwarfism, long panicle, low seed setting and reduced grain yield. In addition, abnormal floral organs were also observed in the afd1 mutant including slender and thick hulls, and hull-like lodicules. AFD1 encoded a DUF640 domain protein and was ex-pressed in all tested tissues and organs. Subcellular localization showed AFD1-green fluorescent fusion protein (GFP) was localized in the nucleus. Meantime, our results suggested that AFD1 regulated the expression of cell division and expansion related genes.

  1. Absence of Y chromosome in human placental site trophoblastic tumor.

    Science.gov (United States)

    Hui, Pei; Wang, Hanlin L; Chu, Peiguo; Yang, Bin; Huang, Jiaoti; Baergen, Rebecca N; Sklar, Jeffrey; Yang, Ximing J; Soslow, Robert A

    2007-10-01

    Placental site trophoblastic tumor is a neoplasm of extravillous intermediate trophoblast at the implantation site, preceded in the majority of cases by a female gestational event. Our pilot investigation suggested that the development of this tumor might require a paternally derived X chromosome and the absence of a Y chromosome. Twenty cases of placental site trophoblastic tumor were included in this study. Genotyping at 15 polymorphic loci and one sex determination locus was performed by multiplex PCR followed by capillary electrophoresis. X chromosome polymorphisms were determined by PCR amplification of exon 1 of the human androgen receptor gene using primers flanking the polymorphic CAG repeats within this region. Genotyping at 15 polymorphic loci was informative and paternal alleles were present in all tumors, confirming the trophoblastic origin of the tumors. The presence of an X chromosome and the absence of a Y chromosome were observed in all tumors. Among 13 cases in which analysis of the X chromosome polymorphism was informative, all but one demonstrated at least two X alleles and seven cases showed one identifiable paternal X allele. These results confirm a unique pathogenetic mechanism in placental site trophoblastic tumor, involving an exclusion of the Y chromosome from the genome and, therefore, a tumor arising from the trophectoderm of a female conceptus. As epigenetic regulations of imprinting during X chromosome inactivation are of significant biological implications, placental site trophoblastic tumor may provide an important model for studying the sex chromosome biology and the proliferative advantage conferred by the paternal X chromosome.

  2. Meiotic abnormalities

    Energy Technology Data Exchange (ETDEWEB)

    NONE

    1993-12-31

    Chapter 19, describes meiotic abnormalities. These include nondisjunction of autosomes and sex chromosomes, genetic and environmental causes of nondisjunction, misdivision of the centromere, chromosomally abnormal human sperm, male infertility, parental age, and origin of diploid gametes. 57 refs., 2 figs., 1 tab.

  3. Periodic assessment of plasma sFlt-1 and PlGF concentrations and its association with placental morphometry in gestational hypertension (GH - a prospective follow-up study

    Directory of Open Access Journals (Sweden)

    Nalliah Sivalingam

    2010-09-01

    Full Text Available Abstract Background Hypertensive disorders in pregnancy contributes to about 12% of maternal deaths in Malaysia and similarly worldwide. Early detection and adequate management are preventable strategies. Biochemical markers of abnormal angiogenesis would be more specific in early detection than routine blood pressure and proteinuria measurements. The aim of this study was to estimate maternal plasma PlGF and sFlt-1 levels in pregnant women with gestational hypertension at three intervals of pregnancy and correlate these biomarker levels with placental morphometry. Methods Venous blood samples (antepartum, intrapartum and post partum periods were drawn to estimate for sFlt-1 and PlGF levels while placental tissue samples were examined for placental morphometry. Results PlGF levels were lower in gestational hypertension (GH compared to normotensive during antepartum and intrapartum period, whereas sFlt-1 levels were elevated in GH at antepartum, intrapartum and postpartum intervals during pregnancy. An inverse relationship between these two biomarkers was observed through correlation analysis. PlGF levels were inversely correlated with total villous surface area of the placental periphery (TCsa-C and villous capillarization (VC-C of the placental periphery. Conclusion We established periodic values of for sFlt-1 and PlGF levels for the first time in an ethnically diverse Malaysian setting. We suggest the development of GH in women is related to defective capillarization. In demonstrating periodic changes, this study suggest the possibility of developing GH and other long term health complications as a result of prolonged exposure to sFlt-1. The correlation between PlGF levels and morphometric findings also support possible capillarization defect.

  4. 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.

  5. Microparasites and Placental Invasiveness in Eutherian Mammals.

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    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.

  6. Skeletal development and abnormalities of the vertebral column and of the fins in hatchery-reared turbot Scophthalmus maximus.

    Science.gov (United States)

    Tong, X H; Liu, Q H; Xu, S H; Ma, D Y; Xiao, Z Z; Xiao, Y S; Li, J

    2012-03-01

    To describe the skeletal development and abnormalities in turbot Scophthalmus maximus, samples were collected every day from hatching to 60 days after hatching (DAH). A whole-mount cartilage and bone-staining technique was used. Vertebral ontogeny started with the formation of anterior haemal arches at 5·1 mm standard length (L(S) ) c. 11 DAH, and was completed by the full attainment of parapophyses at 16·9 mm L(S) c. 31 DAH. Vertebral centra started to develop at 6·3 mm L(S) c. 16 DAH and ossification in all centra was visible at 11·0 mm L(S) c. 25 DAH. The caudal fin appeared at 5·1 mm L(S) c. 11 DAH and ossification was visible at 20·6 mm L(S) c. 37 DAH. The onset of dorsal and anal fin elements appeared at 5·8 mm L(S) c. 15 DAH and 6·3 mm L(S) c. 16 DAH, respectively. Ossifications of both dorsal fin and anal fin were visible at 20·6 mm L(S) c. 37 DAH. The pectorals were the only fins present before first feeding, their ossifications were completed at 23·5 mm L(S) c. 48 DAH. Pelvic fins began forming at 7·2 mm L(S) c. 19 DAH and calcification of the whole structure was visible at 19·8 mm L(S) c. 36 DAH. In the present study, 24 types of skeletal abnormalities were observed. About 51% of individuals presented skeletal abnormalities, and the highest occurrence was found in the haemal region of the vertebral column. As for each developmental stage, the most common abnormalities were in the dorsal fin during early metamorphic period (stage 2), vertebral fusion during climax metamorphosis (stage 3) and caudal fin abnormality during both late-metamorphic period (stage 4) and post-metamorphic period (stage 5). Such research will be useful for early detection of skeletal malformations during different growth periods of reared S. maximus.

  7. Factors affecting the placental transfer of actinides

    Energy Technology Data Exchange (ETDEWEB)

    Sikov, M.R.; Kelman, B.J. (Pacific Northwest Laboratory, Richland, WA (USA))

    1989-01-01

    The primary goal of this paper is to consider factors that affect the availability and transport of actinides from maternal blood, through the placenta, to the conceptus. These factors, of particular importance in scaling results from animals to man, include the route and temporal pattern of administration, the mass and physicochemical state of material administered, metabolism of the pregnant animal and fetal organs or tissue, and species-specific changes in placental structure relative to stage of gestation at exposure. Preliminary concepts for descriptive and kinetic models are proposed to integrate these results, to identify additional information required for developing more comprehensive models, and to provide a basis for scaling to human pregnancies for purposes of radiation dosimetry.

  8. Placental exosomes in normal and complicated pregnancy.

    Science.gov (United States)

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

    2015-10-01

    data support a role in normal placental development and maternal immunotolerance. Similarly, the role of exosomes in the etiology and progression of complications of pregnancy remains in a formative stage. Changes in the release of placenta- and nonplacenta-derived exosomes, their concentration in maternal plasma, composition, and bioactivity have been reported in association with pregnancies complicated by gestational diabetes and preeclampsia. The data, however, are confounded by the use of different isolation methodologies and vesicle subpopulations. The application of specific and well-characterized isolation methodologies is requisite to resolving the precise role of exosomes in complications of pregnancies and their ultimate clinical utility.

  9. Abnormal P-selectin localization during megakaryocyte development determines thrombosis in the gata1low model of myelofibrosis.

    Science.gov (United States)

    Zetterberg, Eva; Verrucci, Maria; Martelli, Fabrizio; Zingariello, Maria; Sancillo, Laura; D'Amore, Emanuela; Rana, Rosa Alba; Migliaccio, Anna Rita

    2014-01-01

    Patients with primary myelofibrosis have increased risk for bleeding and thrombosis. It is debated whether propensity to thrombosis is due to increased numbers of platelet microparticles and/or to pathological platelet-neutrophil interactions. Platelet neutrophil interactions are mediated by P-selectin and even though the megakaryocytes of myelofibrosis patients express normal levels of P-selectin, it remains abnormally localized to the demarcation membrane system rather than being assembled into the α-granules in platelets. Mice carrying the hypomorphic Gata1(low) mutation express the same megakaryocyte abnormalities presented by primary myelofibrosis patients, including abnormal P-selectin localization to the DMS and develop with age myelofibrosis, a disease that closely resembles human primary myelofibrosis. Whether these mice would also develop thrombosis has not been investigated as yet. The aim of this study was to determine whether Gata1(low) mice would develop thrombosis with age and, in this case, the role played by P-selectin in the development of the trait. To this aim, Gata1(low) mice were crossed with P-sel(null) mice according to standard genetic protocols and Gata1(low)P-sel(wt), Gata1(low)P-sel(null) and Gata1(WT)P-sel(null) or Gata1(wt)P-sel(wt) (as controls) littermates obtained. It was shown that platelet counts, but not hematocrit, are reduced in Gata1(low) mice. Moreover, platelet microparticles are reduced in Gata1(low) mice and P-selectin positive platelet microparticles were not found. To determine the phenotypic implications of the different mutations, bleeding time was estimated by a tail cut procedure. Mutant mice were sacrificed and presence of thrombosis was determined by immunohistological staining of organs. Gata1(low) mice with or without the P-selectin null trait had a prolonged bleeding time compared to wild type mice. However, in Gata1(low) mice significantly higher frequency of thrombotic events was seen in adult and old Gata1

  10. 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.

  11. Using mouse models to understand normal and abnormal urogenital tract development.

    Science.gov (United States)

    Mendelsohn, Cathy

    2009-01-01

    Removal of toxic substances from the blood depends on patent connections between the kidneys, ureters and bladder that are established when the ureter is transposed from its original insertion site in the Wolffian duct, to the bladder, its final insertion site. The Ureteral Bud Theory of Mackie and Stephens suggests that repositioning of the ureter orifice occurs as the trigone forms from the common nephric duct (CND), the caudal-most Wolffian duct segment. According to this model, insertion of the CND into the bladder and its expansion into the trigone both repositions the ureter in the bladder and enables it to separate from the Wolffian duct. The availability of new mouse models has enabled to re-examine this hypothesis using morphological analysis and lineage studies to follow the fate of the ureter and CND during the maturation process. We find that in contrast to what has been previously thought, the CND does not differentiate into the trigone but instead, undergoes apoptosis, a step that enables the ureter to separate from the Wolffian duct. Apoptosis occurs as the CND and ureter merge with the urogenital sinus positioning the ureter orifice at a site close to the Wolffian duct. Finally, expansion of the bladder moves the ureter orifice which is now fused with epithelium to its final position which is at the bladder neck. Interestingly, CND apoptosis appears to depend on close proximity to the bladder, suggesting that the bladder may be a source of signals that induce cell death. Together, these studies provide new insights into the normal process of ureter maturation, and shed light on possible causes of obstruction and reflux, ureteral abnormalities that affect 1-2% of the human population.

  12. Abnormal development of Dentalium due to the Amoco Cadiz oil spill

    NARCIS (Netherlands)

    Koster, A.SJ.; Biggelaar, J.A.M. van den

    1980-01-01

    A comparison was made between the development of Dentalium eggs, spawned by animals, collected before and after the Amoco Cadiz oil spill. Development of eggs from animals collected before the oil spill was significantly better than development of eggs from animals collected after the oil spill. It

  13. Overlap of abnormal photoreceptor development and progressive degeneration in Leber congenital amaurosis caused by NPHP5 mutation.

    Science.gov (United States)

    Downs, Louise M; Scott, Erin M; Cideciyan, Artur V; Iwabe, Simone; Dufour, Valerie; Gardiner, Kristin L; Genini, Sem; Marinho, Luis Felipe; Sumaroka, Alexander; Kosyk, Mychajlo S; Swider, Malgorzata; Aguirre, Geoffrey K; Jacobson, Samuel G; Beltran, William A; Aguirre, Gustavo D

    2016-10-01

    Ciliary defects can result in severe disorders called ciliopathies. Mutations in NPHP5 cause a ciliopathy characterized by severe childhood onset retinal blindness, Leber congenital amaurosis (LCA), and renal disease. Using the canine NPHP5-LCA model we compared human and canine retinal phenotypes, and examined the early stages of photoreceptor development and degeneration, the kinetics of photoreceptor loss, the progression of degeneration and the expression profiles of selected genes. NPHP5-mutant dogs recapitulate the human phenotype of very early loss of rods, and relative retention of the central retinal cone photoreceptors that lack function. In mutant dogs, rod and cone photoreceptors have a sensory cilium, but develop and function abnormally and then rapidly degenerate; L/M cones are more severely affected than S-cones. The lack of outer segments in mutant cones indicates a ciliary dysfunction. Genes expressed in mutant rod or both rod and cone photoreceptors show significant downregulation, while those expressed only in cones are unchanged. Many genes in cell-death and -survival pathways also are downregulated. The canine disease is a non-syndromic LCA-ciliopathy, with normal renal structures and no CNS abnormalities. Our results identify the critical time points in the pathogenesis of the photoreceptor disease, and bring us closer to defining a potential time window for testing novel therapies for translation to patients.

  14. Cerebellar cortex development in the weaver condition presents regional and age-dependent abnormalities without differences in Purkinje cells neurogenesis.

    Science.gov (United States)

    Martí, Joaquín; Santa-Cruz, María C; Hervás, José P; Bayer, Shirley A; Villegas, Sandra

    2016-01-01

    Ataxias are neurological disorders associated with the degeneration of Purkinje cells (PCs). Homozygous weaver mice (wv/wv) have been proposed as a model for hereditary cerebellar ataxia because they present motor abnormalities and PC loss. To ascertain the physiopathology of the weaver condition, the development of the cerebellar cortex lobes was examined at postnatal day (P): P8, P20 and P90. Three approaches were used: 1) quantitative determination of several cerebellar features; 2) qualitative evaluation of the developmental changes occurring in the cortical lobes; and 3) autoradiographic analyses of PC generation and placement. Our results revealed a reduction in the size of the wv/wv cerebellum as a whole, confirming previous results. However, as distinguished from these reports, we observed that quantified parameters contribute differently to the abnormal growth of the wv/wv cerebellar lobes. Qualitative analysis showed anomalies in wv/wv cerebellar cytoarchitecture, depending on the age and lobe analyzed. Such abnormalities included the presence of the external granular layer after P20 and, at P90, ectopic cells located in the molecular layer following several placement patterns. Finally, we obtained autoradiographic evidence that wild-type and wv/wv PCs presented similar neurogenetic timetables, as reported. However, the innovative character of this current work lies in the fact that the neurogenetic gradients of wv/wv PCs were not modified from P8 to P90. A tendency for the accumulation of late-formed PCs in the anterior and posterior lobes was found, whereas early-generated PCs were concentrated in the central and inferior lobes. These data suggested that wv/wv PCs may migrate properly to their final destinations. The extrapolation of our results to patients affected with cerebellar ataxias suggests that all cerebellar cortex lobes are affected with several age-dependent alterations in cytoarchitectonics. We also propose that PC loss may be regionally

  15. 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.

  16. The evolution of epitheliochorial placentation.

    Science.gov (United States)

    Carter, Anthony M; Enders, Allen C

    2013-01-01

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

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

    Science.gov (United States)

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

    2012-10-01

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

  18. Analysis of the Sonic Hedgehog signaling pathway in normal and abnormal bladder development.

    Science.gov (United States)

    DeSouza, Kristin R; Saha, Monalee; Carpenter, Ashley R; Scott, Melissa; McHugh, Kirk M

    2013-01-01

    In this study, we examined the expression of Sonic Hedgehog, Patched, Gli1, Gli2, Gli3 and Myocardin in the developing bladders of male and female normal and megabladder (mgb-/-) mutant mice at embryonic days 12 through 16 by in situ hybridization. This analysis indicated that each member of the Sonic Hedgehog signaling pathway as well as Myocardin displayed distinct temporal and spatial patterns of expression during normal bladder development. In contrast, mgb-/- bladders showed both temporal and spatial changes in the expression of Patched, Gli1 and Gli3 as well as a complete lack of Myocardin expression. These changes occurred primarily in the outer mesenchyme of developing mgb-/- bladders consistent with the development of an amuscular bladder phenotype in these animals. These results provide the first comprehensive analysis of the Sonic Hedgehog signaling pathway during normal bladder development and provide strong evidence that this key signaling cascade is critical in establishing radial patterning in the developing bladder. In addition, the lack of detrusor smooth muscle development observed in mgb-/- mice is associated with bladder-specific temporospatial changes in Sonic Hedgehog signaling coupled with a lack of Myocardin expression that appears to result in altered patterning of the outer mesenchyme and poor initiation and differentiation of smooth muscle cells within this region of the developing bladder.

  19. Steroid abnormalities and the developing brain: declarative memory for emotionally arousing and neutral material in children with congenital adrenal hyperplasia.

    Science.gov (United States)

    Maheu, Françoise S; Merke, Deborah P; Schroth, Elizabeth A; Keil, Margaret F; Hardin, Julie; Poeth, Kaitlin; Pine, Daniel S; Ernst, Monique

    2008-02-01

    Steroid hormones modulate memory in animals and human adults. Little is known on the developmental effects of these hormones on the neural networks underlying memory. Using Congenital adrenal hyperplasia (CAH) as a naturalistic model of early steroid abnormalities, this study examines the consequences of CAH on memory and its neural correlates for emotionally arousing and neutral material in children. Seventeen patients with CAH and 17 age- and sex-matched healthy children (ages 12-14 years) completed the study. Subjects were presented positive, negative and neutral pictures. Memory recall occurred about 30min after viewing the pictures. Children with CAH showed memory deficits for negative pictures compared to healthy children (p0.1). In patients, 24h urinary-free cortisol levels (reflecting glucocorticoid replacement therapy) and testosterone levels were not associated with memory performance. These findings suggest that early steroid imbalances affect memory for negative material in children with CAH. Such memory impairments may result from abnormal brain organization and function following hormonal dysfunction during critical periods of development.

  20. Hyperemesis gravidarum and placental dysfunction disorders

    NARCIS (Netherlands)

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

    2016-01-01

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

  1. Leukocyte abnormalities.

    Science.gov (United States)

    Gabig, T G

    1980-07-01

    Certain qualitative abnormalities in neutrophils and blood monocytes are associated with frequent, severe, and recurrent bacterial infections leading to fatal sepsis, while other qualitative defects demonstrated in vitro may have few or no clinical sequelae. These qualitative defects are discussed in terms of the specific functions of locomotion, phagocytosis, degranulation, and bacterial killing.

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

    Science.gov (United States)

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

    2013-06-01

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

  3. Transferência placentária de drogas Placental drug transfer

    Directory of Open Access Journals (Sweden)

    Ricardo de Carvalho Cavalli

    2006-09-01

    fixa de 0,10 mg, apresenta alta taxa de transferência placentária, da ordem de 90%, o que vem alertar para cautela no uso de doses repetidas em analgesia durante o trabalho de parto.Pregnant women may depend on the use of medications to minimize the problems caused by preexisting disease, and pregnancy itself can cause situations that compromise the maternal well-being and that require treatment. The obstetrician should be aware of the placental transfer of drugs and of fetal exposure to teratogenic or toxic agents that might compromise the development of the fetus or even its future life.Transport through the placenta involves the movement of molecules between three compartments: maternal blood, cytoplasm of the syncytiotrophoblast, and fetal blood. This movement can occur through the following mechanisms: simple diffusion, facilitated diffusion, active transport, class P, V, F and large ABC family pumps, and endocytosis. With the use of anticonvulsants the incidence of major malformations in exposed newborns is 4 to 6%, compared to 2 to 4% in the general population. Multidrug treatment is more damaging, especially when valproic acid and hydantoin are part of the combination. The recommendation for epileptic patients who have been clinically asymptomatic for two years is to discontinue the drugs they are taking. However, if seizures occur it is advisable to consult a neurologist to discuss anticonvulsant therapy with better benefits and less side effects.Local anesthetics and opioids are extensively used during the resolution of pregnancy. Lidocaine applied by the perineal route for episiotomy at a fixed dose of 400 mg presents a high concentration in maternal plasma and a high rate of placental transfer at the time of birth, with the need for caution regarding the use of repeated doses. Bupivacaine administered by the epidural route is a safe anesthetic which is present in the racemic form and has a placental transfer of about 30%. Fentanyl, an opioid anesthetic

  4. Radioimmunoassay of human placental protein 14 (PP14)

    Energy Technology Data Exchange (ETDEWEB)

    Bolton, A.E.; Stoker, R.J. (North East London Polytechnic (UK)); Chapman, M.G.; Wass, D. (Queen Charlotte' s Maternity Hospital, London (UK)); Andrew, C.E. (Edgware General Hospital (UK)); Bohn, H. (Behringwerke AG, Marburg/Lahn (Germany, F.R.). Research Labs.)

    1983-12-30

    The development and validation of a radioimmunoassay for the measurement of human placental protein 14 in maternal serum is described. The mean concentration of this protein in serum from 22 normal pregnant women showed a decline during the third trimester from 120 ..mu..g/l at 27 weeks gestation to 65 ..mu..g/l at term. Serum samples from 16 patients with intra-uterine growth retardation tended to contain lower concentrations of placental protein 14, these results reaching significance at weeks 36-38 of gestation. Of seven patients with pre-eclampsia from whom two or more blood samples were taken, four showed increases in concentration of this protein as pregnancy proceeded, compared with the normal pattern of decreasing values.

  5. Prediction of fetal acidemia in placental abruption

    OpenAIRE

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

    2013-01-01

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

  6. Abnormal development of sensory-motor, visual temporal and parahippocampal cortex in children with learning disabilities and borderline intellectual functioning

    Directory of Open Access Journals (Sweden)

    Francesca eBaglio

    2014-10-01

    Full Text Available Borderline intellectual functioning (BIF is a condition characterized by an intelligence quotient (IQ between 70 and 85. BIF children present with cognitive, motor, social and adaptive limitations that result in learning disabilities and are more likely to develop psychiatric disorders later in life. Aim of this study was to investigate brain morphometry and its relation to IQ level in borderline intellectual functioning children.Thirteen children with BIF and 14 age- and sex-matched typically developing children were enrolled. All children underwent a full IQ assessment (WISC-III scale and a Magnetic Resonance (MR examination including conventional sequences to assess brain structural abnormalities and high resolution 3D images for voxel based morphometry (VBM analysis. To investigate to what extent the group influenced gray matter volumes, both univariate and multivariate generalized linear model analysis of variance were used, and the varimax factor analysis was used to explore variable correlations and clusters among subjects. Results showed that BIF children, compared to controls have increased regional gray matter volume in bilateral sensori-motor and right posterior temporal cortices and decreased gray matter volume in right parahippocampal gyrus. Gray matter volumes were highly correlated with IQ indices.Our is a case study of a group of BIF children showing that BIF is associated with abnormal cortical development in brain areas that have a pivotal role in motor, learning and behavioral processes. Our findings, although allowing for little generalization to general population, contributes to the very limited knowledge in this field. Future longitudinal MR studies will be useful in verifying whether cortical features can be modified over time even in association with rehabilitative intervention.

  7. Abnormal development of sensory-motor, visual temporal and parahippocampal cortex in children with learning disabilities and borderline intellectual functioning.

    Science.gov (United States)

    Baglio, Francesca; Cabinio, Monia; Ricci, Cristian; Baglio, Gisella; Lipari, Susanna; Griffanti, Ludovica; Preti, Maria G; Nemni, Raffaello; Clerici, Mario; Zanette, Michela; Blasi, Valeria

    2014-01-01

    Borderline intellectual functioning (BIF) is a condition characterized by an intelligence quotient (IQ) between 70 and 85. BIF children present with cognitive, motor, social, and adaptive limitations that result in learning disabilities and are more likely to develop psychiatric disorders later in life. The aim of this study was to investigate brain morphometry and its relation to IQ level in BIF children. Thirteen children with BIF and 14 age- and sex-matched typically developing (TD) children were enrolled. All children underwent a full IQ assessment (WISC-III scale) and a magnetic resonance (MR) examination including conventional sequences to assess brain structural abnormalities and high resolution 3D images for voxel-based morphometry analysis. To investigate to what extent the group influenced gray matter (GM) volumes, both univariate and multivariate generalized linear model analysis of variance were used, and the varimax factor analysis was used to explore variable correlations and clusters among subjects. Results showed that BIF children, compared to controls have increased regional GM volume in bilateral sensorimotor and right posterior temporal cortices and decreased GM volume in the right parahippocampal gyrus. GM volumes were highly correlated with IQ indices. The present work is a case study of a group of BIF children showing that BIF is associated with abnormal cortical development in brain areas that have a pivotal role in motor, learning, and behavioral processes. Our findings, although allowing for little generalization to the general population, contribute to the very limited knowledge in this field. Future longitudinal MR studies will be useful in verifying whether cortical features can be modified over time even in association with rehabilitative intervention.

  8. 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.

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

    OpenAIRE

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

    2014-01-01

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

  10. A microphysiological model of the human placental barrier.

    Science.gov (United States)

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

    2016-08-02

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

  11. Overexpression of the CmACS-3 gene in melon causes abnormal pollen development.

    Science.gov (United States)

    Zhang, H; Luan, F

    2015-01-01

    Sexual diversity expressed by the Curcurbitaceae family is a primary example of developmental plasticity in plants. Most melon genotypes are andromonoecious, where an initial phase of male flowers is followed by a mixture of bisexual and male flowers. Over-expression of the CmACS-3 gene in melon plants showed an increased number of flower buds, and increased femaleness as demonstrated by a larger number bisexual buds. Transformation of CmACS-3 in melons showed earlier development of and an increased number of bisexual buds that matured to anthesis but also increased the rate of development of the bisexual buds to maturity. Field studies showed that CmACS-3-overexpressing melons had earlier mature bisexual flowers, earlier fruit set, and an increased number of fruits set on closely spaced nodes on the main stem.

  12. Anesthesia for Children With Craniofacial Abnormalities in the Developing Countries: Challenges and Future Directions.

    Science.gov (United States)

    Melookaran, Ann M; Rao, Sirisha A; Antony, Sible B; Herrera, Adriana

    2015-06-01

    Interest in global health to provide safer pediatric surgical care in developing countries has increased during the last decade. A collaborative effort between surgeons and anesthesiologists has provided the opportunity to deliver specialized care to children, particularly in the areas of cleft lip and palate repair. However, medical resources, facilities, and adequately trained personnel, especially in pediatric anesthesia, are often limited in these countries. Challenges, educational efforts, and future directions for the globalization of anesthesia are discussed. Involvement of international entities may help raise awareness, channel efforts, expand programs and encourage volunteerism to ultimately provide safer care to pediatric patients, have better outcomes and reduced anesthesia-related morbidity and mortality.

  13. Functional validation of GWAS gene candidates for abnormal liver function during zebrafish liver development

    Directory of Open Access Journals (Sweden)

    Leah Y. Liu

    2013-09-01

    Genome-wide association studies (GWAS have revealed numerous associations between many phenotypes and gene candidates. Frequently, however, further elucidation of gene function has not been achieved. A recent GWAS identified 69 candidate genes associated with elevated liver enzyme concentrations, which are clinical markers of liver disease. To investigate the role of these genes in liver homeostasis, we narrowed down this list to 12 genes based on zebrafish orthology, zebrafish liver expression and disease correlation. To assess the function of gene candidates during liver development, we assayed hepatic progenitors at 48 hours post fertilization (hpf and hepatocytes at 72 hpf using in situ hybridization following morpholino knockdown in zebrafish embryos. Knockdown of three genes (pnpla3, pklr and mapk10 decreased expression of hepatic progenitor cells, whereas knockdown of eight genes (pnpla3, cpn1, trib1, fads2, slc2a2, pklr, mapk10 and samm50 decreased cell-specific hepatocyte expression. We then induced liver injury in zebrafish embryos using acetaminophen exposure and observed changes in liver toxicity incidence in morphants. Prioritization of GWAS candidates and morpholino knockdown expedites the study of newly identified genes impacting liver development and represents a feasible method for initial assessment of candidate genes to instruct further mechanistic analyses. Our analysis can be extended to GWAS for additional disease-associated phenotypes.

  14. Continuous exposure to bisphenol A during in vitro follicular development induces meiotic abnormalities.

    Science.gov (United States)

    Lenie, Sandy; Cortvrindt, Rita; Eichenlaub-Ritter, Ursula; Smitz, Johan

    2008-03-12

    Bisphenol A (BPA), a widely used environmental contaminant, may exert weak estrogenic, anti-androgenic and anti-thyroidic activities. BPA is suspected to possess aneugenic properties that may affect somatic cells and mammalian oocytes. Oocyte growth and maturation depend upon a complex bi-directional signaling between the oocyte and its companion somatic cells. Consequently, disturbances in oocyte maturation may originate either from direct effects of BPA at the level of the oocyte or from indirect influences at the follicular level, such as alterations in hormonal homeostasis. This study aimed to analyze the effects of chronic BPA exposure (3 nM to 30 microM) on follicle-enclosed growth and maturation of mouse oocytes in vitro. Oocytes were cultured and their spindle and chromosomes were stained by alpha-tubulin immunofluorescence and ethidium homodimer-2, respectively. Confocal microscopy was utilized for subsequent analysis. Only follicles that were exposed to 30 microM BPA during follicular development showed a slightly reduced granulosa cell proliferation and a lower total estrogen production, but they still developed and formed antral-like cavities. However, 18% of oocytes were unable to resume meiosis after stimulation of oocyte maturation, and 37% arrested after germinal vesicle breakdown, significantly different from controls (pabnormal telophase I. Additionally, in many oocytes exposed to low chronic BPA that matured to meiosis II chromosomes failed to congress at the spindle equator. In conclusion, mouse follicle culture reveals non-linear dose-dependent effects of BPA on the meiotic spindle in mouse oocytes when exposure was chronic throughout oocyte growth and maturation.

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

    NARCIS (Netherlands)

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

    2013-01-01

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

  16. Roles of retinoic acid signaling in normal and abnormal development of the palate and tongue.

    Science.gov (United States)

    Okano, Junko; Udagawa, Jun; Shiota, Kohei

    2014-05-01

    Palatogenesis involves various developmental events such as growth, elevation, elongation and fusion of opposing palatal shelves. Extrinsic factors such as mouth opening and subsequent tongue withdrawal are also needed for the horizontal elevation of palate shelves. Failure of any of these steps can lead to cleft palate, one of the most common birth defects in humans. It has been shown that retinoic acid (RA) plays important roles during palate development, but excess RA causes cleft palate in fetuses of both rodents and humans. Thus, the coordinated regulation of retinoid metabolism is essential for normal palatogenesis. The endogenous RA level is determined by the balance of RA-synthesizing (retinaldehyde dehydrogenases: RALDHs) and RA-degrading enzymes (CYP26s). Cyp26b1 is a key player in normal palatogenesis. In this review, we discuss recent progress in the study of the pathogenesis of RA-induced cleft palate, with special reference to the regulation of endogenous RA levels by RA-degrading enzymes.

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

    Science.gov (United States)

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

    2016-05-05

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

  18. Is pancreas development abnormal in the non-obese diabetic mouse, a spontaneous model of type I diabetes?

    Directory of Open Access Journals (Sweden)

    F. Homo-Delarche

    2001-04-01

    Full Text Available Despite extensive genetic and immunological research, the complex etiology and pathogenesis of type I diabetes remains unresolved. During the last few years, our attention has been focused on factors such as abnormalities of islet function and/or microenvironment, that could interact with immune partners in the spontaneous model of the disease, the non-obese diabetic (NOD mouse. Intriguingly, the first anomalies that we noted in NOD mice, compared to control strains, are already present at birth and consist of 1 higher numbers of paradoxically hyperactive ß cells, assessed by in situ preproinsulin II expression; 2 high percentages of immature islets, representing islet neogenesis related to neonatal ß-cell hyperactivity and suggestive of in utero ß-cell stimulation; 3 elevated levels of some types of antigen-presenting cells and FasL+ cells, and 4 abnormalities of extracellular matrix (ECM protein expression. However, the colocalization in all control mouse strains studied of fibroblast-like cells (anti-TR-7 labeling, some ECM proteins (particularly, fibronectin and collagen I, antigen-presenting cells and a few FasL+ cells at the periphery of islets undergoing neogenesis suggests that remodeling phenomena that normally take place during postnatal pancreas development could be disturbed in NOD mice. These data show that from birth onwards there is an intricate relationship between endocrine and immune events in the NOD mouse. They also suggest that tissue-specific autoimmune reactions could arise from developmental phenomena taking place during fetal life in which ECM-immune cell interaction(s may play a key role.

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

    DEFF Research Database (Denmark)

    Mathiesen, Line

    2011-01-01

    To maintain a healthy pregnancy, the exchange of substances between mother and fetus is vital. All transport of these substances takes place through the placenta, which is a temporary organ that serves its purpose from the implantation of the blastula to the birth of the term fetus, supplying...... nutrients, gas and waste transport between the maternal blood and the developing fetus and maintaining pregnancy by producing hormones. The placenta consists of cells of both maternal and fetal origin and forms a complex barrier between the maternal and fetal blood that allows for passage of different...... within two hours of perfusion with a fetal flow rate of 3 mL/min. Negative controls are added to ensure that substance transfer is not due to leakage, e.g. high molecular weight substances that only pass the placental barrier with bulk flow through a leakage in the fetal system. Dextran (40kD) can...

  20. Cardiac defects, nuchal edema and abnormal lymphatic development are not associated with morphological changes in the ductus venosus

    NARCIS (Netherlands)

    Burger, Nicole B.; Haak, Monique C.; Kok, Evelien; de Groot, Christianne J M; Shou, Weinian; Scambler, Peter J.; Lee, Youngsook; Cho, Eunjin; Christoffels, Vincent M.; Bekker, Mireille N.

    2016-01-01

    Background In human fetuses with cardiac defects and increased nuchal translucency, abnormal ductus venosus flow velocity waveforms are observed. It is unknown whether abnormal ductus venosus flow velocity waveforms in fetuses with increased nuchal translucency are a reflection of altered cardiac fu

  1. 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.

  2. Mice with Tak1 deficiency in neural crest lineage exhibit cleft palate associated with abnormal tongue development.

    Science.gov (United States)

    Song, Zhongchen; Liu, Chao; Iwata, Junichi; Gu, Shuping; Suzuki, Akiko; Sun, Cheng; He, Wei; Shu, Rong; Li, Lu; Chai, Yang; Chen, YiPing

    2013-04-12

    Cleft palate represents one of the most common congenital birth defects in humans. TGFβ signaling, which is mediated by Smad-dependent and Smad-independent pathways, plays a crucial role in regulating craniofacial development and patterning, particularly in palate development. However, it remains largely unknown whether the Smad-independent pathway contributes to TGFβ signaling function during palatogenesis. In this study, we investigated the function of TGFβ activated kinase 1 (Tak1), a key regulator of Smad-independent TGFβ signaling in palate development. We show that Tak1 protein is expressed in both the epithelium and mesenchyme of the developing palatal shelves. Whereas deletion of Tak1 in the palatal epithelium or mesenchyme did not give rise to a cleft palate defect, inactivation of Tak1 in the neural crest lineage using the Wnt1-Cre transgenic allele resulted in failed palate elevation and subsequently the cleft palate formation. The failure in palate elevation in Wnt1-Cre;Tak1(F/F) mice results from a malformed tongue and micrognathia, resembling human Pierre Robin sequence cleft of the secondary palate. We found that the abnormal tongue development is associated with Fgf10 overexpression in the neural crest-derived tongue tissue. The failed palate elevation and cleft palate were recapitulated in an Fgf10-overexpressing mouse model. The repressive effect of the Tak1-mediated noncanonical TGFβ signaling on Fgf10 expression was further confirmed by inhibition of p38, a downstream kinase of Tak1, in the primary cell culture of developing tongue. Tak1 thus functions to regulate tongue development by controlling Fgf10 expression and could represent a candidate gene for mutation in human PRS clefting.

  3. Silencing abnormal wing disc gene of the Asian citrus psyllid, Diaphorina citri disrupts adult wing development and increases nymph mortality.

    Directory of Open Access Journals (Sweden)

    Ibrahim El-Shesheny

    Full Text Available Huanglongbing (HLB causes considerable economic losses to citrus industries worldwide. Its management depends on controlling of the Asian citrus Psyllid (ACP, the vector of the bacterium, Candidatus Liberibacter asiaticus (CLas, the causal agent of HLB. Silencing genes by RNA interference (RNAi is a promising tool to explore gene functions as well as control pests. In the current study, abnormal wing disc (awd gene associated with wing development in insects is used to interfere with the flight of psyllids. Our study showed that transcription of awd is development-dependent and the highest level was found in the last instar (5(th of the nymphal stage. Micro-application (topical application of dsRNA to 5(th instar of nymphs caused significant nymphal mortality and adult wing-malformation. These adverse effects in ACP were positively correlated with the amounts of dsRNA used. A qRT-PCR analysis confirmed the dsRNA-mediated transcriptional down-regulation of the awd gene. Significant down-regulation was required to induce a wing-malformed phenotype. No effect was found when dsRNA-gfp was used, indicating the specific effect of dsRNA-awd. Our findings suggest a role for awd in ACP wing development and metamorphosis. awd could serve as a potential target for insect management either via direct application of dsRNA or by producing transgenic plants expressing dsRNA-awd. These strategies will help to mitigate HLB by controlling ACP.

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

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    Dora Baczyk

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

  5. 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 < .01). 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.

  6. Placental pathology and neonatal brain injury%胎盘病理与新生儿脑损伤

    Institute of Scientific and Technical Information of China (English)

    柯华; 李占魁

    2016-01-01

    异常的胎盘主要包括胎盘功能不全、胎盘感染、胎粪污染、胎盘种植异常以及双胎胎盘血管吻合等,这些异常的胎盘病理可导致胎儿、新生儿缺氧缺血或早产,从而引起新生儿脑损伤.%Placental pathologies include placental insufficiency,infection,meconium stained,abnormal planting and placental vascular anastomosis,et al.All those can lead to fetal and neonatal hypoxia ischemia or premature birth,which can cause brain damage.

  7. Electron beam irradiation induces abnormal development and the stabilization of p53 protein of American serpentine leafminer, Liriomyza trifolii (Burgess)

    Energy Technology Data Exchange (ETDEWEB)

    Koo, Hyun-Na; Yun, Seung-Hwan; Yoon, Changmann [Department of Plant Medicine, College of Agriculture, Life and Environment Sciences, Chungbuk National University, Cheongju 361-763 (Korea, Republic of); Kim, Gil-Hah, E-mail: khkim@chungbuk.ac.kr [Department of Plant Medicine, College of Agriculture, Life and Environment Sciences, Chungbuk National University, Cheongju 361-763 (Korea, Republic of)

    2012-01-15

    The American serpentine leafminer fly, Liriomyza trifolii (Burgess), is one of the most destructive polyphagous pests worldwide. In this study, we determined electron beam doses for inhibition of normal development of the leaf miner and investigated the effect of electron beam irradiation on DNA damage and p53 stability. Eggs (0-24 h old), larvae (2nd instar), puparia (0-24 h old after pupariation) and adults (24 h after emergence) were irradiated with increasing doses of electron beam irradiation (six levels between 30 and 200 Gy). At 150 Gy, the number of adults that developed from irradiated eggs, larvae and puparia was lower than in the untreated control. Fecundity and egg hatchability decreased depending on the doses applied. Reciprocal crosses between irradiated and unirradiated flies demonstrated that males were more radiotolerant than females. Adult longevity was not affected in all stages. The levels of DNA damage in L. trifolii adults were evaluated using the alkaline comet assay. Our results indicate that electron beam irradiation increased levels of DNA damage in a dose-dependent manner. Moreover, low doses of electron beam irradiation led to the rapid appearance of p53 protein within 6 h; however, it decreased after exposure to high doses (150 Gy and 200 Gy). These results suggest that electron beam irradiation induced not only abnormal development and reproduction but also p53 stability caused by DNA damage in L. trifolii. We conclude that a minimum dose of 150 Gy should be sufficient for female sterilization of L. trifolii. - Highlights: > Electron beam irradiation inhibited normal development of the leaf miner. > Electron beam irradiation inhibited normal reproduction of the leaf miner. > Electron beam irradiation increased levels of DNA damage. > Electron beam irradiation induced p53 stability.

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

    Science.gov (United States)

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

    2015-01-01

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

  9. Confined placental mosaicism in short term culture

    Directory of Open Access Journals (Sweden)

    Petrović Bojana

    2016-01-01

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

  10. Absence of PTHrP nuclear localization and carboxyl terminus sequences leads to abnormal brain development and function.

    Directory of Open Access Journals (Sweden)

    Zhen Gu

    Full Text Available We assessed whether the nuclear localization sequences (NLS and C terminus of parathyroid hormone-related protein (PTHrP play critical roles in brain development and function. We used histology, immunohistochemistry, histomorphometry, Western blots and electrophysiological recordings to compare the proliferation and differentiation of neural stem cells, neuronal hippocampal synaptic transmission, and brain phenotypes including shape and structures, in Pthrp knock-in mice, which express PTHrP (1-84, a truncated form of the protein that is missing the NLS and the C-terminal region of the protein, and their wild-type littermates. Results showed that Pthrp knock-in mice display abnormal brain shape and structures; decreased neural cell proliferative capacity and increased apoptosis associated with up-regulation of cyclin dependent kinase inhibitors p16, p21, p27 and p53 and down-regulation of the Bmi-1 oncogene; delayed neural cell differentiation; and impaired hippocampal synaptic transmission and plasticity. These findings provide in vivo experimental evidence that the NLS and C-terminus of PTHrP are essential not only for the regulation of neural cell proliferation and differentiation, but also for the maintenance of normal neuronal synaptic transmission and plasticity.

  11. Morphological abnormalities, impaired fetal development and decrease in myostatin expression following somatic cell nuclear transfer in dogs.

    Science.gov (United States)

    Hong, Il-Hwa; Jeong, Yeon-Woo; Shin, Taeyoung; Hyun, Sang-Hwan; Park, Jin-Kyu; Ki, Mi-Ran; Han, Seon-Young; Park, Se-Il; Lee, Ji-Hyun; Lee, Eun-Mi; Kim, Ah-Young; You, Sang-Young; Hwang, Woo-Suk; Jeong, Kyu-Shik

    2011-05-01

    Several mammals, including dogs, have been successfully cloned using somatic cell nuclear transfer (SCNT), but the efficiency of generating normal, live offspring is relatively low. Although the high failure rate has been attributed to incomplete reprogramming of the somatic nuclei during the cloning process, the exact cause is not fully known. To elucidate the cause of death in cloned offspring, 12 deceased offspring cloned by SCNT were necropsied. The clones were either stillborn just prior to delivery or died with dyspnea shortly after birth. On gross examination, defects in the anterior abdominal wall and increased heart and liver sizes were found. Notably, a significant increase in muscle mass and macroglossia lesions were observed in deceased SCNT-cloned dogs. Interestingly, the expression of myostatin, a negative regulator of muscle growth during embryogenesis, was down-regulated at the mRNA level in tongues and skeletal muscles of SCNT-cloned dogs compared with a normal dog. Results of the present study suggest that decreased expression of myostatin in SCNT-cloned dogs may be involved in morphological abnormalities such as increased muscle mass and macroglossia, which may contribute to impaired fetal development and poor survival rates.

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

    Science.gov (United States)

    Stewart, James R; Thompson, Michael B

    2009-04-01

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

  13. An Autopsied Case of Malignant Sarcomatoid Pleural Mesothelioma in Which Chest Pain Developed Several Months Earlier without Abnormality on Imaging.

    Science.gov (United States)

    Yaguchi, Daizo; Ichikawa, Motoshi; Inoue, Noriko; Kobayashi, Daisuke; Matsuura, Akinobu; Shizu, Masato; Imai, Naoyuki; Watanabe, Kazuko

    2015-01-01

    The patient experienced chest pain for about 7 months, but a diagnosis could not be made until after death. He was diagnosed with malignant sarcomatoid pleural mesothelioma on autopsy. In this case report, difficult aspects of the diagnosis are discussed. The 70-year-old Japanese man was a driver who transported ceramic-related products. Right chest pain developed in July 2013, but no abnormality was detected on a chest computed tomography (CT) performed in September 2013, and the pain was managed as right intercostal neuralgia. A chest CT performed in late October 2013 revealed a right pleural effusion, and the patient was referred to our hospital in early November 2013. Thoracentesis was performed, but the cytology was negative, and no diagnosis could be made. Close examination was postponed because the patient developed a subarachnoid hemorrhage. He underwent (18)F-fluorodeoxyglucose positron emission tomography ((18)F-FDG PET) after discharge from the neurosurgery department, and extensive right pleural thickening and (18)F-FDG accumulation in this region were observed. Based on these findings, malignant pleural mesothelioma was suspected, and a thoracoscopy was performed under local anesthesia in early December 2013, but no definite diagnosis could be made. The patient selected best supportive care and died about 7 months after the initial development of right chest pain. The disease was definitively diagnosed as malignant sarcomatoid pleural mesothelioma by a pathological autopsy. When chronic chest pain of unknown cause is observed and past exposure to asbestos is suspected, actions to prevent delay in diagnosis should be taken, including testing for suspicion of malignant pleural mesothelioma.

  14. An Autopsied Case of Malignant Sarcomatoid Pleural Mesothelioma in Which Chest Pain Developed Several Months Earlier without Abnormality on Imaging

    Directory of Open Access Journals (Sweden)

    Daizo Yaguchi

    2015-10-01

    Full Text Available The patient experienced chest pain for about 7 months, but a diagnosis could not be made until after death. He was diagnosed with malignant sarcomatoid pleural mesothelioma on autopsy. In this case report, difficult aspects of the diagnosis are discussed. The 70-year-old Japanese man was a driver who transported ceramic-related products. Right chest pain developed in July 2013, but no abnormality was detected on a chest computed tomography (CT performed in September 2013, and the pain was managed as right intercostal neuralgia. A chest CT performed in late October 2013 revealed a right pleural effusion, and the patient was referred to our hospital in early November 2013. Thoracentesis was performed, but the cytology was negative, and no diagnosis could be made. Close examination was postponed because the patient developed a subarachnoid hemorrhage. He underwent 18F-fluorodeoxyglucose positron emission tomography (18F-FDG PET after discharge from the neurosurgery department, and extensive right pleural thickening and 18F-FDG accumulation in this region were observed. Based on these findings, malignant pleural mesothelioma was suspected, and a thoracoscopy was performed under local anesthesia in early December 2013, but no definite diagnosis could be made. The patient selected best supportive care and died about 7 months after the initial development of right chest pain. The disease was definitively diagnosed as malignant sarcomatoid pleural mesothelioma by a pathological autopsy. When chronic chest pain of unknown cause is observed and past exposure to asbestos is suspected, actions to prevent delay in diagnosis should be taken, including testing for suspicion of malignant pleural mesothelioma.

  15. Structure-based modelling in reproductive toxicology: (Q)SARs for the placental barrier.

    Science.gov (United States)

    Hewitt, M; Madden, J C; Rowe, P H; Cronin, M T D

    2007-01-01

    The replacement of animal testing for endpoints such as reproductive toxicity is a long-term goal. This study describes the possibilities of using simple (quantitative) structure-activity relationships ((Q)SARs) to predict whether a molecule may cross the placental membrane. The concept is straightforward, if a molecule is not able to cross the placental barrier, then it will not be a reproductive toxicant. Such a model could be placed at the start of any integrated testing strategy. To develop these models the literature was reviewed to obtain data relating to the transfer of molecules across the placenta. A reasonable number of data were obtained and are suitable for the modelling of the ability of a molecule to cross the placenta. Clearance or transfer indices data were sought due to their ability to eliminate inter-placental variation by standardising drug clearance to the reference compound antipyrine. Modelling of the permeability data indicates that (Q)SARs with reasonable statistical fit can be developed for the ability of molecules to cross the placental barrier membrane. Analysis of the models indicates that molecular size, hydrophobicity and hydrogen-bonding ability are molecular properties that may govern the ability of a molecule to cross the placental barrier.

  16. Quality assessment of a placental perfusion protocol

    DEFF Research Database (Denmark)

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

    2010-01-01

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

  17. 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.

  18. The trajectory of gray matter development in Broca’s area is abnormal in people who stutter.

    Directory of Open Access Journals (Sweden)

    Deryk Scott Beal

    2015-03-01

    Full Text Available The acquisition and mastery of speech-motor control requires years of practice spanning the course of development. People who stutter often perform poorly on speech-motor tasks thereby calling into question their ability to establish the stable neural motor programs required for masterful speech-motor control. There is evidence to support the assertion that these neural motor programs are represented in the posterior part of Broca’s area, specifically the left pars opercularis. Consequently, various theories of stuttering causation posit that the disorder is related to a breakdown in the formation of the neural motor programs for speech early in development and that this breakdown is maintained throughout life. To date, no study has examined the potential neurodevelopmental signatures of the disorder across pediatric and adult populations. The current study aimed to fill this gap in our knowledge. We hypothesized that the developmental trajectory of cortical thickness in people who stutter would differ across the lifespan in the left pars opercularis relative to a group of control participants. We collected structural magnetic resonance images from 116 males (55 people who stutter ranging in age from 6 to 48 years old. Differences in cortical thickness across ages and between patients and controls were investigated in 30 brain regions previously implicated in speech-motor control. An interaction between age and group was found for the left pars opercularis only. In people who stutter, the pars opercularis did not demonstrate the typical maturational pattern of gradual gray matter thinning with age across the lifespan that we observed in control participants. In contrast, the developmental trajectory of gray matter thickness in other regions of interest within the neural network for speech-motor control was similar for both groups. Our findings indicate that the developmental trajectory of gray matter in left pars opercularis is abnormal in

  19. Epiphyseal abnormalities, trabecular bone loss and articular chondrocyte hypertrophy develop in the long bones of postnatal Ext1-deficient mice.

    Science.gov (United States)

    Sgariglia, Federica; Candela, Maria Elena; Huegel, Julianne; Jacenko, Olena; Koyama, Eiki; Yamaguchi, Yu; Pacifici, Maurizio; Enomoto-Iwamoto, Motomi

    2013-11-01

    Long bones are integral components of the limb skeleton. Recent studies have indicated that embryonic long bone development is altered by mutations in Ext genes and consequent heparan sulfate (HS) deficiency, possibly due to changes in activity and distribution of HS-binding/growth plate-associated signaling proteins. Here we asked whether Ext function is continuously required after birth to sustain growth plate function and long bone growth and organization. Compound transgenic Ext1(f/f);Col2CreERT mice were injected with tamoxifen at postnatal day 5 (P5) to ablate Ext1 in cartilage and monitored over time. The Ext1-deficient mice exhibited growth retardation already by 2weeks post-injection, as did their long bones. Mutant growth plates displayed a severe disorganization of chondrocyte columnar organization, a shortened hypertrophic zone with low expression of collagen X and MMP-13, and reduced primary spongiosa accompanied, however, by increased numbers of TRAP-positive osteoclasts at the chondro-osseous border. The mutant epiphyses were abnormal as well. Formation of a secondary ossification center was significantly delayed but interestingly, hypertrophic-like chondrocytes emerged within articular cartilage, similar to those often seen in osteoarthritic joints. Indeed, the cells displayed a large size and round shape, expressed collagen X and MMP-13 and were surrounded by an abundant Perlecan-rich pericellular matrix not seen in control articular chondrocytes. In addition, ectopic cartilaginous outgrowths developed on the lateral side of mutant growth plates over time that resembled exostotic characteristic of children with Hereditary Multiple Exostoses, a syndrome caused by Ext mutations and HS deficiency. In sum, the data do show that Ext1 is continuously required for postnatal growth and organization of long bones as well as their adjacent joints. Ext1 deficiency elicits defects that can occur in human skeletal conditions including trabecular bone loss

  20. The Relationship between Personality Dimensions and Resiliency to Environmental Stress in Orange-Winged Amazon Parrots (Amazona amazonica), as Indicated by the Development of Abnormal Behaviors.

    Science.gov (United States)

    Cussen, Victoria A; Mench, Joy A

    2015-01-01

    Parrots are popular companion animals, but are frequently relinquished because of behavioral problems, including abnormal repetitive behaviors like feather damaging behavior and stereotypy. In addition to contributing to pet relinquishment, these behaviors are important as potential indicators of diminished psychological well-being. While abnormal behaviors are common in captive animals, their presence and/or severity varies between animals of the same species that are experiencing the same environmental conditions. Personality differences could contribute to this observed individual variation, as they are known risk factors for stress sensitivity and affective disorders in humans. The goal of this study was to assess the relationship between personality and the development and severity of abnormal behaviors in captive-bred orange-winged Amazon parrots (Amazona amazonica). We monitored between-individual behavioral differences in enrichment-reared parrots of known personality types before, during, and after enrichment deprivation. We predicted that parrots with higher scores for neurotic-like personality traits would be more susceptible to enrichment deprivation and develop more abnormal behaviors. Our results partially supported this hypothesis, but also showed that distinct personality dimensions were related to different forms of abnormal behavior. While neuroticism-like traits were linked to feather damaging behavior, extraversion-like traits were negatively related to stereotypic behavior. More extraverted birds showed resiliency to environmental stress, developing fewer stereotypies during enrichment deprivation and showing lower levels of these behaviors following re-enrichment. Our data, together with the results of the few studies conducted on other species, suggest that, as in humans, certain personality types render individual animals more susceptible or resilient to environmental stress. Further, this susceptibility/resiliency can have a long

  1. The Relationship between Personality Dimensions and Resiliency to Environmental Stress in Orange-Winged Amazon Parrots (Amazona amazonica, as Indicated by the Development of Abnormal Behaviors.

    Directory of Open Access Journals (Sweden)

    Victoria A Cussen

    Full Text Available Parrots are popular companion animals, but are frequently relinquished because of behavioral problems, including abnormal repetitive behaviors like feather damaging behavior and stereotypy. In addition to contributing to pet relinquishment, these behaviors are important as potential indicators of diminished psychological well-being. While abnormal behaviors are common in captive animals, their presence and/or severity varies between animals of the same species that are experiencing the same environmental conditions. Personality differences could contribute to this observed individual variation, as they are known risk factors for stress sensitivity and affective disorders in humans. The goal of this study was to assess the relationship between personality and the development and severity of abnormal behaviors in captive-bred orange-winged Amazon parrots (Amazona amazonica. We monitored between-individual behavioral differences in enrichment-reared parrots of known personality types before, during, and after enrichment deprivation. We predicted that parrots with higher scores for neurotic-like personality traits would be more susceptible to enrichment deprivation and develop more abnormal behaviors. Our results partially supported this hypothesis, but also showed that distinct personality dimensions were related to different forms of abnormal behavior. While neuroticism-like traits were linked to feather damaging behavior, extraversion-like traits were negatively related to stereotypic behavior. More extraverted birds showed resiliency to environmental stress, developing fewer stereotypies during enrichment deprivation and showing lower levels of these behaviors following re-enrichment. Our data, together with the results of the few studies conducted on other species, suggest that, as in humans, certain personality types render individual animals more susceptible or resilient to environmental stress. Further, this susceptibility/resiliency can

  2. 胎盘形态对妊娠结局的影响%Effects of Placental Shape on Perinatal Outcome

    Institute of Scientific and Technical Information of China (English)

    2014-01-01

    胎盘作为母亲与胎儿之间营养及信息交流的中介,在维持胎儿宫内生长和发育等方面发挥重要的作用。正常的胎盘形态是胎盘维持自身功能的基础,受妊娠期营养状态、生活方式、妊娠并发症及宫腔操作史等诸多因素的影响。这些因素直接或间接地影响胎盘绒毛血管的生长,进而导致胎盘形态的改变,出现轮状、多叶等异常形态的胎盘。形态失常的胎盘运输营养物质的能力以及代谢等功能下降,从而在一定程度上影响胎儿生长发育,临床上常表现为胎儿生长受限、小于胎龄儿、胎儿窘迫、死胎甚至死产等诸多不良妊娠结局。因此,了解影响胎盘形态的因素及其机制,从多方面加以评估预防,可在一定程度上降低妊娠和胎儿不良结局的发生。%Placenta, serve as a mediation of nutrition and information exchange between mother and fetus, plays a vital role in maintaining the intrauterine growth and development of fetus. Placental function is based on its normal shape. Placental shape is often influenced by many factors, such as mother′s nutritional status, lifestyle, complications of pregnancy and operation history of uterine cavity. Those factors may directly or indirectly affect the growth of villous angiogenesis, leading to abnormally changes in placental shape, such as circumvallate and multi-lobate placenta. Abnormally shaped placenta has low efficiency in nutrients transporting and metabolism function, which to some extent, affects fetal growth and development with clinical manifestations including fetal intrauterine growth restriction, small for gestation age, fetal distress and even stillbirth, and other adverse pregnancy outcomes. Therefore, to understand those factors and their mechanisms that affect placental shape, and to evaluate and prevent those negative influence in many aspects, can reduce the adverse outcomes of pregnancy and fetal development to

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

    Directory of Open Access Journals (Sweden)

    Lori C Albergotti

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

  4. Maternal and fetal factors and placentation: implications for pre-eclampsia.

    Science.gov (United States)

    Huppertz, Berthold

    2014-07-01

    The etiology of preeclampsia is still mysterious and a source of a variety of hypotheses. Accordingly, there is a number of theories present today describing different pathways how this disorder may develop. The most cited hypothesis on the etiology of preeclampsia is based on an inadequate remodeling of uterine spiral arteries in the placental bed due to superficial trophoblast invasion followed by placental hypoxia. Since maternal blood into the placenta is only established after week 12 of gestation, an effect of a failure in arterial remodeling can only affect the placenta starting with the second trimester of pregnancy. Recent studies on early predictive biomarkers for preeclampsia (such as PP13, fetal hemoglobin and PIGF) have indicated that there are changes of the villous trophoblast already weeks before the onset of maternal blood flow into the placenta, i.e. during mid first trimester. Moreover, a number of studies has shown that in cases with impaired trophoblast invasion resulting in inadequate remodeling of uterine spiral arteries placental hypoxia does not occur. In all these studies where mostly indirect assessments of placental oxygen have been performed, a higher oxygen partial pressure within the placenta has been measured. This is in clear contrast to the old hypothesis where placental hypoxia is essential for the etiology of preeclampsia. New biomarkers from the maternal and/or fetal compartment for the early prediction of preeclampsia may help in identifying the real etiology of preeclampsia. We need to use this momentum to decipher the real causes of this syndrome.

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

    Science.gov (United States)

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

    2014-03-01

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

  6. Heterologous expression of a ketohexokinase in potato plants leads to inhibited rates of photosynthesis, severe growth retardation and abnormal leaf development

    DEFF Research Database (Denmark)

    Geigenberger, P.; Regierer, B.; Lytovchenko, A.

    2004-01-01

    of ketohexokinase but did not accumulate fructose 1-phosphate. They were, however, characterised by a severe growth retardation and abnormal leaf development. Studies of (14)CO(2) assimilation and metabolism, and of the levels of photosynthetic pigments, revealed that these lines exhibited restricted photosynthesis...

  7. Placental Malaria: From Infection to Malfunction

    OpenAIRE

    2013-01-01

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

  8. Evolution of placental function in mammals

    DEFF Research Database (Denmark)

    Carter, Anthony Michael

    2012-01-01

    Placenta has a wide range of functions. Some are supported by novel genes that have evolved following gene duplication events while others require acquisition of gene expression by the trophoblast. Although not expressed in the placenta, high-affinity fetal hemoglobins play a key role in placental...

  9. Evolution of factors affecting placental oxygen transfer

    DEFF Research Database (Denmark)

    Carter, A M

    2009-01-01

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

  10. 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.

  11. Principles of Practical Training Organization in a Networking (Development of the Module "Psychological Prevention of Behavioral Disorders and Abnormalities in Development" as Example

    Directory of Open Access Journals (Sweden)

    Bogdanovich N. V.

    2016-01-01

    Full Text Available The article presents principles of inserting study subjects and practices in educational modules running with network organizations (internship sites. We proposed a methodological basis of the modular organization of educational process in the framework of the master's program, combied the activity, competence and psychotechnical approaches. Networking of leading chair and specially selected organizations providing the base for practical training solves the problem of organizing activity-related content of educational module. We discussed the main options for networking with the databases of practice and offered methodological principles of designing the educational practice-oriented module, wherein the main principle is the reflexive and activity character of networking. We proposed activity-based content of educational module "Psychological prevention of behavioral disorders and abnormalities in development", based on the substantial psychological definition of psychoprophylaxis as a directions of professional activity of the psychologist.

  12. 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...

  13. Diagnosis and treatment of severe placental abruption%重型胎盘早剥的诊断和处理

    Institute of Scientific and Technical Information of China (English)

    陈叙; 王妍平

    2011-01-01

    Etiological factors of placental abruption are not found yet; it is a serious complication in the late trimester of pregnancy. Placental abruption onsets abruptly, develops quickly, even leads to death of mother and neonate. If placental abruption is found as early as possible, bad outcome can be avoided, but once serious placental abruption proceeds,diagnosis and treatment timely can improve prognosis.%胎盘早剥病因未明,是妊娠晚期严重并发症,起病急,发展快,甚至危及母儿生命.尽早发现胎盘旱剥能够避免母儿不良结局,如果发生重型胎盘早剥,及时的诊断及处理能够改善母儿预后.

  14. A longitudinal study of angiogenic (placental growth factor) and anti-angiogenic (soluble endoglin and soluble VEGF receptor-1) factors in normal pregnancy and patients destined to develop preeclampsia and deliver a small-for-gestational-age neonate

    Science.gov (United States)

    Romero, Roberto; Nien, Jyh Kae; Espinoza, Jimmy; Todem, David; Fu, Wenjiang; Chung, Hwan; Kusanovic, Juan Pedro; Gotsch, Francesca; Erez, Offer; Mazaki-tovi, Shali; Gomez, Ricardo; Edwin, Sam; Chaiworapongsa, Tinnakorn; Levine, Richard J.; Karumanchi, Ananth

    2008-01-01

    Introduction Accumulating evidence suggests that an imbalance between pro-angiogenic [i.e. vascular endothelial growth factor (VEGF) and placental growth factor (PlGF)] and anti-angiogenic factors [i.e. soluble VEGF receptor-1 (sVEGFR-1, also referred to as sFlt1) is involved in the pathophysiology of preeclampsia (PE). Endoglin is a protein that regulates the pro-angiogenic effects of transforming growth factor β, and its soluble form has been recently implicated in the pathophysiology of PE. The objective of this study was to determine if changes in maternal plasma concentration of these angiogenic and anti-angiogenic factors differ prior to development of disease among patients with normal pregnancies, and those destined to develop PE (preterm and term) or to deliver an SGA neonate. Methods This longitudinal nested case-control study included 144 singleton pregnancies in the following groups: 1) patients with uncomplicated pregnancies who delivered appropriate for gestational age (AGA) neonates (n=46); 2) patients who delivered an SGA neonate but did not develop PE (n=56); and 3) patients who developed PE (n=42). Longitudinal samples were collected at each prenatal visit, which was scheduled at four-week intervals from the first or early second trimester until delivery. Plasma concentrations of soluble endoglin (s-Eng), sVEGFR-1 and PlGF were determined by specific and sensitive ELISA. Results 1) Patients destined to deliver an SGA neonate had higher plasma concentrations of s-Eng throughout gestation than those with normal pregnancies; 2) patients destined to develop preterm PE and term PE had significantly higher concentrations of s-Eng than those with normal pregnancies at 23 and 30 weeks, respectively (for preterm PE: p<0.036 and for term PE: 0=0.002); 3) patients destined to develop PE (term or preterm) and those who delivered an SGA neonate had lower plasma concentrations of PlGF than those with normal pregnancy throughout gestation, and the maternal

  15. Abnormalities of gonadal differentiation.

    Science.gov (United States)

    Berkovitz, G D; Seeherunvong, T

    1998-04-01

    Gonadal differentiation involves a complex interplay of developmental pathways. The sex determining region Y (SRY) gene plays a key role in testis determination, but its interaction with other genes is less well understood. Abnormalities of gonadal differentiation result in a range of clinical problems. 46,XY complete gonadal dysgenesis is defined by an absence of testis determination. Subjects have female external genitalia and come to clinical attention because of delayed puberty. Individuals with 46,XY partial gonadal dysgenesis usually present in the newborn period for the valuation of ambiguous genitalia. Gonadal histology always shows an abnormality of seminiferous tubule formation. A diagnosis of 46,XY true hermaphroditism is made if the gonads contain well-formed testicular and ovarian elements. Despite the pivotal role of the SRY gene in testis development, mutations of SRY are unusual in subjects with a 46,XY karyotype and abnormal gonadal development. 46,XX maleness is defined by testis determination in an individual with a 46,XX karyotype. Most affected individuals have a phenotype similar to that of Klinefelter syndrome. In contrast, subjects with 46,XX true hermaphroditism usually present with ambiguous genitalia. The majority of subjects with 46,XX maleness have Y sequences including SRY in genomic DNA. However, only rare subjects with 46,XX true hermaphroditism have translocated sequences encoding SRY. Mosaicism and chimaerism involving the Y chromosome can also be associated with abnormal gonadal development. However, the vast majority of subjects with 45,X/46,XY mosaicism have normal testes and normal male external genitalia.

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

    Energy Technology Data Exchange (ETDEWEB)

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

    2001-09-15

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

  17. 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

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

    Science.gov (United States)

    Salomon, Carlos; Torres, Maria Jose; Kobayashi, Miharu; Scholz-Romero, Katherin; Sobrevia, Luis; Dobierzewska, Aneta; Illanes, Sebastian E; Mitchell, Murray D; Rice, Gregory E

    2014-01-01

    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 (pexosomes present in maternal plasma increased significantly with gestational age by more that two-fold (pExosomes 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.

  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. Perspectives of SLIT/ROBO signaling in placental angiogenesis.

    Science.gov (United States)

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

    2010-09-01

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

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

    Science.gov (United States)

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

    2017-01-01

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

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

    Science.gov (United States)

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

    2013-01-01

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

  3. Placental accommodations for transport and metabolism during intra-uterine crowding in pigs

    Science.gov (United States)

    Litter size and birth weights are limited by uterine capacity, defined as the ability of the uterus to maintain the appropriate development of some number of conceptuses. Uterine capacity is the result of the combined effects of uterine, placental and embryo/fetal function. The number of living conc...

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

    DEFF Research Database (Denmark)

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

    2014-01-01

    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...

  5. Placentation in mammals once grouped as insectivores

    DEFF Research Database (Denmark)

    Carter, Anthony; Enders, Allen

    2009-01-01

    Interest in insectivoran grade mammals has been reawakened by taxonomic changes that place tenrecs and golden moles in a new order and separate hedgehogs from moles, shrews and solenodons. This survey of their placentation shows there is great variation even within families. As an example three...... 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...... as they have been selected for genome sequencing. One of these, the European hedgehog (Erinaceus europaeus), has not been studied with current methodology and renewed investigation of this or the closely related genus Atelerix should be a priority....

  6. Human placental lactogen and intrauterine growth retardation.

    Science.gov (United States)

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

    1976-04-01

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

  7. Placentation in the Amazonian manatee (Trichechus inunguis)

    DEFF Research Database (Denmark)

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

    2008-01-01

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

  8. 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.

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

    Science.gov (United States)

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

    2010-03-15

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

  10. Magnetic resonance imaging detects placental hypoxia and acidosis in mouse models of perturbed pregnancies.

    Directory of Open Access Journals (Sweden)

    Gabriele Bobek

    Full Text Available Endothelial dysfunction as a result of dysregulation of anti-angiogenic molecules secreted by the placenta leads to the maternal hypertensive response characteristic of the pregnancy complication of preeclampsia. Structural abnormalities in the placenta have been proposed to result in altered placental perfusion, placental oxidative stress, cellular damage and inflammation and the release of anti-angiogenic compounds into the maternal circulation. The exact link between these factors is unclear. Here we show, using Magnetic Resonance Imaging as a tool to examine placental changes in mouse models of perturbed pregnancies, that T 2 contrast between distinct regions of the placenta is abolished at complete loss of blood flow. Alterations in T 2 (spin-spin or transverse relaxation times are explained as a consequence of hypoxia and acidosis within the tissue. Similar changes are observed in perturbed pregnancies, indicating that acidosis as well as hypoxia may be a feature of pregnancy complications such as preeclampsia and may play a prominent role in the signalling pathways that lead to the increased secretion of anti-angiogenic compounds.

  11. Magnetic resonance imaging detects placental hypoxia and acidosis in mouse models of perturbed pregnancies.

    Science.gov (United States)

    Bobek, Gabriele; Stait-Gardner, Tim; Surmon, Laura; Makris, Angela; Lind, Joanne M; Price, William S; Hennessy, Annemarie

    2013-01-01

    Endothelial dysfunction as a result of dysregulation of anti-angiogenic molecules secreted by the placenta leads to the maternal hypertensive response characteristic of the pregnancy complication of preeclampsia. Structural abnormalities in the placenta have been proposed to result in altered placental perfusion, placental oxidative stress, cellular damage and inflammation and the release of anti-angiogenic compounds into the maternal circulation. The exact link between these factors is unclear. Here we show, using Magnetic Resonance Imaging as a tool to examine placental changes in mouse models of perturbed pregnancies, that T 2 contrast between distinct regions of the placenta is abolished at complete loss of blood flow. Alterations in T 2 (spin-spin or transverse) relaxation times are explained as a consequence of hypoxia and acidosis within the tissue. Similar changes are observed in perturbed pregnancies, indicating that acidosis as well as hypoxia may be a feature of pregnancy complications such as preeclampsia and may play a prominent role in the signalling pathways that lead to the increased secretion of anti-angiogenic compounds.

  12. Placental lactogen levels in rhesus isoimmunization.

    Science.gov (United States)

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

    1974-03-02

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

  13. Computer-aided assessment of hepatic contour abnormalities as an imaging biomarker for the prediction of hepatocellular carcinoma development in patients with chronic hepatitis C

    Energy Technology Data Exchange (ETDEWEB)

    Goshima, Satoshi [Department of Radiology, Gifu University Hospital, 1-1 Yanagido, 501-1194 Gifu (Japan); Kanematsu, Masayuki, E-mail: masa_gif@yahoo.co.jp [Department of Radiology, Gifu University Hospital, 1-1 Yanagido, 501-1194 Gifu (Japan); Kondo, Hiroshi; Watanabe, Haruo; Noda, Yoshifumi [Department of Radiology, Gifu University Hospital, 1-1 Yanagido, 501-1194 Gifu (Japan); Fujita, Hiroshi [Department of Intelligent Image Information Division of Regeneration and Advanced Medical Sciences, Graduate School of Medicine, Gifu University, Gifu (Japan); Bae, Kyongtae T. [Department of Radiology, University of Pittsburgh Medical Center, Pittsburgh, PA (United States)

    2015-05-15

    Highlights: • Hepatic contour was quantified and converted to hepatic fibrosis index (HFI). • HFI was a significant risk factor for HCC with an odds ratio of 26.4. • HFI may be an important imaging biomarker for managing cirrhotic patients. - Abstract: Purpose: To evaluate whether a hepatic fibrosis index (HFI), quantified on the basis of hepatic contour abnormality, is a risk factor for the development of hepatocellular carcinoma (HCC) in patients with chronic hepatitis C. Materials and methods: Our institutional review board approved this retrospective study and written informed consent was waved. During a 14-month period, consecutive 98 patients with chronic hepatitis C who had no medical history of HCC treatment (56 men and 42 women; mean age, 70.7 years; range, 48–91 years) were included in this study. Gadoxetic acid-enhanced hepatocyte specific phase was used to detect and analyze hepatic contour abnormality. Hepatic contour abnormality was quantified and converted to HFI using in-house proto-type software. We compared HFI between patients with (n = 54) and without HCC (n = 44). Serum levels of albumin, total bilirubin, aspartate transferase, alanine transferase, percent prothrombin time, platelet count, alpha-fetoprotein, protein induced by vitamin K absence-II, and HFI were tested as possible risk factors for the development of HCC by determining the odds ratio with logistic regression analysis. Results: HFIs were significantly higher in patients with HCC (0.58 ± 0.86) than those without (0.36 ± 0.11) (P < 0.001). Logistic analysis revealed that only HFI was a significant risk factor for HCC development with an odds ratio (95% confidence interval) of 26.4 (9.0–77.8) using a cutoff value of 0.395. Conclusion: The hepatic fibrosis index, generated using a computer-aided assessment of hepatic contour abnormality, may be a useful imaging biomarker for the prediction of HCC development in patients with chronic hepatitis C.

  14. Placentation in mammals once grouped as insectivores.

    Science.gov (United States)

    Carter, Anthony M; Enders, Allen C

    2010-01-01

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

  15. PLACENTAL PATHOLOGY IN PREGNANCY INDUCED HYPERTENSION

    Directory of Open Access Journals (Sweden)

    Sreechithra

    2014-08-01

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

  16. Impact of placental insufficiency on fetal skeletal muscle growth.

    Science.gov (United States)

    Brown, Laura D; Hay, William W

    2016-11-01

    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.

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

    Science.gov (United States)

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

    2013-02-01

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

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

    Science.gov (United States)

    Okafor, II; Ugwu, EO

    2015-01-01

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

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

    Science.gov (United States)

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

    1984-07-01

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

  20. Placental localization by scanning with indium 113m

    Energy Technology Data Exchange (ETDEWEB)

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

    1972-09-15

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

  1. Sonoembryological evaluations of the development of placenta previa and velamentous cord insertion.

    Science.gov (United States)

    Hasegawa, Junichi

    2015-01-01

    Longitudinal and cross-sectional investigations using ultrasound examinations during pregnancy can be used to clarify the mechanisms and pathophysiology of abnormal fetal and placental development. Such sonoembryological assessments are useful as a method for clarifying the etiology of disease. In the present review, we describe current knowledge based on our experience with applying sonoembryological methods to determine the developmental mechanisms of placenta previa and velamentous cord insertion.

  2. [Modification of the obstetric hysterectomy in placental acretism].

    Science.gov (United States)

    Ortiz-Villalobos, Roberto Carlos; González-Gómez, Israel Alejandro; Luna-Covarrubias, Edith Esmeralda; Bañuelos-Franco, Alberto; Serrano-Enríquez, Raymundo Felipe

    2014-03-01

    Acretismo is a condition of abnormal placentation, in which the villi invade the myometrium at the implantation site, Representing a risk of massive obstetric hemorrhage with possible alterations of the coagulation, besides to the damage to other organs. Moving forward even to his death, so it is a challenge for the obstetric services, to make a correct diagnosis and in a timely manner, along with the programming of the interruption of pregnancy, as well as the utilization of proper surgical techniques and the involvement of a multidisciplinary team to the possible complications. The following describes a surgical technique modified for patients with a diagnosis of acretismo placentario, used in the Hospital General de Occidente in Jalisco, Mexico from 1 year ago, presenting two clinical cases of patients who underwent surgery with this technique, considering it necessary to present up to the moment a significant decrease in the amount of bleeding, zero days stay of patients in intensive care, any complications in the mother as well as in the product, and more importantly, it has remained at the hospital with no maternal death by this pathology in the last year, considering the nature of being a referral hospital for the whole entity by the Servicios de Salud Jalisco. It is necessary to consider the risks/benefits in the short, medium and long term for the institution, the mother and the product, allowing present good practices that will impinge on the permanent reduction of the maternal death by this pathology.

  3. Mother's body size and placental size predict coronary heart disease in men

    Science.gov (United States)

    Eriksson, Johan G.; Kajantie, Eero; Thornburg, Kent L.; Osmond, Clive; Barker, David J.P.

    2011-01-01

    Aims People whose birthweights were towards the lower end of the normal range are at increased risk of coronary heart disease. This is attributed to foetal programming through malnutrition, but the cause of the malnutrition is unknown. Methods and results We studied 6975 men born in Helsinki during 1934–44. Their size at birth was recorded. Babies who later developed coronary heart disease tended to have a low ponderal index (birthweight/length3). Three different placental phenotypes predicted the disease. In primiparous mothers who were short, having below median height, the hazard ratio for the disease was 1.14 (95% confidence interval 1.08–1.21, P< 0.0001) for each centimetre increase in the difference between the length and breadth of the placental surface. In tall mothers whose body mass index was above the median, the hazard ratio was 1.25 (1.10–1.42, P= 0.0007) per 40 cm2 decrease in the surface area. In tall mothers whose body mass index was below the median, the hazard ratio was 1.07 (1.02–1.13, P= 0.01) per 1% increase in the placental weight/birthweight ratio. Conclusions Three different combinations of maternal and placental size predicted coronary heart disease. The mother's body size determines the availability of nutrients and is linked to the development and function of the placenta, reflected in its shape and size. We speculate that variations in three processes of normal placental development lead to foetal malnutrition. The processes are (i) implantation and spiral artery invasion, (ii) growth of the chorionic surface, and (iii) compensatory expansion of the chorionic surface. PMID:21632601

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

    Directory of Open Access Journals (Sweden)

    Silvija Cvitic

    2014-01-01

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

  5. 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.

  6. Development of a decision support tool to facilitate primary care management of patients with abnormal liver function tests without clinically apparent liver disease [HTA03/38/02]. Abnormal Liver Function Investigations Evaluation (ALFIE

    Directory of Open Access Journals (Sweden)

    Sullivan Frank M

    2007-04-01

    Full Text Available Abstract Background Liver function tests (LFTs are routinely performed in primary care, and are often the gateway to further invasive and/or expensive investigations. Little is known of the consequences in people with an initial abnormal liver function (ALF test in primary care and with no obvious liver disease. Further investigations may be dangerous for the patient and expensive for Health Services. The aims of this study are to determine the natural history of abnormalities in LFTs before overt liver disease presents in the population and identify those who require minimal further investigations with the potential for reduction in NHS costs. Methods/Design A population-based retrospective cohort study will follow up all those who have had an incident liver function test (LFT in primary care to subsequent liver disease or mortality over a period of 15 years (approx. 2.3 million tests in 99,000 people. The study is set in Primary Care in the region of Tayside, Scotland (pop approx. 429,000 between 1989 and 2003. The target population consists of patients with no recorded clinical signs or symptoms of liver disease and registered with a GP. The health technologies being assessed are LFTs, viral and auto-antibody tests, ultrasound, CT, MRI and liver biopsy. The study will utilise the Epidemiology of Liver Disease In Tayside (ELDIT database to determine the outcomes of liver disease. These are based on hospital admission data (Scottish Morbidity Record 1, dispensed medication records, death certificates, and examination of medical records from Tayside hospitals. A sample of patients (n = 150 with recent initial ALF tests or invitation to biopsy will complete questionnaires to obtain quality of life data and anxiety measures. Cost-effectiveness and cost utility Markov model analyses will be performed from health service and patient perspectives using standard NHS costs. The findings will also be used to develop a computerised clinical decision

  7. Altered mRNA Splicing, Chondrocyte Gene Expression and Abnormal Skeletal Development due to SF3B4 Mutations in Rodriguez Acrofacial Dysostosis

    Science.gov (United States)

    Nevarez, Lisette; Pogue, Robert; Krakow, Deborah; Cohn, Daniel H.

    2016-01-01

    The acrofacial dysostoses (AFD) are a genetically heterogeneous group of inherited disorders with craniofacial and limb abnormalities. Rodriguez syndrome is a severe, usually perinatal lethal AFD, characterized by severe retrognathia, oligodactyly and lower limb abnormalities. Rodriguez syndrome has been proposed to be a severe form of Nager syndrome, a non-lethal AFD that results from mutations in SF3B4, a component of the U2 small nuclear ribonucleoprotein particle (U2 snRNP). Furthermore, a case with a phenotype intermediate between Rodriguez and Nager syndromes has been shown to have an SF3B4 mutation. We identified heterozygosity for SF3B4 mutations in Rodriguez syndrome, confirming that the phenotype is a dominant disorder that is allelic with Nager syndrome. The mutations led to reduced SF3B4 synthesis and defects in mRNA splicing, primarily exon skipping. The mutations also led to reduced expression in growth plate chondrocytes of target genes, including the DLX5, DLX6, SOX9, and SOX6 transcription factor genes, which are known to be important for skeletal development. These data provide mechanistic insight toward understanding how SF3B4 mutations lead to the skeletal abnormalities observed in the acrofacial dysostoses. PMID:27622494

  8. 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...

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

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    Enrrico Bloise

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

  10. Placental pathology in pregnancy complications.

    Science.gov (United States)

    Huppertz, Berthold

    2011-02-01

    Among pregnancy pathologies preeclampsia and fetal growth restriction are among the leading causes of maternal and perinatal mortality and morbidity. For both syndromes, the etiologies are still unclear in many facets. For the development of preeclampsia the presence of the placenta is a prerequisite, while for FGR a variety of other factors may be decisive. Cases with a combination of FGR and preeclampsia are the most severe cases and need clinical intervention. Studies on such cases have misled scientists and clinicians to hypothesize that a failure of trophoblast invasion is a specific feature of the early onset type of preeclampsia. Recent development in preeclampsia specific biomarkers and the intense use of Doppler ultrasound measurements already in the first trimester of pregnancy has resulted in a new understanding of the pathways leading to preeclampsia or FGR.

  11. Placental glucose dehydrogenase polymorphism in Koreans.

    Science.gov (United States)

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

    1994-12-01

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

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

    DEFF Research Database (Denmark)

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

    2002-01-01

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

  13. Arrangement of collagen fibers in human placental stem villi

    NARCIS (Netherlands)

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

    2008-01-01

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

  14. 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...

  15. Placental vascular responses are dependent on surrounding tissue

    DEFF Research Database (Denmark)

    Brøgger, Torbjørn Halle

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

  16. Placental vascular responses are dependent on surrounding tissue

    DEFF Research Database (Denmark)

    Brøgger, Torbjørn Halle

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

  17. Placental characteristics in women with polycystic ovary syndrome

    NARCIS (Netherlands)

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

    2015-01-01

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

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

    Energy Technology Data Exchange (ETDEWEB)

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

    2009-05-15

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

  19. Pravastatin ameliorates placental vascular defects, fetal growth, and cardiac function in a model of glucocorticoid excess.

    Science.gov (United States)

    Wyrwoll, Caitlin S; Noble, June; Thomson, Adrian; Tesic, Dijana; Miller, Mark R; Rog-Zielinska, Eva A; Moran, Carmel M; Seckl, Jonathan R; Chapman, Karen E; Holmes, Megan C

    2016-05-31

    Fetoplacental glucocorticoid overexposure is a significant mechanism underlying fetal growth restriction and the programming of adverse health outcomes in the adult. Placental glucocorticoid inactivation by 11β-hydroxysteroid dehydrogenase type 2 (11β-HSD2) plays a key role. We previously discovered that Hsd11b2(-/-) mice, lacking 11β-HSD2, show marked underdevelopment of the placental vasculature. We now explore the consequences for fetal cardiovascular development and whether this is reversible. We studied Hsd11b2(+/+), Hsd11b2(+/-), and Hsd11b2(-/-) littermates from heterozygous (Hsd11b(+/-)) matings at embryonic day (E)14.5 and E17.5, where all three genotypes were present to control for maternal effects. Using high-resolution ultrasound, we found that umbilical vein blood velocity in Hsd11b2(-/-) fetuses did not undergo the normal gestational increase seen in Hsd11b2(+/+) littermates. Similarly, the resistance index in the umbilical artery did not show the normal gestational decline. Surprisingly, given that 11β-HSD2 absence is predicted to initiate early maturation, the E/A wave ratio was reduced at E17.5 in Hsd11b2(-/-) fetuses, suggesting impaired cardiac function. Pravastatin administration from E6.5, which increases placental vascular endothelial growth factor A and, thus, vascularization, increased placental fetal capillary volume, ameliorated the aberrant umbilical cord velocity, normalized fetal weight, and improved the cardiac function of Hsd11b2(-/-) fetuses. This improved cardiac function occurred despite persisting indications of increased glucocorticoid exposure in the Hsd11b2(-/-) fetal heart. Thus, the pravastatin-induced enhancement of fetal capillaries within the placenta and the resultant hemodynamic changes correspond with restored fetal cardiac function. Statins may represent a useful therapeutic approach to intrauterine growth retardation due to placental vascular hypofunction.

  20. 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.

  1. A STUDY OF PLACENTAL WEIGHT AND FETAL OUTCOME IN DIFFERENT GRADES OF PREGNANCY INDUCED HYPERTENSION

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    Raghavendra. A. Y

    2014-10-01

    Full Text Available Introduction and Objectives: Placenta is a feto-maternal organ which is vital for maintaining pregnancy and promoting normal development of the fetus. The weight of the placenta is functionally significant because it is related to villous surface area and to fetal metabolism. Present study has done to record the placental weight and co-relate with the corresponding fetal weight. Materials and Methods: A total of 100 placentae were studied, out of which 50 placentae belong to pregnancy induced hypertension and 50 placentae were of normotensive pregnant mothers. The weight of placenta and weight of fetus were compared between normotensive (Control and hypertensive mothers (Cases. Results: The mean weight of placenta in study group was low as compared to that in the control group. The birth weight of newborn was low with increasing grades of hypertension compared to control groups. The feto- placental weight ratio was higher in case of mild and severe preeclampsia. The incidence of stillbirth was 0.5%, 12.5% and 20% in mild pre-ecampsia, severe preeclampsia and eclampsia respectively. Conclusion: In present study, the birth weight was low with increasing grades of hypertension compared to control groups. The fetal: placental weight ratio was higher in case of mild and severe preeclampsia. The incidence of eclampsia was more common in primigravida where as mild preeclampsia was more common in multigravida. The mean weight of placenta in study group was low compared to control group. Thus study of placental changes in pregnancy induced hypertension may help us to understand patho-physiological mechanisms and design treatment plans for better maternal and foetal outcome. Modern sophisticated techniques like ultrasonography have made it possible to study the necessary placental parameters in utero. This helps in assessing the foetal outcome and management.

  2. PLACENTAL GROWTH FACTOR AND CORONARY NEOANGIOGENESIS IN CORONARY HEART DISEASE

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    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

  3. Confined placental mosaicisms and uniparental disomy

    Energy Technology Data Exchange (ETDEWEB)

    Kalousek, D.K.; Langlois, S.; Harrison, K.J. [Univ. of British Columbia, Vancouver (Canada)] [and others

    1994-09-01

    Approximately 2% of pregnancies studied with chorionic villous sampling (CVS) show confined placental mosaicism (CPM) which persists to term in 50-70% of cases. An increased frequency of complications, such as intrauterine fetal growth restriction or intrauterine death, is observed in these pregnancies. As trisomic zygote rescue is a common mechanism responsible for CPM, fetal uniparental disomy (UPD), resulting from the loss of the extra trisomic chromosome in the embryonic stem cells, would be expected to occur in a proportion of pregnancies with CPM. We have studied 27 pregnancies with CPM involving trisomies for chromosomes 2, 7, 9, 10, 12, and 16 for involvement of specific cell lineage(s) and levels of mosaicism in term placentas. Also, DNA from the parents and infant was analyzed for UPD or biparental disomy (BPD). Five infants with UPD for chromosome 16 and one infant with UPD for chromosome 7 were detected. All other infants showed BPD for the chromosome involved in CPM. For trisomy 16 mosaic gestations, a close correlation between high levels of trisomic cells in placenta and intrauterine fetal growth restriction has been found irrespective of the type of disomy present in the infant. The effect of other trisomies (2, 7, 9, 10, 12) on placental function appears to be similar, but the low numbers of pregnancies studied and lack of detection of UPD for chromosomes 2, 9, 10 and 12 does not allow a definitive conclusion.

  4. 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.

  5. Placental thrombomodulin expression in recurrent miscarriage

    Directory of Open Access Journals (Sweden)

    Turi Angelo

    2010-01-01

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

  6. A Case of Placental Mesenchymal Dysplasia

    Directory of Open Access Journals (Sweden)

    Shigeki Taga

    2013-01-01

    Full Text Available Placental mesenchymal dysplasia (PMD rarely complicates with pregnancy. A 30-year-old woman, gravida 3, para 3, presenting with placentomegaly, was referred to our department at 18 weeks of gestation. An ultrasonography revealed a normal fetus with a large multicystic placenta, measuring 125 × 42 × 80 mm. The border between the lesion and normal region was not clear. Color doppler revealed little blood flow in the lesion. Magnetic resonance imaging revealed normal fetus and a large multicystic placenta. Serum human chorionic gonadotropin level was 20124.97 U/L, which was normal at 20 weeks of gestation. Thus, placental mesenchymal dysplasia rather than hydatidiform mole with coexistent fetus was suspected. Then, routine checkup was continued. Because she had the history of Cesarean section, an elective Cesarean section was performed at 37 weeks of gestation, and 2520 g female infant with apgar score 8/9 was delivered. The baby was normal with no evidence of Beckwith-Wiedemann syndrome. Placenta of 20 × 16 × 2 cm, weighing 720 g, was bulky with grape like vesicles involving whole placenta. Microscopic examination revealed dilated villi and vessels with thick wall which was lacking trophoblast proliferation. Large hydropic stem villi with myxomatous struma and cistern formation were seen. PMD was histopathologically confirmed.

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

    Science.gov (United States)

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

    2014-02-01

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

  8. Russia: An Abnormal Country

    Directory of Open Access Journals (Sweden)

    Steven Rosefielde

    2005-06-01

    Full Text Available Andrei Shleifer and Daniel Treisman recently rendered a summary verdict on the post Soviet Russian transition experience finding that the Federation had become a normal country with the west's assistance, and predicting that it would liberalize and develop further like other successful nations of its type. This essay demonstrates that they are mistaken on the first count, and are likely to be wrong on the second too. It shows factually, and on the norms elaborated by Pareto, Arrow and Bergson that Russia is an abnormal political economy unlikely to democratize, westernize or embrace free enterprise any time soon

  9. Differential response of ovine placental lactogen levels in maternal and fetal circulations following single umbilical artery ligation in fetal sheep.

    Science.gov (United States)

    Newnham, J P; Lam, R W; Hobel, C J; Padbury, J F; Polk, D H; Fisher, D A

    1986-01-01

    We investigated circulating maternal and fetal serum concentrations of ovine placental lactogen (oPL) following single umbilical artery ligation (SUAL) at 108 to 114 days' gestation. Ovine placental lactogen was isolated and purified from placental cotyledons, and a radioimmunoassay developed using previously described methods. Intrauterine growth retardation (IUGR) was manifest as increasing fetal brain-to-liver weight ratio with increasing duration of survival following SUAL. During the first five to seven days following SUAL, circulating oPL levels in ewes with SUAL fetuses were significantly reduced when compared with levels in ewes with control fetuses. In contrast, oPL levels in SUAL fetuses were significantly increased above levels in control fetuses for the first five to seven days following surgery. Fetal ovine growth hormone levels were elevated in SUAL fetuses, while ovine prolactin levels were similar in the two groups. IUGR was associated with mild fetal acidosis and fetal plasma CAT levels which were similar in SUAL and control fetuses. No correlation was found between fetal pH or CAT and fetal oPL levels. These findings are consistent with the view that circulating levels of oPL in the mother are related to the mass of functioning trophoblast. Elevated fetal oPL levels following SUAL may result from acute placental ischaemia with alterations in placental lactogen secretion at the maternofetal interface.

  10. The utility of quantitative methylation assays at imprinted genes for the diagnosis of fetal and placental disorders.

    Science.gov (United States)

    Bourque, D K; Peñaherrera, M S; Yuen, R K C; Van Allen, M I; McFadden, D E; Robinson, W P

    2011-02-01

    An imbalance of imprinted gene expression within 11p15.5 is observed in Beckwith-Wiedemann syndrome (BWS), as well as in a variety of placental abnormalities including complete hydatidiform mole (CHM), placental mesenchymal dysplasia (PMD) and triploidy. To facilitate the diagnosis of epigenetic errors and chromosomal imbalance of 11p15.5, we validated a pyrosequencing assay to measure methylation at KvDMR1 using blood samples from 13 BWS cases, 8 of which showed reduced methylation as compared to control blood. An imbalance between maternal and paternal genomes as is found in triploidy, CHM or PMD was also associated with altered KvDMR1 methylation. A reciprocal pattern of methylation was obtained in the triploid cases by assaying the proximal 11p15.5 ICR associated with H19. To distinguish chromosome 11 specific alterations from whole genome imbalance, other imprinted differentially methylated regions (DMRs) can be utilized. Thus, pyrosequencing assays for DMRs associated with SGCE, SNRPN, and MEST were also compared for their utility in diagnosing parental imbalance in placental samples. While each of these assays could successfully distinguish parental origin of triploidy, SGCE showed the clearest separation between groups. The combined use of a chromosome 11p15.5 assay (e.g. KvDMR1 or H19-ICR) and non-chromosome 11 assay (e.g. SGCE) provides a potentially valuable diagnostic tool in the rapid screening of methylation errors in placental disorders. These results also show the maintenance of imprinting status at these loci in the human placenta, even in the presence of abnormal pathology.

  11. Simultaneous determination of acrylamide, its metabolite glycidamide and antipyrine in human placental perfusion fluid and placental tissue by liquid chromatography-electrospray tandem mass spectrometry.

    Science.gov (United States)

    Annola, Kirsi; Keski-Rahkonen, Pekka; Vähäkangas, Kirsi; Lehtonen, Marko

    2008-12-15

    A rapid and sensitive method using liquid chromatography-tandem mass spectrometry (LC-MS/MS) was developed for the simultaneous determination of acrylamide (AA) and its genotoxic metabolite glycidamide (GA) with a test marker antipyrine (AP) in placental tissue and perfusion medium used in human placental perfusion studies. An internal standard ((13)C-acrylamide) was added to the samples which were then deproteinized with acetonitrile. Chromatographic separation was performed on a reversed phase column with a gradient elution of acetonitrile and 0.01% formic acid at a flow rate of 0.3 mL/min. Detection and quantification of the analytes were carried out with a triple quadrupole mass spectrometer using positive electrospray ionization (ESI) and multiple reaction monitoring (MRM). The method was validated and linear over a concentration range of 0.5-20 microg/mL for acrylamide and glycidamide and 5-200 microg/mL for antipyrine. The lower limit of quantification for acrylamide and glycidamide was 0.5 microg/mL and for antipyrine 5 microg/mL. The method was selective, and good accuracy, precision, recovery, and stability were obtained for concentrations within the standard curve. The method was successfully used to analyze the placental perfusion medium and tissue samples in a toxicokinetic study for transplacental transfer of acrylamide and glycidamide. This is the first time that acrylamide, glycidamide and antipyrine are measured simultaneously.

  12. [Molecular abnormalities in lymphomas].

    Science.gov (United States)

    Delsol, G

    2010-11-01

    Numerous molecular abnormalities have been described in lymphomas. They are of diagnostic and prognostic value and are taken into account for the WHO classification of these tumors. They also shed some light on the underlying molecular mechanisms involved in lymphomas. Overall, four types of molecular abnormalities are involved: mutations, translocations, amplifications and deletions of tumor suppressor genes. Several techniques are available to detect these molecular anomalies: conventional cytogenetic analysis, multicolor FISH, CGH array or gene expression profiling using DNA microarrays. In some lymphomas, genetic abnormalities are responsible for the expression of an abnormal protein (e.g. tyrosine-kinase, transcription factor) detectable by immunohistochemistry. In the present review, molecular abnormalities observed in the most frequent B, T or NK cell lymphomas are discussed. In the broad spectrum of diffuse large B-cell lymphomas microarray analysis shows mostly two subgroups of tumors, one with gene expression signature corresponding to germinal center B-cell-like (GCB: CD10+, BCL6 [B-Cell Lymphoma 6]+, centerine+, MUM1-) and a subgroup expressing an activated B-cell-like signature (ABC: CD10-, BCL6-, centerine-, MUM1+). Among other B-cell lymphomas with well characterized molecular abnormalies are follicular lymphoma (BCL2 deregulation), MALT lymphoma (Mucosa Associated Lymphoid Tissue) [API2-MALT1 (mucosa-associated-lymphoid-tissue-lymphoma-translocation-gene1) fusion protein or deregulation BCL10, MALT1, FOXP1. MALT1 transcription factors], mantle cell lymphoma (cycline D1 [CCND1] overexpression) and Burkitt lymphoma (c-Myc expression). Except for ALK (anaplastic lymphoma kinase)-positive anaplastic large cell lymphoma, well characterized molecular anomalies are rare in lymphomas developed from T or NK cells. Peripheral T cell lymphomas not otherwise specified are a heterogeneous group of tumors with frequent but not recurrent molecular abnormalities

  13. IFPA meeting 2015 workshop report I: placental mitochondrial function, transport systems and epigenetics.

    Science.gov (United States)

    Bianco-Miotto, T; Blundell, C; Buckberry, S; Chamley, L; Chong, S; Cottrell, E; Dawson, P; Hanna, C; Holland, O; Lewis, R M; Moritz, K; Myatt, L; Perkins, A V; Powell, T; Saffery, R; Sferruzzi-Perri, A; Sibley, C; Simmons, D; O'Tierney-Ginn, P F

    2016-12-01

    Workshops are an important part of the IFPA annual meeting as they allow for discussion of specialized topics. At IFPA meeting 2015 there were twelve themed workshops, three of which are summarized in this report. These workshops covered areas of placental regulation and nutrient handling: 1) placental epigenetics; 2) placental mitochondrial function; 3) placental transport systems.

  14. Urine - abnormal color

    Science.gov (United States)

    ... medlineplus.gov/ency/article/003139.htm Urine - abnormal color To use the sharing features on this page, please enable JavaScript. The usual color of urine is straw-yellow. Abnormally colored urine ...

  15. Associations between intrapartum death and piglet, placental, and umbilical characteristics.

    Science.gov (United States)

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

    2012-12-01

    Intrapartum death in multiparous gestations in sows (Sus scrofa) is often caused by hypoxia. There is little information in the literature on the assessment of the placenta in relation to intrapartum death in piglets. The aim of this study was to evaluate the impact of the placental area and weight upon piglet birth characteristics and intrapartum death. Litters from 26 Landrace-Yorkshire sows were monitored during farrowing and the status of each piglet was recorded, including blood parameters of piglets and their umbilical veins. Of 413 piglets born, 6.5% were stillborn. Blood concentrations of glucose, lactate, and CO(2) partial pressure were increased in the stillborn piglets (P piglets, whereas pH and base excess were decreased (P piglets born dead vs. live (P piglets born dead was not different from live-born piglets (P = 0.631), whereas mean body mass index was reduced (P piglets were not different from live-born piglets (P = 0.662 and P = 0.253, respectively). Blood concentrations of lactate, hemoglobin, and hematocrit recorded in all piglets pooled were associated with placental area (P 0.2). Piglet BW was positively correlated with placental area and placental weight (P piglet birth weight, but not with the probability of being born dead. Placental area was a better predictor of piglet vitality than placental weight. Because umbilical cord rupture and prolonged birth time were associated with being born dead, umbilical cord rupture and placental detachment seem to be probable causes of intrapartum death.

  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. Maternal vitamin C deficiency during pregnancy results in transient fetal and placental growth retardation in guinea pigs

    DEFF Research Database (Denmark)

    Schjoldager, Janne Gram; Paidi, Maya Devi; Lindblad, Maiken Marie

    2015-01-01

    of vitC's impact on intrauterine development is sparse. The aim of this study was to explore the effect of maternal vitC status on fetal and placental development in guinea pigs. METHODS: Twenty pregnant Dunkin Hartley guinea pigs were randomized into four groups to receive diets either sufficient (918...

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

    Directory of Open Access Journals (Sweden)

    Eduardo Reyna-Villasmil

    2015-01-01

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

  19. A new Approach to the Study of Russian Language Acquisition in Preschool Children with Normal and Abnormal Development

    Directory of Open Access Journals (Sweden)

    Lebedeva T.V

    2014-11-01

    Full Text Available We discuss the possibilities of using a standardized method of psychological evaluation of the Russian language development in preschool children. We provide a rationale for the relevance of timely differentiation of children with language and speech difficulties in modern educational practice. We present the results of comparative analysis of language and speech development in the two groups of children 5-6 years old: normally developing (N=92 and with language and speech disorders (N=59. We describe the diagnostic potential of this research tool for clinical sample of children with speech and language disorders, reveal differences in the development of Russian language between the two groups of children. The data obtained can be used in solving the problems of differentiated correctional help to pre-school children with impaired language and speech development.

  20. 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...

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

    DEFF Research Database (Denmark)

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

    2002-01-01

    women with normal singleton pregnancies at approximately 19 and 28 wk gestation. Serum placental GH concentrations were measured by a highly specific immunoradiometric assay, and fetal size was measured by ultrasound. Data on birth weight, gender, prepregnancy body mass index (BMI), parity, and smoking.......002). Placental GH at second examination was positively correlated with gestational age (P = 0.002) and negatively correlated with prepregnancy BMI (P = 0.039). Placental GH correlated with fetal weight at approximately 28 wk gestation (P = 0.002) but did not predict birth weight at term. Our study supports...

  2. [Imbalance of system of glutamin - glutamic acid in the placenta and amniotic fluid at placental insufficiency].

    Science.gov (United States)

    Pogorelova, T N; Gunko, V O; Linde, V A

    2014-01-01

    Metabolism of glutamine and glutamic acid has been investigated in the placenta and amniotic fluid under conditions of placental insufficiency. The development of placental insufficiency is characterized by the increased content of glutamic acid and a decrease of glutamine in both placenta and amniotic fluid. These changes changes were accompanied by changes in the activity of enzymes involved in the metabolism of these amino acids. There was a decrease in glutamate dehydrogenase activity and an increase in glutaminase activity with the simultaneous decrease of glutamine synthetase activity. The compensatory decrease in the activity of glutamine keto acid aminotransferase did not prevent a decrease in the glutamine level. The impairments in the system glutamic acid-glutamine were more pronounced during the development of premature labor.

  3. Distribution of CA 125 in placental tissues.

    Science.gov (United States)

    Fuith, L C; Müller-Holzner, E; Marth, C; Perkmann, E; Zeimet, A; Daxenbichler, G

    1989-01-01

    The presence of the tumor marker CA 125 was studied in different compartments of the human placenta. Levels of CA 125 in the cytosol of chorionic villi ranged from 27-17100 U/g (median 560 U/g). In the placental amnion and chorion concentrations ranged from 175-29000 U/g, median 1060 U/g and were not statistically different. In the umbilical cord values were significantly lower (range 44-7600 U/g; median 180 U/g). Maternal serum probes were above the upper limit of normal in all cases (range 48-500 U/ml; median 131 U/ml). Immunohistochemistry detected CA 125 exclusively within the amniotic cells of the placenta and the umbilical cord. This might be because CA 125 fixes more to insoluble structures in the amnion or because of contamination of chorionic villi with the underlying decidua.

  4. Intestinal and placental zinc transport pathways.

    Science.gov (United States)

    Ford, Dianne

    2004-02-01

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

  5. Superfecundation and dual paternity in a twin pregnancy ending with placental abruption.

    Science.gov (United States)

    Ambach, E; Parson, W; Brezinka, C

    2000-01-01

    A case of superfecundation and dual paternity in a twin pregnancy is presented. Placental abruption developed at week 33 of gestation and the two boys had to be saved by emergency cesarean section. As they shared one placenta, had almost identical weight and had the same sex, they were assumed to be monozygotic. However, a subsequent paternity suit led to the conclusion, based on DNA-analysis, that the twin brothers had been fathered by two different men. Obstetrical implications are discussed.

  6. An evaluation of human placental lactogen levels in hypertension of pregnancy.

    Science.gov (United States)

    Kelly, A M; England, P; Lorimer, J D; Ferguson, J C; Govan, A D

    1975-04-01

    Maternal plasma levels of human placental lactogen (HPL) are decreased in hypertensive pregnancies and the concentration is related to the severity of the condition. Of infants who had HPL concentrations in the fetal danger zone (more than 2 SD's below normal mean) 75 per cent developed fetal distress, neonatal asphyxia or were light for dates. Patients who are identified in this way have lighter infants and placentae than their unidentified counterparts with normal HPL levels.

  7. Lung development in laminin γ2 deficiency: abnormal tracheal hemidesmosomes with normal branching morphogenesis and epithelial differentiation

    Directory of Open Access Journals (Sweden)

    Uitto Jouni

    2006-02-01

    Full Text Available Abstract Background Laminin γ2 (Lamc2, one of the polypeptides in laminin-332 (laminin-5, is prominent in the basement membrane of alveolar walls and airways of developing and adult lung. Laminins are important for lung morphogenesis and based on its localization, a function for laminin γ2 in lung development has been hypothesized. Targeted deletion of the laminin γ2 gene in mice results in skin blistering and neonatal death at 3–5 days after birth due to failure to thrive. Methods Examination of lung development in Lamc2-/- mice through 1–2 days postnatal was accomplished by morphometric analysis, lung bud culture, electron microscopy, immunohistochemical and immunofluorescence staining. Results Compared to littermate controls, Lamc2-/- lungs were similar in morphology during embryonic life. At post-natal day 1–2, distal saccules were mildly dilated by chord length measurements. Epithelial differentiation as evaluated by immunohistochemical staining for markers of ciliated cells, Clara cells, alveolar type I cells and alveolar type II cells did not reveal a difference between Lamc2-/- and littermate control lungs. Likewise, vascular development, smooth muscle cell differentiation, and elastic fiber formation looked similar, as did airway basement membrane ultrastructure. Branching morphogenesis by lung bud culture was similar in Lamc2-/- and littermate control lungs. Since laminin-332 is important for hemidesmosome formation, we examined the structure of tracheal hemidesmosomes by transmission electron microscopy. Compared to littermate controls, Lamc2-/- tracheal hemidesmosomes were less organized and lacked the increased electron density associated with the basement membrane abutting the hemidesmosome. Conclusion These findings indicate that laminin γ2 and laminin-332, despite their prominence in the lung, have a minimal role in lung development through the saccular stage.

  8. Placental Size Is Associated Differentially With Postnatal Bone Size and Density

    Science.gov (United States)

    Holroyd, Christopher R; Osmond, Clive; Barker, David JP; Ring, Sue M; Lawlor, Debbie A; Tobias, Jon H; Smith, George Davey; Harvey, Nicholas C

    2016-01-01

    offspring bone development persist into older childhood, even during puberty, and that placental size is differentially related to bone size and volumetric density. © 2016 The Authors. Journal of Bone and Mineral Research Published by Wiley Periodicals, Inc. on behalf of American Society for Bone and Mineral Research (ASBMR). PMID:26999363

  9. Metallothionein expression in placental tissue in Menkes' disease

    DEFF Research Database (Denmark)

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

    1995-01-01

    . The avidin-biotin-complex (ABC)-technique was used. The copper content was measured by neutron activation analysis (NAA). In all placental tissue sections positive MT immunostaining appeared only in the trophoblast and only in proliferating cells. In placental tissue sections obtained from foetuses......Menkes' disease is a recessive X-linked disturbance of copper metabolism, resulting in accumulation of copper in several extra-hepatic tissues including the placenta. Metallothionein (MT) is a low-molecular weight protein with a high affinity for group II metal ions, such as copper. Its synthesis...... is induced by the presence of the ions. The aim of this study was to investigate the pattern of the MT immunoreactivity in placental tissue obtained from women at-risk of Menkes' disease in order to examine whether the MT occurrence and distribution may reflect the copper content. Placental tissue from six...

  10. Loss of Thrombomodulin in Placental Dysfunction in Preeclampsia

    NARCIS (Netherlands)

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

    2016-01-01

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

  11. The effect of smoking on serum human placental lactogen levels.

    Science.gov (United States)

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

    1977-02-01

    Serial serum samples (162) were drawn weekly from normal pregnant women (53) during the last month of gestation and measurements were made of the human placental lactogen (HPL) content. The women were interviewed as to their smoking habits and divided into nonsmokers (32) and smokers of from one to two packages of cigarettes per day (21). The infant birth weight and placental weights were not significantly different. The HPL levels were elevated in the women who smoked and the differences were significant at the thirty-sixth and thirty-eighth weeks. The importance of this in interpreting HPL as a placental function test and in terms of the biology of placental function and the control of protein hormone synthesis is emphasized.

  12. 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....

  13. Adiponectin supplementation in pregnant mice prevents the adverse effects of maternal obesity on placental function and fetal growth.

    Science.gov (United States)

    Aye, Irving L M H; Rosario, Fredrick J; Powell, Theresa L; Jansson, Thomas

    2015-10-13

    Mothers with obesity or gestational diabetes mellitus have low circulating levels of adiponectin (ADN) and frequently deliver large babies with increased fat mass, who are susceptible to perinatal complications and to development of metabolic syndrome later in life. It is currently unknown if the inverse correlation between maternal ADN and fetal growth reflects a cause-and-effect relationship. We tested the hypothesis that ADN supplementation in obese pregnant dams improves maternal insulin sensitivity, restores normal placental insulin/mechanistic target of rapamycin complex 1 (mTORC1) signaling and nutrient transport, and prevents fetal overgrowth. Compared with dams on a control diet, female C57BL/6J mice fed an obesogenic diet before mating and throughout gestation had increased fasting serum leptin, insulin, and C-peptide, and reduced high-molecular-weight ADN at embryonic day (E) 18.5. Placental insulin and mTORC1 signaling was activated, peroxisome proliferator-activated receptor-α (PPARα) phosphorylation was reduced, placental transport of glucose and amino acids in vivo was increased, and fetal weights were 29% higher in obese dams. Maternal ADN infusion in obese dams from E14.5 to E18.5 normalized maternal insulin sensitivity, placental insulin/mTORC1 and PPARα signaling, nutrient transport, and fetal growth without affecting maternal fat mass. Using a mouse model with striking similarities to obese pregnant women, we demonstrate that ADN functions as an endocrine link between maternal adipose tissue and fetal growth by regulating placental function. Importantly, maternal ADN supplementation reversed the adverse effects of maternal obesity on placental function and fetal growth. Improving maternal ADN levels may serve as an effective intervention strategy to prevent fetal overgrowth caused by maternal obesity.

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

    Science.gov (United States)

    Huppertz, Berthold; Ghosh, Debabrata; Sengupta, Jayasree

    2014-01-01

    The placenta is an indispensable organ for intrauterine protection, development and growth of the embryo and fetus. It provides tight contact between mother and conceptus, enabling the exchange of gas, nutrients and waste products. The human placenta is discoidal in shape, and bears a hemo-monochorial interface as well as villous materno-fetal interdigitations. Since Peter Medawar's astonishment to the paradoxical nature of the mother-fetus relationship in 1953, substantial knowledge in the domain of placental physiology has been gathered. In the present essay, an attempt has been made to build an integrated understanding of morphological dynamics, cell biology, and functional aspects of genomic and proteomic expression of human early placental villous trophoblast cells followed by a commentary on the future directions of research in this field.

  15. The Role of Secretory Autophagy in Zika Virus Transfer through the Placental Barrier

    Science.gov (United States)

    Zhang, Zhong-Wei; Li, Zi-Lin; Yuan, Shu

    2017-01-01

    Recent studies indicated that the Zika virus genome could be detected in the amniotic fluid and the fetal brain, which confirms that the virus can cross the placental barrier. Secretory autophagy or exosome pathways may participate in this virus transfer. Autophagy modulators regulate autophagosome formation or membrane fusion with lysosomal vesicles and therefore inhibit viral nucleocapsid releasing or virus transfer to the fetus hypothetically. However, some autophagy modulators may enhance virus replication. Autophagy inhibitors may arrest placental development; while exaggeration of autophagy in human placenta may be associated with the fetal growth restriction. Therefore, autophagy modulators should be used carefully due to their complex clinical effects. Alternatively, exosome-specific inhibitors might be also considered, although their safety of both maternal and fetal conditions must be carefully assessed before any advancement to human clinical trials. PMID:28119857

  16. 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...... muscle and elastic lamina. We conclude that invasion depth and spiral artery remodelling are basically similar in chimpanzees and humans, although the seemingly different time of onset may have implications for uteroplacental oxygen supply and fetal development....

  17. Ablation of Mrds1/Ofcc1 induces hyper-γ-glutamyl transpeptidasemia without abnormal head development and schizophrenia-relevant behaviors in mice.

    Directory of Open Access Journals (Sweden)

    Tetsuo Ohnishi

    Full Text Available Mutations in the Opo gene result in eye malformation in medaka fish. The human ortholog of this gene, MRDS1/OFCC1, is a potentially causal gene for orofacial cleft, as well as a susceptibility gene for schizophrenia, a devastating mental illness. Based on this evidence, we hypothesized that this gene could perform crucial functions in the development of head and brain structures in vertebrates. To test this hypothesis, we created Mrds1/Ofcc1-null mice. Mice were examined thoroughly using an abnormality screening system referred to as "the Japan Mouse Clinic". No malformations of the head structure, eye or other parts of the body were apparent in these knockout mice. However, the mutant mice showed a marked increase in serum γ-glutamyl transpeptidase (GGT, a marker for liver damage, but no abnormalities in other liver-related measurements. We also performed a family-based association study on the gene in schizophrenia samples of Japanese origin. We found five single nucleotide polymorphisms (SNPs located across the gene that showed significant transmission distortion, supporting a prior report of association in a Caucasian cohort. However, the knockout mice showed no behavioral phenotypes relevant to schizophrenia. In conclusion, disruption of the Mrds1/Ofcc1 gene elicits asymptomatic hyper-γ-glutamyl-transpeptidasemia in mice. However, there were no phenotypes to support a role for the gene in the development of eye and craniofacial structures in vertebrates. These results prompt further examination of the gene, including its putative contribution to hyper-γ-glutamyl transpeptidasemia and schizophrenia.

  18. Abnormalities of Endocytosis, Phagocytosis, and Development Process in Dictyostelium Cells That Over-Express Acanthamoeba castellanii Metacaspase Protein.

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    Entsar Saheb

    2015-06-01

    Full Text Available Acanthamoeba castellanii forms a resistant cyst that protects the parasite against the host's immune response. Acanthamoeba Type-I metacaspase (Acmcp is a caspase-like protein that has been found to be expressed during the encystations. Dictyostelium discoideum is an organism closely related to Acanthamoeba useful for studying the molecular function of this protozoan caspase-like protein.The full length of Acmcp and a mutated version of the same gene, which lacks the proline rich N-terminal region (Acmcp-dpr, were cloned into the pDneo2a-GFP vector separately. The pDneo2a-GFP-Acmcp and pDneo2a-GFPAcmcp-dpr were electro-transfected into wild type D. discoideum cells to create cell lines that over-expressed Acmcp or Acmcp-dpr.Both cell lines that over-expressed Acmcp and Acmcp-dpr showed a significant increase in the fluid phase internalization and phagocytosis rate compared to the control cells. Additionally, the cells expressing the Acmcp-dpr mutant were unable to initiate early development and failed to aggregate or form fruiting bodies under starvation conditions, whereas Acmcp over-expressing cells showed the opposite phenomena. Quantitative cell death analysis provided additional support for these findings.Acmcp is involved in the processes of endocytosis and phagocytosis. In addition, the proline rich region in Acmcp is important for cellular development in Dictyostelium. Given its important role in the development process, metacaspase protein is proposed as a candidate drug target against infections caused by A. castellanii.

  19. Development of a new biomonitoring method to detect the abnormal activity of Daphnia magna using automated Grid Counter device.

    Science.gov (United States)

    Jeon, Junho; Kim, Joon Ha; Lee, Byung Cheun; Kim, Sang Don

    2008-01-25

    The aim of the present study was to develop a biological early warning system (BEWS), equipped with six monitoring channels to individually observe the activity of Daphnia magna, using a digital 'Grid Counter', which would trigger an alarm within an appropriate time, and examine the functional performance of the newly developed BEWS for detecting unusual water quality. In order to detect the changes in the activity of D. magna, six relative activity parameter values (Z(a)) were computed from the 6 individual monitoring channels; with the activity data for D. magna calculated every 5 min. The Student's t-test was used to verify the difference between the mean value of the system in a steady state, as a control, and the exposure values during a sudden pollution event. The test results illustrate that the threshold value for the alarm can be at p=0.0093 for 3 consecutive detections. The time period, defined as the average time taken from the detection of hyper to retarded activity of the organism, for Cu concentrations of 50, 100, 200 and 400 ppb were 7.17+/-1.75, 3.94+/-2.02, 1.85+/-0.49 and 1.00+/-0.18 h, respectively. Based on the results of this study, it is proposed that p values from the t-test, with Z(a), are more accurate, stable and predictable parameters for the detection of chemical exposures than the other values, such as the swimming speed and trajectory, etc. Consequently, it would be possible to reduce the number of false alarms and achieve confidence for a system, with the ability of highly accurate detection, such as with the six-channel monitoring system developed in this study.

  20. The development of behavioral and endocrine abnormalities in rats after repeated exposure to direct and indirect stress.

    Science.gov (United States)

    Daniels, Willie Mark Uren; de Klerk Uys, Joachim; van Vuuren, Petra; Stein, Daniel Joseph

    2008-04-01

    The present study compared the effects of direct and indirect stress on the behavior and hypothalamic-pituitary-adrenal axis of rats. Animals were placed in a two compartment box. In one compartment the direct stressed rat was subjected to electric foot shocks randomly applied for 10 minutes (0.5 mA of 1 s duration). In the adjacent compartment, the indirect stressed rats witnessed the application of these electric foot shocks. Our data showed substantial behavioral changes in the open field test, but limited effects in the elevated plus maze. The findings suggested that single and repeated stress exposure may have different consequences, that the effects of stress exposure may develop over time and persist for an extended period, and that both direct and indirect stressed rats displayed a hyposensitive HPA axis following acute restraint stress. Overall our observations moderately indicate direct exposure to elicit behavioral changes, and both direct and indirect exposure to stress to result in aberrations within the neuroendocrine system. With additional development our stress models may be considered for studying the complex interrelationship between an external stressor, and the experience of the organism.

  1. Microvessel density in the placental bed among preeclampsia patients

    Directory of Open Access Journals (Sweden)

    Tarcisio Mota Coelho

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

  2. PLACENTAL LOCATION AT SECOND TRIMESTER AND PREGNANCY OUTCOMES

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    Seadati N

    2013-04-01

    Full Text Available The aimed of this study was to find association between location of placental at second trimester and pregnancy outcomes. It was a descriptive -analytic epidemiological study which has performed on 250 pregnant women by simple random sampling in Razi hospital and Imam Khomeini hospital during July 2011 – October 2012 in Ahvaz city, Iran. Placental location was determined by sonography at 18 - 22 weeks of gestation, and it was classified to high / low category and anterior / posterior category. In this study has been assessed placental location with incidence of preeclampsia, intrauterine growth restriction and preterm birth. The incidence of preeclampsia and intrauterine growth restriction was 5.6%, 1.6% respectively, these parameters were not associated with placental location (p=0.84, p=0.69. The incidence of preterm birth was 7.2% and it was associated with low placental location (p=0.01.There was no significant difference between anterior and posterior placenta in all of outcomes. Low placental location was associated with increased risk of preterm labor and preterm delivery.

  3. Metabolism of bupropion by baboon hepatic and placental microsomes.

    Science.gov (United States)

    Wang, Xiaoming; Abdelrahman, Doaa R; Fokina, Valentina M; Hankins, Gary D V; Ahmed, Mahmoud S; Nanovskaya, Tatiana N

    2011-08-01

    The aim of this investigation was to determine the biotransformation of bupropion by baboon hepatic and placental microsomes, identify the enzyme(s) catalyzing the reaction(s) and determine its kinetics. Bupropion was metabolized by baboon hepatic and placental microsomes to hydroxybupropion (OH-BUP), threo- (TB) and erythrohydrobupropion (EB). OH-bupropion was the major metabolite formed by hepatic microsomes (Km 36±6 μM, Vmax 258±32 pmol mg protein(-1) min(-1)), however the formation of OH-BUP by placental microsomes was below the limit of quantification. The apparent Km values of bupropion for the formation of TB and EB by hepatic and placental microsomes were similar. The selective inhibitors of CYP2B6 (ticlopidine and phencyclidine) and monoclonal antibodies raised against human CYP2B6 isozyme caused 80% inhibition of OH-BUP formation by baboon hepatic microsomes. The chemical inhibitors of aldo-keto reductases (flufenamic acid), carbonyl reductases (menadione), and 11β-hydroxysteroid dehydrogenases (18β-glycyrrhetinic acid) significantly decreased the formation of TB and EB by hepatic and placental microsomes. Data indicate that CYP2B of baboon hepatic microsomes is responsible for biotransformation of bupropion to OH-BUP, while hepatic and placental short chain dehydrogenases/reductases and to a lesser extent aldo-keto reductases are responsible for the reduction of bupropion to TB and EB.

  4. 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.

  5. Relationships between ovulation rate and embryonic and placental characteristics in multiparous sows at 35 days of pregnancy

    NARCIS (Netherlands)

    Silva, Da C.L.; Brand, van den H.; Laurenssen, B.F.A.; Broekhuijse, M.L.W.J.; Knol, E.F.; Kemp, B.; Soede, N.M.

    2016-01-01

    The objective of this study was to investigate relationships between ovulation rate (OR) and embryonic and placental development in sows. Topigs Norsvin® sows (n=91, parity 2 to 17) from three different genetic backgrounds were slaughtered at 35 days of pregnancy and the reproductive tract was colle

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

    DEFF Research Database (Denmark)

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

    2011-01-01

    and chondroitin sulfate A (CSA) in the placental intervillous space and lack of protective antibodies. PM impairs fetal development mainly by excessive inflammation processes. After infections during pregnancy women acquire immunity to PM conferred by antibodies against VAR2CSA. Ideally, a vaccine against PM...

  7. Morphological Characteristics of Placental Complex in Pregnant Women without Complications in Pregnancy and in the Presence of Severe Preeclampsia

    Science.gov (United States)

    Umbetov, Turakbai Zh.; Berdalinova, Akzhenis K.; Tusupkalieyv, Akylbek B.; Koishybayev, Arip K.; Zharilkasynov, Karaman Ye.

    2016-01-01

    According to the WHO data, preeclampsia develops during late pregnancy in 2-8% of women. Preeclampsia is a major cause of maternal and perinatal morbidity and mortality, therefore, the study of the morphological features of placental complex, taking into account gestational complications in postpartum women with severe preeclampsia is an important…

  8. Placental involvement by non-Hodgkin lymphoma in a Crohn disease patient on long-term thiopurine therapy.

    Science.gov (United States)

    Chen, G; Crispin, P; Cherian, M; Dahlstrom, J E; Sethna, F F; Kaye, G; Pavli, P; Subramaniam, K

    2016-01-01

    We report the first published case of aggressive diffuse large B-cell (non-Hodgkin) lymphoma in a 35-year-old pregnant woman who had Crohn disease and was taking long-term thiopurine therapy: the patient developed placental insufficiency, and there was intrauterine fetal death.

  9. Abnormal differentiation of dopaminergic neurons in zebrafish trpm7 mutant larvae impairs development of the motor pattern.

    Science.gov (United States)

    Decker, Amanda R; McNeill, Matthew S; Lambert, Aaron M; Overton, Jeffrey D; Chen, Yu-Chia; Lorca, Ramón A; Johnson, Nicolas A; Brockerhoff, Susan E; Mohapatra, Durga P; MacArthur, Heather; Panula, Pertti; Masino, Mark A; Runnels, Loren W; Cornell, Robert A

    2014-02-15

    Transient receptor potential, melastatin-like 7 (Trpm7) is a combined ion channel and kinase implicated in the differentiation or function of many cell types. Early lethality in mice and frogs depleted of the corresponding gene impedes investigation of the functions of this protein particularly during later stages of development. By contrast, zebrafish trpm7 mutant larvae undergo early morphogenesis normally and thus do not have this limitation. The mutant larvae are characterized by multiple defects including melanocyte cell death, transient paralysis, and an ion imbalance that leads to the development of kidney stones. Here we report a requirement for Trpm7 in differentiation or function of dopaminergic neurons in vivo. First, trpm7 mutant larvae are hypomotile and fail to make a dopamine-dependent developmental transition in swim-bout length. Both of these deficits are partially rescued by the application of levodopa or dopamine. Second, histological analysis reveals that in trpm7 mutants a significant fraction of dopaminergic neurons lack expression of tyrosine hydroxylase, the rate-limiting enzyme in dopamine synthesis. Third, trpm7 mutants are unusually sensitive to the neurotoxin 1-methyl-4-phenylpyridinium, an oxidative stressor, and their motility is partially rescued by application of the iron chelator deferoxamine, an anti-oxidant. Finally, in SH-SY5Y cells, which model aspects of human dopaminergic neurons, forced expression of a channel-dead variant of TRPM7 causes cell death. In summary, a forward genetic screen in zebrafish has revealed that both melanocytes and dopaminergic neurons depend on the ion channel Trpm7. The mechanistic underpinning of this dependence requires further investigation.

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

    Science.gov (United States)

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

    2003-07-01

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

  11. Development of an Abnormal Curvature Cervical Spine Finite Element Model%曲度异常颈椎三维有限元模型的建立#

    Institute of Scientific and Technical Information of China (English)

    何帆

    2015-01-01

    目的:建立生理曲度异常的人颈椎三维有限元模型,并进行应力分析。方法:采集1位颈椎生理曲度变直患者的CT数据,利用 MIMICS软件进行数据处理,建立实体模型,然后导入有限元分析软件 Abaqus,建立颈椎有限元模型。在此模型上施加作用力,模拟颈椎在后伸工况下的状态。结果:建立了包括完整颈椎椎体、椎间盘和模拟主要韧带的颈椎模型,得到了在外力作用下的颈椎应力云图。结论:建立的有限元模型可用于生理曲度异常颈椎的生物力学研究。%Objective: To develop an abnormal curvature cervical spine finite element model, for the use of subsequent biomechanical analyses of human cervical.Methods:The computed tomography data of an abnormal cervical curvature patient were used in the study. The data were input to MIMICS software to process and output a three dimension entity model, then the model was input into the finite element software abaqus to obtain a cervical finite element model. The model accuracy was tested in vitro experimental results for the movement of rear bending.Results:The finite element model comprised all cervical vertebras, discs and the main ligaments was established. The nephogram of the cervical spine under the force was got.Conclusion:The established finite element model is competent in the use of the biomechanical analysis in clinical study of abnormal curvature cervical spine.

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

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    Ross MG

    2012-07-01

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

  13. Assessment of electron beam-induced abnormal development and DNA damage in Spodoptera litura (F.) (Lepidoptera: Noctuidae)

    Science.gov (United States)

    Yun, Seung-Hwan; Lee, Seon-Woo; Koo, Hyun-Na; Kim, Gil-Hah

    2014-03-01

    The armyworm, Spodoptera litura (F.) is a polyphagous and important agricultural pest worldwide. In this study, we examined the effect of electron beam irradiation on developmental stages, reproduction, and DNA damage of S. litura. Eggs (0-24 h old), larvae (3rd instar), pupae (3 days old after pupation), and adults (24 h after emergence) were irradiated with electron beam irradiation of six levels between 30 and 250 Gy. When eggs were irradiated with 100 Gy, egg hatching was completely inhibited. When the larvae were irradiated, the larval period was significantly delayed, depending on the doses applied. At 150 Gy, the fecundity of adults that developed from irradiated pupae was entirely inhibited. However, electron beam irradiation did not induce the instantaneous death of S. litura adults. Reciprocal crosses between irradiated and unirradiated moths demonstrated that females were more radiosensitive than males. We also conducted the comet assay immediately after irradiation and over the following 5 days period. Severe DNA fragmentation in S. litura cells was observed just after irradiation and the damage was repaired during the post-irradiation period in a time-dependent manner. However, at more than 100 Gy, DNA damage was not fully recovered.

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

    Science.gov (United States)

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

    2016-03-03

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

  15. Fetal nutrition in lecithotrophic squamate reptiles: toward a comprehensive model for evolution of viviparity and placentation.

    Science.gov (United States)

    Stewart, James R

    2013-07-01

    The primary pattern of embryonic nutrition for squamate reptiles is lecithotrophy; with few exceptions, all squamate embryos mobilize nutrients from yolk. The evolution of viviparity presents an opportunity for an additional source of embryonic nutrition through delivery of uterine secretions, or placentotrophy. This pattern of embryonic nutrition is thought to evolve through placental supplementation of lecithotrophy, followed by increasing dependence on placentotrophy. This review analyzes the relationship between reproductive mode and pattern of embryonic nutrition in three lecithotrophic viviparous species, and oviparous counterparts, for concordance with a current model for the evolution of viviparity and placentation. The assumptions of the model, that nutrients for oviparous embryos are mobilized from yolk, and that this source is not disrupted in the transition to viviparity, are supported for most nutrients. In contrast, calcium, an essential nutrient for embryonic development, is mobilized from both yolk and eggshell by oviparous embryos and reduction of eggshell calcium is correlated with viviparity. If embryonic fitness is compromised by disruption of a primary source of calcium, selection may not favor evolution of viviparity, yet viviparity has arisen independently in numerous squamate lineages. Studies of fetal nutrition in reproductively bimodal species suggest a resolution to this paradox. If uterine calcium secretion occurs during prolonged intrauterine egg retention, calcium placentotrophy evolves prior to viviparity as a replacement for eggshell calcium and embryonic nutrition will not be compromised. This hypothesis is integrated into the current model for evolution of viviparity and placentation to address the unique attributes of calcium nutrition. The sequence of events requires a shift in timing of uterine calcium secretion and the embryonic mechanism of calcium retrieval to be responsive to calcium availability. Regulation of uterine

  16. The MRI features of placental adhesion disorder-a pictorial review.

    Science.gov (United States)

    Cuthbert, Faye; Teixidor Vinas, Mireia; Whitby, Elspeth

    2016-09-01

    Placental adhesion disorder (PAD) comprises placenta accreta, increta and percreta lesions; these are classified according to the depth of uterine invasion. Although PAD is considered a rare condition, its incidence has increased 10-fold in the last 50 years. Ultrasound is the primary imaging modality for the assessment of the placenta and in the majority of cases, it is sufficient for diagnosis; however, when ultrasound findings are suspicious or inconclusive, MRI is recommended as an adjunct imaging technique. Numerous MRI features of PAD have been described, including dark intraplacental bands, disorganized intraplacental vascularity and abnormal uterine bulging. This pictorial review describes and illustrates these characteristics and discusses their implications in planning delivery. In addition, we present a series of "pitfall" cases to aid the interpreting radiologist and discuss management of PAD. PAD is a clinical and diagnostic challenge that is encountered with increasing frequency, requiring a cohesive multidisciplinary approach to its management.

  17. Maternal Pre-Pregnancy Obesity Is Associated with Altered Placental Transcriptome

    Science.gov (United States)

    Segura, Maria Teresa; Esteban, Francisco J.; Bartel, Sabine; Brandi, Pilar; Irmler, Martin; Beckers, Johannes; Demmelmair, Hans; López-Sabater, Carmen; Koletzko, Berthold; Krauss-Etschmann, Susanne; Campoy, Cristina

    2017-01-01

    Maternal obesity has a major impact on pregnancy outcomes. There is growing evidence that maternal obesity has a negative influence on placental development and function, thereby adversely influencing offspring programming and health outcomes. However, the molecular mechanisms underlying these processes are poorly understood. We analysed ten term placenta’s whole transcriptomes in obese (n = 5) and normal weight women (n = 5), using the Affymetrix microarray platform. Analyses of expression data were carried out using non-parametric methods. Hierarchical clustering and principal component analysis showed a clear distinction in placental transcriptome between obese and normal weight women. We identified 72 differentially regulated genes, with most being down-regulated in obesity (n = 61). Functional analyses of the targets using DAVID and IPA confirm the dysregulation of previously identified processes and pathways in the placenta from obese women, including inflammation and immune responses, lipid metabolism, cancer pathways, and angiogenesis. In addition, we detected new molecular aspects of obesity-derived effects on the placenta, involving the glucocorticoid receptor signalling pathway and dysregulation of several genes including CCL2, FSTL3, IGFBP1, MMP12, PRG2, PRL, QSOX1, SERPINE2 and TAC3. Our global gene expression profiling approach demonstrates that maternal obesity creates a unique in utero environment that impairs the placental transcriptome. PMID:28125591

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

    Science.gov (United States)

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

    2016-01-01

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

  19. Maternal and feto-placental prostanoid responses to a single course of antenatal betamethasone.

    Science.gov (United States)

    Cho, Steve; Beharry, Kay D A; Valencia, Arwin M; Guajardo, Leonel; Nageotte, Michael P; Modanlou, Houchang D

    2005-12-01

    We tested the hypothesis that antenatal betamethasone alters prostanoid levels in the maternal and feto-placental compartments. Forty-three singleton pregnancies were studied. Group I were women treated with a single course of antenatal betamethasone and who delivered 38 weeks. Maternal and mixed cord blood; and placental samples were collected at delivery and analyzed for PGE2, PGF(2alpha), 6-ketoPGF(1alpha), and TxB2 levels. Antenatal betamethasone decreased maternal PGE2 levels with concomitant increases in the feto-placental compartment. Umbilical cord TxB2 levels in the treated group were significantly lower than the non-treated pre-term and term groups resulting in a higher 6-ketoPGF(1alpha):TxB2 ratio. Considering the regulatory role of PGE2 and PGI2 in fetal lung development and neonatal transition homeostasis, these results suggest a mechanism, at least in part, for the beneficial effects of antenatal steroids on fetal lung maturation and neonatal cardio-pulmonary homeostasis at birth.

  20. Placental morphology in pre-eclampsia and eclampsia and the likely role of NK cells

    Directory of Open Access Journals (Sweden)

    Maham Akhlaq

    2012-01-01

    Full Text Available Background: Placenta has long been a neglected organ as far as its pathology is concerned. This study is an attempt to observe the morphological features of placentae both gross and microscopic in normal pregnancy, preeclampsia, and eclampsia. Materials and Methods: A total of 150 placentae were collected; of these, 50 belonged to normal pregnancy, 50 belonged to pre-eclamptic women, and 50 were from patients of eclampsia. Results: Placental trimmed weight was seen to be decreased in patients of preeclampsia and eclampsia. Placental infarcts were more commonly seen in the diseased group and they were more centrally located. Hypertrophy of the spiral arterioles was observed in the decidual portion found in placental disc and membranes. Distal villous hypoplasia was also frequently seen in the diseased group. Fetal membranes were thickened and showed infarcts in preeclampsia and eclampsia. Conclusions: Morphological features seen in eclamptic placentae were similar but exaggerated compared to preeclampsia. In conclusion, the pathological changes were found to be more severe and frequent in preeclampsia and eclampsia, but more so in eclamptic placentae as compared with placenta of normal pregnancy. CD56 immunomarker was also used to identify NK cells. They were found to be present only in the diseased group and were located in the decidual portion of the basal plate, implicating their role in the development of the disease.

  1. Human placental lactogen levels in multiple pregnancies.

    Science.gov (United States)

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

    1978-08-01

    Serum human placental lactogen (hPL) levels were measured in duplicate with a radioimmunoassay in 206 serum samples at 30 and 36 weeks' gestation from women with normal singleton pregnancies (75) or pregnancies with twins (37). One triplet pregnancy was also studied. The results show a significant elevation of hPL in the women with twin pregnancies at both the 30th (7.0 vs 6.0 microgram/ml) and the 36th (9.2 vs 7.4 microgram/ml) weeks. One-third of the twin pregnancies had values of hPL in excess of 8.0 microgram/ml at 30 weeks and more than half had values in excess of 9.0 microgram/ml at 36 weeks. The triplet pregnancy had an hPL value of 11.0 microgram/ml at 36 weeks' gestation. These data support the potential usefulness of serum hPL measurements in the screening profile for the detection of high-risk pregnancies.

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

    Science.gov (United States)

    Pijnenborg, R; Vercruysse, L

    2007-01-01

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

  3. Placental Cadmium Levels Are Associated with Increased Preeclampsia Risk.

    Science.gov (United States)

    Laine, Jessica E; Ray, Paul; Bodnar, Wanda; Cable, Peter H; Boggess, Kim; Offenbacher, Steven; Fry, Rebecca C

    2015-01-01

    Environmental exposure to heavy metals is a potentially modifiable risk factor for preeclampsia (PE). Toxicologically, there are known interactions between the toxic metal cadmium (Cd) and essential metals such as selenium (Se) and zinc (Zn), as these metals can protect against the toxicity of Cd. As they relate to preeclampsia, the interaction between Cd and these essential metals is unknown. The aims of the present study were to measure placental levels of Cd, Se, and Zn in a cohort of 172 pregnant women from across the southeast US and to examine associations of metals levels with the odds of PE in a nested case-control design. Logistic regressions were performed to assess odds ratios (OR) for PE with exposure to Cd controlling for confounders, as well as interactive models with Se or Zn. The mean placental Cd level was 3.6 ng/g, ranging from 0.52 to 14.5 ng/g. There was an increased odds ratio for PE in relationship to placental levels of Cd (OR = 1.5; 95% CI: 1.1-2.2). The Cd-associated OR for PE increased when analyzed in relationship to lower placental Se levels (OR = 2.0; 95% CI: 1.1-3.5) and decreased with higher placental Se levels (OR = 0.98; 95% CI: 0.5-1.9). Similarly, under conditions of lower placental Zn, the Cd-associated OR for PE was elevated (OR = 1.8; 95% CI: 0.8-3.9), whereas with higher placental Zn it was reduced (OR = 1.3; 95% CI: 0.8-2.0). Data from this pilot study suggest that essential metals may play an important role in reducing the odds of Cd-associated preeclampsia and that replication in a larger cohort is warranted.

  4. Hereditary urea cycle abnormality

    Science.gov (United States)

    ... vitro so the specific genetic cause is known. Teamwork between parents, the affected child, and doctors can help prevent severe illness. Alternative Names Abnormality of the urea cycle - hereditary; Urea cycle - hereditary abnormality Images Male urinary system Urea cycle References Lichter-Konecki ...

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

    Directory of Open Access Journals (Sweden)

    Adjimon Gatien Lokossou

    2014-11-01

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

  6. 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

  7. 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 h...

  8. AKAP13 Rho-GEF and PKD-binding domain deficient mice develop normally but have an abnormal response to β-adrenergic-induced cardiac hypertrophy.

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    Matthew J Spindler

    Full Text Available BACKGROUND: A-kinase anchoring proteins (AKAPs are scaffolding molecules that coordinate and integrate G-protein signaling events to regulate development, physiology, and disease. One family member, AKAP13, encodes for multiple protein isoforms that contain binding sites for protein kinase A (PKA and D (PKD and an active Rho-guanine nucleotide exchange factor (Rho-GEF domain. In mice, AKAP13 is required for development as null embryos die by embryonic day 10.5 with cardiovascular phenotypes. Additionally, the AKAP13 Rho-GEF and PKD-binding domains mediate cardiomyocyte hypertrophy in cell culture. However, the requirements for the Rho-GEF and PKD-binding domains during development and cardiac hypertrophy are unknown. METHODOLOGY/PRINCIPAL FINDINGS: To determine if these AKAP13 protein domains are required for development, we used gene-trap events to create mutant mice that lacked the Rho-GEF and/or the protein kinase D-binding domains. Surprisingly, heterozygous matings produced mutant mice at Mendelian ratios that had normal viability and fertility. The adult mutant mice also had normal cardiac structure and electrocardiograms. To determine the role of these domains during β-adrenergic-induced cardiac hypertrophy, we stressed the mice with isoproterenol. We found that heart size was increased similarly in mice lacking the Rho-GEF and PKD-binding domains and wild-type controls. However, the mutant hearts had abnormal cardiac contractility as measured by fractional shortening and ejection fraction. CONCLUSIONS: These results indicate that the Rho-GEF and PKD-binding domains of AKAP13 are not required for mouse development, normal cardiac architecture, or β-adrenergic-induced cardiac hypertrophic remodeling. However, these domains regulate aspects of β-adrenergic-induced cardiac hypertrophy.

  9. A higher-level MRP supertree of placental mammals

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    Bininda-Emonds Olaf RP

    2006-11-01

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

  10. Compensatory placental growth after restricted maternal nutrition in early pregnancy.

    Science.gov (United States)

    Lumey, L H

    1998-01-01

    This study examined the effects of undernutrition in pregnancy on fetal and placental growth among infants born in 1944-1946 in The Netherlands, including infants born during the war-induced Dutch famine of 1944-1945. There was an increase in placental weight, but not in birthweight, in infants whose mothers' nutrition was compromised around conception or in the first trimester of pregnancy. Therefore, the placental index was also increased. Compared to pre-famine controls, the relative increase after first trimester exposure to undernutrition was larger in the northern part of the country (5.2 per cent, 95 per cent confidence interval 1.4, 9.0) where nutritional deprivation was presumably moderate compared to the west (3.5 per cent, 95 per cent confidence interval 0.2, 7.2) where nutritional deprivation was severe. The increase in placental weight is interpreted as compensatory for the reduction in maternal caloric intake. Whereas this suggests that pregnancy undernutrition can stimulate compensatory placental growth, the latter was only seen after first trimester undernutrition, which does not affect infant size at birth. For these infants, therefore, birthweight is not an appropriate proxy measure of undernutrition in pregnancy. These factors need to be considered in future studies relating pregnancy nutrition to adult health outcomes.

  11. Histopathological placental lesions in mild gestational hyperglycemic and diabetic women

    Directory of Open Access Journals (Sweden)

    Rudge Marilza VC

    2011-08-01

    Full Text Available Abstract Objective To investigate and compare the incidence of histopathological placental lesions in mild gestational hyperglycemia, gestational diabetes and overt diabetes at term and preterm gestation. Research design and methods One-hundred-and-thirty-one placental samples were collected from Diabetes mellitus (DM positive screened patients. Two diagnostic tests, glycemic profile and 100 g oral glucose tolerance test (OGTT in parallel identified 4 groups normoglycemic, mild gestational hyperglycemia (MGH, gestational DM (GDM or overt DM (DM. Placental tissue specimens and sections from 4 groups were obtained by uniform random sampling and stained with hematoxylin-eosin. Results Placentas from MGH group presented 17 types of histopathological change and higher rates of syncytial nodes and endarteritis. GDM placentas presented only nine types of histopathological change, high rates of dysmaturity, low rates of calcification and no syncytial nodes. Overt DM placentas showed 22 types of histopathological change, 21 of which were present in the preterm period. There were histopathological similarities between MGH and DM placentas, but the former exhibited a higher incidence of endarteritis, which has been described as a "post-mortem" phenomenon. Conclusion Our results confirmed that the distinct placental changes associated with DM and MGH depend on gestational period during which the diabetic insult occurs. It may reasonably be inferred that subclinical maternal hyperglycemia during pregnancy, as showed in MGH group, is responsible for increased placental endarteritis, a postmortem lesion in the live fetus.

  12. Relação entre a quantidade de AgNORS, atividade proliferativa e o estágio de desenvolvimento placentário em equinos Relationship between the amount of AgNORs, proliferative activity and stage of placental development in horses

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    Ana C.F. Mançanares

    2012-12-01

    silver nitrate and are related to the activity of rRNA synthesis and to the agility and speed of cell proliferation in the tissues studied. The objective of this study was to relate the amount of AgNORs, proliferative activity and stage of pregnancy in horses, using the coloring of Silver Nitrate. The embryonic attachments were collected, fixed in 10% buffered formaldehyde, embedded in paraplast and stained by silver nitrate. The groups were determined according to the gestational age. The amount of the corium NOR found in early pregnancy indicates the onset of cell activity, and in that the pregnancy progresses, the amount of NOR increases, suggesting higher activity and increased synthesis of their importance in maintaining the fetus. Contrary to what occurs in the corium, the quantification of NORs was higher in late pregnancy than in the beginning, suggesting the stabilization of these membranes in late pregnancy. The chorionic girdle and the yolk sac were found in early pregnancy and had lots of NORs, suggesting synthesis function and proliferation in early pregnancy, since their functions is maintenance of the embryo until the complete formation of the true placenta (chorio-allantoic membranes. We conclude that the membranes that develop in a progressive manner in accordance with the growing embryo/fetal (chorion, amnion and allantoic membranes have an increased number of NORs and the membranes that involute after the formation of the embryo/fetus (yolk sac and chorionic girdle have a decrease in number, suggesting a reduction in proliferative activity in these membranes.

  13. A LIGHT AND SCANNING ELECTRON MICROSCOPY STUDY OF PLACENTAL VILLI ASSOCIATED WITH OBESITY AND HYPERTENSIÓN

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    Castejón Sandoval OC

    2013-05-01

    Full Text Available The aim of this study was to examine the structure of the placental villi associated with obesity and hypertension using light and scanning electron microscopy.Two placentas at term obtained of woman pregnancy associated to stillborn were taken for microscopical analysis. Woman pregnancy weighed 75 and 85 Kg as body mass index and their hypertension with more of 90/150 mmHg. They had 39 and 41 years old. The placental weights were 600 and 650 gr respectively after of draining all their blood during 30 minutes post delivery. Five small fragments were taken by each placenta and evaluated with light and scanning electron microscopy. Stem villi showed obstructive vessels with damage in their walls and reticular tissue under the syncytio was a permanent finding. Immature intermediate villi were frequent. Severe degenerative changes are noted in peripheric stem villi. Fibrotic villi, very poor developed mature intermediate villi, filiform terminal villi, corangiosis, deposition of fibrinoid and vasodilatation were found in placental villi. No inflammation and low arborization was seen. These results indicate immaturity persistent, low maturation degree and severe degenerative changes affecting the structure of placental villi without inflammation

  14. Determination of the Transport Rate of Xenobiotics and Nanomaterials Across the Placenta using the ex vivo Human Placental Perfusion Model

    Science.gov (United States)

    Grafmüller, Stefanie; Manser, Pius; Krug, Harald F.; Wick, Peter; von Mandach, Ursula

    2013-01-01

    Decades ago the human placenta was thought to be an impenetrable barrier between mother and unborn child. However, the discovery of thalidomide-induced birth defects and many later studies afterwards proved the opposite. Today several harmful xenobiotics like nicotine, heroin, methadone or drugs as well as environmental pollutants were described to overcome this barrier. With the growing use of nanotechnology, the placenta is likely to come into contact with novel nanoparticles either accidentally through exposure or intentionally in the case of potential nanomedical applications. Data from animal experiments cannot be extrapolated to humans because the placenta is the most species-specific mammalian organ 1. Therefore, the ex vivo dual recirculating human placental perfusion, developed by Panigel et al. in 1967 2 and continuously modified by Schneider et al. in 1972 3, can serve as an excellent model to study the transfer of xenobiotics or particles. Here, we focus on the ex vivo dual recirculating human placental perfusion protocol and its further development to acquire reproducible results. The placentae were obtained after informed consent of the mothers from uncomplicated term pregnancies undergoing caesarean delivery. The fetal and maternal vessels of an intact cotyledon were cannulated and perfused at least for five hours. As a model particle fluorescently labelled polystyrene particles with sizes of 80 and 500 nm in diameter were added to the maternal circuit. The 80 nm particles were able to cross the placental barrier and provide a perfect example for a substance which is transferred across the placenta to the fetus while the 500 nm particles were retained in the placental tissue or maternal circuit. The ex vivo human placental perfusion model is one of few models providing reliable information about the transport behavior of xenobiotics at an important tissue barrier which delivers predictive and clinical relevant data. PMID:23851364

  15. Determination of the transport rate of xenobiotics and nanomaterials across the placenta using the ex vivo human placental perfusion model.

    Science.gov (United States)

    Grafmüller, Stefanie; Manser, Pius; Krug, Harald F; Wick, Peter; von Mandach, Ursula

    2013-06-18

    Decades ago the human placenta was thought to be an impenetrable barrier between mother and unborn child. However, the discovery of thalidomide-induced birth defects and many later studies afterwards proved the opposite. Today several harmful xenobiotics like nicotine, heroin, methadone or drugs as well as environmental pollutants were described to overcome this barrier. With the growing use of nanotechnology, the placenta is likely to come into contact with novel nanoparticles either accidentally through exposure or intentionally in the case of potential nanomedical applications. Data from animal experiments cannot be extrapolated to humans because the placenta is the most species-specific mammalian organ (1). Therefore, the ex vivo dual recirculating human placental perfusion, developed by Panigel et al. in 1967 (2) and continuously modified by Schneider et al. in 1972 (3), can serve as an excellent model to study the transfer of xenobiotics or particles. Here, we focus on the ex vivo dual recirculating human placental perfusion protocol and its further development to acquire reproducible results. The placentae were obtained after informed consent of the mothers from uncomplicated term pregnancies undergoing caesarean delivery. The fetal and maternal vessels of an intact cotyledon were cannulated and perfused at least for five hours. As a model particle fluorescently labelled polystyrene particles with sizes of 80 and 500 nm in diameter were added to the maternal circuit. The 80 nm particles were able to cross the placental barrier and provide a perfect example for a substance which is transferred across the placenta to the fetus while the 500 nm particles were retained in the placental tissue or maternal circuit. The ex vivo human placental perfusion model is one of few models providing reliable information about the transport behavior of xenobiotics at an important tissue barrier which delivers predictive and clinical relevant data.

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

    DEFF Research Database (Denmark)

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

    2013-01-01

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

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

    DEFF Research Database (Denmark)

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

    2007-01-01

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

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

    Directory of Open Access Journals (Sweden)

    Qun Shu

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

  19. "Jeopardy" in Abnormal Psychology.

    Science.gov (United States)

    Keutzer, Carolin S.

    1993-01-01

    Describes the use of the board game, Jeopardy, in a college level abnormal psychology course. Finds increased student interaction and improved application of information. Reports generally favorable student evaluation of the technique. (CFR)

  20. Chromosomal Abnormalities in ADHD

    Directory of Open Access Journals (Sweden)

    J Gordon Millichap

    2002-07-01

    Full Text Available The prevalence of fragile X syndrome, velocardiofacial syndrome (VCFS, and other cytogenetic abnormalities among 100 children (64 boys with combined type ADHD and normal intelligence was assessed at the NIMH and Georgetown University Medical Center.

  1. Abnormal menstrual periods (image)

    Science.gov (United States)

    ... may have a variety of causes, such as endometrial hyperplasia, endometrial polyps, uterine fibroids, and abnormal thyroid or ... the endometrium becomes unusually thick it is called endometrial ... Hyperplasia may cause profuse or extended menstrual bleeding.

  2. Chromosomal abnormalities and autism

    Directory of Open Access Journals (Sweden)

    Farida El-Baz

    2016-01-01

    Conclusion: Chromosomal abnormalities were not detected in the studied autistic children, and so the relation between the genetics and autism still needs further work up with different study methods and techniques.

  3. Abnormal protein aggregationand neurodegenerativediseases

    Institute of Scientific and Technical Information of China (English)

    2001-01-01

    Abnormal protein aggregation or amyloid is the major cause ofmany neurodegenerative disorders. The present review focuses on the correlation between sequence and structure features of proteins related to the diseases and abnormal protein aggregation. Recent progress has improved our knowledge on understand-ing the mechanism of amyloid formation. We suggest a nucleation model for ordered protein aggregation, which can also explain pathogenesis mechanisms of these neurodegenerative diseases in vivo.

  4. HIV-1 Nef breaches placental barrier in rat model.

    Science.gov (United States)

    Singh, Poonam; Agnihotri, Saurabh Kumar; Tewari, Mahesh Chandra; Kumar, Sadan; Sachdev, Monika; Tripathi, Raj Kamal

    2012-01-01

    The vertical transmission of HIV-1 from the mother to fetus is known, but the molecular mechanism regulating this transmission is not fully characterized. The fetus is highly protected by the placenta, which does not permit microbial pathogens to cross the placental barrier. In the present study, a rat model was established to observe the effect of HIV-1 protein Nef on placental barrier. Evans blue dye was used to assay permeability of placental barrier and fourteen day pregnant Sprague Dawley rats were injected intravenously with 2% Evans blue dye along with various concentrations of recombinant Nef. After an hour, animals were sacrificed and dye migration was observed through the assimilation of peripheral blood into fetus. Interestingly, traces of recombinant Nef protein were detected in the embryo as well as amniotic fluid and amniotic membrane along with placenta and uterus. Our study indicates that recombinant HIV-1-Nef protein breaches the placental barrier and allows the migration of Evans blue dye to the growing fetus. Further the concentration of Nef protein in blood is directly proportional to the intensity of dye migration and to the amount of Nef protein detected in uterus, placenta, amniotic membrane, amniotic fluid and embryo. Based on this study, it can be concluded that the HIV-1 Nef protein has a direct effect on breaching of the placental barrier in the model we have established in this study. Our observations will be helpful to understand the molecular mechanisms related to this breach of placental barrier by Nef in humans and may be helpful to identify specific Nef inhibitors.

  5. 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

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

    Directory of Open Access Journals (Sweden)

    O. I. Stepanova

    2011-01-01

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

  7. Placental oxidative stress and decreased global DNA methylation are corrected by copper in the Cohen diabetic rat

    Energy Technology Data Exchange (ETDEWEB)

    Ergaz, Zivanit, E-mail: zivanit@hadassah.org.il [Hebrew University Hadassah Medical School, Jerusalem (Israel); Guillemin, Claire [Department of Pharmacology and Therapeutics, McGill University, Montreal (Canada); Neeman-azulay, Meytal; Weinstein-Fudim, Liza [Hebrew University Hadassah Medical School, Jerusalem (Israel); Stodgell, Christopher J.; Miller, Richard K. [Department of Obstetrics and Gynecology, University of Rochester, Rochester (United States); Szyf, Moshe [Department of Pharmacology and Therapeutics, McGill University, Montreal (Canada); Ornoy, Asher [Hebrew University Hadassah Medical School, Jerusalem (Israel)

    2014-05-01

    Fetal Growth Restriction (FGR) is a leading cause for long term morbidity. The Cohen diabetic sensitive rats (CDs), originating from Wistar, develop overt diabetes when fed high sucrose low copper diet (HSD) while the original outbred Sabra strain do not. HSD induced FGR and fetal oxidative stress, more prominent in the CDs, that was alleviated more effectively by copper than by the anti-oxidant vitamins C and E. Our aim was to evaluate the impact of copper or the anti-oxidant Tempol on placental size, protein content, oxidative stress, apoptosis and total DNA methylation. Animals were mated following one month of HSD or regular chow diet and supplemented throughout pregnancy with either 0, 1 or 2 ppm of copper sulfate or Tempol in their drinking water. Placental weight on the 21st day of pregnancy decreased in dams fed HSD and improved upon copper supplementation. Placental/fetal weight ratio increased among the CDs. Protein content decreased in Sabra but increased in CDs fed HSD. Oxidative stress biochemical markers improved upon copper supplementation; immunohistochemistry for oxidative stress markers was similar between strains and diets. Caspase 3 was positive in more placentae of dams fed HSD than those fed RD. Placental global DNA methylation was decreased only among the CDs dams fed HSD. We conclude that FGR in this model is associated with smaller placentae, reduced DNA placental methylation, and increased oxidative stress that normalized with copper supplementation. DNA hypomethylation makes our model a unique method for investigating genes associated with growth, oxidative stress, hypoxia and copper. - Highlights: • Sensitive Cohen diabetic rats (CDs) had small placentae and growth restricted fetuses. • CDs dams fed high sucrose low copper diet had placental global DNA hypomethylation. • Caspase 3 was positive in more placentae of dams fed HSD than those fed RD. • Oxidative stress parameters improved by Tempol and resolved by copper

  8. Communication and abnormal behaviour.

    Science.gov (United States)

    Crown, S

    1979-01-01

    In this paper the similarities between normal and abnormal behaviour are emphasized and selected aspects of communication, normal and aberrant, between persons are explored. Communication in a social system may be verbal or non-verbal: one person's actions cause a response in another person. This response may be cognitive, behavioural or physiological. Communication may be approached through the individual, the social situation or social interaction. Psychoanalysis approaches the individual in terms of the coded communications of psychoneurotic symptoms or psychotic behaviour; the humanist-existential approach is concerned more with emotional expression. Both approaches emphasize the development of individual identity. The interaction between persons and their social background is stressed. Relevant are sociological concepts such as illness behaviour, stigma, labelling, institutionalization and compliance. Two approaches to social interactions are considered: the gamesplaying metaphor, e.g. back pain as a psychosocial manipulation--the 'pain game'; and the 'spiral of reciprocal perspectives' which emphasizes the interactional complexities of social perceptions. Communicatory aspects of psychological treatments are noted: learning a particular metaphor such as 'resolution' of the problem (psychotherapy), learning more 'rewarding' behaviour (learning theory) or learning authenticity or self-actualization (humanist-existential).

  9. Transferência placentária de drogas Placental drug transfer

    OpenAIRE

    Ricardo de Carvalho Cavalli; Cláudia de Oliveira Baraldi; Sérgio Pereira da Cunha

    2006-01-01

    Grávidas podem depender do uso de medicações para minimizar os agravos da doença preexistente. A gravidez, por si só, pode causar situações que comprometem o bem-estar materno, como náuseas e vômitos, as quais necessitam de tratamento. O obstetra deve estar atento à transferência placentária de drogas e à exposição do feto a agentes teratogênicos ou tóxicos, que podem comprometer o seu desenvolvimento ou mesmo sua vida futura.O transporte através da placenta envolve o movimento de moléculas e...

  10. Early studies of placental ultrastructure by electron microscopy

    DEFF Research Database (Denmark)

    Carter, A M; Enders, A C

    2016-01-01

    BACKGROUND: Transmission electron microscopy (TEM) was first applied to study placental ultrastructure in the 1950's. We review those early studies and mention the scientists that employed or encouraged the use of TEM. FINDINGS: Among the pioneers Edward W. Dempsey was a key figure who attracted...... many other scientists to Washington University in St. Louis. Work on human placental ultrastructure was initiated at Cambridge and Kyoto whilst domestic animals were initially studied by Björkman in Stockholm and electron micrographs of bat placenta were published by Wimsatt of Cornell University...

  11. Metabolism of bupropion by baboon hepatic and placental microsomes

    OpenAIRE

    2011-01-01

    The aim of this investigation was to determine the biotransformation of bupropion by baboon hepatic and placental microsomes, identify the enzyme(s) catalyzing the reaction(s) and determine its kinetics. Bupropion was metabolized by baboon hepatic and placental microsomes to hydroxybupropion (OH-BUP), threo- (TB) and erythrohydrobupropion (EB). OH-bupropion was the major metabolite formed by hepatic microsomes (Km 36 ± 6 µM, Vmax 258 ± 32 pmol mg protein−1 min−1), however the formation of OH-...

  12. Influence of placental position on obstetric morbidity in placenta previa

    Directory of Open Access Journals (Sweden)

    Shripad S. Hebbar

    2014-06-01

    Conclusions: It is difficult to assign a maternal or perinatal morbidity risk to a particular type of placental location. The need for specialized surgical intervention such as uterine / internal iliac artery ligation, peripartum hysterectomy can arise irrespective of placental location, whether underneath the surgical incision (anterior, proximity to main uterine trunks (lateral or encountered after the delivery of the baby (posterior. Pregnancies complicated by placenta previa must be delivered in the hospitals having expertise of senior and skilled surgeons and well equipped blood bank and good neonatal intensive care unit. [Int J Reprod Contracept Obstet Gynecol 2014; 3(3.000: 585-591

  13. Human placental alkaline phosphatase electrophoretic alleles: Quantitative studies

    Science.gov (United States)

    Lucarelli, Paola; Scacchi, Renato; Corbo, Rosa Maria; Benincasa, Alberto; Palmarino, Ricciotti

    1982-01-01

    Human placental alkaline phosphatase (ALP) activity has been determined in specimens obtained from 562 Italian subjects. The mean activities of the three common homozygotes (Pl 2 = 4.70 ± 0.24, Pl 1 = 4.09 ± 0.08, and Pl 3 = 2.15 ± 0.71 μmol of p-nitrophenol produced) were significantly different. The differences among the various allelic forms account for 10% of the total quantitative variation of the human placental alkaline phosphatase. PMID:7072721

  14. Excessive astrocyte-derived neurotrophin-3 contributes to the abnormal neuronal dendritic development in a mouse model of fragile X syndrome.

    Science.gov (United States)

    Yang, Qi; Feng, Bin; Zhang, Kun; Guo, Yan-yan; Liu, Shui-bing; Wu, Yu-mei; Li, Xiao-qiang; Zhao, Ming-gao

    2012-01-01

    Fragile X syndrome (FXS) is a form of inherited mental retardation in humans that results from expansion of a CGG repeat in the Fmr1 gene. Recent studies suggest a role of astrocytes in neuronal development. However, the mechanisms involved in the regulation process of astrocytes from FXS remain unclear. In this study, we found that astrocytes derived from a Fragile X model, the Fmr1 knockout (KO) mouse which lacks FMRP expression, inhibited the proper elaboration of dendritic processes of neurons in vitro. Furthermore, astrocytic conditioned medium (ACM) from KO astrocytes inhibited proper dendritic growth of both wild-type (WT) and KO neurons. Inducing expression of FMRP by transfection of FMRP vectors in KO astrocytes restored dendritic morphology and levels of synaptic proteins. Further experiments revealed elevated levels of the neurotrophin-3 (NT-3) in KO ACM and the prefrontal cortex of Fmr1 KO mice. However, the levels of nerve growth factor (NGF), brain-derived neurotrophic factor (BDNF), glial cell-derived neurotrophic factor (GDNF), and ciliary neurotrophic factor (CNTF) were normal. FMRP has multiple RNA-binding motifs and is involved in translational regulation. RNA-binding protein immunoprecipitation (RIP) showed the NT-3 mRNA interacted with FMRP in WT astrocytes. Addition of high concentrations of exogenous NT-3 to culture medium reduced the dendrites of neurons and synaptic protein levels, whereas these measures were ameliorated by neutralizing antibody to NT-3 or knockdown of NT-3 expression in KO astrocytes through short hairpin RNAs (shRNAs). Prefrontal cortex microinjection of WT astrocytes or NT-3 shRNA infected KO astrocytes rescued the deficit of trace fear memory in KO mice, concomitantly decreased the NT-3 levels in the prefrontal cortex. This study indicates that excessive NT-3 from astrocytes contributes to the abnormal neuronal dendritic development and that astrocytes could be a potential therapeutic target for FXS.

  15. Excessive astrocyte-derived neurotrophin-3 contributes to the abnormal neuronal dendritic development in a mouse model of fragile X syndrome.

    Directory of Open Access Journals (Sweden)

    Qi Yang

    Full Text Available Fragile X syndrome (FXS is a form of inherited mental retardation in humans that results from expansion of a CGG repeat in the Fmr1 gene. Recent studies suggest a role of astrocytes in neuronal development. However, the mechanisms involved in the regulation process of astrocytes from FXS remain unclear. In this study, we found that astrocytes derived from a Fragile X model, the Fmr1 knockout (KO mouse which lacks FMRP expression, inhibited the proper elaboration of dendritic processes of neurons in vitro. Furthermore, astrocytic conditioned medium (ACM from KO astrocytes inhibited proper dendritic growth of both wild-type (WT and KO neurons. Inducing expression of FMRP by transfection of FMRP vectors in KO astrocytes restored dendritic morphology and levels of synaptic proteins. Further experiments revealed elevated levels of the neurotrophin-3 (NT-3 in KO ACM and the prefrontal cortex of Fmr1 KO mice. However, the levels of nerve growth factor (NGF, brain-derived neurotrophic factor (BDNF, glial cell-derived neurotrophic factor (GDNF, and ciliary neurotrophic factor (CNTF were normal. FMRP has multiple RNA-binding motifs and is involved in translational regulation. RNA-binding protein immunoprecipitation (RIP showed the NT-3 mRNA interacted with FMRP in WT astrocytes. Addition of high concentrations of exogenous NT-3 to culture medium reduced the dendrites of neurons and synaptic protein levels, whereas these measures were ameliorated by neutralizing antibody to NT-3 or knockdown of NT-3 expression in KO astrocytes through short hairpin RNAs (shRNAs. Prefrontal cortex microinjection of WT astrocytes or NT-3 shRNA infected KO astrocytes rescued the deficit of trace fear memory in KO mice, concomitantly decreased the NT-3 levels in the prefrontal cortex. This study indicates that excessive NT-3 from astrocytes contributes to the abnormal neuronal dendritic development and that astrocytes could be a potential therapeutic target for FXS.

  16. Inflammatory Cytokines in Maternal Circulation and Placenta of Chromosomally Abnormal First Trimester Miscarriages

    Directory of Open Access Journals (Sweden)

    Jean Calleja-Agius

    2012-01-01

    Full Text Available The impact of abnormal placental karyotype on the inflammatory response within the villous tissue and peripheral circulation of women with miscarriage was evaluated. Villous (=38 and venous blood samples (=26 were obtained from women with missed miscarriage. Tissue chromosome analysis indicated 23 abnormal and 15 normal karyotypes. Concentration of tumour necrosis factor alpha (TNF, TNF-R1 and TNF-R2, and interleukin (IL-10 were measured using flowcytometric bead array in fresh villous homogenate, cultured villous extracts, culture medium, maternal whole blood, and plasma. Plasma TNF/IL-10 ratios were significantly (<0.05 lower in miscarriages with abnormal karyotype. In the abnormal karyotype group, there were significantly higher levels of TNF (<0.01, IL-10 (<0.01, TNF-R1 (<0.001, and TNF-R2 (<0.001 in the villous extracts and culture-conditioned medium compared to normal karyotype group. In miscarriage with abnormal karyotype, there is an exacerbated placental inflammatory response, in contrast to miscarriage of normal karyotype where maternal systemic response is increased.

  17. Neuroendocrine abnormalities in Parkinson's disease.

    Science.gov (United States)

    De Pablo-Fernández, Eduardo; Breen, David P; Bouloux, Pierre M; Barker, Roger A; Foltynie, Thomas; Warner, Thomas T

    2017-02-01

    Neuroendocrine abnormalities are common in Parkinson's disease (PD) and include disruption of melatonin secretion, disturbances of glucose, insulin resistance and bone metabolism, and body weight changes. They have been associated with multiple non-motor symptoms in PD and have important clinical consequences, including therapeutics. Some of the underlying mechanisms have been implicated in the pathogenesis of PD and represent promising targets for the development of disease biomarkers and neuroprotective therapies. In this systems-based review, we describe clinically relevant neuroendocrine abnormalities in Parkinson's disease to highlight their role in overall phenotype. We discuss pathophysiological mechanisms, clinical implications, and pharmacological and non-pharmacological interventions based on the current evidence. We also review recent advances in the field, focusing on the potential targets for development of neuroprotective drugs in Parkinson's disease and suggest future areas for research.

  18. Identification of Patients at Risk for Early Onset and/or Severe Preeclampsia With the Use of Uterine Artery Doppler Velocimetry and Placental Growth Factor

    Science.gov (United States)

    Espinoza, Jimmy; Romero, Roberto; Nien, Jyh Kae; Gomez, Ricardo; Kusanovic, Juan Pedro; Gonçalves, Luis F.; Medina, Luis; Edwin, Sam; Hassan, Sonia; Carstens, Mario; Gonzalez, Rogelio

    2007-01-01

    OBJECTIVE: Preeclampsia has been proposed to be an anti-angiogenic state that may be detected by the determination of the concentrations of the soluble vascular endothelial growth factor receptor-1 (sVEGFR-1) and placental growth factor (PlGF) in maternal blood even before the clinical development of the disease. The purpose of this study was to determine the role of the combined use of uterine artery Doppler velocimetry (UADV) and maternal plasma PlGF and sVEGFR-1 concentrations in the second trimester for the identification of patients at risk for severe and/or early onset preeclampsia. STUDY DESIGN: A prospective cohort study was designed to examine the relationship between abnormal UADV and plasma concentrations of PlGF and sVEGFR-1 in 3348 pregnant women. Plasma samples were obtained between 22 and 26 weeks of gestation at the time of ultrasound examination. Abnormal UADV was defined as the presence of bilateral uterine artery notches and/or a mean pulsatility index above the 95th percentile for the gestational age. Maternal plasma PlGF and sVEGFR-1 concentrations were determined with the use of sensitive and specific immunoassays. The primary outcome was the development of early onset preeclampsia (≤34 weeks of gestation) and/or severe preeclampsia. Secondary outcomes included preeclampsia, the delivery of a small for gestational age (SGA) neonate without preeclampsia, spontaneous preterm birth at ≤32 and ≤35 weeks of gestation, and a composite of severe neonatal morbidity. Contingency tables, chi-square test, receiver operating characteristic curve, and multivariate logistic regression were used for statistical analyses. A probability value of <.05 was considered significant. RESULTS: (1) The prevalence of preeclampsia, severe preeclampsia, and early onset preeclampsia were 3.4% (113/3296), 1.0% (33/3296), and 0.8% (25/3208), respectively. UADV was performed in 95.4% (3146/3296) and maternal plasma PlGF concentrations were determined in 93.5% (3081

  19. Investigating the effect of excess caffeine exposure on placental angiogenesis using chicken 'functional' placental blood vessel network.

    Science.gov (United States)

    Ma, Zheng-Lai; Wang, Guang; Lu, Wen-Hui; Cheng, Xin; Chuai, Manli; Lee, Kenneth Ka Ho; Yang, Xuesong

    2016-02-01

    It is now known that over-consumption of caffeine by pregnant mothers could have detrimental effects on normal fetal development. However, it remains obscure how caffeine's harmful effect impacts directly or indirectly on the developing embryo/fetus through damaging placenta development. In this study, we demonstrated the morphological similarities between the yolk sac and chorioallantoic membranes (CAM) of chick embryos and the villi of the mammalian placenta. Using the chick yolk sac and the CAM as a model, we found that 5-15 µmol per egg of caffeine exposure inhibited angiogenesis. Under the same condition, cell proliferation in extraembryonic mesoderm was reduced while apoptosis was enhanced. Semi-quantitative RT-PCR analysis revealed that caffeine treatment down-regulated VEGF, VEGFR2, PIGF, IGF2 and NRP1 expression, but up-regulated Ang1 and Ang2 expression. We performed in situ hybridization to show VE-cadherin expression and as to demonstrate the blood vessels in the CAM and yolk sac membranes. This distribution of the VE-cadherin(+) blood vessels was determined to be reduced after caffeine treatment. Furthermore, MDA activity was induced after caffeine exposure, but GSH-PX activity was inhibited after caffeine exposure; SOD activity was unchanged as compared with the control. In summary, our results suggest that caffeine exposure could negatively impact on angiogenesis in the chick yolk sac and CAM by targeting angiogenesis-related genes. Some of these genes are also involved in regulating excess ROS generation. The results implied that the negative impact of caffeine on fetal development was partly attributed to impaired placental angiogenesis.

  20. Development and validation of an high-performance liquid chromatography-diode array detector method for the simultaneous determination of six phenolic compounds in abnormal savda munziq decoction

    Directory of Open Access Journals (Sweden)

    Shuge Tian

    2015-01-01

    Full Text Available Aims: Given the high-effectiveness and low-toxicity of abnormal savda munziq (ASMQ, its herbal formulation has long been used in traditional Uyghur medicine to treat complex diseases, such as cancer, diabetes, and cardiovascular diseases. Settings and Design: ASMQ decoction by reversed-phase high-performance liquid chromatography coupled with a diode array detector was successfully developed for the simultaneous quality assessment of gallic acid, protocatechuic acid, caffeic acid, rutin, rosmarinic acid, and luteolin. The six phenolic compounds were separated on an Agilent TC-C18 reversed-phase analytical column (4.6 × 250 mm, 5 μm by gradient elution using 0.3% aqueous formic acid (v/v and 0.3% methanol formic acid (v/v at 1.0 mL/min. Materials and Methods: The plant material was separately ground and mixed at the following ratios (10: Cordia dichotoma (10.6, Anchusa italic (10.6, Euphorbia humifusa (4.9, Adiantum capillus-veneris (4.9, Ziziphus jujube (4.9, Glycyrrhiza uralensis (7.1, Foeniculum vulgare (4.9, Lavandula angustifolia (4.9, Dracocephalum moldavica L. (4.9, and Alhagi pseudoalhagi (42.3. Statistical Analysis Used: The precisions of all six compounds were 0.999. Results: The proposed method was successfully applied to determine the levels of six active components in ASMQ. Conclusions: Given the simplicity, precision, specificity, and sensitivity of the method, it can be utilized as a quality control approach to simultaneously determining the six phenolic compounds in AMSQ.

  1. Analysis the Complicated with Placental Abruption Early Diagnosis and Treatment%胎膜早破并发胎盘早剥的早期诊治

    Institute of Scientific and Technical Information of China (English)

    沈倩倩

    2013-01-01

    目的:分析胎膜早破并发胎盘早剥的早期诊治。方法:研究自09年2月~13年1月收治的胎膜早破产妇,有18例并发胎盘早剥,其为观察组;对照组为22例非胎膜早破而并发胎盘早剥的产妇。比较2组胎盘早剥的发生率。结果:导致胎盘早剥首位诱因是胎膜早破,占45%。在胎膜早破组产妇中,并发胎盘早剥概率为2.97%(18/606);而非胎膜早破组的产妇并发胎盘早剥概率为0.30%(22/7390),前者明显高于后者,P<0.001,差异具有显著性。结论:对胎膜早破患者要密切注意其异常临床表现,对其进行早期诊治。%Objective:To analyze the complicated with placental abruption early diagnosis and treatment.Methods:Study from February 09 to 13 years of premature rupture of fetal membrane puerpera admitted in January , 18 cases were complicated with pla-cental abruption, as observed group.Results:The control group of 22 cases of premature rupture of membranes and complicated with placental abruption maternal.Compare two groups the incidence of placental abruption.First cause as a result of placental ab-ruption, premature rupture of membranes is 45%.Premature rupture of membranes in the group of women, the concurrent probabil-ity of placental abruption was 2.97% (18/606); Premature rupture of membranes, rather than group complicated with placental abruption maternal probability was 0.30% (22/7390), significantly higher than the latter, the former (P <0.001, with signifi-cant difference.Conclusion:Patients with premature rupture of membranes to pay close attention to the abnormal clinical manifesta-tions, on the early diagnosis and treatment.

  2. Placentation in the Hottentot golden mole, Amblysomus hottentotus (Afrosoricida: Chrysochloridae)

    DEFF Research Database (Denmark)

    Jones, C J P; Carter, A M; Bennett, N C;

    2009-01-01

    The placentation of the Hottentot golden mole (Amblysomus hottentotus) has been examined using light and electron microscopy and lectin histochemistry of nine specimens at both mid and late gestation. The placentae were lobulated towards the allantoic surface and the lobules contained roughly par...

  3. Placentation in dolphins from the Amazon River Basin

    DEFF Research Database (Denmark)

    da Silva, Vera M F; Carter, Anthony M; Ambrosio, Carlos E

    2007-01-01

    A recent reassessment of the phylogenetic affinities of cetaceans makes it timely to compare their placentation with that of the artiodactyls. We studied the placentae of two sympatric species of dolphin from the Amazon River Basin, representing two distinct families. The umbilical cord branched...

  4. 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 "n...

  5. Polyaromatic compounds alter placental protein synthesis in pregnant rats

    Energy Technology Data Exchange (ETDEWEB)

    Shiverick, K.T.; Ogilvie, S.; Medrano, T. (Univ. of Florida, Gainesville (United States))

    1991-03-15

    The administration of the polyaromatic compounds {beta}-naphthoflavone ({beta}NF) and 3-methylcholanthrene (3MC) to pregnant rats during mid-gestation has been shown to produce marked feto-placental growth retardation. This study examined secretory protein synthesis in placental tissue from rats following administration of {beta}NF on gestation days (gd) 11-14 or 3MC on gd 12-14. Explants of placental basal zone tissue were cultured for 24 hours in serum-free medium in the presence of ({sup 3}H)leucine. Secreted proteins were analyzed by two-dimensional SDS-polyacrylamide gel electrophoresis followed by either fluorography or immunostaining. Total incorporation of ({sup 3}H)leucine into secreted proteins was not altered in BZ explants from {beta}NF or 3MC-treated animals. However a selective decrease was observed in ({sup 3}H)leucine incorporation into a major complex of proteins with apparent molecular weight of 25-30,000 and isoelectric point between 5.3 to 5.7. This group of proteins has been further identified as being related to rat pituitary growth hormone (GH) using N-terminal amino acid microsequencing of individual spots from 2-D SDS-PA gels. This is the first report that synthesis of GH-related proteins by rat placenta is decreased following {beta}NF and 3MC administration, a change which may underlie the feto-placental growth retardation associated with these polyaromatic compounds.

  6. Evaluation of placental glycogen storage in mild diabetic rats Avaliação dos estoques de glicogênio placentário em ratas com diabete moderado

    Directory of Open Access Journals (Sweden)

    Aline Bueno

    2010-04-01

    Full Text Available PURPOSE: To evaluate the placental glycogen storage and fetal development in the pregnancy of neonatally streptozocin-induced diabetic rats and to establish relation with glycemia and insulin levels. METHODS: At the birth day, 147 female rats were randomly distributed in two experimental groups: 1 Non-diabetic Group (Control, n=45 - received the vehicle; 2 Diabetic Group (STZ, n=102 - received 100 mg streptozocin/kg in neonatal period. At day 0 of pregnancy, adult female rats were included in the control group when presented glycemia below 120 mg/dL and, in the group STZ with glycemia between 120 and 300 mg/dL. At day 21 of pregnancy, blood samples were collected for glycemia and insulin determination, and placentas withdrawn for placental glycogen determination. The newborns (NB were classified in small (SGA, appropriate (AGA and large (LGA for gestational age. RESULTS: Rats STZ presented higher glycemia at days 0 and 14 of pregnancy. At end of pregnancy, rats STZ showed higher proportion of NB SGA and LGA; reduced rate of NB AGA and unaltered glycemia, insulin and placental glycogen determinations. CONCLUSION: Mild diabetes altered the maternal glycemia in the early pregnancy, impairing future fetal development, but it caused no alteration on insulin and placental glycogen determination, confirming that this glycemic intensity was insufficient to change glycogen metabolism.OBJETIVO: Avaliar os estoques de glicogênio placentário e o desenvolvimento fetal na prenhez de ratas com diabete moderado induzido no período neonatal e relacionar com glicemia e níveis de insulina. MÉTODOS: No dia de nascimento, foram distribuídas aleatoriamente 147 ratas em dois grupos experimentais: 1 Grupo Não-diabético (Controle, n=45 - recebeu o veículo; 2 Grupo Diabético (STZ, n=102 - recebeu 100 mg streptozocin/kg peso corpóreo. No dia 0 de prenhez, foram incluídas ratas controle que apresentassem glicemia baixo de 120 mg/dL e, no grupo STZ, com glicemia

  7. Brain size, life history, and metabolism at the marsupial/placental dichotomy.

    Science.gov (United States)

    Weisbecker, Vera; Goswami, Anjali

    2010-09-14

    The evolution of mammalian brain size is directly linked with the evolution of the brain's unique structure and performance. Both maternal life history investment traits and basal metabolic rate (BMR) correlate with relative brain size, but current hypotheses regarding the details of these relationships are based largely on placental mammals. Using encephalization quotients, partial correlation analyses, and bivariate regressions relating brain size to maternal investment times and BMR, we provide a direct quantitative comparison of brain size evolution in marsupials and placentals, whose reproduction and metabolism differ extensively. Our results show that the misconception that marsupials are systematically smaller-brained than placentals is driven by the inclusion of one large-brained placental clade, Primates. Marsupial and placental brain size partial correlations differ in that marsupials lack a partial correlation of BMR with brain size. This contradicts hypotheses stating that the maintenance of relatively larger brains requires higher BMRs. We suggest that a positive BMR-brain size correlation is a placental trait related to the intimate physiological contact between mother and offspring during gestation. Marsupials instead achieve brain sizes comparable to placentals through extended lactation. Comparison with avian brain evolution suggests that placental brain size should be constrained due to placentals' relative precociality, as has been hypothesized for precocial bird hatchlings. We propose that placentals circumvent this constraint because of their focus on gestation, as opposed to the marsupial emphasis on lactation. Marsupials represent a less constrained condition, demonstrating that hypotheses regarding placental brain size evolution cannot be generalized to all mammals.

  8. Anti-TPO antibodies diffusion through the placental barrier during pregnancy.

    Directory of Open Access Journals (Sweden)

    Jérémy Seror

    Full Text Available BACKGROUND: Hashimoto's thyroiditis is the principal aetiology of hypothyroidism with presence of anti-thyroperoxidase antibodies (anti-TPO. The association between anti-TPO and foeto-placental complications has been observed in previous studies. To go further in the understanding, the current study compares the level of anti-TPO in maternal blood and in the cord blood of her fetus at the moment of childbirth to demonstrate the passage of anti-TPO through the placenta barrier. METHODS AND FINDINGS: This study was realised in a maternity ward located in the Northern district of Paris, France from 2006 to 2007. Women with normal pregnancy were included in a first study and only women with no abnormal thyroid dosage at baseline and tested positive with anti-TPO were prospectively enrolled. Maternal blood samples were collected in the third trimester and at the arrival to the ward when patients came to deliver. After delivery, cord blood sample was collected. Pearson's correlation coefficient was computed. 5941 patients delivered in the ward during the study, 33 pregnant women were included. We found a correlation between the anti-TPO levels in maternal and in the cord blood of their fetus with a correlation coefficient of 0.98 and a p-value<0.001. CONCLUSIONS: This is the first demonstration of the free passage through the placental barrier of anti-TPO from the mother to the fetus at the moment of childbirth. These findings can be extrapolated all along pregnancy and open the door to a direct action of the anti-TPO on fetus and to a possible action on the fetal thyroid.

  9. [Hair shaft abnormalities].

    Science.gov (United States)

    Itin, P H; Düggelin, M

    2002-05-01

    Hair shaft disorders may lead to brittleness and uncombable hair. In general the hair feels dry and lusterless. Hair shaft abnormalities may occur as localized or generalized disorders. Genetic predisposition or exogenous factors are able to produce and maintain hair shaft abnormalities. In addition to an extensive history and physical examination the most important diagnostic examination to analyze a hair shaft problem is light microscopy. Therapy of hair shaft disorders should focus to the cause. In addition, minimizing traumatic influences to hair shafts, such as dry hair with an electric dryer, permanent waves and dyes is important. A short hair style is more suitable for such patients with hair shaft disorders.

  10. Differential regulation of placental amino acid transport by saturated and unsaturated fatty acids.

    Science.gov (United States)

    Lager, Susanne; Jansson, Thomas; Powell, Theresa L

    2014-10-15

    Fatty acids are critical for normal fetal development but may also influence placental function. We have previously reported that oleic acid (OA) stimulates amino acid transport in primary human trophoblasts (PHTs). In other tissues, saturated and unsaturated fatty acids have distinct effects on cellular signaling, for instance, palmitic acid (PA) but not OA reduces IκBα expression. We hypothesized that saturated and unsaturated fatty acids differentially affect trophoblast amino acid transport and cellular signaling. To test this hypothesis, PHTs were cultured in docosahexaenoic acid (DHA; 50 μM), OA (100 μM), or PA (100 μM). DHA and OA were also combined to test whether DHA could counteract the OA stimulatory effect on amino acid transport. The effects of fatty acids were compared against a vehicle control. Amino acid transport was measured by isotope-labeled tracers. Activation of inflammatory-related signaling pathways and the mechanistic target of rapamycin (mTOR) pathway were determined by Western blot analysis. Exposure of PHTs to DHA for 24 h reduced amino acid transport and phosphorylation of p38 MAPK, STAT3, mTOR, eukaryotic initiation factor 4E-binding protein 1, and ribosomal protein (rp)S6. In contrast, OA increased amino acid transport and phosphorylation of ERK, mTOR, S6 kinase 1, and rpS6. The combination of DHA with OA increased amino acid transport and rpS6 phosphorylation. PA did not affect amino acid transport but reduced IκBα expression. In conclusion, these fatty acids differentially regulated placental amino acid transport and cellular signaling. Taken together, these findings suggest that dietary fatty acids could alter the intrauterine environment by modifying placental function, thereby having long-lasting effects on the developing fetus.

  11. Are There Gender-Specific Pathways from Early Adolescence Psychological Distress Symptoms toward the Development of Substance Use and Abnormal Eating Behavior?

    Science.gov (United States)

    Beato-Fernandez, Luis; Rodriguez-Cano, Teresa; Pelayo-Delgado, Esther; Calaf, Myralys

    2007-01-01

    The aim of the present longitudinal community study was to test whether psychological distress at 13 years of age predicted reported substance use problems in boys and abnormal eating behavior in girls 2 years later. The sample consisted of 500 male and 576 female students. The use of substances was evaluated using a semi-structured interview,…

  12. Differential transferrin expression in placentae from normal and abnormal pregnancies: a pilot study

    Directory of Open Access Journals (Sweden)

    Bukovsky Antonin

    2008-07-01

    Full Text Available Abstract Background The placenta is an important site for iron metabolism in humans. It transfers iron from the mother to the fetus. One of the major iron transport proteins is transferrin, which is a blood plasma protein crucial for iron uptake. Its localization and expression may be one of the markers to distinguish placental dysfunction. Methods In the experimental study we used antibody preparation, mass spectrometric analysis, biochemical and immunocytochemical methods for characterization of transferrin expression on the human choriocarcinoma cell line JAR (JAR cells, placental lysates, and cryostat sections. Newly designed monoclonal antibody TRO-tf-01 to human transferrin was applied on human placentae from normal (n = 3 and abnormal (n = 9 pregnancies. Results Variations of transferrin expression were detected in villous syncytiotrophoblast, which is in direct contact with maternal blood. In placentae from normal pregnancies, the expression of transferrin in the syncytium was significantly lower (p Conclusion These observations suggest that in the case of abnormal pregnancies, the fetus may require higher levels of transferrin in order to prevent iron depletion due to the stress from the placental dysfunction.

  13. Relational development in children with cleft lip and palate: influence of the waiting period prior to the first surgical intervention and parental psychological perceptions of the abnormality

    Directory of Open Access Journals (Sweden)

    Grollemund Bruno

    2012-06-01

    Full Text Available Abstract Background The birth of a child with a cleft lip, whether or not in association with a cleft palate, is a traumatic event for parents. This prospective, multidisciplinary and multi-centre study aims to explore the perceptions and feelings of parents in the year following the birth of their child, and to analyse parent–child relationships. Four inclusion centres have been selected, differing as to the date of the first surgical intervention, between birth and six months. The aim is to compare results, also distinguishing the subgroups of parents who were given the diagnosis in utero and those who were not. Methods/Design The main hypothesis is that the longer the time-lapse before the first surgical intervention, the more likely are the psychological perceptions of the parents to affect the harmonious development of their child. Parents and children are seen twice, when the child is 4 months (T0 and when the child is one year old (T1. At these two times, the psychological state of the child and his/her relational abilities are assessed by a specially trained professional, and self-administered questionnaires measuring factors liable to affect child–parent relationships are issued to the parents. The Alarme Détresse BéBé score for the child and the Parenting Stress Index score for the parents, measured when the child reaches one year, will be used as the main criteria to compare children with early surgery to children with late surgery, and those where the diagnosis was obtained prior to birth with those receiving it at birth. Discussion The mental and psychological dimensions relating to the abnormality and its correction will be analysed for the parents (the importance of prenatal diagnosis, relational development with the child, self-image, quality of life and also, for the first time, for the child (distress, withdrawal. In an ethical perspective, the different time lapses until surgery in the different protocols and their

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

    Science.gov (United States)

    Aye, Irving L M H; Keelan, Jeffrey A

    2013-04-25

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

  15. Deoxynivalenol transport across the human placental barrier.

    Science.gov (United States)

    Nielsen, Jeanette K S; Vikström, Anna C; Turner, Paul; Knudsen, Lisbeth E

    2011-09-01

    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 revealed frequent human exposure. This study reports on DON transfer across the human placenta. Firstly, in vitro studies with the BeWo b30 clone were used as a rapid screening model showing transfer of DON through a stable confluent cell monolayer. Five term placentas were then used to study DON transfer with the ex vivo dual perfusion model. The concentration of DON on the foetal side after 4h was about 21% of that on the maternal side at t=0. These results support the data from the BeWo monolayer model in respect to the transport rate of DON, and are consistent with our hypothesis of foetal exposure to DON during pregnancy.

  16. Prenatal diagnosis of a placental infarction hematoma associated with fetal growth restriction, preeclampsia and fetal death: clinicopathological correlation.

    Science.gov (United States)

    Aurioles-Garibay, Alma; Hernandez-Andrade, Edgar; Romero, Roberto; Qureshi, Faisal; Ahn, Hyunyoung; Jacques, Suzanne M; Garcia, Maynor; Yeo, Lami; Hassan, Sonia S

    2014-01-01

    The lesion termed 'placental infarction hematoma' is associated with fetal death and adverse perinatal outcome. Such a lesion has been associated with a high risk of fetal death and abruption placentae. The fetal and placental hemodynamic changes associated with placental infarction hematoma have not been reported. This paper describes a case of early and severe growth restriction with preeclampsia, and progressive deterioration of the fetal and placental Doppler parameters in the presence of a placental infarction hematoma.

  17. Cortical Abnormalities in ADHD

    Directory of Open Access Journals (Sweden)

    J Gordon Millichap

    2003-12-01

    Full Text Available Grey-matter abnormalities at the cortical surface and regional brain size were mapped by high-resolution MRI and surface-based, computational image analytical techniques in a group of 27 children and adolescents with attention deficit hyperactivity disorder (ADHD and 46 controls, matched by age and sex, at the University of California at Los Angeles.

  18. Neurological abnormalities predict disability

    DEFF Research Database (Denmark)

    Poggesi, Anna; Gouw, Alida; van der Flier, Wiesje

    2014-01-01

    To investigate the role of neurological abnormalities and magnetic resonance imaging (MRI) lesions in predicting global functional decline in a cohort of initially independent-living elderly subjects. The Leukoaraiosis And DISability (LADIS) Study, involving 11 European centres, was primarily aimed...

  19. Lacrimal system abnormalities.

    Science.gov (United States)

    Moore, B D

    1994-03-01

    This report outlines several of the more important abnormalities of the lacrimal system in infants and young children. Although rare, alacrima can be a very difficult clinical problem to treat. The most common cause of alacrima is the Riley-Day syndrome. Nasolacrimal duct obstruction is a very common anomaly in children. The clinical appearance and treatment of this disorder are discussed.

  20. Effects of preeclampsia-like symptoms at early gestational stage on feto-placental outcomes in a mouse model

    Institute of Scientific and Technical Information of China (English)

    MA Rui-qiong; SUN Min-na; YANG Zi

    2010-01-01

    Background Early and late-onset preeclampsia is thought to be different disease entities. This study aimed to determine the effects of early-onset preeclampsia-like symptoms on feto-placental outcomes and the adverse impacts of various factors on placental and fetal growth and development at different gestational stages in a mouse model. Methods Pregnant C57BL/6J mice were divided into control and preeclampsia (PE) groups, and injected subcutaneously with the nitric oxide synthase inhibitor L-arginine methyl ester (L-NAME) 50 mg·kg~(-1)·d~(-1). The PE group was divided into early-, mid- and late-PE groups with L-NAME injections starting on days 7, 11 and 16 of pregnancy, respectively. Corresponding control groups were injected with saline at the same time points. Blood pressure was measured until days 14 and 18, when the fetuses and placentas were removed under anesthesia. Blood pressure, urinary protein, and fetal and placental conditions were analyzed. Results Blood pressure and urinary protein increased following L-NAME injection. The fetal survival rate and fetal weight were reduced and the fetal absorption rate was increased in the early-PE group on days 14 and 18 of pregnancy, compared with the control group. There were no significant differences in these parameters between the late-PE group and the respective control group. Placental weights in the early- and mid-PE groups were significantly reduced at days 14 and 18 of pregnancy compared with the control groups, but there was no significant difference in placental weight between the late-PE group and the respective control group. Morphologic examination of placentas from the early- and mid-PE groups showed varying degrees of fibrinoid necrosis and villous interstitial edema, but no significant pathologic changes were found in the placentas from the late-PE or control groups. Conclusion Preeclampsia-like symptoms occurring during the early stage of pregnancy are more likely to affect placental and fetal

  1. Investigation of confined placental mosaicism (CPM) at multiple sites in post-delivery placentas derived through intracytoplasmic sperm injection (ICSI).

    Science.gov (United States)

    Minor, Agata; Harmer, Karynn; Peters, Nicole; Yuen, Basil Ho; Ma, Sai

    2006-01-01

    Although earlier studies on pregnancies derived through intracytoplasmic sperm injection (ICSI) reported increased non-mosaic aneuploidy among ICSI children, undetected mosaicism, such as confined placental mosaicism (CPM) has not been evaluated. We investigated the incidence of CPM in post-delivery placentas derived from ICSI, evaluated whether CPM was increased and whether it was a contributing factor to negative pregnancy outcome. [Fifty-one post-delivery placentas were collected from patients who underwent ICSI with a normal or negative pregnancy outcome]. Trophoblast and chorionic stroma from three sites were analyzed by comparative genomic hybridization (CGH) and flow cytometry. Detected abnormalities were confirmed by fluorescence in situ hybridization (FISH). The incidence of CPM in the ICSI population was compared to the general population from published data. We detected three cases of CPM in our study. One abnormality was found by CGH analysis; partial trisomy 7q and a partial monosomy Xp limited to the trophoblast at two sites. The abnormality was associated with a child affected by spina bifida. Two cases of mosaic tetraploidy were observed by flow cytometry in pregnancies with a normal outcome. All three abnormalities were confirmed by FISH analysis. The incidence of CPM in the ICSI study population was 5.88% (3/51), which was not statistically different from published reports in the general population (5.88% (42/714), Chi square, P > 0.05). The post-ICSI population was not at risk for CPM in this study.

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

    Directory of Open Access Journals (Sweden)

    Yi-na Sun

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

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

    Science.gov (United States)

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

    2014-01-01

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

  4. Alterations of placental cytochrome P450 1A1 and P-glycoprotein in tobacco-induced intrauterine growth retardation in rats

    Institute of Scientific and Technical Information of China (English)

    You-e YAN; Hui WANG; Ying-hong FENG

    2005-01-01

    Aim: To investigate the alterations of placental P-glycoprotein (P-gp) and cytochrome P450 1A1 (CYP1A1) at different gestational days (GD), and to explore the possible significance of placental P-gp and CYP1A1 in tobacco smoke-induced intrauterine growth retardation (IUGR) in rats. Methods: An IUGR model was produced by passive tobacco smoking from GD 7 to parturition (GD 21) and predicted using fetal development parameters. Placental structure and function were monitored by observing pathological alteration and antioxidative function, including the content of malondialdehyde and the activities of superoxide dismutase and catalase (CAT). The expressions of CYP1A1 and P-gp (mdr 1a and mdr 1b)were detected using a reverse transcription polymerase chain reaction and immunohistochemistry. Results: Placental pathological changes occurred and the malondialdehyde content increased, whereas the activities ofsuperoxide dismutase and CAT lowered, when compared to their controls. In the rat placenta of the tobacco group, the level of CYP1A1 mRNA increased significantly; the level of mdr1a mRNA increased significantly at GD 21 but not at GD 14, whereas the level of mdr1b mRNA in different term remained stable; the expression of P-gp increased significantly only in full-term placenta. Conclusion: The expression of placental CYP1A1 and P-gp increased in tobacco-induced IUGR. Overexpression of placental CYP1A1 can attribute to the metabolism of tobacco and the generation of reactive metabolites, which can trigger IUGR. As a compulsory mechanism,upregulation of P-gp might decrease tobacco exposure to a developing fetus with IUGR.

  5. X-linked Christianson syndrome: heterozygous female Slc9a6 knockout mice develop mosaic neuropathological changes and related behavioral abnormalities

    Directory of Open Access Journals (Sweden)

    Jakub Sikora

    2016-01-01

    Full Text Available Christianson syndrome (CS is an X-linked neurodevelopmental and neurological disorder characterized in males by core symptoms that include non-verbal status, intellectual disability, epilepsy, truncal ataxia, postnatal microcephaly and hyperkinesis. CS is caused by mutations in the SLC9A6 gene, which encodes a multipass transmembrane sodium (potassium-hydrogen exchanger 6 (NHE6 protein, functional in early recycling endosomes. The extent and variability of the CS phenotype in female heterozygotes, who presumably express the wild-type and mutant SLC9A6 alleles mosaically as a result of X-chromosome inactivation (XCI, have not yet been systematically characterized. Slc9a6 knockout mice (Slc9a6 KO were generated by insertion of the bacterial lacZ/β-galactosidase (β-Gal reporter into exon 6 of the X-linked gene. Mutant Slc9a6 KO male mice have been shown to develop late endosomal/lysosomal dysfunction associated with glycolipid accumulation in selected neuronal populations and patterned degeneration of Purkinje cells (PCs. In heterozygous female Slc9a6 KO mice, β-Gal serves as a transcriptional/XCI reporter and thus facilitates testing of effects of mosaic expression of the mutant allele on penetrance of the abnormal phenotype. Using β-Gal, we demonstrated mosaic expression of the mutant Slc9a6 allele and mosaically distributed lysosomal glycolipid accumulation and PC pathology in the brains of heterozygous Slc9a6 KO female mice. At the behavioral level, we showed that heterozygous female mice suffer from visuospatial memory and motor coordination deficits similar to but less severe than those observed in X-chromosome hemizygous mutant males. Our studies in heterozygous Slc9a6 KO female mice provide important clues for understanding the likely phenotypic range of Christianson syndrome among females heterozygous for SLC9A6 mutations and might improve diagnostic practice and genetic counseling by helping to characterize this presumably

  6. Robust time estimation reconciles views of the antiquity of placental mammals.

    Directory of Open Access Journals (Sweden)

    Yasuhiro Kitazoe

    Full Text Available BACKGROUND: Molecular studies have reported divergence times of modern placental orders long before the Cretaceous-Tertiary boundary and far older than paleontological data. However, this discrepancy may not be real, but rather appear because of the violation of implicit assumptions in the estimation procedures, such as non-gradual change of evolutionary rate and failure to correct for convergent evolution. METHODOLOGY/PRINCIPAL FINDINGS: New procedures for divergence-time estimation robust to abrupt changes in the rate of molecular evolution are described. We used a variant of the multidimensional vector space (MVS procedure to take account of possible convergent evolution. Numerical simulations of abrupt rate change and convergent evolution showed good performance of the new procedures in contrast to current methods. Application to complete mitochondrial genomes identified marked rate accelerations and decelerations, which are not obtained with current methods. The root of placental mammals is estimated to be approximately 18 million years more recent than when assuming a log Brownian motion model. Correcting the pairwise distances for convergent evolution using MVS lowers the age of the root about another 20 million years compared to using standard maximum likelihood tree branch lengths. These two procedures combined revise the root time of placental mammals from around 122 million years ago to close to 84 million years ago. As a result, the estimated distribution of molecular divergence times is broadly consistent with quantitative analysis of the North American fossil record and traditional morphological views. CONCLUSIONS/SIGNIFICANCE: By including the dual effects of abrupt rate change and directly accounting for convergent evolution at the molecular level, these estimates provide congruence between the molecular results, paleontological analyses and morphological expectations. The programs developed here are provided along with sample

  7. Monocarboxylate transporter 8 modulates the viability and invasive capacity of human placental cells and fetoplacental growth in mice.

    OpenAIRE

    Vasilopoulou, E.; Loubière, LS; Heuer, H.; Trajkovic-Arsic, M; Darras, VM; Visser, TJ; Lash, GE; Whitley, GS; McCabe, CJ; Franklyn, JA; Kilby, MD; Chan, SY

    2013-01-01

    textabstractMonocarboxylate transporter 8 (MCT8) is a well-established thyroid hormone (TH) transporter. In humans, MCT8 mutations result in changes in circulating TH concentrations and X-linked severe global neurodevelopmental delay. MCT8 is expressed in the human placenta throughout gestation, with increased expression in trophoblast cells from growth-restricted pregnancies. We postulate that MCT8 plays an important role in placental development and transplacental TH transport. We investiga...

  8. Multiorgan dysfunction in a gravid woman with placental abruption and disseminated intravascular coagulation

    Directory of Open Access Journals (Sweden)

    Kezić Aleksandra

    2007-01-01

    Full Text Available The most frequent obstetrical cause of coagulation disorders as disseminated intravascular coagulation is placental abruption, which can be found in women without any apparent clinical disturbances or in the state of established preeclampsia. Hypertension occurs in 5-8% of all pregnancies and may be complicated by preeclampsia. Preeclampsia is a complex clinical syndrome with insufficiently clear pathophysiology based on the damage of the vascular endothelium. As a result of this, generalized endothelial disruption in preeclampsia, a multiorgan dysfunction, can develop, most frequently reflected in the clinical presentation with hematological and renal disturbances and with a disordered function of the liver and central nervous system. We are presenting a case of a gravid woman with poorly regulated hypertension that resulted from development of preeclampsia, later complicated by placental abruption and disseminated intravascular coagulation (DIC with multi-organ dysfunction. The importance of rapid recognition of coagulation disorder and the attempt at surgical treatment aiming at removal of the triggering mechanisms of DIC was shown, suggesting all the symptomatic therapeutic measures would be ineffective. Although our patient was surgically treated in the phase of generalized disorder characterized by development of coma, acute respiratory distress syndrome and renal insufficiency when mortality was 70%, the recovery of functions of all involved organs was achieved, except for the renal function that required chronic haemodialysis treatment.

  9. Major mouse placental compartments revealed by diffusion-weighted MRI, contrast-enhanced MRI, and fluorescence imaging.

    Science.gov (United States)

    Solomon, Eddy; Avni, Reut; Hadas, Ron; Raz, Tal; Garbow, Joel Richard; Bendel, Peter; Frydman, Lucio; Neeman, Michal

    2014-07-15

    Mammalian models, and mouse studies in particular, play a central role in our understanding of placental development. Magnetic resonance imaging (MRI) could be a valuable tool to further these studies, providing both structural and functional information. As fluid dynamics throughout the placenta are driven by a variety of flow and diffusion processes, diffusion-weighted MRI could enhance our understanding of the exchange properties of maternal and fetal blood pools--and thereby of placental function. These studies, however, have so far been hindered by the small sizes, the unavoidable motions, and the challenging air/water/fat heterogeneities, associated with mouse placental environments. The present study demonstrates that emerging methods based on the spatiotemporal encoding (SPEN) of the MRI information can robustly overcome these obstacles. Using SPEN MRI in combination with albumin-based contrast agents, we analyzed the diffusion behavior of developing placentas in a cohort of mice. These studies successfully discriminated the maternal from the fetal blood flows; the two orders of magnitude differences measured in these fluids' apparent diffusion coefficients suggest a nearly free diffusion behavior for the former and a strong flow-based component for the latter. An intermediate behavior was observed by these methods for a third compartment that, based on maternal albumin endocytosis, was associated with trophoblastic cells in the interphase labyrinth. Structural features associated with these dynamic measurements were consistent with independent intravital and ex vivo fluorescence microscopy studies and are discussed within the context of the anatomy of developing mouse placentas.

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

    Directory of Open Access Journals (Sweden)

    Kremsner Peter G

    2004-07-01

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

  11. Abnormal Behavior in Relation to Cage Size in Rhesus Monkeys

    Science.gov (United States)

    Paulk, H. H.; And Others

    1977-01-01

    Examines the effects of cage size on stereotyped and normal locomotion and on other abnormal behaviors in singly caged animals, whether observed abnormal behaviors tend to co-occur, and if the development of an abnormal behavior repertoire leads to reduction in the number of normal behavior categories. (Author/RK)

  12. The Spacing Principle for Unlearning Abnormal Neuronal Synchrony

    OpenAIRE

    Popovych, Oleksandr V.; Markos N Xenakis; Tass, Peter A.

    2015-01-01

    Desynchronizing stimulation techniques were developed to specifically counteract abnormal neuronal synchronization relevant to several neurological and psychiatric disorders. The goal of our approach is to achieve an anti-kindling, where the affected neural networks unlearn abnormal synaptic connectivity and, hence, abnormal neuronal synchrony, by means of desynchronizing stimulation, in particular, Coordinated Reset (CR) stimulation. As known from neuroscience, psychology and education, lear...

  13. Ultrasound assessment of placental function: the effectiveness of placental biometry in a low-risk population as a predictor of a small for gestational age neonate.

    LENUS (Irish Health Repository)

    McGinty, Patricia

    2012-07-01

    The aims of the study were to establish reference ranges for placental length and thickness in a low-risk obstetric population and to assess the likelihood of a small for gestational age (SGA) neonate on the basis of placental length at 18-24 weeks\\' gestation.

  14. Insight into Antigenic Diversity of VAR2CSA-DBL5 epsilon Domain from Multiple Plasmodium falciparum Placental Isolates

    DEFF Research Database (Denmark)

    Gnidehou, Sedami; Jessen, Leon Ivar; Gangnard, Stephane;

    2010-01-01

    attractive targets for vaccine development. Methodology/Principal Findings: VAR2CSA DBL5e-domain sequences obtained from cDNA of 40 placental isolates were analysed by a combination of experimental and in silico methods. Competition ELISA assays on two DBL5e variants, using plasma samples from women from two...... on the surface of placental parasites. Despite high DBL5e sequence homology among parasite isolates, sequence analyses identified motifs in DBL5e that discriminate parasites according to donor's parity. Moreover, recombinant proteins of two VAR2CSA DBL5e variants displayed diverse recognition patterns by plasma...... from malaria-exposed women, and diverse proteoglycan binding abilities. Conclusions/Significance: This study provides insights into conserved and exposed B cell epitopes in DBL5e that might be a focus for cross reactivity. The importance of sequence variation in VAR2CSA as a critical challenge...

  15. Nitrofurantoin and congenital abnormalities

    DEFF Research Database (Denmark)

    Czeizel, A.E.; Rockenbauer, M.; Sørensen, Henrik Toft;

    2001-01-01

    Objective: To study human teratogenic potential of oral nitrofurantoin treatment during pregnancy. Materials and Methods: Pair analysis of cases with congenital abnormalities and matched population controls in the population-based dataset of the Hungarian Case-Control Surveillance of Congenital...... or fetuses with Down’s syndrome (patient controls), 23 (2.8%) pregnant women were treated with nitrofurantoin. The above differences between population controls and cases may be connected with recall bias, because the case-control pair analysis did not indicate a teratogenic potential of nitrofurantoin use...... during the second and the third months of gestation, i.e. in the critical period for major congenital abnormalities. Conclusion: Treatment with nitrofurantoin during pregnancy does not present detectable teratogenic risk to the fetus....

  16. Evolution of placental specializations in viviparous African and South American lizards.

    Science.gov (United States)

    Flemming, Alexander F; Blackburn, Daniel G

    2003-09-01

    Phylogenetic information offers an important resource in analyses of reproductive diversity, including interpretations of fetal membrane evolution. In this paper, we draw upon ongoing studies of South American and African lizards to consider the value of combining phylogenetic and reproductive evidence in the construction of evolutionary interpretations. South American lizards of the genus Mabuya exhibit several reproductive specializations that are convergent on those of eutherian mammals, including viviparity, long gestation periods, ovulation of tiny eggs, and placental supply of the nutrients for development. Studies of placental morphology and development indicate that New World Mabuya share several other derived features, including chorionic areolae and a "Type IV" epitheliochorial placenta with a villous, mesometrial placentome. Some characteristics of these lizards are shared by two African skinks, M. ivensii and Eumecia anchietae, including minuscule eggs, placentotrophy, an absorptive chorioallantois, and features of the yolk sac. Available evidence is consistent with two explanations: (1) placentotrophy originated in Africa, predating a trans-Atlantic colonization by Mabuya of the New World; and (2) placentotrophy arose two or three separate times among these closely related skinks. As illustrated by analysis of these animals, not only can data on fetal membrane morphology yield phylogenetic information, but phylogenetic evidence in turn provides a valuable way to reconstruct the evolution of fetal membranes in a biogeographic context. When appropriately interpreted, morphological and phylogenetic evidence can be combined to yield robust evolutionary conclusions that avoid the pitfalls of circular reasoning.

  17. Dimorphic placental stress: A repercussion of interaction between endocrine disrupting chemicals (EDCs) and fetal sex.

    Science.gov (United States)

    Sood, Surbhi; Shekhar, Sudhanshu; Santosh, Winkins

    2017-02-01

    Placental homeostasis is critical for fetal development as it determines the health of mother and fetus during pregnancy and in later life. Interestingly even the fetus, in a sexually dimorphic manner, influences the pedantic growth and development of placenta. Although placenta is thought to act as a protective barrier against chemical exposures, certain endocrine disrupting chemicals (EDCs) that are circulating in mother's blood tend to cross placenta. These EDCs have been reported to cause changes in expression levels of certain genes, immunogenic factors and non-coding RNAs such as micro RNA (miRNA) and long non-coding RNA (lncRNA) leading to placental stress. We hypothesize that these changes in placenta occur in a sexually dimorphic manner as a result of interaction between EDC exposure and fetal sex. Therefore, we propose that the ability of placenta to respond and buffer EDC exposure depends on fetal sex and, hence the EDC associated disease susceptibility of one sex differs from the other.

  18. Placental Leucine Aminopeptidase- and Aminopeptidase A- Deficient Mice Offer Insight concerning the Mechanisms Underlying Preterm Labor and Preeclampsia

    Directory of Open Access Journals (Sweden)

    Shigehiko Mizutani

    2011-01-01

    Full Text Available Preeclampsia and preterm delivery are important potential complications in pregnancy and represent the leading causes for maternal and perinatal morbidity and mortality. The mechanisms underlying both diseases remain unknown, thus available treatments (beta2-stimulants and magnesium sulfate are essentially symptomatic. Both molecules have molecular weights less than 5–8 kDa, cross the placental barrier, and thus exert their effects on the fetus. The fetus produces peptides that are highly vasoactive and uterotonic and increase in response to maternal stress and with continued development. Fetal peptides are also small molecules that inevitably leak across into the maternal circulation. Aminopeptidases such as placental leucine aminopeptidase (P-LAP and aminopeptidase A (APA are large molecules that do not cross the placental barrier. We have shown that APA acts as an antihypertensive agent in the pregnant spontaneously hypertensive rat by degrading vasoactive peptides and as a result returns the animal to a normotensive state. P-LAP also acts as an antiuterotonic agent by degrading uterotonic peptides and thus prolongs gestation in the pregnant mouse. Given the ever increasing worldwide incidences of preeclampsia and preterm labor, it is imperative that new agents be developed to safely prolong gestation. We believe that the use of aminopeptidases hold promise in this regard.

  19. Placental Protein 13 Administration to Pregnant Rats Lowers Blood Pressure and Augments Fetal Growth and Venous Remodeling.

    Science.gov (United States)

    Gizurarson, Sveinbjorn; Sigurdardottir, Elisabet Run; Meiri, Hamutal; Huppertz, Berthold; Sammar, Marei; Sharabi-Nov, Adi; Mandalá, Maurizio; Osol, George

    2016-01-01

    Reduced first-trimester concentrations of placental protein 13 (PP13) are associated with subsequent development of preeclampsia, a major pregnancy disorder. We previously showed that PP13 has a vasodilatory effect, reduces blood pressure and augments expansive remodeling of the uteroplacental vasculature in pregnant rats. In this study, slow-release osmotic pumps were implanted in gravid rats (on day 8) to provide 1 week of PP13 supplementation. Treatment was associated with a reversible blood pressure reduction that returned to normal on day 15. In addition, PP13 caused venous expansion that is larger in the venous branches closer to the placenta. Then, it increased placental and pup weights. Similar administration of a truncated PP13 variant (DelT221) that is unable to bind carbohydrates (a rare spontaneous mutation associated with a high frequency of severe early preeclampsia among Blacks in South Africa) produced a hypotensive effect similar to the full-length molecule, but without venous remodeling and increased placental and pup weights. These results indicate the importance of PP13 carbohydrate binding for inducing vascular remodeling and improving reproductive outcome. Future studies are needed to determine whether beneficial effects would be evident in animal models of preeclampsia or in women predisposed to the development of preeclampsia.

  20. Parvovirus infection: an immunohistochemical study using fetal and placental tissue.

    Science.gov (United States)

    Li, Jing Jing; Henwood, Tony; Van Hal, Sebastian; Charlton, Amanda

    2015-01-01

    Parvovirus B19 infection causes 5% to 15% of cases of nonimmune hydrops fetalis. The aim of our study was to evaluate the use of immunohistochemistry in diagnosing parvovirus infection in fetal and placental tissue during routine fetal and perinatal autopsies. Histology slides of 20 cases of confirmed parvovirus infection were reviewed, and immunohistochemistry was applied to selected blocks of fetal and placental tissue. Immunohistochemistry was positive in all 20 cases, and histologic viral inclusions were seen in 19 cases. Immunohistochemical staining was closely correlated with histology and was more sensitive than histology in detecting virally infected cells, especially in autolyzed tissue. All cases also had confirmatory evidence of parvovirus infection by polymerase chain reaction of fetal liver and positive maternal serology, where it was available. We conclude that parvovirus immunohistochemistry is a reliable method for diagnosing parvovirus infection, especially in autolyzed tissue where histologic assessment may be suboptimal.

  1. Placental transfer of radiopharmaceuticals and dosimetry in pregnancy

    Energy Technology Data Exchange (ETDEWEB)

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

    1999-01-01

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

  2. Placental lactogen levels as guide to outcome of threatened abortion.

    Science.gov (United States)

    Niven, P A; Landon, J; Chard, T

    1972-09-30

    The clinical value has been assessed of circulating placental lactogen levels as a pointer to the outcome in a patient with vaginal bleeding in early pregnancy. By using a semiautomated radioimmunoassay the normal range of values for the first and second trimesters has been established. In patients admitted with vaginal bleeding after the eighth week of gestation estimation of plasma human placental lactogen showed that patients with low levels were those in whom the abortion was completed during the first admission. Women whose pregnancies continued normally or who aborted after their first discharge from hospital had normal levels. In a small group sampled before the onset of bleeding but who later aborted the mean levels were lower than normal. This simple and inexpensive test can indicate those women in whom abortion is inevitable and could be used to reduce substantially the length of hospital stay in this common complication of early pregnancy.

  3. Is placental iodine content related to dietary iodine intake?

    LENUS (Irish Health Repository)

    Burns, R

    2011-08-01

    Delivery of iodine to the foetus depends not only on maternal dietary iodine intake but also on the presence of a functioning placental transport system. A role for the placenta as an iodine storage organ has been suggested, and this study compares the iodine content of placentas from women giving birth at term in Ireland and Iran, areas with median urinary iodine of 79 and 206 μg\\/l respectively.

  4. Effect on the growth and development and induction of abnormalities by a glyphosate commercial formulation and its active ingredient during two developmental stages of the South-American Creole frog, Leptodactylus latrans.

    Science.gov (United States)

    Bach, Nadia Carla; Natale, Guillermo Sebastián; Somoza, Gustavo Manuel; Ronco, Alicia Estela

    2016-12-01

    We evaluated the acute lethal and sublethal effects of technical-grade glyphosate (GLY) and the GLY-based commercial formulation Roundup ULTRA MAX® (RU) on two Gosner stages (Gss) 25 and 36 of the South-American Creole frog, Leptodactylus latrans. Bioassays were performed following standardized methods within a wide range of concentrations (0.0007-9.62 mg of acid equivalents per liter-a.e./L-of RU and 3-300 mg/L of GLY). The endpoints evaluated were mortality, swimming activity, growth, development, and the presence of morphologic abnormalities, especially in the mouthparts. No lethal effects were observed on larvae exposed to GLY during either Gs-25 or Gs-36. The concentrations inducing 50 % lethality in RU-exposed larvae at different exposure times and Gss ranged from 3.26 to 9.61 mg a.e./L. Swimming activity was affected by only RU. Effects on growth and development and the induction of morphologic abnormalities-like oral abnormalities and edema-were observed after exposure to either GLY or RU. Gs-25 was the most sensitive stage to both forms of the herbicide. The commercial formulation was much more toxic than the active ingredient on all the endpoints assessed. Effects on growth, development, and the induction of morphologic abnormalities observed in the range of environmental concentrations reported for agroecosystems of Argentina constitute an alert to the potential detrimental effects of the herbicide that could be affecting the fitness and survival of anurans in agroecosystems.

  5. Good practices in collecting umbilical cord and placental blood

    Directory of Open Access Journals (Sweden)

    Lauren Auer Lopes

    Full Text Available Abstract Objective: to identify the factors related to the quality of umbilical cord and placental blood specimens, and define best practices for their collection in a government bank of umbilical cord and placental blood. Method: this was a descriptive study, quantitative approach, performed at a government umbilical cord and placental blood bank, in two steps: 1 verification of the obstetric, neonatal and operational factors, using a specific tool for gathering data as non-participant observers; 2 definition of best practices by grouping non-conformities observed before, during and after blood collection. The data was analyzed using descriptive statistics and the following statistical software: Statistica(r and R(r. Results: while there was a correlation with obstetrical and neonatal factors, there was a larger correlation with operational factors, resulting in the need to adjust the professional practices of the nursing staff and obstetrical team involved in collecting this type of blood. Based on these non-conformities we defined best practices for nurses before, during and after blood collection. Conclusion: the best practices defined in this study are an important management tool for the work of nurses in obtaining blood specimens of high cell quality.

  6. Osmotic flow through the placental barrier of chronically prepared sheep.

    Science.gov (United States)

    Armentrout, T; Katz, S; Thornburg, K L; Faber, J J

    1977-10-01

    An electromagnetic flow sensor was placed on the distal aorta of sheep fetuses in utero, and catheters were placed in a femoral artery and the common umbilical vein. Catheters were also placed in a carotid artery and a uterine vein of the pregnant ewe. Three days postoperatively maternal plasma was hyperosmotic with respect to fetal plasma by all methods: +5.8 +/- 1.4 SE by vapor-pressure osmometry, +2.2 +/- 0.7 SE by freezing-point depression osmometry corrected for bicarbonate loss; and +3.26 mosmol/liter by chemical measurement of plasma constituents. Maternal or fetal plasma was made hypertonic in vivo by infusion of concentrated solutions of mannitol, sucrose, or NaCl. Transplacental water flux was calculated from placental blood flows and arteriovenous differences in water content of the blood. The apparent osmotic conductivity of the placenta was 61 ml2-mosmol-1-kg-1, but this value should be divided by an unknown reflection coefficient to yield the true osmotic conductivity. Separate measurements were made of the placental diffusional permeability of Na+ and Cl- in five chronically prepared sheep fetuses: PSNa+ =0.20 +/- 0.04, PSCl- = 0.27 +/- 0.04 ml/(min-kg fetus). There was a highly significant positive regression between (total) placental permeability and fetal weight.

  7. Feeling Abnormal: Simulation of Deviancy in Abnormal and Exceptionality Courses.

    Science.gov (United States)

    Fernald, Charles D.

    1980-01-01

    Describes activity in which student in abnormal psychology and psychology of exceptional children classes personally experience being judged abnormal. The experience allows the students to remember relevant research, become sensitized to the feelings of individuals classified as deviant, and use caution in classifying individuals as abnormal.…

  8. Clinical Analysis of 238 Cases of Patients With Placental Abruption%238例胎盘早剥的临床分析

    Institute of Scientific and Technical Information of China (English)

    郭海洁

    2015-01-01

    目的:分析探讨胎盘早剥的诱发因素、临床特点、漏诊误诊及处理方法,以期提高诊断率、降低并发症。方法利用回顾性病例分析法,对我院自2003年1月~2012年12月收治的238例胎盘早剥病例进行分析。结果胎盘早剥的发生率是0.53%,其中,有明确诱因者占44%,通过急诊入院者占46.3%。除此之外,胎盘异常、脐带异常、羊水过多和妊娠期高血压也是胎盘早剥的诱发因素。结论胎盘早剥诱因多样、发病隐匿、症状不典型,容易导致B超漏诊,孕妇定期进行体检、预防孕期高血压等对预防和尽早处理胎盘早剥有重要的作用。%Objective To study the inducing factors, clinical features, misdiagnosis and treatment method about placental abruption, in order to improve the diagnostic rate and reduce the complication. Methods Retrospectively analyzed the 238 cases of patients with placental abruption in our hospital from January 2003 to December 2012. Results The incidence of placental abruption was 0.53%, among them, 44% with clear incentive, 63% through emergency admissions. In addition, the placenta, an abnormal umbilical cord, hydramnios and gestational hypertension were also causative factors of placental abruption. Conclusion Placental abruption with diverse causes, concealment and untypical symptoms, easily lead to misdiagnosis by ultrasound. So regular physical examination and prevention of high blood pressure during pregnancy play a key role in early treatment of placental abruption.

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

    Science.gov (United States)

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

    2012-01-01

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

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

    Directory of Open Access Journals (Sweden)

    Matthew Schrader

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

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

    Science.gov (United States)

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

    2013-12-01

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

  12. High food abundance permits the evolution of placentotrophy: evidence from a placental lizard, Pseudemoia entrecasteauxii.

    Science.gov (United States)

    Van Dyke, James U; Griffith, Oliver W; Thompson, Michael B

    2014-08-01

    Mechanisms of reproductive allocation are major determinants of fitness because embryos cannot complete development without receiving sufficient nutrition from their parents. The nourishment of offspring via placentas (placentotrophy) has evolved repeatedly in vertebrates, including multiple times in squamate reptiles (lizards and snakes). Placentotrophy has been suggested to evolve only if food is sufficiently abundant throughout gestation to allow successful embryogenesis. If scarcity of food prevents successful embryogenesis, females should recoup nutrients allocated to embryos via abortion, reabsorption, and/or cannibalism. We tested these hypotheses in the placentotrophic southern grass skink Pseudemoia entrecasteauxii. We fed females one of four diets (high constant, high variable, low constant, and low variable) during gestation and tested the effects of both food amount and schedule of feeding on developmental success, cannibalism rate, placental nutrient transport, offspring size, and maternal growth and body condition. Low food availability reduced developmental success, placental nutrient transport, offspring size, and maternal growth and body condition. Cannibalism of offspring also increased when food was scarce. Schedule of feeding did not affect offspring or mothers. We suggest that high food abundance and ability to abort and cannibalize poor-quality offspring are permissive factors necessary for placentotrophy to be a viable strategy of reproductive allocation.

  13. Clinical analysis of severe preeclampsia complicated by placental abruption%重度子痫前期并发胎盘早剥的临床分析

    Institute of Scientific and Technical Information of China (English)

    张喜红

    2012-01-01

    Objective: To investigate the clinical features of severe preeclampsia complicated by placental abruption in order to intervene as soon as possible. Methods: From Feb 2005 to Feb 2009, 106 inpatients with severe preeclampsia in our hospital were randomly selected. Of the 106 cases, 19 patients who had placental abruption were taken as study group, 87 patients who had not placental abruption were taken as control group. The clinical data of patients in the two groups were retrospectively analyzed and compared. Results: The incidence of placental abruption complicated by severe preeclampsia was 17. 92% (19/106) . Three patients ( 15. 7% ) in study group and 62 patients (71. 26% ) in control group were received regular prenatal care, the difference between the two groups was statistically significant ( P < 0. 05 ) . The incidence of the fluctuations of systolic blood pressure and diastolic blood pressure, complications ( GFR, hypoproteine-mia, abnormal umbilical blood flow) were significantly difference (P<0. 05) .Conclusion: Irregular prenatal care, increased volatility of blood pressure, mergers GFR, hypoproteinemia, abnormal umbilical blood flow are the clinical features of severe preeclampsia complicated by placental abruption. A good prenatal care, slow smooth step - down blood pressure is the key for prevention and treatment of placental abruption. For the inpatients with severe preeclampsia complicated by placental abruption, the early signs of placental abruption should be closely monitored and timely intervention.%目的:探讨重度子痫前期并发胎盘早剥的临床特征,以便尽早采取干预措施.方法:回顾性分析2005年2月~ 2009年2月郑州市人民医院产科住院的重度子痫前期患者106例的临床资料.结果:重度子痫前期并发胎盘早剥的发生率为17.92% (19/106).在胎盘早剥的19例中有3例(15.7%)、未发生胎盘早剥的87例中有62例(71.26%)接受过正规产前检查,两

  14. A population-based study of race-specific risk for placental abruption

    Directory of Open Access Journals (Sweden)

    Stamilio David M

    2008-09-01

    Full Text Available Abstract Background Efforts to elucidate risk factors for placental abruption are imperative due to the severity of complications it produces for both mother and fetus, and its contribution to preterm birth. Ethnicity-based differences in risk of placental abruption and preterm birth have been reported. We tested the hypotheses that race, after adjusting for other factors, is associated with the risk of placental abruption at specific gestational ages, and that there is a greater contribution of placental abruption to the increased risk of preterm birth in Black mothers, compared to White mothers. Methods We conducted a population-based cohort study using the Missouri Department of Health's maternally-linked database of all births in Missouri (1989–1997 to assess racial effects on placental abruption and the contribution of placental abruption to preterm birth, at different gestational age categories (n = 664,303. Results Among 108,806 births to Black mothers and 555,497 births to White mothers, 1.02% (95% CI 0.96–1.08 of Black births were complicated by placental abruption, compared to 0.71% (95% CI 0.69–0.73 of White births (aOR 1.32, 95% CI 1.22–1.43. The magnitude of risk of placental abruption for Black mothers, compared to White mothers, increased with younger gestational age categories. The risk of placental abruption resulting in term and extreme preterm births ( Conclusion Black women have an increased risk of placental abruption compared to White women, even when controlling for known coexisting risk factors. This risk increase is greatest at the earliest preterm gestational ages when outcomes are the poorest. The relative contribution of placental abruption to term births was greater in Black women, whereas the relative contribution of placental abruption to preterm birth was greater in White women.

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

    DEFF Research Database (Denmark)

    Carter, Anthony Michael; Mess, Andrea

    2017-01-01

    Molecular phylogenetics has made a substantial contribution to our understanding of the relationships between mammalian orders and has generated trees that can be used to examine the evolution of anatomical and physiological traits. We here summarize findings on fetal membranes and placentation i...... proteins including placental lactogens and pregnancy-associated glycoproteins. Evolutionary innovations of the placental system may contribute to the high diversity of lifestyles within Ferungulata and be linked to the evolution of highly precocial offspring in ungulates....

  16. Monocarboxylate transporter 8 modulates the viability and invasive capacity of human placental cells and fetoplacental growth in mice.

    Science.gov (United States)

    Vasilopoulou, Elisavet; Loubière, Laurence S; Heuer, Heike; Trajkovic-Arsic, Marija; Darras, Veerle M; Visser, Theo J; Lash, Gendie E; Whitley, Guy S; McCabe, Christopher J; Franklyn, Jayne A; Kilby, Mark D; Chan, Shiao Y

    2013-01-01

    Monocarboxylate transporter 8 (MCT8) is a well-established thyroid hormone (TH) transporter. In humans, MCT8 mutations result in changes in circulating TH concentrations and X-linked severe global neurodevelopmental delay. MCT8 is expressed in the human placenta throughout gestation, with increased expression in trophoblast cells from growth-restricted pregnancies. We postulate that MCT8 plays an important role in placental development and transplacental TH transport. We investigated the effect of altering MCT8 expression in human trophoblast in vitro and in a Mct8 knockout mouse model. Silencing of endogenous MCT8 reduced T3 uptake into human extravillous trophoblast-like cells (SGHPL-4; 40%, PMCT8 over-expression transiently increased T3 uptake (SGHPL-4∶30%, PMCT8 did not significantly affect SGHPL-4 invasion, but with MCT8 over-expression T3 treatment promoted invasion compared with no T3 (3.3-fold; PMCT8 silencing increased cytotrophoblast viability (∼20%, PMCT8 over-expression reduced cytotrophoblast viability independently of T3 (∼20%, PMct8 knockout reduced fetal:placental weight ratios compared with wild-type controls at gestational day 18 (25%, Pfetal and placental weights were not significantly different. The volume fraction of the labyrinthine zone of the placenta, which facilitates maternal-fetal exchange, was reduced in Mct8 knockout placentae (10%, PMCT8 makes a significant contribution to T3 uptake into human trophoblast cells and has a role in modulating human trophoblast cell invasion and viability. In mice, Mct8 knockout has subtle effects upon fetoplacental growth and does not significantly affect placental cell viability probably due to compensatory mechanisms in vivo.

  17. Resolution among major placental mammal interordinal relationships with genome data imply that speciation influenced their earliest radiations

    Directory of Open Access Journals (Sweden)

    Janke Axel

    2008-05-01

    Full Text Available Abstract Background A number of the deeper divergences in the placental mammal tree are still inconclusively resolved despite extensive phylogenomic analyses. A recent analysis of 200 kbp of protein coding sequences yielded only limited support for the relationships among Laurasiatheria (cow, dog, bat and shrew, probably because the divergences occurred only within a few million years from each other. It is generally expected that increasing the amount of data and improving the taxon sampling enhance the resolution of narrow divergences. Therefore these and other difficult splits were examined by phylogenomic analysis of the hitherto largest sequence alignment. The increasingly complete genome data of placental mammals also allowed developing a novel and stringent data search method. Results The rigorous data handling, recursive BLAST, successfully removed the sequences from gene families, including those from well-known families hemoglobin, olfactory, myosin and HOX genes, thus avoiding alignment of possibly paralogous sequences. The current phylogenomic analysis of 3,012 genes (2,844,615 nucleotides from a total of 22 species yielded statistically significant support for most relationships. While some major clades were confirmed using genomic sequence data, the placement of the treeshrew, bat and the relationship between Boreoeutheria, Xenarthra and Afrotheria remained problematic to resolve despite the size of the alignment. Phylogenomic analysis of divergence times dated the basal placental mammal splits at 95–100 million years ago. Many of the following divergences occurred only a few (2–4 million years later. Relationships with narrow divergence time intervals received unexpectedly limited support even from the phylogenomic analyses. Conclusion The narrow temporal window within which some placental divergences took place suggests that inconsistencies and limited resolution of the mammalian tree may have their natural explanation in

  18. Abnormal ionization in sonoluminescence

    Science.gov (United States)

    Zhang, Wen-Juan; An, Yu

    2015-04-01

    Sonoluminescence is a complex phenomenon, the mechanism of which remains unclear. The present study reveals that an abnormal ionization process is likely to be present in the sonoluminescing bubble. To fit the experimental data of previous studies, we assume that the ionization energies of the molecules and atoms in the bubble decrease as the gas density increases and that the decrease of the ionization energy reaches about 60%-70% as the bubble flashes, which is difficult to explain by using previous models. Project supported by the Research Fund for the Doctoral Program of Higher Education of China (Grant No. 20120002110031) and the National Natural Science Foundation of China (Grant No. 11334005).

  19. Evolution of the placenta during the early radiation of placental mammals

    DEFF Research Database (Denmark)

    Mess, Andrea; Carter, Anthony M

    2007-01-01

    . This interhaemal barrier occurs in three principal variants. The focus of this review is on determining how the barrier evolved in placental mammals. The analysis was based on current knowledge of placental structure, as far as possible using ultrastructural data, and on current views about the evolution...... of placental mammals, derived from molecular phylogenetics. We show that epitheliochorial placentation, the least invasive type, is a derived state and discuss factors that may have determined its evolution with reference to conflict theory, as applied to the allocation of resources between mother and fetus...

  20. 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.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-implantation trophoblast responses to nutrition.

  1. Relationship between abnormal blood rheology and development and recovery of hypertension and cerebral infarction%血液流变学异常与高血压和脑梗死发生、转归的相关性

    Institute of Scientific and Technical Information of China (English)

    赵刚

    2002-01-01

    Background:Increased blood pressure in hypertension is related to vessels resistance,cardiac output,as well as blood viscosity.Stroke is common following hypertension.A number of studies reported that abnormal blood rheology was frequent in stroke suggesting correlation of blood rheology with onset,development,recovery of hypertension.Hypertension is the most one of independent risk factors of stroke.In the current paper,we investigated pathogenesis and development of hypertension and cerebral infarction to provide principle foundation for early prevention and treatment of cerebral infarciton.

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

    Institute of Scientific and Technical Information of China (English)

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

    2006-01-01

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

  3. Normal newborn with prenatal suspicion of X chromosome monosomy due to confined placental mosaicism.

    Science.gov (United States)

    Serapinas, Danielius; Bartkeviciene, Daiva; Valantinaviciene, Emilija; Machtejeviene, Egle

    2016-10-01

    The recent introduction of cell-free DNA (cfDNA)-based noninvasive prenatal testing (NIPT) offers pregnant women a more accurate method than traditional serum screening methods for detecting fetal aneuploidies. Clinical trials have demonstrated the efficacy of NIPT for Down, Edwards and Patau syndromes. However NIPT approaches that take advantage of single-nucelotide polymorphism (SNP) information potentially allow the identification of triploidy, chromosomal microdeletion syndromes and other unusual genetic variants. To highlight this approach of NIPT we present a rare case of confined placental X chromosome monosomy mosaicism that was prenatally suspected with a single-nucleotide polymorphism-based noninvasive prenatal test. The results of invasive tests (amniocentesis) showed small proportion of X chromosome mosaicism (45, X[5]/46, XX[95]). After birth karyotype of the girl revealed no abnormalities (46 XX), confirming that mosaicism was limited to the placenta. These results highlight the need of patient's informed consent and thorough pretest and postest counseling to ensure that they understand the limitations and advantages of the tests and the implications of the resultss.

  4. Detection of suspected placental invasion by MRI: Do the results depend on observer’ experience?

    Energy Technology Data Exchange (ETDEWEB)

    Alamo, Leonor, E-mail: leonor.alamo@chuv.ch [Centre Hospitalier Universitaire Vaudois, Lausanne (Switzerland); Anaye, Anass; Rey, Jannick; Denys, Alban [Centre Hospitalier Universitaire Vaudois, Lausanne (Switzerland); Bongartz, Georg [Universitätsspital Basel (Switzerland); Terraz, Sylvain [Hôpitaux Universitaires Genève (Switzerland); Artemisia, Simona; Meuli, Reto; Schmidt, Sabine [Centre Hospitalier Universitaire Vaudois, Lausanne (Switzerland)

    2013-02-15

    Purpose: To evaluate the diagnostic value of previously described MR features used for detecting suspected placental invasion according to observers’ experience. Materials and methods: Our population included 25 pregnant women (mean age 35.16) investigated by prenatal MRI (1.5 T, T1- and T2-weighted MR-sequences without i.v. contrast), among them 12 with histopathologically proven placental invasion and 13 women (52%) without placental invasion used as control group. Two senior and two junior radiologists blindly and independently reviewed MR-examinations in view of 6 previously defined MR-features indicating presence and degree of placental invasion (placenta increta, accreta or percreta). For each reader the sensibility, specificity, and receiver operating curve (ROC) were calculated. Interobserver agreements between senior and junior readers were determined. Stepwise logistic regression was performed including the 6 MR-features predictive of placental invasion. Results: Demographics between both groups were statistically equivalent. Overall sensitivity and specificity for placental invasion was 90.9% and 75.0% for seniors and 81.8% and 61.8% for juniors, respectively. The best single MR-feature indicating placental invasion was T2-hypointense placental bands (r{sup 2} = 0.28), followed by focally interrupted myometrial border, infiltration of pelvic organs and tenting of the bladder (r{sup 2} = 0.36). Interobserver agreement for detecting placental invasion was 0.64 for seniors and 0.41 for juniors, thus substantial and moderate, respectively. Seniors detected placental invasion and depth of infiltration with significantly higher diagnostic certitude than juniors (p = 0.0002 and p = 0.0282, respectively). Conclusion: MRI can be a reliable and reproducible tool for the detection of suspected placental invasion, but the diagnostic value significantly depends on observers’ experience.

  5. A Rare Stapes Abnormality

    Directory of Open Access Journals (Sweden)

    Hala Kanona

    2015-01-01

    Full Text Available The aim of this study is to increase awareness of rare presentations, diagnostic difficulties alongside management of conductive hearing loss and ossicular abnormalities. We report the case of a 13-year-old female reporting progressive left-sided hearing loss and high resolution computed tomography was initially reported as normal. Exploratory tympanotomy revealed an absent stapedius tendon and lack of connection between the stapes superstructure and footplate. The footplate was fixed. Stapedotomy and stapes prosthesis insertion resulted in closure of the air-bone gap by 50 dB. A review of world literature was performed using MedLine. Middle ear ossicular discontinuity can result in significant conductive hearing loss. This can be managed effectively with surgery to help restore hearing. However, some patients may not be suitable or decline surgical intervention and can be managed safely conservatively.

  6. Lower levels of placental growth hormone in early pregnancy in women with type 1 diabetes and large for gestational age infants

    DEFF Research Database (Denmark)

    Ringholm, Lene; Juul, Anders; Pedersen-Bjergaard, Ulrik

    2015-01-01

    OBJECTIVE: To evaluate whether levels of placental growth hormone (GH) and Insulin-like Growth Factor-I (IGF-I) are associated with development of LGA infants in pregnant women with type 1 diabetes. DESIGN: Observational study of 103 consecutive pregnant women with long-term type 1 diabetes...... and median HbA1c 6.6% (range 4.9-10.5) (49 mmol/mol (30-91)) in early pregnancy. At 8, 14, 21, 27 and 33 weeks weight was recorded and blood was sampled for measurements of placental GH, IGF-I and HbA1c. LGA was defined as birth weight >90th percentile after adjustment for gender and gestational age. RESULTS......: Throughout pregnancy placental GH levels were similar in 51 (50%) women delivering LGA infants compared with the remaining women except at 8 weeks where placental GH levels were lower in women with LGA infants (1.1 ng/ml (0.1-4.3) vs. 1.7 (0.3-11.7), p = 0.04). IGF-I levels were similar in women...

  7. The impact of placental malaria on neurodevelopment of exposed infants: a role for the complement system?

    Science.gov (United States)

    McDonald, Chloe R; Elphinstone, Robyn E; Kain, Kevin C

    2013-05-01

    The in utero environment can have a profound impact on early brain development and subsequent childhood school performance and behavior. Over 125 million pregnant women are at risk of malaria each year, yet the impact of in utero malaria exposure on the neurological and cognitive development of their exposed infants is unknown. Based on recent evidence supporting a role for the complement system in regulating neurodevelopment, and mediating neuroinflammation and neurodegenerative diseases, we hypothesize that excessive complement activation induced by placental malaria may disrupt normal neurodevelopment resulting in neurocognitive impairment of infants exposed to malaria in utero. Complement components may mediate these effects through the initiation of neuroinflammation, dysregulation of neurovascular angiogenesis, and the disruption of normal synaptic pruning.

  8. Placental vascular pathology and increased thrombin generation as mechanisms of disease in obstetrical syndromes

    Directory of Open Access Journals (Sweden)

    Salvatore Andrea Mastrolia

    2014-11-01

    Full Text Available Obstetrical complications including preeclampsia, fetal growth restriction, preterm labor, preterm prelabor rupture of membranes and fetal demise are all the clinical endpoint of several underlying mechanisms (i.e., infection, inflammation, thrombosis, endocrine disorder, immunologic rejection, genetic, and environmental, therefore, they may be regarded as syndromes. Placental vascular pathology and increased thrombin generation were reported in all of these obstetrical syndromes. Moreover, elevated concentrations of thrombin-anti thrombin III complexes and changes in the coagulation as well as anticoagulation factors can be detected in the maternal circulation prior to the clinical development of the disease in some of these syndromes. In this review, we will assess the changes in the hemostatic system during normal and complicated pregnancy in maternal blood, maternal–fetal interface and amniotic fluid, and describe the contribution of thrombosis and vascular pathology to the development of the great obstetrical syndromes.

  9. Placental pseudo-malignancy from a DNA methylation perspective: unanswered questions and future directions

    Directory of Open Access Journals (Sweden)

    Boris eNovakovic

    2013-12-01

    Full Text Available The growing fetus is dependent on adequate placental function for delivery of essential nutrients and oxygen, and for waste removal. The placenta also plays an important protective role; shielding the developing baby from the maternal immune system and adverse environmental exposures. Fundamental to these processes is correct invasion of the decidua and remodelling of maternal vasculature, each of which show remarkable parallels to tumourogenesis, with the obvious exception that the former is usually a tightly controlled process. It is not surprising that these physiological similarities are mirrored in gene expression and epigenetic parallels, many not found in any other aspect of human development. In this perspective, we summarise known DNA methylation similarities between placenta and human tumours, and discuss the implications and knowledge gaps associated with these findings. We also speculate on the potential origin of common DNA methylation features in these two disparate aspects of human physiology.

  10. Monocarboxylate transporter 8 modulates the viability and invasive capacity of human placental cells and fetoplacental growth in mice.

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    Elisavet Vasilopoulou

    Full Text Available Monocarboxylate transporter 8 (MCT8 is a well-established thyroid hormone (TH transporter. In humans, MCT8 mutations result in changes in circulating TH concentrations and X-linked severe global neurodevelopmental delay. MCT8 is expressed in the human placenta throughout gestation, with increased expression in trophoblast cells from growth-restricted pregnancies. We postulate that MCT8 plays an important role in placental development and transplacental TH transport. We investigated the effect of altering MCT8 expression in human trophoblast in vitro and in a Mct8 knockout mouse model. Silencing of endogenous MCT8 reduced T3 uptake into human extravillous trophoblast-like cells (SGHPL-4; 40%, P<0.05 and primary cytotrophoblast (15%, P<0.05. MCT8 over-expression transiently increased T3 uptake (SGHPL-4∶30%, P<0.05; cytotrophoblast: 15%, P<0.05. Silencing MCT8 did not significantly affect SGHPL-4 invasion, but with MCT8 over-expression T3 treatment promoted invasion compared with no T3 (3.3-fold; P<0.05. Furthermore, MCT8 silencing increased cytotrophoblast viability (∼20%, P<0.05 and MCT8 over-expression reduced cytotrophoblast viability independently of T3 (∼20%, P<0.05. In vivo, Mct8 knockout reduced fetal:placental weight ratios compared with wild-type controls at gestational day 18 (25%, P<0.05 but absolute fetal and placental weights were not significantly different. The volume fraction of the labyrinthine zone of the placenta, which facilitates maternal-fetal exchange, was reduced in Mct8 knockout placentae (10%, P<0.05. However, there was no effect on mouse placental cell proliferation in vivo. We conclude that MCT8 makes a significant contribution to T3 uptake into human trophoblast cells and has a role in modulating human trophoblast cell invasion and viability. In mice, Mct8 knockout has subtle effects upon fetoplacental growth and does not significantly affect placental cell viability probably due to compensatory mechanisms in

  11. Evaluating the abnormal ossification in tibiotarsi of developing chick embryos exposed to 1.0ppm doses of platinum group metals by spectroscopic techniques.

    Science.gov (United States)

    Stahler, Adam C; Monahan, Jennifer L; Dagher, Jessica M; Baker, Joshua D; Markopoulos, Marjorie M; Iragena, Diane B; NeJame, Britney M; Slaughter, Robert; Felker, Daniel; Burggraf, Larry W; Isaac, Leon A C; Grossie, David; Gagnon, Zofia E; Sizemore, Ioana E Pavel

    2013-04-01

    Platinum group metals (PGMs), i.e., palladium (Pd), platinum (Pt) and rhodium (Rh), are found at pollutant levels in the environment and are known to accumulate in plant and animal tissues. However, little is known about PGM toxicity. Our previous studies showed that chick embryos exposed to PGM concentrations of 1mL of 5.0ppm (LD50) and higher exhibited severe skeletal deformities. This work hypothesized that 1.0ppm doses of PGMs will negatively impact the mineralization process in tibiotarsi. One milliliter of 1.0ppm of Pd(II), Pt(IV), Rh(III) aqueous salt solutions and a PGM-mixture were injected into the air sac on the 7th and 14th day of incubation. Control groups with no-injection and vehicle injections were included. On the 20th day, embryos were sacrificed to analyze the PGM effects on tibiotarsi using four spectroscopic techniques. 1) Micro-Raman imaging: Hyperspectral Raman data were collected on paraffin embedded cross-sections of tibiotarsi, and processed using in-house-written MATLAB codes. Micro-Raman univariate images that were created from the ν1(PO4(3-)) integrated areas revealed anomalous mineral inclusions within the bone marrow for the PGM-mixture treatment. The age of the mineral crystals (ν(CO3(2-))/ν1(PO4(3-))) was statistically lower for all treatments when compared to controls (p≤0.05). 2) FAAS: The percent calcium content of the chemically digested tibiotarsi in the Pd and Pt groups changed by ~45% with respect to the no-injection control (16.1±0.2%). 3) Micro-XRF imaging: Abnormal calcium and phosphorus inclusions were found within the inner longitudinal sections of tibiotarsi for the PGM-mixture treatment. A clear increase in the mineral content was observed for the outer sections of the Pd treatment. 4) ICP-OES: PGM concentrations in tibiotarsi were undetectable (<5ppb). The spectroscopic techniques gave corroborating results, confirmed the hypothesis, and explained the observed pathological (skeletal developmental abnormalities

  12. Extensive intron gain in the ancestor of placental mammals

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    Kordiš Dušan

    2011-11-01

    Full Text Available Abstract Background Genome-wide studies of intron dynamics in mammalian orthologous genes have found convincing evidence for loss of introns but very little for intron turnover. Similarly, large-scale analysis of intron dynamics in a few vertebrate genomes has identified only intron losses and no gains, indicating that intron gain is an extremely rare event in vertebrate evolution. These studies suggest that the intron-rich genomes of vertebrates do not allow intron gain. The aim of this study was to search for evidence of de novo intron gain in domesticated genes from an analysis of their exon/intron structures. Results A phylogenomic approach has been used to analyse all domesticated genes in mammals and chordates that originated from the coding parts of transposable elements. Gain of introns in domesticated genes has been reconstructed on well established mammalian, vertebrate and chordate phylogenies, and examined as to where and when the gain events occurred. The locations, sizes and amounts of de novo introns gained in the domesticated genes during the evolution of mammals and chordates has been analyzed. A significant amount of intron gain was found only in domesticated genes of placental mammals, where more than 70 cases were identified. De novo gained introns show clear positional bias, since they are distributed mainly in 5' UTR and coding regions, while 3' UTR introns are very rare. In the coding regions of some domesticated genes up to 8 de novo gained introns have been found. Intron densities in Eutheria-specific domesticated genes and in older domesticated genes that originated early in vertebrates are lower than those for normal mammalian and vertebrate genes. Surprisingly, the majority of intron gains have occurred in the ancestor of placentals. Conclusions This study provides the first evidence for numerous intron gains in the ancestor of placental mammals and demonstrates that adequate taxon sampling is crucial for

  13. Detection and clinical manifestation of placental malaria in southern Ghana

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    Acquah Patrick A

    2006-12-01

    Full Text Available Abstract Background Plasmodium falciparum can be detected by microscopy, histidine-rich-protein-2 (HRP2 capture test or PCR but the respective clinical relevance of the thereby diagnosed infections in pregnant women is not well established. Methods In a cross-sectional, year-round study among 839 delivering women in Agogo, Ghana, P. falciparum was screened for in both, peripheral and placental blood samples, and associations with maternal anaemia, low birth weight (LBW and preterm delivery (PD were analysed. Results In peripheral blood, P. falciparum was observed in 19%, 34%, and 53% by microscopy, HRP2 test, and PCR, respectively. For placental samples, these figures were 35%, 41%, and 59%. Irrespective of diagnostic tool, P. falciparum infection increased the risk of anaemia. Positive peripheral blood results of microscopy and PCR were not associated with LBW or PD. In contrast, the HRP2 test performed well in identifying women at increased risk of poor pregnancy outcome, particularly in case of a negative peripheral blood film. Adjusting for age, parity, and antenatal visits, placental HRP2 was the only marker of infection associated with LBW (adjusted odds ratio (aOR, 1.5 (95%CI, 1.0–2.2 and, at borderline statistical significance, PD (aOR, 1.4 (1.0–2.1 in addition to anaemia (aOR, 2.3 (1.7–3.2. Likewise, HRP2 in peripheral blood of seemingly aparasitaemic women was associated with PD (aOR, 1.7 (1.0–2.7 and anaemia (aOR, 2.1 (1.4–3.2. Conclusion Peripheral blood film microscopy not only underestimates placental malaria. In this highly endemic setting, it also fails to identify malaria as a cause of foetal impairment. Sub-microscopic infections detected by a HRP2 test in seemingly aparasitaemic women increase the risks of anaemia and PD. These findings indicate that the burden of malaria in pregnancy may be even larger than thought and accentuate the need for effective anti-malarial interventions in pregnancy.

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

    DEFF Research Database (Denmark)

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

    2008-01-01

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

  15. Placentation in the Egyptian slit-faced bat Nycteris thebaica (Chiroptera: Nycteridae)

    DEFF Research Database (Denmark)

    Enders, A C; Jones, C J P; Taylor, P J;

    2009-01-01

    Bats are a highly successful, widely distributed group, with considerable variation in placental structure. The Egyptian slit-faced bat Nycteris thebaica is a member of one of the few families with previously undescribed placentation. It was found that, although the interhemal type of the Nycteri...

  16. Placental histology in spontaneous and indicated preterm birth : A case control study

    NARCIS (Netherlands)

    Nijman, Tobias A J; van Vliet, Elvira O G; Benders, Manon J N; Mol, Ben Willem J; Franx, Arie; Nikkels, Peter G J; Oudijk, Martijn A

    2016-01-01

    INTRODUCTION: Placental pathology is an important contributor in preterm birth, both spontaneous and indicated. The aim of this study was to describe and compare placental histological features of spontaneous preterm birth versus indicated preterm birth. METHODS: A case control study was performed a

  17. Cardiac diastolic dysfunction and metabolic syndrome in young women after placental syndrome.

    NARCIS (Netherlands)

    Zandstra, M.; Stekkinger, E.; Vlugt, M.J. van der; Dijk, A.P.J. van; Lotgering, F.K.; Spaanderman, M.E.A.

    2010-01-01

    OBJECTIVE: To estimate whether women with a recent history of a placental syndrome and concomitant metabolic syndrome have reduced cardiac diastolic function. METHODS: In this cohort study, wom