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Sample records for circulating placental mrna

  1. Cell-free placental mRNA in maternal plasma to predict placental invasion in patients with placenta accreta.

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    El Behery, Manal M; Rasha L, Etewa; El Alfy, Yehya

    2010-04-01

    To evaluate whether measuring cell-free placental mRNA in maternal plasma improves the diagnostic accuracy of ultrasound and color Doppler in detecting placental invasion in patients at risk for placenta accreta. Thirty-five singleton pregnant women of more than 28 weeks of gestation and at risk for placenta accreta underwent ultrasound and color Doppler assessment. Cell-free placental mRNA in maternal plasma was measured using real-time reverse-transcription polymerase chain reaction. Patients were classified into 2 groups based on the findings at cesarean delivery and histological examination: women with placenta accreta (n=7) and women without placenta accreta (n=28). The median MoM (multiples of the median) value of cell-free placental mRNA was significantly higher in patients with placenta accreta than in those without placenta accreta (6.50 vs 2.60; Pplacental mRNA was significantly elevated in patients with placenta increta and percreta than in those with simple accreta. Six false-positive results were found on ultrasound, all from patients without placenta accreta and an insignificant rise in cell-free placental mRNA levels. Measuring cell-free placental mRNA in maternal plasma may increase the accuracy of ultrasound and color Doppler in prenatal prediction of placental invasion in patients with suspected placenta accreta. Copyright 2009 International Federation of Gynecology and Obstetrics. Published by Elsevier Ireland Ltd. All rights reserved.

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

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

    2017-12-01

    Background: Little is known about placental vitamin D metabolism and its impact on maternal circulating vitamin D concentrations in humans. Objective: This study sought to advance the current understanding of placental vitamin D metabolism and its role in modulating maternal circulating vitamin D metabolites during pregnancy. Design: Nested within a feeding study, 24 healthy pregnant women (26-29 wk of gestation) consumed a single amount of vitamin D (511 IU/d from diet and a cholecalciferol supplement) for 10 wk. Concentrations of placental and blood vitamin D metabolites and placental messenger RNA (mRNA) abundance of vitamin D metabolic pathway components were quantified. In addition, cultured human trophoblasts were incubated with 13 C-cholecalciferol to examine the intracellular generation and secretion of vitamin D metabolites along with the regulation of target genes. Results: In placental tissue, 25-hydroxyvitamin D 3 [25(OH)D 3 ] was strongly correlated ( r = 0.83, P D 3 Moreover, these placental metabolites were strongly correlated ( r ≤ 0.85, P ≤ 0.04) with their respective metabolites in maternal circulation. Positive associations ( P ≤ 0.045) were also observed between placental mRNA abundance of vitamin D metabolic components and circulating vitamin D metabolites [i.e., LDL-related protein 2 ( LRP2 , also known as megalin) with 25(OH)D 3 and the C3 epimer of 25(OH)D 3 [3-epi-25(OH)D 3 ]; cubilin ( CUBN ) with 25(OH)D 3 ; 25-hydroxylase ( CYP2R1 ) with 3-epi-25(OH)D 3 ; 24-hydroxylase ( CYP24A1 ) with 25(OH)D 3 , 3-epi-25(OH)D 3 , and 1,25-dihydroxyvitamin D 3 [1,25(OH) 2 D 3 ]; and 1α-hydroxylase [( CYP27B1 ) with 3-epi-25(OH)D 3 and 1,25(OH) 2 D 3 ]. Notably, in vitro experiments with trophoblasts showed increased production and secretion of 25(OH)D 3 and higher CYP24A1 gene transcript abundance in response to cholecalciferol treatment. Conclusions: The numerous associations of many of the placental biomarkers of vitamin D metabolism with

  3. Clinical importance of radioisotope measurement of placental circulation

    International Nuclear Information System (INIS)

    Doszpod, J.; Vittay, P.; Csakany, M.Gy.; Misak, L.; Gati, I.

    1980-01-01

    Placental circulation was measured by scintigraphic technique after administration of 18.5 MBq (0.5 mCi) 113 In. Scintigrams of the placenta and of the myometrium were taken with a time interval of 3 s for 3 minutes, and with an interval of 1 min for further 8 min. The placental perfusion index (PPI) was calculated on the basis of the time-activity histograms. The examination was carried out in 14 patients, with the following indications: toxicosis gravidarum, stenosis of the aortic valve, diabetes mellitus, placenta praevia, and suspicion of intrauterine retardation. In 13 cases the PPI was in accordance with the birth weight, whereas in one case significant difference was found. Intrauterine death occurred in cases where the PPI was near 1.0, whereas healthy mature babies were born with PPIs above 1.5. (L.E.)

  4. Clinical importance of radioisotope measurement of placental circulation

    Energy Technology Data Exchange (ETDEWEB)

    Doszpod, J; Vittay, P; Csakany, M Gy; Misak, L; Gati, I [Orvostovabbkepzoe Intezet, Budapest (Hungary)

    1980-12-27

    Placental circulation was measured by scintigraphic technique after administration of 18.5 MBq (0.5 mCi) /sup 113/In. Scintigrams of the placenta and of the myometrium were taken with a time interval of 3 s for 3 minutes, and with an interval of 1 min for further 8 min. The placental perfusion index (PPI) was calculated on the basis of the time-activity histograms. The examination was carried out in 14 patients, with the following indications: toxicosis gravidarum, stenosis of the aortic valve, diabetes mellitus, placenta praevia, and suspicion of intrauterine retardation. In 13 cases the PPI was in accordance with the birth weight, whereas in one case significant difference was found. Intrauterine death occurred in cases where the PPI was near 1.0, whereas healthy mature babies were born with PPIs above 1.5.

  5. Elevated circulating homocyst(e)ine levels in placental vascular disease and associated pre-eclampsia.

    Science.gov (United States)

    Wang, J; Trudinger, B J; Duarte, N; Wilcken, D E; Wang, X L

    2000-07-01

    We examined the hypothesis that hyperhomocyst(e)inaemia in the maternal or fetal circulation is associated with placental vascular disease with either the maternal syndrome of pre-eclampsia and/or fetal syndrome of growth restriction. Maternal plasma homocyst(e)ine levels were significantly higher in pregnancies complicated by pre-eclampsia, pregnancies with evidence of umbilical placental vascular disease, and pregnancies with both complications compared with the normal pregnancy group. In the fetal circulation mean plasma homocyst(e)ine concentration was significantly higher in the pre-eclampsia group compared with the normal group. The results suggest that hyperhomocyst(e)inaemia may be a risk marker for placental vascular disease and maternal pre-eclampsia. The elevated fetal plasma homocyst(e)ine concentrations, found only in the group of pregnancies with pre-eclampsia in the absence of umbilical placental vascular disease, may be due to an effect of placental vascular disease on homocyst(e)ine transfer from the maternal to fetal circulation.

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

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    Anne Helbig

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

  7. All-in-one detector of circulating mRNA based on a smartphone

    Science.gov (United States)

    Cmiel, Vratislav; Gumulec, Jaromir; Svoboda, Ondrej; Raudenska, Martina; Hudcova, Kristyna; Sekora, Jiri; Balogh, Jaroslav; Masarik, Michal; Provaznik, Ivo

    2016-03-01

    Metallothionein is significantly elevated in various tumors, notably in prostate cancer on both mRNA and protein level. We demonstrated a strong predictive potential of free circulating metallothionein 2A isoform mRNA for patients with this cancer. Circulating mRNA detection relies on expensive equipment and requires high level of expertise. In this work we developed compact "all-in-one" laboratory system which replace microvolume spectrophotometer, thermocycler and realtime PCR machines. We managed to design and construct a microprocessor controlled heating/cooling chamber that ensures required temperature gradient. The chamber includes implemented optical system to enable fluorescence excitation and fluorescence analysis using a smart-phone.

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

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    Alejandra Perez-Sepulveda

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

  9. Placental growth factor concentration in maternal circulation decreases after fetal death: lessons from a case series study.

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    Beharier, Ofer; Shusterman, Eden; Szaingurten-Solodkin, Irit; Weintraub, Adi Y; Sheiner, Eyal; Swissa, Shani S; Gitler, Daniel; Hershkovitz, Reli

    2015-11-01

    Placental growth factor (PlGF) has been suggested as a possible biomarker for major placenta-related disorders such as preeclampsia and intrauterine growth restriction. However, experimental findings suggest that PlGF concentrations may be influenced by other factors besides the placenta. In the present study, we examined how acute fetal injury affects PlGF concentrations in maternal circulation. We therefore monitored PlGF concentrations in maternal circulation before and after feticide. A prospective comparative study was performed. Blood samples were drawn prospectively between January and July 2012, before and after feticide at predetermined time points in relation to the procedure (0, 30, 60, and 120 min). The levels of lactate dehydrogenase (LDH) in the maternal circulation were measured to detect acute tissue damage. PlGF concentrations were measured by standard human ELISA. Following feticide (60 and 120 min), PlGF concentrations decreased significantly compared to the concentrations before feticide. LDH concentrations did not change before and after feticide. Our finding, along with the detailed review of the literature described in our work, supports a new concept in which primary fetal distress can affect PlGF concentration in maternal circulation. A large-scale study is required to strengthen our finding.

  10. Circulating soluble endoglin levels in pregnant women in Cameroon and Malawi--associations with placental malaria and fetal growth restriction.

    Science.gov (United States)

    Silver, Karlee L; Conroy, Andrea L; Leke, Rose G F; Leke, Robert J I; Gwanmesia, Philomina; Molyneux, Malcolm E; Taylor, Diane Wallace; Wallace, Diane Taylor; Rogerson, Stephen J; Kain, Kevin C

    2011-01-01

    Placental infections with Plasmodium falciparum are associated with fetal growth restriction resulting in low birth weight (LBW). The mechanisms that mediate these effects have yet to be completely described; however, they are likely to involve inflammatory processes and dysregulation of angiogenesis. Soluble endoglin (sEng), a soluble receptor of transforming growth factor (TGF)-β previously associated with preeclampsia in pregnant women and with severe malaria in children, regulates the immune system and influences angiogenesis. We hypothesized that sEng may play a role in development of LBW associated with placental malaria (PM). Plasma levels of sEng were measured in women (i) followed prospectively throughout pregnancy in Cameroon (n = 52), and (ii) in a case-control study at delivery in Malawi (n = 479). The relationships between sEng levels and gravidity, peripheral and placental parasitemia, gestational age, and adverse outcomes of PM including maternal anemia and LBW were determined. In the longitudinal cohort from Cameroon, 28 of 52 women (54%) experienced at least one malaria infection during pregnancy. In Malawi we enrolled two aparasitemic gravidity-matched controls for every case with PM. sEng levels varied over the course of gestation and were significantly higher in early and late gestation as compared to delivery (Pwomen and PM in Malawian women were each associated with elevated sEng levels following correction for gestational age and gravidity (p = 0.006 and p = 0.033, respectively). Increased sEng was also associated with the delivery of LBW infants in primigravid Malawian women (p = 0.017); the association was with fetal growth restriction (p = 0.003) but not pre-term delivery (p = 0.286). Increased circulating maternal sEng levels are associated with P. falciparum infection in pregnancy and with fetal growth restriction in primigravidae with PM.

  11. Performance of Circulating Placental Growth Factor as A Screening Marker for Diagnosis of Ovarian Endometriosis: A Pilot Study

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    Cinzia Zucchini

    2016-12-01

    Full Text Available Background: The aim of this study is to compare the circulating placental growth factor (PlGF concentration in women with and without endometrioma to verify the performance of this marker to diagnose the disease. Materials and Methods: In this case-control study, thirteen women with histological diagnosis of ovarian endometriosis were compared with women without endometriosis disease. PlGF plasma levels of endometriotic patients and controls were investigated using a fluorescence immunoassay technique. Results: PlGF showed a direct correlation with body mass index (BMI only in the control group (P=0.013. After adjustment for BMI values, PlGF median value in endometriosis group (14.7 pg/mL resulted higher than in control group (13.8 pg/ mL, P=0.004. Conclusion: PlGF is a promising peripheral blood marker that can discriminate between patients with and without ovarian endometriosis.

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

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

    2011-12-01

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

  13. Placental release of distinct DNA-associated microparticles into maternal circulation: reflective of gestation time and preeclampsia

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    Orozco, Aaron F.; Jorgez, Carolina J.; Ramos-Perez, William D.; Popek, Edwina J.; Yu, Xiaoying; Kozinetz, Claudia A.; Bischoff, Farideh Z.; Lewis, Dorothy E.

    2009-01-01

    Background The aim of this study was to determine whether DNA-associated micro-particles (MPs) in maternal plasma express fetal-derived human leukocyte antigen-G (HLA-G) or placental alkaline phosphatase (PLAP) and whether the levels differ between women with normotensive pregnancies and preeclampsia. Methods DNA-associated MPs expressing HLA-G or PLAP were examined in the plasma of normal pregnant women and preeclamptic patients using flow cytometric analysis. Results DNA-associated HLA-G+ MPs were significantly increased in maternal plasma compared to plasma from non-pregnant controls (p < 0.005), with highest levels found in first and second trimesters. DNA-associated PLAP+ MPs were also increased in maternal plasma compared to plasma from non-pregnant controls (p < 0.006), with highest levels in second and third trimesters. Term preeclamptic women had higher levels of DNA-associated MPs than control pregnant women. HLA-G+ MPs from the plasma of preeclamptic women had more DNA per MP than HLA-G+ MPs from the plasma of normal pregnant women (p < 0.03). Conclusions HLA-G and PLAP MPs increase in maternal circulation at different times during gestation. DNA amounts per HLA-G+ MP increase in preeclamptic women which might indicate dysfunctional extravillous cytotrophoblasts. PMID:19692120

  14. mRNA Levels of Placental Iron and Zinc Transporter Genes Are Upregulated in Gambian Women with Low Iron and Zinc Status.

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    Jobarteh, Modou Lamin; McArdle, Harry J; Holtrop, Grietje; Sise, Ebrima A; Prentice, Andrew M; Moore, Sophie E

    2017-07-01

    Background: The role of the placenta in regulating micronutrient transport in response to maternal status is poorly understood. Objective: We investigated the effect of prenatal nutritional supplementation on the regulation of placental iron and zinc transport. Methods: In a randomized trial in rural Gambia [ENID (Early Nutrition and Immune Development)], pregnant women were allocated to 1 of 4 nutritional intervention arms: 1 ) iron and folic acid (FeFol) tablets (FeFol group); 2 ) multiple micronutrient (MMN) tablets (MMN group); 3 ) protein energy (PE) as a lipid-based nutrient supplement (LNS; PE group); and 4 ) PE and MMN (PE+MMN group) as LNS. All arms included iron (60 mg/d) and folic acid (400 μg/d). The MMN and PE+MMN arms included 30 mg supplemental Zn/d. In a subgroup of ∼300 mother-infant pairs, we measured maternal iron status, mRNA levels of genes encoding for placental iron and zinc transport proteins, and cord blood iron levels. Results: Maternal plasma iron concentration in late pregnancy was 45% and 78% lower in the PE and PE+MMN groups compared to the FeFol and MMN groups, respectively ( P Zinc supplementation in the MMN arm was associated with higher maternal plasma zinc concentrations (10% increase; P zinc-uptake proteins, in this case zrt, irt-like protein (ZIP) 4 and ZIP8, were 96-205% lower in the PE+MMN arm than in the intervention arms without added zinc ( P zinc, the placenta upregulates the gene expression of iron and zinc uptake proteins, presumably in order to meet fetal demands in the face of low maternal supply. The ENID trial was registered at www.controlled-trials.com as ISRCTN49285450.

  15. Associação entre a antropometria e a leptina circulante nos compartimentos materno, fetal e placentário, na gravidez normal Association between anthropometry and circulating leptin in maternal, fetal and placental compartments, in healthy pregnancy

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    Flávia Cipriano Castro

    2004-10-01

    Full Text Available OBJETIVO: avaliar a importância da leptina materna e fetal circulantes na gestação saudável por meio da avaliação de sua associação com variáveis antropométricas materna, placentária e fetal ao nascimento e as relações entre os compartimentos avaliados. MÉTODOS: em estudo transversal foi incluída amostra de 33 gestações únicas, a termo, com fetos saudáveis. As variáveis avaliadas foram idade materna, peso materno, índice de massa corporal, peso do recém-nascido, peso placentário e índice placentário. Amostras de sangue materno foram obtidas imediatamente antes do parto e em sangue do cordão umbilical ao nascimento. A dosagem da leptina sérica foi realizada por meio de radioimunoensaio convencional. As relações entre as concentrações de leptina sérica materna e da artéria e veia umbilicais com as variáveis de estudo foram verificadas através da regressão linear. RESULTADOS: a leptina foi detectada no sangue de todas as 33 gestantes e seus respectivos recém-nascidos, sendo a concentração no sangue materno (17,1±1,77 ng/ml superior à dos vasos umbilicais (veia 9,0±1,16 ng/mL; artéria 8,2±1,02 ng/mL, pPURPOSE: to evaluate the importance of circulating maternal and fetal leptin in the healthy gestation, using its association with maternal, placental and fetal anthropometric variables, obtained at birth, and the relationship between the evaluated compartments. METHODS: in a transversal study a population of 33 single, healthy and term gestations was studied. The evaluated variables were maternal age, maternal weight, body mass index (BMF, weight of the newborn, placental weight, and placental index. Samples of maternal blood were immediately obtained before birth and from fetal umbilical cord blood at birth. Determination of serum leptin was performed using conventional radioimmunoassay. The relationships between serum leptin concentrations in maternal blood, umbilical artery and vein and the studied

  16. Clinical significance of serum circulating insulin-like growth factor-1 (IGF-1) mRNA in hepatocellular carcinoma.

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    Karabulut, S; Duranyıldız, D; Tas, F; Gezer, U; Akyüz, F; Serilmez, M; Ozgür, E; Yasasever, C T; Vatansever, S; Aykan, N F

    2014-03-01

    The principal aim of our study was to investigate the usefulness of serum protein and circulating mRNA of insulin-like growth factor-1 (IGF-1) as a diagnostic and prognostic tool in hepatocellular carcinoma (HCC). Fifty-four HCC patients and age- and sex-matched 20 healthy controls were enrolled into this study. Pretreatment serum IGF-1 and IGF-1 mRNA were determined by the solid-phase sandwich ELISA and quantitative RT-PCR method, respectively. The median age at diagnosis was 60 years, range 36-77 years; where majority of group were male (n = 48, 88.8%). All patients had cirrhotic history. Forty-six percent (n = 25) of patients had Child-Pugh score A, 30% (n = 16) had score B or C. All of the patients were treated with local therapies and none of them received sorafenib. The baseline serum IGF-1 mRNA levels were significantly higher in HCC patients than in the control group (p = 0.04), whereas no significant difference was observed for IGF-1 protein levels between the two group (p = 0.18). Patients with history of HBV infection, who were not treated, and who received multiple palliative treatment for HCC had higher serum IGF-1 mRNA levels (p = 0.03, 0.03, and 0.05, respectively). Poor performance status (p IGF-1 nor serum IGF-1 mRNA had significantly adverse effect on survival (p = 0.53 and 0.42, respectively).

  17. Exploring sexual dimorphism in placental circulation at 22-24 weeks of gestation: A cross-sectional observational study.

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    Widnes, Christian; Flo, Kari; Acharya, Ganesh

    2017-01-01

    Placental blood flow is closely associated with fetal growth and wellbeing. Recent studies suggest that there are differences in blood flow between male and female fetuses. We hypothesized that sexual dimorphism exists in fetal and placental blood flow at 22-24 weeks of gestation. This was a prospective cross-sectional study of 520 healthy pregnant women. Blood flow velocities of the middle cerebral artery (MCA), umbilical artery (UA), umbilical vein (UV) and the uterine arteries (UtA) were measured using Doppler ultrasonography. UV and UtA diameters were measured using two-dimensional ultrasonography and power Doppler angiography. Volume blood flows (Q) of the UV and UtA were calculated. Maternal haemodynamics was assessed with impedance cardiography. UtA resistance (R uta ) was computed as MAP/Q uta . UA PI was significantly (p = 0.008) higher in female fetuses (1.19 ± 0.15) compared with male fetuses (1.15 ± 0.14). MCA PI, cerebro-placental ratio (MCA PI/UA PI), Q uv, UtA PI, Q uta and R uta were not significantly different between groups. At delivery, the mean birth weight and placental weight of female infants (3504 g and 610 g) were significantly (p = 0.0005 and p = 0.039) lower than that of the male infants (3642 g and 634 g). We have demonstrated sexual dimorphism in UA PI, a surrogate for placental vascular resistance, at 22-24 weeks of gestation. Therefore, it would be useful to know when this difference emerges and whether it translates into blood flow differences that may impact upon the fetal growth trajectory. Copyright © 2016 Elsevier Ltd. All rights reserved.

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

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

    2014-01-01

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

  19. 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. Placental chorangioma

    African Journals Online (AJOL)

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

  1. Circulating free soluble fms-like tyrosine kinase-1 during late first trimester in relation with placental volume as a surrogate for trophoblastic production: a physiology study in low-risk cohort.

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    Manthati, Sudtawin; Pratumvinit, Busadee; Hanyongyuth, Ratchaneekorn; Udompunthurak, Suthipol; Phaophan, Amprapha; Wataganara, Tuangsit

    2017-08-01

    Data on first-trimester circulating soluble fms-like tyrosine kinase-1 (sFlt-1) and ischemic placental disease is limited and conflicting. This study aimed to study its physiology in relation to trophoblastic mass as the source of production. Low-risk (representing normal placentation) women from 11 0/7 to 13 6/7 weeks' gestation were prospectively enrolled. Selective measurement of serum free sFlt-1 using a new automated assay from 100 eligible subjects was analyzed with gestational age, maternal weight, fetal crown-rump length (CRL), and mean uterine artery Doppler pulsatility index (PI). Placental volume (surrogate for trophoblastic mass) was estimated using 3-dimensional ultrasound and was assessed for its association with serum free sFlt-1. There was no significant association between serum free sFlt-1 and placental volume in either arithmetic (r = 0.053, p = 0.600), logarithmic (r = 0.005, p = 0.963), or quartile (p = 0.703) scale. There was a significant negative correlation between free sFlt-1 level and maternal weight (r=-0.213, p = 0.033). No significant correlation was found between free sFlt-1 level and gestational age (r = 0.007, p = 0.947), CRL (r = 0.027, p = 0.788), and uterine artery Doppler mean PI (r = 0.020, p = 0.828). Lack of correlation between circulating free sFlt-1 level and placental volume suggests that trophoblasts are not its major source during first trimester with presumably physiologic placentation.

  2. Maternal vitamin D sufficiency and reduced placental gene expression in angiogenic biomarkers related to comorbidities of pregnancy.

    Science.gov (United States)

    Schulz, Elizabeth V; Cruze, Lori; Wei, Wei; Gehris, John; Wagner, Carol L

    2017-10-01

    Maternal circulating 25-hydroxyvitamin D [25(OH)D] has been shown to optimize production of 1,25-dihydroxyvitamin D [1,25(OH) 2 D] during pregnancy at approximately 100nmoles/L, which has pronounced effects on fetal health outcomes. Additionally, associations are noted between low maternal 25(OH)D concentrations and vascular pregnancy complications, such as preeclampsia. To further elucidate the effects of vitamin D activity in pregnancy, we investigated the role of maternal 25(OH)D, the nutritional indicator of vitamin D status, in relation to placental maintenance and, specifically, expression of placental gene targets related to angiogenesis and vitamin D metabolism. A focused analysis of placental mRNA expression related to angiogenesis, pregnancy maintenance, and vitamin D metabolism was conducted in placentas from 43 subjects enrolled in a randomized controlled trial supplementing 400IU or 4400IU of vitamin D 3 per day during pregnancy. Placental mRNA was isolated from biopsies within one hour of delivery, followed by quantitative PCR. We classified pregnant women with circulating concentrations of D concentrations D ≥100ng/mL compared to the subgroup vitamin D status and the expression of sFlt-1 and VEGF at the mRNA level. Achieving maternal circulating 25(OH)D ≥100nmoles/L suggests the impact of maternal vitamin D 3 supplementation on gene transcription in the placenta, thereby potentially decreasing antiangiogenic factors that may contribute to vascular pregnancy complications. Published by Elsevier Ltd.

  3. [Detection and clinical value of epithelial cellular adhesion molecule (EpCAM) mRNA positive circulating tumor cells in metastatic breast cancer].

    Science.gov (United States)

    Yan, Ying; Cheng, Jian-ping; Di, Li-jun; Song, Guo-hong; Ren, Jun

    2012-04-18

    To test for circulating tumor cells (CTCs) relying on epithelial cellular adhesion molecule (EpCAM) expression in metastatic breast cancer by quantitative real-time reverse transcription-PCR. In the study,47 metastatic breast cancer patients were evaluated by quantitative real-time PCR for detecting EpCAM mRNA. In addition, analyses were carried out for their correlation with patients' clinicopathologic features, response, and the time to progression (TTP). The sensitivity of EpCAM mRNA in the metastatic breast cancer patients was about 40%. However, the specificity of EpCAM mRNA for 20 healthy controls was 100%. TTP was calculated, and compared with that between EpCAM mRNA-positive and EpCAM mRNA-negative groups. For the retrospective study, the median TTP was 7.1 months and 11.1 months (P=0.013) for patients with EpCAM mRNA-positive and EpCAM mRNA-negative, respectively, after the first cycle chemotherapy. Moreover, a statistically significant correlation was demonstrated between EpCAM mRNA and TTP in patients who underwent the first or the second-line chemotherapy (P=0.018), but there was no significance in the patients pretreated with two or more previous chemotherapy lines (P=0.471). This study provides evidence of the presence of EpCAM mRNA in approximately 40% of patients with metastatic breast cancer. There is a strong correlation between EpCAM mRNA results after the first cycle therapy and TTP in metastatic breast cancer patients, and EpCAM mRNA positive after chemotherapy may predict shorter TTP.

  4. Induction of Robust B Cell Responses after Influenza mRNA Vaccination Is Accompanied by Circulating Hemagglutinin-Specific ICOS+ PD-1+ CXCR3+ T Follicular Helper Cells

    Directory of Open Access Journals (Sweden)

    Gustaf Lindgren

    2017-11-01

    Full Text Available Modified mRNA vaccines have developed into an effective and well-tolerated vaccine platform that offers scalable and precise antigen production. Nevertheless, the immunological events leading to strong antibody responses elicited by mRNA vaccines are largely unknown. In this study, we demonstrate that protective levels of antibodies to hemagglutinin were induced after two immunizations of modified non-replicating mRNA encoding influenza H10 encapsulated in lipid nanoparticles (LNP in non-human primates. While both intradermal (ID and intramuscular (IM administration induced protective titers, ID delivery generated this response more rapidly. Circulating H10-specific memory B cells expanded after each immunization, along with a transient appearance of plasmablasts. The memory B cell pool waned over time but remained detectable throughout the 25-week study. Following prime immunization, H10-specific plasma cells were found in the bone marrow and persisted over time. Germinal centers were formed in vaccine-draining lymph nodes along with an increase in circulating H10-specific ICOS+ PD-1+ CXCR3+ T follicular helper cells, a population shown to correlate with high avidity antibody responses after seasonal influenza vaccination in humans. Collectively, this study demonstrates that mRNA/LNP vaccines potently induce an immunological repertoire associated with the generation of high magnitude and quality antibodies.

  5. Tris(2-butoxyethyl)phosphate and triethyl phosphate alter embryonic development, hepatic mRNA expression, thyroid hormone levels, and circulating bile acid concentrations in chicken embryos

    Energy Technology Data Exchange (ETDEWEB)

    Egloff, Caroline [National Wildlife Research Centre, Environment Canada, Ottawa, ON K1A 0H3 (Canada); Crump, Doug, E-mail: doug.crump@ec.gc.ca [National Wildlife Research Centre, Environment Canada, Ottawa, ON K1A 0H3 (Canada); Porter, Emily; Williams, Kim L.; Letcher, Robert J.; Gauthier, Lewis T. [National Wildlife Research Centre, Environment Canada, Ottawa, ON K1A 0H3 (Canada); Kennedy, Sean W. [National Wildlife Research Centre, Environment Canada, Ottawa, ON K1A 0H3 (Canada); Department of Biology, University of Ottawa, Ottawa, ON K1N 6N5 (Canada)

    2014-09-15

    The organophosphate flame retardants tris(2-butoxyethyl) phosphate (TBOEP) and triethyl phosphate (TEP) are used in a wide range of applications to suppress or delay the ignition and spread of fire. Both compounds have been detected in the environment and TBOEP was recently measured in free-living avian species. In this study, TBOEP and TEP were injected into the air cell of chicken embryos at concentrations ranging from 0 to 45,400 ng/g and 0 to 241,500 ng/g egg, respectively. Pipping success, development, hepatic mRNA expression of 9 target genes, thyroid hormone levels, and circulating bile acid concentrations were determined. Exposure to the highest doses of TBOEP and TEP resulted in negligible detection of the parent compounds in embryonic contents at pipping indicating their complete metabolic degradation. TBOEP exposure had limited effects on chicken embryos, with the exception of hepatic CYP3A37 mRNA induction. TEP exposure decreased pipping success to 68%, altered growth, increased liver somatic index (LSI) and plasma bile acids, and modulated genes associated with xenobiotic and lipid metabolism and the thyroid hormone pathway. Plasma thyroxine levels were decreased at all TEP doses, including an environmentally-relevant concentration (8 ng/g), and gallbladder hypotrophy was evident at ≥ 43,200 ng/g. Tarsus length and circulating thyroxine concentration emerged as potential phenotypic anchors for the modulation of transthyretin mRNA. The increase in plasma bile acids and LSI, gallbladder hypotrophy, and discoloration of liver tissue represented potential phenotypic outcomes associated with modulation of hepatic genes involved with xenobiotic and lipid metabolism. - Highlights: • TBOEP is not embryolethal to chicken embryos. • TEP affected embryonic viability, morphometric endpoints, and thyroid hormone levels. • TEP altered mRNA levels of xenobiotic and lipid metabolism genes. • TEP increased plasma bile acids and caused gallbladder hypotrophy

  6. Lower placental growth factor and higher free β-hCG and PAPP-A levels in the fetal circulation of near-term pregnancies complicated with severe preeclampsia.

    Science.gov (United States)

    Paredes, Verónica; Espinoza-Caicedo, Jasson A; Salazar-Pousada, Danny; Escobar, Gustavo S; Pérez-López, Faustino R; Chedraui, Peter

    2017-01-01

    An imbalance between anti- and angiogenic factors during early placentation is key for the development of preeclampsia. Nevertheless, the majority of studies addressing this issue relate to maternal blood and not the fetal circulation. To measure placental growth factor (PlGF), free beta human chorionic gonadotropin (β-hCG), and pregnancy-associated plasma protein-A (PAPP-A) levels in the fetal circulation of near-term pregnancies complicated with severe preeclampsia (n = 20), and their controls matched for parity, and maternal and gestational age. Upon delivery, a blood sample was withdrawn from the umbilical artery and vein of each case and its control in order to measure the proposed analytes using direct fluoroimmunoassay. Preeclampsia cases showed significantly lower median PlGF levels in fetal circulation as compared to controls (25.2 versus 36.9 and 23.6 versus 33.9 pg/mL, artery and vein, respectively, p < 0.05). Contrarily, cases displayed higher concentrations of PAPP-A (1024.0 versus 720.9 [median] and 1027.0 ± 298.4 versus 690.3 ± 401.9 mIU/L, artery and vein, respectively, p < 0.05), and free β-hCG (mean: 33.9 ± 4.3 versus 17.2 ± 4.0 and 30.1 ± 5.2 versus 13.7 ± 3.3 ng/mL, artery, and vein respectively, p < 0.05). Lower PlGF and higher PAPP-A and free β-hCG levels were found in the fetal circulation of near-term severe preeclamptic pregnancies. There is a need for more research in this regard.

  7. Mammalian Placentation

    DEFF Research Database (Denmark)

    Carter, Anthony Michael; Mess, A. M.

    2014-01-01

    This guide to animal models of human placentation assesses the strengths and weaknesses of species in common use. We argue that structural differences from human placenta, though important in some contexts, are less of a drawback than differences in reproductive strategy. Many laboratory rodents...... of the placenta. This information is collated both to assess common animal models such as mouse, sheep, and primates and to introduce some alternatives that we consider worthy of attention....... have brief gestations resulting in the birth of poorly developed young. They can provide useful insights on placental development and function relevant to early human pregnancy. However, to model the events of a 9-month gestation, which imposes added requirements on the placenta, it is necessary...

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

    Science.gov (United States)

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

    2013-02-01

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

  9. Molecular detection of peripheral blood breast cancer mRNA transcripts as a surrogate biomarker for circulating tumor cells.

    Directory of Open Access Journals (Sweden)

    Adriana Lasa

    Full Text Available Circulating tumor cells (CTCs are becoming a scientifically recognized indicator of primary tumors and/or metastasis. These cells can now be accurately detected and characterized as the result of technological advances. We analyzed the presence of CTCs in the peripheral blood of patients with metastatic breast cancer by real-time reverse-transcription PCR (RT-qPCR using a panel of selected genes. The analysis of a single marker, without an EpCAM based enrichment approach, allowed the positive identification of 35% of the metastatic breast cancer patients. The analysis of five genes (SCGB2, TFF1, TFF3, Muc1, KRT20 performed in all the samples increased the detection to 61%. We describe a sensitive, reproducible and easy to implement approach to characterize CTC in patients with metastasic breast cancer.

  10. Vascular Endothelial Growth Factor (VEGF) mRNA Isoforms are Altered in Bovine Granulosa Cells (GC) by Circulating Progestin Concentrations (P4) and May Indicate Follicle Status and Oocyte Competence

    Science.gov (United States)

    Previously, Melengestrol Acetate (MGA) fed for 14 d (0.5mg/cow/d; < 1 ng/ml P4) resulted in persistent follicles with increased size, decreased number of GC/follicular fluid (FF) volume, and less fertile oocytes. An experiment was conducted to determine effects of circulating P4 on amount of mRNA fo...

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

    Science.gov (United States)

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

    2017-04-01

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

  12. A comparison of cell-free placental messenger ribonucleic acid and color Doppler ultrasound for the prediction of placental invasion in patients with placenta accreta

    OpenAIRE

    Naghshineh, Elham; Khorvash, Elahe; Kamali, Sara

    2015-01-01

    Background: The aim of the present study was to comparison between cell-free placental messenger ribonucleic acid (mRNA) and Doppler ultrasound for the prediction of placental invasion in women with placenta accreta. Materials and Methods: In this cross-sectional study, 50 pregnant women at risk for placenta accreta underwent color Doppler and assessment of cell-free placental mRNA. Real-time reverse-transcription polymerase chain reaction was used for measurement of cell-free placental m...

  13. 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...

  14. Cadmium-induced neural tube defects and fetal growth restriction: Association with disturbance of placental folate transport

    International Nuclear Information System (INIS)

    Zhang, Gui-Bin; Wang, Hua; Hu, Jun; Guo, Min-Yin; Wang, Ying; Zhou, Yan; Yu, Zhen; Fu, Lin; Chen, Yuan-Hua; Xu, De-Xiang

    2016-01-01

    Previous studies found that maternal Cd exposure on gestational day (GD)9 caused forelimb ectrodactyly and tail deformity, the characteristic malformations. The aim of the present study was to investigate whether maternal Cd exposure on GD8 induces fetal neural tube defects (NTDs). Pregnant mice were intraperitoneally injected with CdCl 2 (2.5 or 5.0 mg/kg) on GD8. Neither forelimb ectrodactyly nor tail deformity was observed in mice injected with CdCl 2 on GD8. Instead, maternal Cd exposure on GD8 resulted in the incidence of NTDs. Moreover, maternal Cd exposure on GD8 resulted in fetal growth restriction. In addition, maternal Cd exposure on GD8 reduced placental weight and diameter. The internal space of maternal and fetal blood vessels in the labyrinth layer was decreased in the placentas of mice treated with CdCl 2 . Additional experiment showed that placental PCFT protein and mRNA, a critical folate transporter, was persistently decreased when dams were injected with CdCl 2 on GD8. Correspondingly, embryonic folate content was markedly decreased in mice injected with CdCl 2 on GD8, whereas Cd had little effect on folate content in maternal serum. Taken together, these results suggest that maternal Cd exposure during organogenesis disturbs transport of folate from maternal circulation to the fetuses through down-regulating placental folate transporters. - Highlights: • Maternal Cd exposure during organogenesis causes NTDs and FGR. • Maternal Cd exposure during organogenesis impairs placental development. • Cd disturbs transport of folate by down-regulating placental folate transporters.

  15. Cadmium-induced neural tube defects and fetal growth restriction: Association with disturbance of placental folate transport

    Energy Technology Data Exchange (ETDEWEB)

    Zhang, Gui-Bin; Wang, Hua, E-mail: wanghuadev@126.com; Hu, Jun; Guo, Min-Yin; Wang, Ying; Zhou, Yan; Yu, Zhen; Fu, Lin; Chen, Yuan-Hua; Xu, De-Xiang, E-mail: xudex@126.com

    2016-09-01

    Previous studies found that maternal Cd exposure on gestational day (GD)9 caused forelimb ectrodactyly and tail deformity, the characteristic malformations. The aim of the present study was to investigate whether maternal Cd exposure on GD8 induces fetal neural tube defects (NTDs). Pregnant mice were intraperitoneally injected with CdCl{sub 2} (2.5 or 5.0 mg/kg) on GD8. Neither forelimb ectrodactyly nor tail deformity was observed in mice injected with CdCl{sub 2} on GD8. Instead, maternal Cd exposure on GD8 resulted in the incidence of NTDs. Moreover, maternal Cd exposure on GD8 resulted in fetal growth restriction. In addition, maternal Cd exposure on GD8 reduced placental weight and diameter. The internal space of maternal and fetal blood vessels in the labyrinth layer was decreased in the placentas of mice treated with CdCl{sub 2}. Additional experiment showed that placental PCFT protein and mRNA, a critical folate transporter, was persistently decreased when dams were injected with CdCl{sub 2} on GD8. Correspondingly, embryonic folate content was markedly decreased in mice injected with CdCl{sub 2} on GD8, whereas Cd had little effect on folate content in maternal serum. Taken together, these results suggest that maternal Cd exposure during organogenesis disturbs transport of folate from maternal circulation to the fetuses through down-regulating placental folate transporters. - Highlights: • Maternal Cd exposure during organogenesis causes NTDs and FGR. • Maternal Cd exposure during organogenesis impairs placental development. • Cd disturbs transport of folate by down-regulating placental folate transporters.

  16. Variable EBV DNA Load Distributions and Heterogeneous EBV mRNA Expression Patterns in the Circulation of Solid Organ versus Stem Cell Transplant Recipients

    Directory of Open Access Journals (Sweden)

    A. E. Greijer

    2012-01-01

    Full Text Available Epstein-Barr virus (EBV driven post-transplant lymphoproliferative disease (PTLD is a heterogeneous and potentially life-threatening condition. Early identification of aberrant EBV activity may prevent progression to B-cell lymphoma. We measured EBV DNA load and RNA profiles in plasma and cellular blood compartments of stem cell transplant (SCT; n=5, solid organ transplant recipients (SOT; n=15, and SOT having chronic elevated EBV-DNA load (n=12. In SCT, EBV DNA was heterogeneously distributed, either in plasma or leukocytes or both. In SOT, EBV DNA load was always cell associated, predominantly in B cells, but occasionally in T cells (CD4 and CD8 or monocytes. All SCT with cell-associated EBV DNA showed BARTs and EBNA1 expression, while LMP1 and LMP2 mRNA was found in 1 and 3 cases, respectively. In SOT, expression of BARTs was detected in all leukocyte samples. LMP2 and EBNA1 mRNA was found in 5/15 and 2/15, respectively, but LMP1 mRNA in only 1, coinciding with severe PTLD and high EBV DNA. Conclusion: EBV DNA is differently distributed between white cells and plasma in SOT versus SCT. EBV RNA profiling in blood is feasible and may have added value for understanding pathogenic virus activity in patients with elevated EBV-DNA.

  17. Inverse correlation between maternal plasma asymmetric dimethylarginine (ADMA) and birthweight percentile in women with impaired placental perfusion: circulating ADMA as an NO-independent indicator of fetal growth restriction?

    Science.gov (United States)

    Tsikas, Dimitrios; Bollenbach, Alexander; Savvidou, Makrina D

    2018-02-01

    L-Arginine (Arg) is the enzymatic precursor of nitric oxide (NO) which has multiple biological functions. Asymmetric dimethylarginine (ADMA) and symmetric dimethylarginine (SDMA) are endogenous inhibitors of NO. We hypothesized that the ADMA and SDMA have additional biological functions in pregnancy, beyond NO synthesis, and may play a role in the regulation of birthweight (BW). To investigate this issue, we measured the plasma concentration of ADMA, SDMA, Arg and the NO metabolites nitrite and nitrate, at 23-25 weeks of gestation in women with normal placental function (Group 1) and in women with impaired placental perfusion; 19 of these women had normal outcome (Group 2), 14 had a fetus that was growth restricted (Group 3), and 10 women eventually developed preeclampsia (Group 4). BW percentile was found to inversely correlate with maternal plasma ADMA concentration in Group 3 (r = - 0.872, P restriction in women with impaired placental perfusion independent of NO.

  18. Circulating Tyrosinase and MART-1 mRNA does not Independently Predict Relapse or Survival in Patients with AJCC Stage I–II Melanoma

    DEFF Research Database (Denmark)

    Schmidt, Henrik; Sørensen, Boe S; Sjoegren, Pia

    2006-01-01

    The detection of melanoma cells in peripheral blood has been proposed to select patients with a high risk of relapse. In this study, tyrosinase and melanoma antigen recognized by T cells 1 (MART-1) mRNA expression was evaluated in serial samples obtained before definitive surgery and during follow......-up in patients with American Joint Committee on Cancer stage I-II melanoma. Serial samples (n=2,262) were collected from 236 patients from 1997 to 2002. Analyses of the RNA samples were performed with a calibrated reverse transcriptase-PCR assay. Gender, age, primary tumor site, ulceration, thickness, Clark...

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

    Science.gov (United States)

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

    2015-06-01

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

  20. Loss of Thrombomodulin in Placental Dysfunction in Preeclampsia.

    Science.gov (United States)

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

    2016-04-01

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

  1. Soluble FLT-1 rules placental destiny.

    Science.gov (United States)

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

    2018-02-19

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

  2. 1,2-Dibromo-4-(1,2-dibromoethyl)-cyclohexane and tris(methylphenyl) phosphate cause significant effects on development, mRNA expression, and circulating bile acid concentrations in chicken embryos

    Energy Technology Data Exchange (ETDEWEB)

    Crump, Doug, E-mail: doug.crump@ec.gc.ca [National Wildlife Research Centre, Environment Canada, Ottawa, ON K1A 0H3 (Canada); Porter, Emily; Egloff, Caroline; Williams, Kim L.; Letcher, Robert J.; Gauthier, Lewis T. [National Wildlife Research Centre, Environment Canada, Ottawa, ON K1A 0H3 (Canada); Kennedy, Sean W. [National Wildlife Research Centre, Environment Canada, Ottawa, ON K1A 0H3 (Canada); Department of Biology, University of Ottawa, Ottawa, ON K1N 6N5 (Canada)

    2014-06-15

    1,2-Dibromo-4-(1,2-dibromoethyl)-cyclohexane (DBE-DBCH; formerly abbreviated as TBECH) and tris(methylphenyl) phosphate (TMPP; formerly abbreviated as TCP) are additive flame retardants that are detected in the environment and biota. A recent avian in vitro screening study of 16 flame retardants identified DBE-DBCH and TMPP as important chemicals for follow-up in ovo evaluation based on their effects on cytotoxicity and mRNA expression in avian hepatocytes. In this study, technical mixtures of DBE-DBCH and TMPP were injected into the air cell of chicken embryos at concentrations ranging from 0 to 54,900 ng/g and from 0 to 261,400 ng/g, respectively, to determine effects on pipping success, development, hepatic mRNA expression, thyroid hormone levels, and circulating bile acid concentrations. Both compounds were detectable in embryos at pipping and the β-DBE-DBCH isomer was depleted more rapidly than the α-isomer in tissue samples. DBE-DBCH had limited effects on the endpoints measured, with the exception of the up-regulation of two phase I metabolizing enzymes, CYP3A37 and CYP2H1. TMPP exposure caused embryonic deformities, altered growth, increased liver somatic index (LSI) and plasma bile acid concentrations, and altered mRNA expression levels of genes associated with xenobiotic and lipid metabolism and the thyroid hormone pathway. Overall, TMPP elicited more adverse molecular and phenotypic effects than DBE-DBCH albeit at concentrations several orders of magnitude greater than those detected in the environment. The increase in plasma bile acid concentrations was a useful phenotypic anchor as it was associated with a concomitant increase in LSI, discoloration of the liver tissue, and modulation of hepatic genes involved with xenobiotic and lipid metabolism. - Highlights: • DBE-DBCH and TMPP are not embryolethal to chicken embryos. • TMPP caused deformities, morphometric alterations, and increased plasma bile acids. • DBE-DBCH and TMPP altered mRNA levels

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

    Directory of Open Access Journals (Sweden)

    Nandor Gabor Than

    2014-08-01

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

  4. The Umbilical Artery Resistive Index and the Cerebro-Placental ...

    African Journals Online (AJOL)

    The Umbilical Artery Resistive Index and the Cerebro-Placental Ratio as a Predictor of Adverse Foetal Outcome in Patients with Hypertensive Disorders of ... East and Central African Journal of Surgery ... Background: Hypertensive disorders of pregnancy causes adverse effects both the maternal and faetal circulations.

  5. Forensic pregnancy diagnostics with placental mRNA markers

    NARCIS (Netherlands)

    J. Gauvin (Jeanot); D. Zubakov (Dmitry); J. van Rhee-Binkhorst (Joke); A. Kloosterman (Ate); E.A.P. Steegers (Eric); M.H. Kayser (Manfred)

    2010-01-01

    textabstractCurrent methods for pregnancy diagnostics are based on immunodetection of pregnancy-specific proteins and in a forensic context suffer from sensitivity and specificity issues. Here, we applied reverse transcriptase polymerase chain reaction (RT-PCR) technology to 11 genes previously

  6. Placental perfusion in 3rd trimester pregnancy

    Science.gov (United States)

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

    2018-03-01

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

  7. A stochastic model for early placental development.

    KAUST Repository

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

    2014-01-01

    In the human, placental structure is closely related to placental function and consequent pregnancy outcome. Studies have noted abnormal placental shape in small-for-gestational-age infants which extends to increased lifetime risk of cardiovascular

  8. MicroRNAs in Human Placental Development and Pregnancy Complications

    Directory of Open Access Journals (Sweden)

    Chun Peng

    2013-03-01

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

  9. Placental Growth Factor Reduces Blood Pressure in a Uteroplacental Ischemia Model of Preeclampsia in Nonhuman Primates.

    Science.gov (United States)

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

    2016-06-01

    An imbalance in the angiogenesis axis during pregnancy manifests as clinical preeclampsia because of endothelial dysfunction. Circulating soluble fms-like tyrosine kinase 1 (sFLT-1) increases and placental growth factor (PlGF) reduces before and during disease. We investigated the clinical and biochemical effects of replenishing the reduced circulating PlGF with recombinant human PlGF (rhPlGF) and thus restoring the angiogenic balance. Hypertensive proteinuria was induced in a nonhuman primate (Papio hamadryas) by uterine artery ligation at 136 days gestation (of a 182-day pregnancy). Two weeks after uteroplacental ischemia, rhPlGF (rhPlGF, n=3) or normal saline (control, n=4) was administered by subcutaneous injection (100 μg/kg per day) for 5 days. Blood pressure was monitored by intra-arterial radiotelemetry and sFLT-1 and PlGF by ELISA. Uteroplacental ischemia resulted in experimental preeclampsia evidenced by increased blood pressure, proteinuria, and endotheliosis on renal biopsy and elevated sFLT-1. PlGF significantly reduced after uteroplacental ischemia. rhPlGF reduced systolic blood pressure in the treated group (-5.2±0.8 mm Hg; from 132.6±6.6 mm Hg to 124.1±7.6 mm Hg) compared with an increase in systolic blood pressure in controls (6.5±3 mm Hg; from 131.3±1.5 mm Hg to 138.6±1.5 mm Hg). Proteinuria reduced in the treated group (-72.7±55.7 mg/mmol) but increased in the control group. Circulating levels of total sFLT-1 were not affected by the administration of PlGF; however, a reduction in placental sFLT-1 mRNA expression was demonstrated. There was no significant difference between the weights or lengths of the neonates in the rhPlGF or control group; however, this study was not designed to assess fetal safety or outcomes. Increasing circulating PlGF by the administration of rhPlGF improves clinical parameters in a primate animal model of experimental preeclampsia. © 2016 American Heart Association, Inc.

  10. Effects from placental exposure

    Energy Technology Data Exchange (ETDEWEB)

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

    1975-12-01

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

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

    Science.gov (United States)

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

    2017-05-09

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

  12. Observer reliability in assessing placental maturity by histology.

    OpenAIRE

    Khong, T Y; Staples, A; Bendon, R W; Chambers, H M; Gould, S J; Knowles, S; Shen-Schwarz, S

    1995-01-01

    AIMS--To evaluate the ability of five experienced perinatal pathologists to assess placental maturity reliably by histology. METHODS--Twenty four haematoxylin and eosin slides, six each from placentas of 27, 31, 35, and 39 weeks' gestation, were circulated to five pathologists on three separate occasions. The slides were labelled with the correct or incorrect gestational ages. RESULTS--The mean absolute error over all 360 readings was 2.72 weeks. Only 54% of the slides were assessed within tw...

  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...... between the mother and foetus. Dual perfusion of a single cotyledon in the human placenta can contribute to a better understanding of the placental barrier, transport rate and mechanisms of different substances and placental metabolism. The perfusion system has recently been established in Copenhagen...

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

    Science.gov (United States)

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

    2007-09-01

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

  15. EFFECTS OF SECRETABLE PLACENTAL FACTORS UPON SECRETION OF CYTOKINES BY THP-1 MONOCYTE-LIKE CELLS

    Directory of Open Access Journals (Sweden)

    Ya. S. Onokhina

    2013-01-01

    Full Text Available Abstract. Мonocytes in feto-placental circulation are exposed to factors secreted by placental tissue. These factors influence monocyte functions in pregnancy. In present study, an in vitro model (monocyte-like THP-1 cells was used for assessing effects of soluble placental factors obtained from women with physiological pregnancies, or preeclampsia cases. The following effects of placental factors were revealed: increased secretion of VEGF by THP-1 cells along with decreased secretion of IL-6, IL-8 and MCP-1 under the influence of placental factors from the I. trimester of pregnancy in comparison with III. trimester. Secretion of IL-6 and MCP-1 by THP-1 cells was increased, and secretion of soluble TNFRII was decreased upon co-cultivation with soluble placental factors from the women with preeclampsia, as compared with placental products from physiological pregnancies.The work is supported by grants ГК № 02.740.11.0711 from Ministry of Education and Science, and НШ-3594.2010.7 grant from the President of Russian Federation.

  16. Placental Histopathologic Changes Associated with Subclinical Malaria Infection and Its Impact on the Fetal Environment

    Science.gov (United States)

    Parekh, Falgunee K.; Davison, Billie B.; Gamboa, Dionicia; Hernandez, Jean; Branch, OraLee H.

    2010-01-01

    Microscopic examination of placental tissue can provide an accurate assessment of malaria infection during pregnancy. In this cross-sectional study of 193 women in Iquitos, Peru, 1.0% and 6.6% had parasites in the peripheral blood as detected by microscopy and polymerase chain reaction, respectively. However, 22% had placental malaria pigment indicating past, subclinical infections. Placental tissues with pigment from 24 cases were matched by gravidity and month of delivery to 24 controls and histopathologically examined. Cases had significantly higher number of monocytes in the intervillous space (44.7 versus 25.5; P = 0.012). Pigmented monocytes in fetal vessels were present in 33.3% of cases. This study demonstrated that subclinical malarial infection occurred frequently in pregnant women and is associated with increased presence of monocytes in the placenta. Pigmented monocytes in fetal vessels suggest parasites can breach the placental barrier and enter the fetal circulation. PMID:21036823

  17. Preclinical chorioamnionitis dysregulates CXCL1/CXCR2 signaling throughout the placental-fetal-brain axis.

    Science.gov (United States)

    Yellowhair, Tracylyn R; Noor, Shahani; Maxwell, Jessie R; Anstine, Christopher V; Oppong, Akosua Y; Robinson, Shenandoah; Milligan, Erin D; Jantzie, Lauren L

    2018-03-01

    In the United States, perinatal brain injury (PBI) is a major cause of infant mortality and childhood disability. For a large proportion of infants with PBI, central nervous system (CNS) injury begins in utero with inflammation (chorioamnionitis/CHORIO) and/or hypoxia-ischemia. While studies show CHORIO contributes to preterm CNS injury and is also a common independent risk factor for brain injury in term infants, the molecular mechanisms mediating inflammation in the placental-fetal-brain axis that result in PBI remain a gap in knowledge. The chemokine (C-X-C motif) ligand 1 (CXCL1), and its cognate receptor, CXCR2, have been clinically implicated in CHORIO and in mature CNS injury, although their specific role in PBI pathophysiology is poorly defined. Given CXCL1/CXCR2 signaling is essential to neural cell development and neutrophil recruitment, a key pathological hallmark of CHORIO, we hypothesized CHORIO would upregulate CXCL1/CXCR2 expression in the placenta and fetal circulation, concomitant with increased CXCL1/CXCR2 signaling in the developing brain, immune cell activation, neutrophilia, and microstructural PBI. On embryonic day 18 (E18), a laparotomy was performed in pregnant Sprague Dawley rats to induce CHORIO. Specifically, uterine arteries were occluded for 60min to induce placental transient systemic hypoxia-ischemia (TSHI), followed by intra-amniotic injection of lipopolysaccharide (LPS). Pups were born at E22. Placentae, serum and brain were collected along an extended time course from E19 to postnatal day (P)15 and analyzed using multiplex electrochemiluminescence (MECI), Western blot, qPCR, flow cytometry (FC) and diffusion tensor imaging (DTI). Results demonstrate that compared to sham, CHORIO increases placental CXCL1 and CXCR2 mRNA levels, concomitant with increased CXCR2 + neutrophils. Interestingly, pup serum CXCL1 expression in CHORIO parallels this increase, with sustained elevation through P15. Analyses of CHORIO brains reveal similarly

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

    Science.gov (United States)

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

    2015-01-01

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

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

    Directory of Open Access Journals (Sweden)

    Pricilla E Day

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

  20. Fatty acid profile of maternal and fetal erythrocytes and placental expression of fatty acid transport proteins in normal and intrauterine growth restriction pregnancies.

    Science.gov (United States)

    Assumpção, Renata P; Mucci, Daniela B; Fonseca, Fernanda C P; Marcondes, Henrique; Sardinha, Fátima L C; Citelli, Marta; Tavares do Carmo, Maria G

    2017-10-01

    Long-chain polyunsaturated fatty acids (LC-PUFA), mainly docosahexaenoic (DHA) and arachidonic acids (AA), are critical for adequate fetal growth and development. We investigated mRNA expression of proteins involved in hydrolysis, uptake and/or transport of fatty acids in placenta of fifteen full term normal pregnancies and eleven pregnancies complicated by intrauterine growth restriction (IUGR) with normal umbilical blood flows. The mRNA expression of LPL, FATPs (-1, -2 and -4) and FABPs (-1 and -3) was increased in IUGR placentas, however, tissue profile of LC-PUFA was not different between groups. Erythrocytes from both mothers and fetuses of the IUGR group showed lower concentrations of AA and DHA and inferior DHA/ALA ratio compared to normal pregnancies (P < 0.05). We hypothesize that reduced circulating levels of AA and DHA could up-regulate mRNA expression of placental fatty acids transporters, as a compensatory mechanism, however this failed to sustain normal LC-PUFA supply to the fetus in IUGR. Copyright © 2017 Elsevier Ltd. All rights reserved.

  1. Intrapritoneal Hemorrhage after Placental Abruption

    Directory of Open Access Journals (Sweden)

    Nahid Sakhavar

    2012-06-01

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

  2. Imaging of placental transport mechanisms: a review.

    Science.gov (United States)

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

    2009-05-01

    application of strict quantitative criteria. The thresholding procedure is suitable for automation and produces reproducible, objectifiable results. Thresholded images were subjected to image calculation procedures designed to highlight image elements (pixels) containing (green) fluorescence associated with the tracer protein; all other sources of fluorescence were visualised in the final images only if no green fluorescence was detectable in that pixel. The resulting images were maps, showing the distribution of tracer molecules at a predefined time interval after perfusion of the tracer into the vital (term) cotyledon. Spatial resolution was routinely better than 1 microm and temporal resolution was approximately 5s. At timepoints up to 10 min after intravital application into the fetal vascular circulation, tracer was associated with capillaries in the villous structures, and no tracer was observed in the syncytiotrophoblast. Clear distinction was achieved between the four tissue compartments relevant to placental transfers, thus providing a novel technology capable of generating high-quality data concerning the regulation of transfers of any molecule that can bear a fluorescent tag. The potential applications of this methodology lie in analyses of factors influencing the rates of fetomaternal and maternofetal exchanges (for example, drugs), and of functional responses of the placental regulation to pathophysiological conditions such as hypoxia.

  3. Relationships between Arachidonic Acid, Uterine Activity and Metabolic Regulation of Placental Lactogen Secretion.

    Science.gov (United States)

    1982-08-01

    and R.E. Fellows. 1976. Circulating placental lactogen levels in dairy and beef cattle . Endocrinology 99:1273. Brinsmead, M.W., B.J. Bancroft, G.D... castrate sows. Am. J. Physiol. 217:1431. Felber, J.P., N. Zaragza, M. Benu7zi-Badoni and A.R. Genazzani. 1972. The double effect of HCS and pregnancy

  4. Placental Adaptations in Growth Restriction

    Science.gov (United States)

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

    2015-01-01

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

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

    Science.gov (United States)

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

    2017-08-02

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

  6. 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.

  7. Triazole fungicide tebuconazole disrupts human placental trophoblast cell functions

    International Nuclear Information System (INIS)

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

    2016-01-01

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

  8. Triazole fungicide tebuconazole disrupts human placental trophoblast cell functions

    Energy Technology Data Exchange (ETDEWEB)

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

    2016-05-05

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

  9. A comparison of cell-free placental messenger ribonucleic acid and color Doppler ultrasound for the prediction of placental invasion in patients with placenta accreta.

    Science.gov (United States)

    Naghshineh, Elham; Khorvash, Elahe; Kamali, Sara

    2015-01-01

    The aim of the present study was to comparison between cell-free placental messenger ribonucleic acid (mRNA) and Doppler ultrasound for the prediction of placental invasion in women with placenta accreta. In this cross-sectional study, 50 pregnant women at risk for placenta accreta underwent color Doppler and assessment of cell-free placental mRNA. Real-time reverse-transcription polymerase chain reaction was used for measurement of cell-free placental mRNA in maternal plasma. Based on the findings at cesarean delivery and histological examination, patients were divided into two groups of women with and without placenta accrete. To compare of the mean of mRNA levels between the two groups we used independent t-test and to compare of the mean of age and gestational age at sonography we used Mann-Whitney test. For determination of sensitivity and specificity and the cut-off point of mRNA levels we used the receiver operating characteristic curve. A total of 50 women with a mean age of 30.24 ± 4.905 years entered the study and 12 (24%) patients were diagnosed with placenta accreta. The sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) of Doppler ultrasound were 83.3%, 78.9%, 56% and 94%, respectively. Results of our study showed if we consider a cut-off point equal to 3.325, with sensitivity and specificity of 0.917 and 0.789, respectively and the sensitivity, specificity, PPV and NPV of mRNA with were cut-off point of 3.325 were 91.7%, 78.9%, 57.9% and 96.8%, respectively. Cell-free mRNA is an acceptable, easy made, functional test with sensitivity, specificity, PPV and NPV more than Doppler ultrasound for diagnosis and prediction of incidence of placenta accrete and we recommend the use of cell-free mRNA test for diagnosis of placenta accreta.

  10. MRI of placental adhesive disorder

    Science.gov (United States)

    Prapaisilp, P; Bangchokdee, S

    2014-01-01

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

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

    International Nuclear Information System (INIS)

    Wu, Yi-meng; Luo, Han-wen; Kou, Hao; Wen, Yin-xian; Shen, Lang; Pei, Ling-guo; Zhou, Jin; Zhang, Yuan-zhen; Wang, Hui

    2015-01-01

    It's known that blood leptin level is reduced in intrauterine growth retardation (IUGR) fetus, and placental leptin is the major source of fetal blood leptin. This study aimed to investigate the decreased fetal blood leptin level by prenatal caffeine exposure (PCE) and its underlying placental mechanisms. Pregnant Wistar rats were intragastrically administered caffeine (30–120 mg/kg day) from gestational day 9 to 20. The level of fetal serum leptin and the expression of placental leptin-related genes were analyzed. Furthermore, we investigated the molecular mechanism of the reduced placental leptin's expression by treatment with caffeine (0.8–20 μM) in the BeWo cells. In vivo, PCE significantly decreased fetal serum leptin level in caffeine dose-dependent manner. Meanwhile, placental mRNA expression of adenosine A2a receptor (Adora2a), cAMP-response element binding protein (CREB), a short-type leptin receptor (Ob-Ra) and leptin was reduced in the PCE groups. In vitro, caffeine significantly decreased the mRNA expression of leptin, CREB and ADORA2A in concentration and time-dependent manners. The addition of ADORA2A agonist or adenylyl cyclase (AC) agonist reversed the inhibition of leptin expression induced by caffeine. PCE induced a lower level of fetal blood leptin, which the primary mechanism is that caffeine inhibited antagonized Adora2a and AC activities to decreased cAMP synthesis, thus inhibited the expression of the transcription factor CREB and target gene leptin in the placenta. Meantime, the reduced transportation of maternal leptin by placental Ob-Ra also contributed to the reduced fetal blood leptin. Together, PCE decreased fetal blood leptin mainly via reducing the expression and transportation of leptin in the placenta. - Highlights: • Caffeine reduced fetal blood leptin level. • Caffeine inhibited placental leptin production and transport. • Caffeine down-regulated placental leptin expression via antagonizing ADORA2.

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

    Energy Technology Data Exchange (ETDEWEB)

    Wu, Yi-meng [Department of Pharmacology, Basic Medical School of Wuhan University, Wuhan 430071 (China); Luo, Han-wen [Department of Orthopedic Surgery, Zhongnan Hospital of Wuhan University, Wuhan 430071 (China); Kou, Hao [Department of Pharmacology, Basic Medical School of Wuhan University, Wuhan 430071 (China); Wen, Yin-xian [Department of Orthopedic Surgery, Zhongnan Hospital of Wuhan University, Wuhan 430071 (China); Shen, Lang; Pei, Ling-guo; Zhou, Jin [Department of Pharmacology, Basic Medical School of Wuhan University, Wuhan 430071 (China); Zhang, Yuan-zhen [Department of Obstetrics and Gynecology, Zhongnan Hospital of Wuhan University, Wuhan 430071 (China); Hubei Provincial Key Laboratory of Developmentally Originated Disease, Wuhan 430071 (China); Wang, Hui, E-mail: wanghui19@whu.edu.cn [Department of Pharmacology, Basic Medical School of Wuhan University, Wuhan 430071 (China); Hubei Provincial Key Laboratory of Developmentally Originated Disease, Wuhan 430071 (China)

    2015-11-15

    It's known that blood leptin level is reduced in intrauterine growth retardation (IUGR) fetus, and placental leptin is the major source of fetal blood leptin. This study aimed to investigate the decreased fetal blood leptin level by prenatal caffeine exposure (PCE) and its underlying placental mechanisms. Pregnant Wistar rats were intragastrically administered caffeine (30–120 mg/kg day) from gestational day 9 to 20. The level of fetal serum leptin and the expression of placental leptin-related genes were analyzed. Furthermore, we investigated the molecular mechanism of the reduced placental leptin's expression by treatment with caffeine (0.8–20 μM) in the BeWo cells. In vivo, PCE significantly decreased fetal serum leptin level in caffeine dose-dependent manner. Meanwhile, placental mRNA expression of adenosine A2a receptor (Adora2a), cAMP-response element binding protein (CREB), a short-type leptin receptor (Ob-Ra) and leptin was reduced in the PCE groups. In vitro, caffeine significantly decreased the mRNA expression of leptin, CREB and ADORA2A in concentration and time-dependent manners. The addition of ADORA2A agonist or adenylyl cyclase (AC) agonist reversed the inhibition of leptin expression induced by caffeine. PCE induced a lower level of fetal blood leptin, which the primary mechanism is that caffeine inhibited antagonized Adora2a and AC activities to decreased cAMP synthesis, thus inhibited the expression of the transcription factor CREB and target gene leptin in the placenta. Meantime, the reduced transportation of maternal leptin by placental Ob-Ra also contributed to the reduced fetal blood leptin. Together, PCE decreased fetal blood leptin mainly via reducing the expression and transportation of leptin in the placenta. - Highlights: • Caffeine reduced fetal blood leptin level. • Caffeine inhibited placental leptin production and transport. • Caffeine down-regulated placental leptin expression via antagonizing ADORA2.

  13. Placental Origins of Chronic Disease

    Science.gov (United States)

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

    2016-01-01

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

  14. Ovine placental steroid synthesis and metabolism in late gestation.

    Science.gov (United States)

    Reynolds, Lawrence P; Legacki, Erin L; Corbin, C Jo; Caton, Joel S; Vonnahme, Kimberly A; Stanley, Scott; Conley, Alan J

    2018-04-14

    Steroid synthesis is required for pregnancy maintenance and for parturition but comparatively little is known about the major metabolic routes that influence circulating concentrations. Dietary intake changes progesterone and estradiol concentrations in pregnant ewes but whether this reflects placental synthesis is unknown. Progesterone metabolism by 5alpha-reduction is a major metabolic route in other species and can influence the onset of parturition. Therefore, studies were conducted to 1) determine placental enzyme activity, progesterone and estradiol measured by immuno-assay in late gestation ewes on low, moderate and high nutritional planes, 2) to assess the significance of 5alpha-reduction of progesterone in determining progesterone concentrations in late gestation ewes (gestation day 145) given finasteride to inhibit 5alpha-reductase metabolism. In the second experiment, steroid profiles were examined comprehensively in blood and tissues by liquid chromatography tandem mass spectrometry for the first time in this species. Dietary intake altered progesterone and estradiol serum concentrations but without correlated changes in placental 3beta-hydroxysteroid dehydrogenase, 17alpha-hydroxylase/17,20-lyase cytochrome P450 or aromatase activity. 5alpha-reduced pregnane metabolites were identified in ewes at 145 days of gestation, but concentrations were lower than those of progesterone. Finasteride inhibited 5alpha-reduced progesterone metabolism but did not impact serum progesterone concentrations in these ewes. We conclude 1) that diet-induced changes in serum progesterone and estradiol concentrations are not likely a result of altered placental synthesis of sex steroid but most likely by their metabolism, and 2) metabolism by 5α-reduction is not a major determinant of systemic progesterone concentrations in late gestation ewes.

  15. Hans Strahl's pioneering studies in comparative placentation

    DEFF Research Database (Denmark)

    Carter, Anthony Michael; Mess, A

    2010-01-01

    Hans Strahl, a contemporary of Duval and Hubrecht, made many important contributions to comparative placentation. Despite this he is not well known and some of his original observations tend to be attributed to later authors. Strahl published a classification of placental types based on their shape...... of the most important findings made by Strahl including work on placentation in carnivores and higher primates that remains unsurpassed....

  16. Effect of Maternal Obesity on Fetal Growth and Expression of Placental Fatty Acid Transporters.

    Science.gov (United States)

    Ye, Kui; Li, Li; Zhang, Dan; Li, Yi; Wang, Hai Qing; Lai, Han Lin; Hu, Chuan Lai

    2017-12-15

    To explore the effects of maternal high-fat (HF) diet-induced obesity on fetal growth and the expression of placental nutrient transporters. Maternal obesity was established in rats by 8 weeks of pre-pregnancy fed HF diet, while rats in the control group were fed normal (CON) diet. Diet-induced obesity (DIO) rats and diet-induced obesity-resistant (DIR) rats were selected according to body weight gain over this period. After copulation, the CON rats were divided into two groups: switched to HF diet (CON-HF group) or maintained on the CON diet (CON-CON group). The DIO rats and DIR rats were maintained on the HF diet throughout pregnancy. Pregnant rats were euthanized at day 21 gestation, fetal and placental weights were recorded, and placental tissue was collected. Reverse transcription-polymerase chain reaction was used to determine mRNA expression of placental nutrient transporters. Protein expression was determined by Western blot. Average fetal weight of DIO dams was reduced by 6.9%, and the placentas of CON-HF and DIO dams were significantly heavier than the placentas of CON-CON and DIR dams at day 21 of gestation (pobesity induced by a HF diet led to intrauterine growth retardation and down-regulated the expression of placental fatty acid transporters.

  17. 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.

  18. Protein structure of fetal antigen 1 (FA1). A novel circulating human epidermal-growth-factor-like protein expressed in neuroendocrine tumors and its relation to the gene products of dlk and pG2

    DEFF Research Database (Denmark)

    Jensen, Charlotte Harken; Krogh, Thomas N; Højrup, Peter

    1994-01-01

    The present paper describes the primary structure, glycosylation and tissue localization of fetal antigen 1 (FA1) isolated from second-trimester human amniotic fluid. FA1 is a single-chained, heterogeneous glycoprotein of 225-262 amino acid residues. FA1 has six well conserved epidermal...... extends with minor corrections to the human adrenal-specific mRNA, pG2 as well. Immunohistochemical analysis demonstrated the presence of FA1 in 10 out of 14 lung tumors containing neuroendocrine elements, and in the placental villi where FA1 was exclusively seen in stromal cells in close contact...... to the vascular structure. In the pancreas, FA1 co-localized with insulin in the insulin secretory granules of the beta cells within the islets of Langerhans. Our findings suggest that FA1 is synthesized as a membrane anchored protein and released into the circulation after enzymic cleavage, and that circulating...

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

    Science.gov (United States)

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

    2014-11-15

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

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

    African Journals Online (AJOL)

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

  1. 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

  2. Microparasites and Placental Invasiveness in Eutherian Mammals.

    Directory of Open Access Journals (Sweden)

    Isabella Capellini

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

  3. Animal Models of Human Placentation - A Review

    DEFF Research Database (Denmark)

    Carter, Anthony Michael

    2007-01-01

    This review examines the strengths and weaknesses of animal models of human placentation and pays particular attention to the mouse and non-human primates. Analogies can be drawn between mouse and human in placental cell types and genes controlling placental development. There are, however...... and delivers poorly developed young. Guinea pig is a good alternative rodent model and among the few species known to develop pregnancy toxaemia. The sheep is well established as a model in fetal physiology but is of limited value for placental research. The ovine placenta is epitheliochorial...... and endometrium is similar in macaques and baboons, as is the subsequent lacunar stage. The absence of interstitial trophoblast cells in the monkey is an important difference from human placentation. However, there is a strong resemblance in the way spiral arteries are invaded and transformed in the macaque...

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

    Science.gov (United States)

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

    2013-06-01

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

  5. The effects from placental exposure

    International Nuclear Information System (INIS)

    Kawamoto, Sadahisa

    1975-01-01

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

  6. Role of transporters in placental transfer of drugs

    International Nuclear Information System (INIS)

    Ganapathy, Vadivel; Prasad, Puttur D.

    2005-01-01

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

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

    Science.gov (United States)

    Toscano, Marcello Pecoraro; Schultz, Regina

    2014-01-01

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

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

    OpenAIRE

    Marcello Pecoraro Toscano; Regina Schultz

    2014-01-01

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

  9. 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.

  10. Placental transfer of ritodrine hydrochloride in sheep

    International Nuclear Information System (INIS)

    Fujimoto, Seiichiro; Akahane, Masuo; Uzuki Katsuya; Inagawa, Akira; Sakai, Keiichiro; Sakai, Akira

    1984-01-01

    This study examines the placental passage of ritodrine hydrochloride in relation to the drug's effects on the fetal circulation. Studies were carried out on nine mulliparous pregnant (120-140 days) ewes with chronically implanted cannulae of measurements of maternal and fetal arterial pressures and for blood sampling. One group of animals received sequential infusions of doses ranging from 0.1 to 30 μg/kg per min for 30 min (group 1). A second group was given a constant infusion of the drug at a dose of 3.0 μg/kg per min for 4 h (group 2). The peak concentrations of ritodrine in maternal and fetal blood were determined by radioimmunoassay. In group 1 they were 313.4 +- 24.1 ng/ml (mean +-S.E.) and 12.6 +- 3.7 ng/ml at the finish of 30.0 ug/kg per min infusion for maternal and fetal blood, respectively. In group 2, maternal drug levels were 81.3 +- 20.4 ng/ml after 30 min and 95.9 +- 17.1 ng/ml after 4 h of the infusion. Fetal plasma concentrations increased slowly from trace levels at 30 min to 3.3 +- 0.7 ng/ml at 4 h. Fetal blood pressure and heart rate did not show any significant changes during and after the infusion of ritodrine in both treatment groups. The findings demonstrate the maternal administration of ritodrine produces no significant effects on the circulatory system of the fetal lamb because of the low transplacental passage of this drug. (author)

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

    OpenAIRE

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

    2016-01-01

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

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

    Science.gov (United States)

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

    2016-06-01

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

  13. 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.

  14. Review: Maternal health and the placental microbiome.

    Science.gov (United States)

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

    2017-06-01

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

  15. Placentation in the Amazonian manatee (Trichechus inunguis)

    DEFF Research Database (Denmark)

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

    2008-01-01

    Evidence from several sources supports a close phylogenetic relationship between elephants and sirenians. To explore whether this was reflected in similar placentation, we examined eight delivered placentae from the Amazonian manatee using light microscopy and immunohistochemistry. In addition, t...

  16. Protein Profiling of Preeclampsia Placental Tissues

    OpenAIRE

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

    2014-01-01

    Preeclampsia is a multi-system disorder involved in pregnancy without an effective treatment except delivery. The precise pathogenesis of this complicated disorder is still not completely understood. The objective of this study is to evaluate the alterations of protein expression and phosphorylations that are important in regulating placental cell function in preterm and term preeclampsia. Using the Protein Pathway Array, 38 proteins in placental tissues were found to be differentially expres...

  17. Comparative aspects of trophoblast development and placentation

    Directory of Open Access Journals (Sweden)

    Enders Allen C

    2004-07-01

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

  18. Blood vessels in subcaruncular and intercaruncular bovine endometriun possess oxytocin receptors (ORT) and express otr mRNA during pregnancy

    DEFF Research Database (Denmark)

    Fuchs, Anna-Ritta; Balvers, Marga; Ivell, Richard

    2002-01-01

    is taking place; marked changes were observed with advancing pregnancy. The epithelial cells of the trophoblast were strongly stained for ir OTR and OTR mRNA, as reported last year, but the fetal connective tissue and blood vessels within the trophoblast did not show any stain for ir OTR or OTR m...... placentation because episodic secretion of OT occurs throughout bovine pregnancy...

  19. 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.

  20. Placental fatty acid transport in maternal obesity.

    Science.gov (United States)

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

    2012-12-01

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

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

    Science.gov (United States)

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

    1997-08-01

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

  2. SEX STEROIDS MODULATE UTERINE-PLACENTAL VASCULATURE: IMPLICATIONS FOR OBSTETRICS AND NEONATAL OUTCOMES

    Directory of Open Access Journals (Sweden)

    Manuel eMaliqueo

    2016-04-01

    Full Text Available Adequate blood supply to the uterine-placental region is crucial to ensure the transport of oxygen and nutrients to the growing fetus. Multiple factors intervene to achieve appropriate uterine blood flow and the structuring of the placental vasculature during the early stages of pregnancy. Among these factors, oxygen concentrations, growth factors, cytokines and steroid hormones are the most important. Sex steroids are present in extremely high concentrations in the maternal circulation and are important paracrine and autocrine regulators of a wide range of maternal and placental functions. In this regard, progesterone and estrogens act as modulators of uterine vessels and decrease the resistance of the spiral uterine arteries. On the other hand, androgens have the opposite effect, increasing the vascular resistance of the uterus. Moreover, progesterone and estrogens modulate the synthesis and release of angiogenic factors by placental cells, which regulates trophoblastic invasion and uterine artery remodeling. In this scenario, it is not surprising that women with pregnancy-related pathologies, such as early miscarriages, preterm delivery, preeclampsia and fetal growth restriction, exhibit altered sex steroid concentrations.

  3. Increased Umbilical Cord PAI-1 Levels in Placental Insufficiency Are Associated with Fetal Hypoxia and Angiogenesis

    Directory of Open Access Journals (Sweden)

    Maxim D. Seferovic

    2016-01-01

    Full Text Available In intrauterine growth restriction (IUGR, a subset of pregnancies undergoes placental vascular dysregulation resulting in restricted blood flow and fetal hypoxemia. Altered transcription of hypoxic regulated plasminogen activator inhibitor 1 (PAI-1 has been associated with pregnancy complications and angiogenic regulation. Here we assessed circulating PAI-1 as an indicator of placental insufficiency. Venous umbilical PAI-1 of hypoxemic (VpO2 20 versus 35 mmHg, p<0.0001 placental insufficient pregnancies (resistance index 0.9 versus 0.63, p<0.05 (n=18 was compared to controls (n=12. PAI-1 was increased (~10-fold, p<0.001 and had a positive predictive ratio of 6.7. Further, PAI-1 levels correlated to blood oxygen (r=-0.68, p<0.0001. The plasma’s angiogenic potency measured in vitro was associated with umbilical cord blood PAI-1 levels (r=0.65, p<0.01. This association was attenuated by PAI-1 inhibiting antibody (p<0.001. The results demonstrate PAI-1 as a potential marker of placental insufficiency and identify its close association with pathological hypoxia and angiogenesis in a subset of growth restricted pregnancies.

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

    DEFF Research Database (Denmark)

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

    2006-01-01

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

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

    DEFF Research Database (Denmark)

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

    2006-01-01

    Maternal diabetes can cause fetal macrosomia and increased risk of obesity, diabetes, and cardiovascular disease in adulthood of the offspring. Although increased transplacental lipid transport could be involved, the impact of maternal type 1 diabetes on molecular mechanisms for lipid transport...... in placenta is largely unknown. To examine whether maternal type 1 diabetes affects placental lipid metabolism, we measured lipids and mRNA expression of lipase-encoding genes in placentas from women with type 1 diabetes (n = 27) and a control group (n = 21). The placental triglyceride (TG) concentration....... These results suggest that maternal type 1 diabetes is associated with TG accumulation and increased EL and HSL gene expression in placenta and that optimal metabolic control reduces these effects....

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

    Science.gov (United States)

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

    2017-08-01

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

  7. Placental Expressions of CDKN1C and KCNQ1OT1 in Monozygotic Twins with Selective Intrauterine Growth Restriction.

    Science.gov (United States)

    Gou, Chenyu; Liu, Xiangzhen; Shi, Xiaomei; Chai, Hanjing; He, Zhi-Ming; Huang, Xuan; Fang, Qun

    2017-10-01

    CDKN1C and KCNQ1OT1 are imprinted genes that might be potential regulators of placental development. This study investigated placental expressions of CDKN1C and KCNQ1OT1 in monozygotic twins with and without selective intrauterine growth restriction (sIUGR). Seventeen sIUGR and fifteen normal monozygotic(MZ) twin pairs were examined. Placental mRNA expressions of CDKN1C and KCNQ1OT1 were detected by real-time fluorescent quantitative PCR. CDKN1C protein expression was detected by immunohistochemical assay and Western-blotting. In the sIUGR group, smaller fetuses had a smaller share of the placenta, and CDKN1C protein expression was significantly increased while KCNQ1OT1 mRNA expression was significantly decreased. The CDKN1C/KCNQ1OT1 mRNA ratio was lower in the larger fetus than in the smaller fetus (p < .05). In the control group, CDKN1C protein expression showed no difference between larger and smaller fetuses, while KCNQ1OT1 mRNA expression was significantly lower in the larger fetus, and the CDKN1C/KCNQ1OT1 mRNA ratio was higher in the larger fetus than in the smaller fetus (p < .05). Our findings showed that pathogenesis of sIUGR may be related to the co-effect of the up-regulated protein expression of CDKN1C and down-regulated mRNA expression of KCNQ1OT1 in the placenta.

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

    African Journals Online (AJOL)

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

  9. The effect of androgen excess on maternal metabolism, placental function and fetal growth in obese dams.

    Science.gov (United States)

    Fornes, Romina; Maliqueo, Manuel; Hu, Min; Hadi, Laila; Jimenez-Andrade, Juan M; Ebefors, Kerstin; Nyström, Jenny; Labrie, Fernand; Jansson, Thomas; Benrick, Anna; Stener-Victorin, Elisabet

    2017-08-14

    Pregnant women with polycystic ovary syndrome (PCOS) are often overweight or obese. To study the effects of maternal androgen excess in obese dams on metabolism, placental function and fetal growth, female C57Bl6J mice were fed a control (CD) or a high fat/high sucrose (HF/HS) diet for 4-10 weeks, and then mated. On gestational day (GD) 15.5-17.5, dams were injected with dihydrotestosterone (CD-DHT, HF/HS-DHT) or a vehicle (CD-Veh, HF/HS-Veh). HF/HS dams had higher fat content, both before mating and on GD18.5, with no difference in glucose homeostasis, whereas the insulin sensitivity was higher in DHT-exposed dams. Compared to the CD groups, the livers from HF/HS dams weighed more on GD18.5, the triglyceride content was higher, and there was a dysregulation of liver enzymes related to lipogenesis and higher mRNA expression of Fitm1. Fetuses from HF/HS-Veh dams had lower liver triglyceride content and mRNA expression of Srebf1c. Maternal DHT exposure, regardless of diet, decreased fetal liver Pparg mRNA expression and increased placental androgen receptor protein expression. Maternal diet-induced obesity, together with androgen excess, affects maternal and fetal liver function as demonstrated by increased triglyceride content and dysfunctional expression of enzymes and transcription factors involved in de novo lipogenesis and fat storage.

  10. Tumor and placental histaminase. II

    International Nuclear Information System (INIS)

    Wellin, C.; Angellis, D.

    1981-01-01

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

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

    Directory of Open Access Journals (Sweden)

    Marcello Pecoraro Toscano

    2014-12-01

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

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

    Science.gov (United States)

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

    2017-06-01

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

  13. Immunoinformatics of Placental Malaria Vaccine Development

    DEFF Research Database (Denmark)

    Jessen, Leon Eyrich

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

  14. Evolution of factors affecting placental oxygen transfer

    DEFF Research Database (Denmark)

    Carter, A M

    2009-01-01

    A review is given of the factors determining placental oxygen transfer and the oxygen supply to the fetus. In the case of continuous variables, such as the rate of placental blood flow, it is not possible to trace evolutionary trends. Discontinuous variables, for which we can define character sta......, where fetal and adult haemoglobin are not different, developmental regulation of 2, 3-diphosphoglycerate ensures the high oxygen affinity of fetal blood. Oxygen diffusing capacity is dependent on diffusion distance, which may vary with the type of interhaemal barrier. It has been shown...

  15. [Examination of placental three-dimensional power Doppler indices and perinatal outcome in pregnancies complicated by intrauterine growth restriction].

    Science.gov (United States)

    Molnár, András; Surányi, Andrea; Jakó, Mária; Nyári, Tibor; Németh, Gábor

    2017-07-01

    Development of intrauterine growth restriction (IUGR) can be traced back to maternal or fetal factors, but in many cases we find placental factors (reduced placental circulation) in the background. Our aim was to examine whether the reduced placental bloodperfusion and vascularity show any correlation with cesarean section frequency and the clinical outcome in IUGR pregnancies. The aim of the present study was also to use a properly calibrated and reproducible method for evaluating placental blood flow, that can later be incorporated into the routine examination. 254 women were recruited in our prospective case-control study. The 3 dimensional power Doppler (3DPD) ultrasound indices; vascularisation index (VI), flow index (FI) and vascularization flow index (VFI) were measured on each participant. Median VI was 3.7% (interquartile range [IQR] 3.2%-4.2%) in the IUGR group and 10.1% (IQR 8.6%-10.9%) in the control group (p = 0.001). Median FI value was 40.0 (IQR 39.7-42.5) in the IUGR group and 45.1 (IQR 44.1-53.1) in the control group (p = 0.012). Median VFI was 2.2 (IQR 2.1-2.4) in the IUGR group and 4.8 (IQR 4.4-5.3) in the control. The 3DPD indices may be useful for examining changes in circulation in IUGR pregnancies to characterize the underlying pathology. Orv Hetil. 2017; 158(26): 1008-1013.

  16. Review: Adiponectin – The Missing Link between Maternal Adiposity, Placental Transport and Fetal Growth?

    Science.gov (United States)

    Aye, Irving L. M. H.; Powell, Theresa L.; Jansson, Thomas

    2012-01-01

    Adiponectin has well-established insulin-sensitizing effects in non-pregnant individuals. Pregnant women who are obese or have gestational diabetes typically have low circulating levels of adiponectin, which is associated with increased fetal growth. Lean women, on the other hand, have high circulating levels of adiponectin. As a result, maternal serum adiponectin is inversely correlated to fetal growth across the full range of birth weights, suggesting that maternal adiponectin may limit fetal growth. In the mother, adiponectin is predicted to promote insulin sensitivity and stimulate glucose uptake in maternal skeletal muscle thereby reducing nutrient availability for placental transfer. Adiponectin prevents insulin-stimulated amino acid uptake in cultured primary human trophoblast cells by modulating insulin receptor substrate phosphorylation. Furthermore, chronic administration of adiponectin to pregnant mice inhibits placental insulin and mammalian target of rapamycin complex 1 (mTORC1) signaling, down-regulates the activity and expression of key placental nutrient transporters and decreases fetal growth. Preliminary findings indicate that adiponectin binds to the adiponectin receptor-2 on the trophoblast cell and activates p38 MAPK and PPAR-α, which inhibits the insulin/IGF-1 signaling pathway. In contrast to maternal adiponectin, recent reports suggest that fetal adiponectin may promote expansion of adipose tissue and stimulate fetal growth. Regulation of placental function by adiponectin constitutes a novel physiological mechanism by which the endocrine functions of maternal adipose tissue influence fetal growth. These findings may help us better understand the factors determining birth weight in normal pregnancies and in pregnancy complications associated with altered maternal adiponectin levels such as obesity and gestational diabetes. PMID:23245987

  17. Weekly intra-amniotic IGF-1 treatment increases growth of growth-restricted ovine fetuses and up-regulates placental amino acid transporters.

    Directory of Open Access Journals (Sweden)

    Jibran A Wali

    Full Text Available Frequent treatment of the growth-restricted (IUGR ovine fetus with intra-amniotic IGF-1 increases fetal growth. We aimed to determine whether increased growth was maintained with an extended dosing interval and to examine possible mechanisms. Pregnant ewes were allocated to three groups: Control, and two IUGR groups (induced by placental embolization treated with weekly intra-amniotic injections of either saline (IUGR or 360 µg IGF-1 (IGF1. IUGR fetuses were hypoxic, hyperuremic, hypoglycemic, and grew more slowly than controls. Placental glucose uptake and SLC2A1 (GLUT2 mRNA levels decreased in IUGR fetuses, but SLC2A3 (GLUT3 and SLC2A4 (GLUT4 levels were unaffected. IGF-1 treatment increased fetal growth rate, did not alter uterine blood flow or placental glucose uptake, and increased placental SLC2A1 and SLC2A4 (but not SLC2A3 mRNA levels compared with saline-treated IUGR animals. Following IGF-1 treatment, placental mRNA levels of isoforms of the system A, y(+, and L amino acid transporters increased 1.3 to 5.0 fold, while the ratio of phosphorylated-mTOR to total mTOR also tended to increase. Weekly intra-amniotic IGF-1 treatment provides a promising avenue for intra-uterine treatment of IUGR babies, and may act via increased fetal substrate supply, up-regulating placental transporters for neutral, cationic, and branched-chain amino acids, possibly via increased activation of the mTOR pathway.

  18. 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

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

    Science.gov (United States)

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

    2013-01-30

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

  20. Responses of mRNA expression of PepT1 in small intestine to ...

    African Journals Online (AJOL)

    To study the effect of circulation small peptides concentration on mRNA expression in small intestine, graded amount of soybean small peptides (SSP) were infused into lactating goats through duodenal fistulas. Peptide-bound amino acid (PBAA) concentration in arterial plasma and the mRNA expression of PepT1 was ...

  1. Quality assessment of a placental perfusion protocol

    DEFF Research Database (Denmark)

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

    2010-01-01

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

  2. Placental malaria and immunity to infant measles

    NARCIS (Netherlands)

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

    2006-01-01

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

  3. Placental transfer of plutonium and other actinides

    International Nuclear Information System (INIS)

    Griessl, I.; Stieve, F.E.

    1988-10-01

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

  4. 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.

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

    African Journals Online (AJOL)

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

  6. Placentation in mammals once grouped as insectivores

    DEFF Research Database (Denmark)

    Carter, Anthony; Enders, Allen

    2009-01-01

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

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

    Science.gov (United States)

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

    2015-08-15

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

  8. Fresh look at the doppler changes in pregnancies with placental-based complications

    Directory of Open Access Journals (Sweden)

    S Dikshit

    2011-01-01

    Full Text Available Placental-based complications of pregnancy can be classified as acute and chronic. An example of acute placental complication is abruptio placenta. The chronic placental complications include pregnancy induced hypertension (PIH and idiopathic Intrauterine growth restriction (IUGR. The fetus is at risk for perinatal complications in both acute and chronic conditions. Here we take a look at the natural history of the Doppler parameters in chronic conditions. The techniques used for assessing the fetal well-being include, clinical methods, biophysical tests, conventional ultrasonography, and fetal Doppler studies. Arterial Doppler studies are used to assess the well-being of the fetus and to determine the timing of delivery. However, arterial Dopplers predict only the subset of fetuses at risk of having perinatal complications. Venous Dopplers have been used to improve upon the prognostication. However, by the time the commonly used venous Doppler signs, that is, ′A′ wave reversal in ductus venosus (DV is present, the fetus is likely to be already compromised. The fetus tries to adapt to the environment of deprivation by making a series of changes in the umbilical artery circulation, cerebral circulation, and hepatic circulation. As a result of these adaptations, the fetus overcomes the state of chronic hypoxia. This article takes a look at these changes and also the effect of these adaptations. It is suggested that serial comparisons of the venous flow characteristics of the DV and inferior vena cava (IVC can provide an early indication of the impending decompensation and can be used to predict the time the delivery.

  9. The Placental Secretome: Identifying Potential Cross-Talk Between Placenta and Islet β-Cells

    Directory of Open Access Journals (Sweden)

    Robert Drynda

    2018-02-01

    Full Text Available Background/Aims: Insulin-secreting islet β-cells adapt to the insulin resistance associated with pregnancy by increasing functional β-cell mass, but the placental signals involved in this process are not well defined. In the current study, we analysed expression of G-protein coupled receptor (GPCR mRNAs in mouse islets and islet GPCR ligand mRNAs in placenta during pregnancy to generate an atlas of potential interactions between the placenta and β-cells to inform future functional studies of islet adaptive responses to pregnancy. Methods: Quantative RT-PCR arrays were used to measure mRNA expression levels of: (i 342 GPCRs in islets from non-pregnant mice, and in islets isolated from mice on gestational days 12 and 18; (ii 126 islet GPCR ligands in mouse placenta at gestational days 12 and 18. Results: At gestational day 12, a time of rapid expansion of the β-cell mass, 189 islet GPCR mRNAs were quantifiable, while 79 of the 126 known islet GPCR ligand mRNAs were detectable in placental extracts. Approximately half of the quantifiable placental GPCR ligand genes were of unknown function in β-cells. The expression of some islet GPCR and placental ligand mRNAs varied during pregnancy, with altered expression of both GPCR and ligand mRNAs by gestational day 18. Conclusion: The current study has revealed numerous potential routes for interaction between the placenta and islets, and offers an atlas to inform further functional studies of their roles in adaptive responses to pregnancy, and in the regulation of the β-cell mass.

  10. Gene expression of placental hormones regulating energy balance in small for gestational age neonates.

    Science.gov (United States)

    Struwe, Ellen; Berzl, Gabriele M; Schild, Ralf L; Dötsch, Jörg

    2009-01-01

    Fetal growth restriction is associated with an increased risk for metabolic and cardiovascular disease in later life. To further elucidate mechanisms that might be involved in the process of prenatal programming, we measured the adipokines leptin, resistin, and adiponectin and the GH-releasing hormone ghrelin in the placenta of small for gestational age (SGA) neonates. The control group included 24 placentas of appropriate for gestational age (AGA) newborns, in the study group were 16 placentas of SGA neonates. Gene expression of leptin, resistin, adiponectin, and ghrelin was examined. For hormones showing alterations in gene regulation placental protein expression was measured by Western blot. Placental mRNA expression of leptin was significantly increased in SGA placentas (p=0.0035, related to beta-actin). Protein concentration was increased, as well. There were no differences in placental resistin, adiponectin, or ghrelin gene expressions between SGA neonates and controls. Leptin was the only hormone to demonstrate a significant inverse correlation with birth weight (r=-0.44, p=0.01). Adiponectin correlated significantly with leptin (r=0.53, p=0.0023) and ghrelin (r=0.50, p=0.0045). Placental leptin gene expression and protein concentration showed the expected increase in the SGA group. Leptin was inversely correlated with birth weight. Positive correlation of adiponectin with leptin and ghrelin expression suggests an interaction between these hormones in the placenta. However, the unchanged expression of resistin, adiponectin, and ghrelin in SGA placentas and the absence of correlation with birth weight cast doubt whether these hormones produced in the placenta play a key role in fetal programming.

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

    International Nuclear Information System (INIS)

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

    2013-01-01

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

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

    Energy Technology Data Exchange (ETDEWEB)

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

    2013-04-01

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

  13. mRNA related to insulin family in human placenta

    International Nuclear Information System (INIS)

    Younes, M.A.; D'Agostino, J.B.; Frazier, M.L.; Besch, P.K.

    1986-01-01

    The authors have previously reported that human term placenta contains mRNA displaying sequence homology to a rat preproinsulin I cDNA clone (p119). When placental poly(A + ) RNA was analyzed for homology to p119 by RNA/DNA blot hybridization, prominent hybridization was observed which was found by densitometric analysis to be three-fold higher than control. To further characterize this insulin-like message, a cDNA library was generated (approx.7000 transformants) using normal term cesarean-sectioned tissue to prepare placental poly(A + ) RNA templates. Five hundred transformants were initially screened by colony hybridization using a 32 P-labeled rat preproinsulin I cDNA as probe. Of the ten initial positives obtained, three were found to be true positives based on Southern hybridization analyses of the recombinant plasmids. Using Taq I digested pBr322 as a size marker, the cDNAs were found to be approximately 300 bp in length. Preliminary DNA sequencing using the Sanger dideoxy chain termination method has revealed that one of these clones displays significant homology to the 5' region of human insulin-like growth factors I and II

  14. mRNA related to insulin family in human placenta

    Energy Technology Data Exchange (ETDEWEB)

    Younes, M.A.; D' Agostino, J.B.; Frazier, M.L.; Besch, P.K.

    1986-03-01

    The authors have previously reported that human term placenta contains mRNA displaying sequence homology to a rat preproinsulin I cDNA clone (p119). When placental poly(A/sup +/) RNA was analyzed for homology to p119 by RNA/DNA blot hybridization, prominent hybridization was observed which was found by densitometric analysis to be three-fold higher than control. To further characterize this insulin-like message, a cDNA library was generated (approx.7000 transformants) using normal term cesarean-sectioned tissue to prepare placental poly(A/sup +/) RNA templates. Five hundred transformants were initially screened by colony hybridization using a /sup 32/P-labeled rat preproinsulin I cDNA as probe. Of the ten initial positives obtained, three were found to be true positives based on Southern hybridization analyses of the recombinant plasmids. Using Taq I digested pBr322 as a size marker, the cDNAs were found to be approximately 300 bp in length. Preliminary DNA sequencing using the Sanger dideoxy chain termination method has revealed that one of these clones displays significant homology to the 5' region of human insulin-like growth factors I and II.

  15. 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.

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

    International Nuclear Information System (INIS)

    Kawakami, Takashige; Yoshimi, Masaki; Kadota, Yoshito; Inoue, Masahisa; Sato, Masao; Suzuki, Shinya

    2014-01-01

    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

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

    Science.gov (United States)

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

    2013-06-01

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

  18. 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.

  19. Study on placental blood flow in late pregnancy by intravenous sup(99m)Tc method

    International Nuclear Information System (INIS)

    Kitagawa, Hiroshi

    1985-01-01

    A method for the continuous recording of uteroplacental blood flow (PBF) in late pregnancies by using sup(99m)Tc-albumin has been described. 1) The PBF curve of toxemia of pregnancy has been plotted to indicate small artery spasm in proving ischemic necrosis of placenta. 2) In the PBF of placental insufficiency evidenced by the values for urinary E 3 , an unfavorable build-up and a delayed build-up time were observed. The pathologic diagnosis showed condensation, fusion and necrosis of villi. 3) In the PBF in which a intrauterine fetal death (IUFD) was caused by placental factors, a sudden change in the PBF was observed showing the presence of an ischemia. 4) In the PBF of pregnancy with diabetes, a large wave pattern change was observed indicating a decrease in the PBF. The pathologic diagnosis showed the fusion, hyalinization and necrosis of villi. 5) The PBF wave patterns were classified into four kinds: (1) normal pattern, (2) angio-spasm pattern, (3) delayed build-up pattern, (4) circulation pattern. It has become clear that these abnormal wave patterns are frequently observed in toxemia of pregnancy, placental insufficiency and pregnancy with diabetes. (author)

  20. 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.

  1. IMMUNOLOGICAL MECHANISMS OF APOPTOSIS IN PLACENTAL DEVELOPMENT

    Directory of Open Access Journals (Sweden)

    D. I. Sokolov

    2008-01-01

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

  2. 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.

  3. Maternal plasma levels of cell-free β-HCG mRNA as a prenatal diagnostic indicator of placenta accrete.

    Science.gov (United States)

    Zhou, J; Li, J; Yan, P; Ye, Y H; Peng, W; Wang, S; Wang, X Tong

    2014-09-01

    Several biomarkers, including maternal serum creatinine kinase and α-fetoprotein, have been described as potential tools for the diagnosis of placental abnormalities. This study aimed to determine whether maternal plasma mRNA levels of the β subunit of human chorionic gonadotropin (β-HCG) could predict placenta accreta prenatally. Sixty-eight singleton pregnant women with prior cesarean deliveries (CDs) were classified into three groups: normal placentation (35 women, control group); placenta previa alone (21 women, placenta previa group); and both placenta previa and placenta accreta (12 women, placenta previa/accreta group). Maternal plasma concentrations of cell-free β-HCG mRNA were measured by real-time reverse-transcription polymerase chain reaction and were expressed as multiples of the median (MoM). Cell-free β-HCG mRNA concentrations (MoM, range) were significantly higher in women with placenta accreta (3.65, 2.78-7.19) than in women with placenta previa (0.94, 0.00-2.97) or normal placentation (1.00, 0.00-2.69) (Steel-Dwass test, P accreta group, the concentration of cell-free β-HCG mRNA was significantly higher among women who underwent CDs with hysterectomy (4.41, 3.49-7.19) than among women whose CDs did not result in hysterectomy (3.20, 2.78-3.70) (Mann-Whitney U test, P = 0.012). An increased level of cell-free β-HCG mRNA in the maternal plasma of women with placenta accreta may arise from direct uteroplacental transfer of cell-free placental mRNA molecules. The concentration of cell-free β-HCG mRNA in maternal plasma may be applicable to the prenatal diagnosis of placenta accreta, especially to identify women with placenta accreta likely to require hysterectomy. Copyright © 2014 Elsevier Ltd. All rights reserved.

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

    Science.gov (United States)

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

    2013-06-01

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

  5. Placental Nutrient Transport in Gestational Diabetic Pregnancies

    Directory of Open Access Journals (Sweden)

    Marisol Castillo-Castrejon

    2017-11-01

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

  6. Circulating microRNAs in breast cancer

    DEFF Research Database (Denmark)

    Hamam, Rimi; Hamam, Dana; Alsaleh, Khalid A.

    2017-01-01

    Effective management of breast cancer depends on early diagnosis and proper monitoring of patients' response to therapy. However, these goals are difficult to achieve because of the lack of sensitive and specific biomarkers for early detection and for disease monitoring. Accumulating evidence...... in the past several years has highlighted the potential use of peripheral blood circulating nucleic acids such as DNA, mRNA and micro (mi)RNA in breast cancer diagnosis, prognosis and for monitoring response to anticancer therapy. Among these, circulating miRNA is increasingly recognized as a promising...... circulating miRNAs as diagnostic, prognostic or predictive biomarkers in breast cancer management....

  7. Placental three-dimensional power Doppler indices in mid-pregnancy and late pregnancy complicated by gestational diabetes mellitus.

    Science.gov (United States)

    Surányi, A; Kozinszky, Z; Molnár, A; Nyári, T; Bitó, T; Pál, A

    2013-10-01

    The aim of our study was to evaluate placental three-dimensional power Doppler indices in diabetic pregnancies in the second and third trimesters and to compare them with those of the normal controls. Placental vascularization of pregnant women was determined by three-dimensional power Doppler ultrasound technique. The calculated indices included vascularization index (VI), flow index (FI), and vascularization flow index (VFI). Uncomplicated pregnancies (n = 113) were compared with pregnancies complicated by gestational diabetes mellitus (n = 56) and diabetes mellitus (n = 43). The three-dimensional power Doppler indices were not significantly different between the two diabetic subgroups. All the indices in diabetic patients were significantly reduced compared with those in non-diabetic individuals (p power Doppler indices are slightly diminished throughout diabetic pregnancy [regression coefficients: -0.23 (FI), -0.06 (VI), and -0.04 (VFI)] and normal pregnancy [regression coefficients: -0.13 (FI), -0.20 (VI), and -0.11 (VFI)]. The uteroplacental circulation (umbilical and uterine artery) was not correlated significantly to the three-dimensional power Doppler indices. If all placental indices are low during late pregnancy, then the odds of the diabetes are significantly high (adjusted odds ratio: 1.10). A decreased placental vascularization could be an adjunct sonographic marker in the diagnosis of diabetic pregnancy in mid-gestation and late gestation. © 2013 John Wiley & Sons, Ltd.

  8. Placental transport and in vitro effects of Bisphenol A

    DEFF Research Database (Denmark)

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

    2010-01-01

    Bisphenol A (BPA), an estrogen-like chemical, leaches from consumer products potentially causing human exposure. To examine the effects of BPA exposure during pregnancy, we performed studies using the BeWo trophoblast cell line, placental explant cultures, placental perfusions and skin diffusion...... transfer of BPA was observed across the term placentae and the BeWo cell monolayer. Further, transdermal transport of BPA was observed. These results indicate that fetal BPA exposure through placental exchange occurs with potential adverse implications for placental and fetal development. This battery...

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

    Science.gov (United States)

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

    2015-02-24

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

  10. Placental Abnormalities and Preeclampsia in Trisomy 13 Pregnancies

    Directory of Open Access Journals (Sweden)

    Chih-Ping Chen

    2009-03-01

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

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

    Science.gov (United States)

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

    2015-04-01

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

  12. Increasing maternal body mass index is associated with systemic inflammation in the mother and the activation of distinct placental inflammatory pathways.

    Science.gov (United States)

    Aye, Irving L M H; Lager, Susanne; Ramirez, Vanessa I; Gaccioli, Francesca; Dudley, Donald J; Jansson, Thomas; Powell, Theresa L

    2014-06-01

    Obese pregnant women have increased levels of proinflammatory cytokines in maternal circulation and placental tissues. However, the pathways contributing to placental inflammation in obesity are largely unknown. We tested the hypothesis that maternal body mass index (BMI) was associated with elevated proinflammatory cytokines in maternal and fetal circulations and increased activation of placental inflammatory pathways. A total of 60 women of varying pre-/early pregnancy BMI, undergoing delivery by Cesarean section at term, were studied. Maternal and fetal (cord) plasma were collected for analysis of insulin, leptin, IL-1beta, IL-6, IL-8, monocyte chemoattractant protein (MCP) 1, and TNFalpha by multiplex ELISA. Activation of the inflammatory pathways in the placenta was investigated by measuring the phosphorylated and total protein expression of p38-mitogen-activated protein kinase (MAPK), c-Jun-N-terminal kinase (JNK)-MAPK, signal transducer-activated transcription factor (STAT) 3, caspase-1, IL-1beta, IkappaB-alpha protein, and p65 DNA-binding activity. To determine the link between activated placental inflammatory pathways and elevated maternal cytokines, cultured primary human trophoblast (PHT) cells were treated with physiological concentrations of insulin, MCP-1, and TNFalpha, and inflammatory signaling analyzed by Western blot. Maternal BMI was positively correlated with maternal insulin, leptin, MCP-1, and TNFalpha, whereas only fetal leptin was increased with BMI. Placental phosphorylation of p38-MAPK and STAT3, and the expression of IL-1beta protein, were increased with maternal BMI; phosphorylation of p38-MAPK was also correlated with birth weight. In contrast, placental NFkappaB, JNK and caspase-1 signaling, and fetal cytokine levels were unaffected by maternal BMI. In PHT cells, p38-MAPK was activated by MCP-1 and TNFalpha, whereas STAT3 phosphorylation was increased following TNFalpha treatment. Maternal BMI is associated with elevated maternal

  13. Increasing Maternal Body Mass Index Is Associated with Systemic Inflammation in the Mother and the Activation of Distinct Placental Inflammatory Pathways1

    Science.gov (United States)

    Aye, Irving L.M.H.; Lager, Susanne; Ramirez, Vanessa I.; Gaccioli, Francesca; Dudley, Donald J.; Jansson, Thomas; Powell, Theresa L.

    2014-01-01

    ABSTRACT Obese pregnant women have increased levels of proinflammatory cytokines in maternal circulation and placental tissues. However, the pathways contributing to placental inflammation in obesity are largely unknown. We tested the hypothesis that maternal body mass index (BMI) was associated with elevated proinflammatory cytokines in maternal and fetal circulations and increased activation of placental inflammatory pathways. A total of 60 women of varying pre-/early pregnancy BMI, undergoing delivery by Cesarean section at term, were studied. Maternal and fetal (cord) plasma were collected for analysis of insulin, leptin, IL-1beta, IL-6, IL-8, monocyte chemoattractant protein (MCP) 1, and TNFalpha by multiplex ELISA. Activation of the inflammatory pathways in the placenta was investigated by measuring the phosphorylated and total protein expression of p38-mitogen-activated protein kinase (MAPK), c-Jun-N-terminal kinase (JNK)-MAPK, signal transducer-activated transcription factor (STAT) 3, caspase-1, IL-1beta, IkappaB-alpha protein, and p65 DNA-binding activity. To determine the link between activated placental inflammatory pathways and elevated maternal cytokines, cultured primary human trophoblast (PHT) cells were treated with physiological concentrations of insulin, MCP-1, and TNFalpha, and inflammatory signaling analyzed by Western blot. Maternal BMI was positively correlated with maternal insulin, leptin, MCP-1, and TNFalpha, whereas only fetal leptin was increased with BMI. Placental phosphorylation of p38-MAPK and STAT3, and the expression of IL-1beta protein, were increased with maternal BMI; phosphorylation of p38-MAPK was also correlated with birth weight. In contrast, placental NFkappaB, JNK and caspase-1 signaling, and fetal cytokine levels were unaffected by maternal BMI. In PHT cells, p38-MAPK was activated by MCP-1 and TNFalpha, whereas STAT3 phosphorylation was increased following TNFalpha treatment. Maternal BMI is associated with elevated

  14. Reversible effects of oxygen partial pressure on genes associated with placental angiogenesis and differentiation in primary-term cytotrophoblast cell culture.

    Science.gov (United States)

    Debiève, F; Depoix, C; Gruson, D; Hubinont, C

    2013-09-01

    Timely regulated changes in oxygen partial pressure are important for placental formation. Disturbances could be responsible for pregnancy-related diseases like preeclampsia and intrauterine growth restriction. We aimed to (i) determine the effect of oxygen partial pressure on cytotrophoblast differentiation; (ii) measure mRNA expression and protein secretion from genes associated with placental angiogenesis; and (iii) determine the reversibility of these effects at different oxygen partial pressures. Term cytotrophoblasts were incubated at 21% and 2.5% O2 for 96 hr, or were switched between the two oxygen concentrations after 48 hr. Real-time PCR and enzyme-linked immunosorbent assays (ELISAs) were used to evaluate cell fusion and differentiation, measuring transcript levels for those genes involved in cell fusion and placental angiogenesis, including VEGF, PlGF, VEGFR1, sVEGFR1, sENG, INHA, and GCM1. Cytotrophoblasts underwent fusion and differentiation in 2.5% O2 . PlGF expression was inhibited while sVEGFR1 expression increased. VEGF and sENG mRNA expressions increased in 2.5% compared to 21% O2 , but no protein was detected in the cell supernatants. Finally, GCM1 mRNA expression increased during trophoblast differentiation at 21% O2 , but was inhibited at 2.5% O2 . These mRNA expression effects were reversed by returning the cells to 21% O2 . Thus, low-oxygen partial pressure does not inhibit term-cytotrophoblast cell fusion and differentiation in vitro. Lowering the oxygen partial pressure from 21% to 2.5% caused normal-term trophoblasts to reversibly modify their expression of genes associated with placental angiogenesis. This suggests that modifications observed in pregnancy diseases such as preeclampsia or growth retardation are probably due to an extrinsic effect on trophoblasts. Copyright © 2013 Wiley Periodicals, Inc.

  15. Increased placental trophoblast inclusions in placenta accreta.

    Science.gov (United States)

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

    2014-12-01

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

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

    Science.gov (United States)

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

    2017-11-01

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

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

    Science.gov (United States)

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

    2018-01-01

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

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

    International Nuclear Information System (INIS)

    Kiran, N.; Zubair, A.; Malik, T.M.

    2015-01-01

    To evaluate the histopathological parameters of the placenta like weight, infarct and syncytial knots, at different maternal hemoglobin levels, in both qualitative and quantitative manner. Study design: Descriptive study Place and Duration of Study: Army Medical College, National University of Sciences and Technology in collaboration with Department of Obstetrics and Gynecology, Military Hospital, Rawalpindi, Pakistan, from December 2011 to November 2012. Patients and Methods: A total of 75 placentas were included, that were collected from full term mothers at the time of childbirth. Placental weight was taken without umbilical cord and gross placental infarcts were noted. Samples of placental tissue were taken and stained by haematoxylin and eosin (H and E). Microscopic study was done to evaluate placental infarcts and syncytial knots. Results: Mean placental weight at normal and low maternal hemoglobin was 581.67 ± 83.97g and 482.58 ± 104.74g respectively. Gross placental infarcts were found in all cases having low maternal hemoglobin concentration (60% cases). Syncytial knots were found in all placentas but they were considerably more at decreasing levels of maternal hemoglobin (19.79 ± 5.22). Conclusion: The present study showed decrease in placental weight, increase in placental infarcts and syncytial knot hyperplasia at low maternal hemoglobin concentration, displaying adaptive alterations. (author)

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

    Science.gov (United States)

    Howell, Kristy R.; Powell, Theresa L.

    2017-01-01

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

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

    NARCIS (Netherlands)

    Veerbeek, J.H.W.

    2015-01-01

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

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

    Science.gov (United States)

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

    2012-12-01

    Intrapartum death in multiparous gestations in sows (Sus scrofa) is often caused by hypoxia. There is little information in the literature on the assessment of the placenta in relation to intrapartum death in piglets. The aim of this study was to evaluate the impact of the placental area and weight upon piglet birth characteristics and intrapartum death. Litters from 26 Landrace-Yorkshire sows were monitored during farrowing and the status of each piglet was recorded, including blood parameters of piglets and their umbilical veins. Of 413 piglets born, 6.5% were stillborn. Blood concentrations of glucose, lactate, and CO(2) partial pressure were increased in the stillborn piglets (P birth was increased for piglets born dead vs. live (P birth weight for piglets born dead was not different from live-born piglets (P = 0.631), whereas mean body mass index was reduced (P 0.2). Piglet BW was positively correlated with placental area and placental weight (P birth order group, and broken umbilical cords explained 71% of the stillbirths (P = 0.001). We conclude that placental area and placental weight are both positively associated with piglet birth weight, but not with the probability of being born dead. Placental area was a better predictor of piglet vitality than placental weight. Because umbilical cord rupture and prolonged birth time were associated with being born dead, umbilical cord rupture and placental detachment seem to be probable causes of intrapartum death.

  2. Placental transfer of 14C-hexoprenaline

    International Nuclear Information System (INIS)

    Lipshitz, J.; Broyles, K.; Whybrew, W.D.; Ahokas, R.A.; Anderson, G.D.

    1982-01-01

    The placental transfer of a single intravenous injection of 14 C-hexoprenaline was studied in eight pregnant New Zealand white rabbits. Maternal and fetal blood was sampled intermittently for 60 minutes after the injection. An initial rapid decrease in the levels of 14 C-hexoprenaline in maternal blood was followed by a second slower phase, whereas fetal heart rate after the administration of a single maternal intravenous injection of hexoprenaline in the treatment of fetal distress is due to the action on the uterus and/or on maternal cardiovascular function, and not to direct stimulation of the fetus

  3. Clinical development of placental malaria vaccines and immunoassays harmonization

    DEFF Research Database (Denmark)

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

    2016-01-01

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

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

    Science.gov (United States)

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

    2016-12-01

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

  5. 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

  6. Characterization of chlorpyrifos-induced apoptosis in placental cells

    International Nuclear Information System (INIS)

    Saulsbury, Marilyn D.; Heyliger, Simone O.; Wang, Kaiyu; Round, Dorothy

    2008-01-01

    The mechanism by which chlorpyrifos exerts its toxicity in fetal and perinatal animals has yet to be elucidated. Since the placenta is responsible for transport of nutrients and is a major supplier hormone to the fetus, exposure to xenobiotics that alter the function or viability of placenta cells could ostensibly alter the development of the fetus. In this study, JAR cells were used to determine if CPF and the metabolites 3,5,6-trichloro-2-pyridinol (TCP) and chlorpyrifos-oxon (CPO) are toxic to the placenta. Our results indicate that chlorpyrifos (CPF), and its metabolite chlorpyrifos-oxon (CPO) caused a dose-dependent reduction in cellular viability with CPF being more toxic than its metabolites. Chlorpyrifos-induced toxicity was characterized by the loss of mitochondrial potential, the appearance of nuclear condensation and fragmentation, down-regulation of Bcl-2 as well as up-regulation of TNFα and FAS mRNA. Pharmacological inhibition of FAS, nicotinic and TNF-α receptors did not attenuate CPF-induced toxicity. Atropine exhibited minimal ability to reverse toxicity. Furthermore, signal transduction inhibitors PD98059, SP600125, LY294002 and U0126 failed to attenuate toxicity; however, SB202190 (inhibitor of p38α and p38ss MAPK) sensitized cells to CPF-induced toxicity. Pan-caspase inhibitor Q-VD-OPh produced a slight but significant reversal of CPF-induced toxicity indicating that the major caspase pathways are not integral to CPF-induced toxicity. Taken collectively, these results suggest that chlorpyrifos induces apoptosis in placental cells through pathways not dependent on FAS/TNF signaling, activation of caspases or inhibition of cholinesterase. In addition, our data further indicates that activation of p38 MAPK is integral to the protection cells against CPF-induced injury

  7. C-14-activity incorporation into the protein of fetal organs of guinea pigs with different maternal placental blood flow and fetal arterial O2-saturation

    International Nuclear Information System (INIS)

    Duenzl, B.

    1981-01-01

    In anaesthesised gravid guinea-pigs the dilate, end section of a placental radial artery was connected to the A.carotis via a flow meter and a throttle in order to measure and widely alter the maternal placental blood flow. Blood samples are taken from the fetal A.carotis, the fetal arterial O 2 -saturation and the Hb-content were determined. By altering the maternal placental blood circulation the fetal arterial O 2 -concentration can stabilised at various levels. In order to study the protein synthesis, under these conditions one infused 185 kBq C-14-leucine over a period of 3 hours into the jugular vein of the fetus. During infusion the radioactive concentrations in whole plasma and plasma water were measured. After the infusion the radioactive concentrations in the tissue fluid, the intracellular fluid and the acid-insoluble tissue fraction (protein) of the heart, kidenys, liver, the muscles of the upper end lower part of the body, the brain and the placenta were measured. The following deductions were drawn from the findings: The maternal placental blood flow vitally influences the activity incorporation per activity concentration in the plasma water. These findings agree with the hypotheses that the maternal blood circulation has an essential influence on the fetal proteins synthesis and that this influence can be attributed to the connection between placenta connection blood flow and oxygen saturation of fetal arterial blood. (orig.) [de

  8. Placental Underperfusion in a Rat Model of Intrauterine Growth Restriction Induced by a Reduced Plasma Volume Expansion.

    Directory of Open Access Journals (Sweden)

    Karine Bibeau

    Full Text Available Lower maternal plasma volume expansion was found in idiopathic intrauterine growth restriction (IUGR but the link remains to be elucidated. An animal model of IUGR was developed by giving a low-sodium diet to rats over the last week of gestation. This treatment prevents full expansion of maternal circulating volume and the increase in uterine artery diameter, leading to reduced placental weight compared to normal gestation. We aimed to verify whether this is associated with reduced remodeling of uteroplacental circulation and placental hypoxia. Dams were divided into two groups: IUGR group and normal-fed controls. Blood velocity waveforms in the main uterine artery were obtained by Doppler sonography on days 14, 18 and 21 of pregnancy. On day 22 (term = 23 days, rats were sacrificed and placentas and uterine radial arteries were collected. Diameter and myogenic response of uterine arteries supplying placentas were determined while expression of hypoxia-modulated genes (HIF-1α, VEGFA and VEGFR2, apoptotic enzyme (Caspase -3 and -9 and glycogen cells clusters were measured in control and IUGR term-placentas. In the IUGR group, impaired blood velocity in the main uterine artery along with increased resistance index was observed without alteration in umbilical artery blood velocity. Radial uterine artery diameter was reduced while myogenic response was increased. IUGR placentas displayed increased expression of hypoxia markers without change in the caspases and increased glycogen cells in the junctional zone. The present data suggest that reduced placental and fetal growth in our IUGR model may be mediated, in part, through reduced maternal uteroplacental blood flow and increased placental hypoxia.

  9. 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.

  10. Hypoxia: From Placental Development to Fetal Programming.

    Science.gov (United States)

    Fajersztajn, Lais; Veras, Mariana Matera

    2017-10-16

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

  11. Placental effects of lead in mice.

    Science.gov (United States)

    Fuentes, M; Torregrosa, A; Mora, R; Götzens, V; Corbellla, J; Domingo, J L

    1996-01-01

    Although a number of studies in animal models have shown embryolethal and teratogenic lead effects when this element is administered by a parenteral route, the mechanism of the embryonary changes is well not established. In this study, the embryonic effects of parenteral lead exposure on day 9 of gestation were assessed in the Swiss mouse. Lead acetate trihydrate was injected intraperitoneally at 14, 28, 56 and 112 mg/kg. There was no maternal toxicity evidenced by death, reduced body weight gain or reduced food consumption. However, absolute placental weight at 112 mg/kg and relative placental weight at 14, 56 and 112 mg/kg were diminished significantly. The number of total implants, live and dead fetuses, sex ratio and fetal body weight were unaffected by lead exposure. Most sections of placenta showed vascular congestion, an increase of intracellular spaces and deposits of hyaline material of perivascular predominance. Trophoblast hyperplasia was also observed, whereas there was a reinforcement of the fibrovascular network in the labyrinth. It is concluded that the trophoblast hyperplasia observed in the placenta of pregnant mice after parenteral lead exposure at doses that are not toxic for the dam could act as a repairing mechanism of the extraembryonary tissues.

  12. Protein profiling of preeclampsia placental tissues.

    Directory of Open Access Journals (Sweden)

    Chang Shu

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

  13. Protein Profiling of Preeclampsia Placental Tissues

    Science.gov (United States)

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

    2014-01-01

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

  14. Placental Chorangiosis: Increased Risk for Cesarean Section

    Directory of Open Access Journals (Sweden)

    Shariska S. Petersen

    2017-01-01

    Full Text Available We describe a patient with Class C diabetes who presented for nonstress testing at 36 weeks and 4 days of gestation with nonreassuring fetal heart tones (NRFHT and oligohydramnios. Upon delivery, thrombosis of the umbilical cord was grossly noted. Pathological analysis of the placenta revealed chorangiosis, vascular congestion, and 40% occlusion of the umbilical vein. Chorangiosis is a vascular change of the placenta that involves the terminal chorionic villi. It has been proposed to result from longstanding, low-grade hypoxia in the placental tissue and has been associated with such conditions such as diabetes, intrauterine growth restriction (IUGR, and hypertensive conditions in pregnancy. To characterize chorangiosis and its associated obstetric outcomes we identified 61 cases of “chorangiosis” on placental pathology at Henry Ford Hospital from 2010 to 2015. Five of these cases were omitted due to lack of complete records. Among the 56 cases, the cesarean section rate was 51%, indicated in most cases for nonreassuring fetal status. Thus, we suggest that chorangiosis, a marker of chronic hypoxia, is associated with increased rates of cesarean sections for nonreassuring fetal status because of long standing hypoxia coupled with the stress of labor.

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

    Energy Technology Data Exchange (ETDEWEB)

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

    2013-06-01

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

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

    International Nuclear Information System (INIS)

    Tan, Wenjuan; Huang, Hui; Wang, Yanfei; Wong, Tsz Yan; Wang, C.C.; Leung, Lai K.

    2013-01-01

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

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

    International Nuclear Information System (INIS)

    Blazquez, Alba G.; Briz, Oscar; Gonzalez-Sanchez, Ester; Perez, Maria J.; Ghanem, Carolina I.; Marin, Jose J.G.

    2014-01-01

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

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

    Energy Technology Data Exchange (ETDEWEB)

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

    2014-05-15

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

  19. Knockdown of the placental growth factor gene inhibits laser induced choroidal neovascularization in a murine model.

    Science.gov (United States)

    Nourinia, Ramin; Soheili, Zahra-Soheila; Ahmadieh, Hamid; Akrami, Hassan; Rezaei Kanavi, Mozhgan; Samiei, Shahram

    2013-01-01

    To evaluate the effect of placental growth factor (PlGF) gene knockdown in a murine model of laser-induced choroidal neovascularization. Choroidal neovascularization was induced in the left eyes of 11 mice by infrared laser. Small interfering RNA (siRNA, 20 picomoles/10 μl) corresponding to PlGF mRNA was administered intravitreally by Hamilton syringe in all subjects. One month later, fluorescein angiography and histolologic examination were performed. No leakage was apparent in the 11 eyes treated with siRNA cognate to PlGF. The results of histological evaluation were consistent with angiographic findings showing absence of choroidal neovascularization. Knockdown of the PlGF gene can inhibit the growth of laser-induced choroidal neovascularization in mice.

  20. Knockdown of the Placental Growth Factor Gene Inhibits Laser Induced Choroidal Neovascularization in a Murine Model

    Directory of Open Access Journals (Sweden)

    Ramin Nourinia

    2013-01-01

    Full Text Available Purpose: To evaluate the effect of placental growth factor (PlGF gene knockdown in a murine model of laser-induced choroidal neovascularization. Methods: Choroidal neovascularization was induced in the left eyes of 11 mice by infrared laser. Small interfering RNA (siRNA, 20 picomoles/10 μl corresponding to PlGF mRNA was administered intravitreally by Hamilton syringe in all subjects. One month later, fluorescein angiography and histolologic examination were performed. Results: No leakage was apparent in the 11 eyes treated with siRNA cognate to PlGF. The results of histological evaluation were consistent with angiographic findings showing absence of choroidal neovascularization. Conclusion: Knockdown of the PlGF gene can inhibit the growth of laser-induced choroidal neovascularization in mice.

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

    Science.gov (United States)

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

    2016-02-01

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

  2. 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.

  3. Aberrant Expression of TNF-α and TGF-β1 mRNA in Spontaneous Abortion

    Institute of Scientific and Technical Information of China (English)

    Ji-fen HU; Hong-chu BAO; Feng-chuan ZHU; Cai-ling YOU

    2004-01-01

    Objective To investigate the aberrant expressions of TNF-α and TGF-β1 in peripheral blood mononuclear cells (PBMCs) and placental tissues in patients with early spontaneous abortionMethods Using the technique of semi-quantitative reverse transcript-polymerase chain reaction (RT-PCR), TNF-α mRNA and TGF-β1 mRNA in PBMCs were measured in spontaneous abortion group (30 cases), normal pregnancy group (25 cases) and nonpregnant group (25 cases). The expressive intension of TNF-α protein and TGF-β1 protein in placental tissues was also identified by immunohistochemistry.Results Both levels of TNF-α mRNA and TGF-β1 mRNA expressed in PBMCs were significantly different between the three groups respectively (P<0. 05). Levels of TNF-α in syncytiotrophoblastic and cytotrophoblastic cells of the two aborted groups were substantially higher than those of the non-pregnant group (P<0. 01), but the levels of TGF-β1 in syncytiotrophoblastic cells of the two aborted groups were markedly lower than those of the non-pregnant group (P<0. 01).Conclusion There is potential relation between TGF-β1 at the fetomaternal interface and spontaneous abortion. TGF-β1 may contribute to the maintenance of pregnancy,and low-level expression of TGF-β1 may be associated with pregnancy failure.

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

    DEFF Research Database (Denmark)

    Frederiksen, Marie; Vorkamp, Katrin; Mathiesen, Line

    2010-01-01

    high concern due to critical windows in fetal development. METHODS: A human ex vivo placenta perfusion system was used to study the kinetics and extent of the placental transfer of BDE-47, BDE-99 and BDE-209 during four-hour perfusions. The PBDEs were added to the maternal circulation and monitored...... should be included in risk assessment of PBDE exposure of women of child-bearing age....

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

    DEFF Research Database (Denmark)

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

    2017-01-01

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

  6. 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.

  7. A computational model of the fetal circulation to quantify blood redistribution in intrauterine growth restriction.

    Directory of Open Access Journals (Sweden)

    Patricia Garcia-Canadilla

    2014-06-01

    Full Text Available Intrauterine growth restriction (IUGR due to placental insufficiency is associated with blood flow redistribution in order to maintain delivery of oxygenated blood to the brain. Given that, in the fetus the aortic isthmus (AoI is a key arterial connection between the cerebral and placental circulations, quantifying AoI blood flow has been proposed to assess this brain sparing effect in clinical practice. While numerous clinical studies have studied this parameter, fundamental understanding of its determinant factors and its quantitative relation with other aspects of haemodynamic remodeling has been limited. Computational models of the cardiovascular circulation have been proposed for exactly this purpose since they allow both for studying the contributions from isolated parameters as well as estimating properties that cannot be directly assessed from clinical measurements. Therefore, a computational model of the fetal circulation was developed, including the key elements related to fetal blood redistribution and using measured cardiac outflow profiles to allow personalization. The model was first calibrated using patient-specific Doppler data from a healthy fetus. Next, in order to understand the contributions of the main parameters determining blood redistribution, AoI and middle cerebral artery (MCA flow changes were studied by variation of cerebral and peripheral-placental resistances. Finally, to study how this affects an individual fetus, the model was fitted to three IUGR cases with different degrees of severity. In conclusion, the proposed computational model provides a good approximation to assess blood flow changes in the fetal circulation. The results support that while MCA flow is mainly determined by a fall in brain resistance, the AoI is influenced by a balance between increased peripheral-placental and decreased cerebral resistances. Personalizing the model allows for quantifying the balance between cerebral and peripheral-placental

  8. Placental transfer of 14C-hexoprenaline

    International Nuclear Information System (INIS)

    Lipshitz, J.; Broyles, K.; Whybrew, W.D.; Ahokas, R.A.; Anderson, G.D.

    1982-01-01

    The placental transfer of a single intravenous injection of 14C-hexoprenaline was studied in eight pregnant New Zealand white rabbits. Maternal and fetal blood was sampled intermittently for 60 minutes after the injection. An initial rapid decrease in the levels of 14C-hexoprenaline in maternal blood was followed by a second slower phase, whereas fetal levels remained insignificant. The conclusion, therefore, is that the rapid improvement in fetal heart rate after the administration of a single maternal intravenous injection of hexoprenaline in the treatment of fetal distress is due to the action on the uterus and/or on maternal cardiovascular function, and not to direct stimulation of the fetus

  9. Effects of tributyltin on placental cytokine production.

    Science.gov (United States)

    Arita, Yuko; Kirk, Michael; Gupta, Neha; Menon, Ramkumar; Getahun, Darios; Peltier, Morgan R

    2018-03-15

    Tributyltin (TBT) is a persistent pollutant but its effects on placental function are poorly understood as are its possible interactions with infection. We hypothesized that TBT alters the production of sex hormones and biomarkers for inflammation and neurodevelopment in an infection-dependent manner. Placental explant cultures were treated with 0-5000 nM TBT in the presence and absence of Escherichia coli. A conditioned medium was harvested and concentrations of steroids (progesterone, P4; testosterone, T and estradiol, E2) as well as biomarkers of inflammation [interleukin (IL)-1β (IL-1β), tumor necrosis factor (TNF-α), IL-10, IL-6, soluble glycoprotein 130 (sgp-130) and heme oxygenase-1 (HO-1)], oxidative stress [8-iso-prostaglandin (8-IsoP)] and neurodevelopment [brain-derived neurotrophic factor (BDNF)] were quantified. TBT increased P4 slightly but had little or no effect on T or E2 production. IL-1β, IL-6, sgp-130, IL-10 and 8-IsoP production was enhanced by TBT. P4 and IL-6 production was also enhanced by TBT for bacteria-stimulated cultures but TBT significantly inhibited bacteria-induced IL-1β and sgp-130 production. High doses of TBT also inhibited BDNF production. TBT increases P4 but has minimal effect on downstream steroids. It enhances the production of inflammatory biomarkers such as IL-1β, TNF-α, IL-10 and IL-6. Inhibition of sgp-130 by TBT suggests that TBT may increase bioactive IL-6 production which has been associated with adverse neurodevelopmental outcomes. Reduced expression of BDNF also supports this possibility.

  10. Altered expressions of endothelial junction protein of placental capillaries in premature infants with intraventricular hemorrhage

    Directory of Open Access Journals (Sweden)

    Maria Ekawati

    2016-10-01

    Full Text Available Background: Placental hypoxia may lead to oxidative stress, which inflicts damage to capillary protein junction. The aim of this study was to evaluate altered expression of endothelial junction protein of capillaries in hypoxia condition and to observe its correlation with the incidence of  intraventricular hemorrhage in premature infants.Methods: A cross-sectional study was conducted by using placental tissues of premature infants as amodel of capillary integrity (29 hypoxic and 29 non-hypoxic. Hypoxia inducible factor (HIF-1α was measured to define placental tissue response to hypoxia; malondialdehyde (MDA and glutathione (GSH served as markers of oxidative stress. The expressions of junctional proteins, N-cadherin and occludin were analyzed by immunohistochemistry. Intraventricular hemorrhage (IVH was detected by cranial ultrasound at the third day. Unpaired t test, Mann-Whitney, and Chi-square tests were used to analyze the data.Results: The HIF-1α and MDA levels were slightly, but not significantly, higher in hypoxia group {13.64±8.70 pg/mg protein and 10.31 pmol/mg tissue (ranged 1.92–93.61, respectively}  compared to non- hypoxia group {10.65±5.35 pg/mg protein and 9.77 pmol/mg tissue (ranged 2.42–93.31}. GSH levels were not different in both groups (38.14 (ranged 9.44–118.91 and  38.47(ranged 16.49–126.76 ng/mg protein, respectively. mRNA expression of N-cadherin (0.13 and occludin (0.096 were significantly lower in hypoxia comparedto non-hypoxia group (p=0,001, while protein expression of  N-cadherin (3.4; 75.9; 6.9; 13.8% and occludin  (20.7; 3.4; 69.0; 3.4; 6.9%  in hypoxia group was not associated with IVH (p=0.783 and p=0.743.Conclusion: Hypoxia altered expression of endothelial junction protein in placental capillaries, but no association with intraventricular hemorrhage was observed.

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

    Science.gov (United States)

    Jauniaux, E; Burton, G J

    2016-10-01

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

  12. Fetal adaptations in insulin secretion result from high catecholamines during placental insufficiency.

    Science.gov (United States)

    Limesand, Sean W; Rozance, Paul J

    2017-08-01

    Placental insufficiency and intrauterine growth restriction (IUGR) of the fetus affects approximately 8% of all pregnancies and is associated with short- and long-term disturbances in metabolism. In pregnant sheep, experimental models with a small, defective placenta that restricts delivery of nutrients and oxygen to the fetus result in IUGR. Low blood oxygen concentrations increase fetal plasma catecholamine concentrations, which lower fetal insulin concentrations. All of these observations in sheep models with placental insufficiency are consistent with cases of human IUGR. We propose that sustained high catecholamine concentrations observed in the IUGR fetus produce developmental adaptations in pancreatic β-cells that impair fetal insulin secretion. Experimental evidence supporting this hypothesis shows that chronic elevation in circulating catecholamines in IUGR fetuses persistently inhibits insulin concentrations and secretion. Elevated catecholamines also allow for maintenance of a normal fetal basal metabolic rate despite low fetal insulin and glucose concentrations while suppressing fetal growth. Importantly, a compensatory augmentation in insulin secretion occurs following inhibition or cessation of catecholamine signalling in IUGR fetuses. This finding has been replicated in normally grown sheep fetuses following a 7-day noradrenaline (norepinephrine) infusion. Together, these programmed effects will potentially create an imbalance between insulin secretion and insulin-stimulated glucose utilization in the neonate which probably explains the transient hyperinsulinism and hypoglycaemia in some IUGR infants. © 2017 The Authors. The Journal of Physiology © 2017 The Physiological Society.

  13. Placental histopathology after Coxiella burnetii infection during pregnancy

    NARCIS (Netherlands)

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

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

  14. Placental malaria and neonatal anti-tetanus antibody status: Any ...

    African Journals Online (AJOL)

    Globally, neonatal tetanus accounts for 7% of neonatal mortality,[1] ... There was a statistically significant association between type of placental malaria .... Also excluded were mothers with diabetes ..... Tetanus Vaccine: WHO Position Paper.

  15. Placental polyp: a rare cause of iron deficiency anemia

    Directory of Open Access Journals (Sweden)

    Fernando Peixoto Ferraz de Campos

    2011-12-01

    Full Text Available Placental polyps are defined as pedunculated or polypoid fragments of placentaor ovular membranes retained for an indefinite period of time into the uterus afterabortion or child birth. An important cause of retention is placental accretism, anabnormal adherence of the placenta into the uterine wall. Chronic cases are rarelyreported in the literature. In these cases, the placental retention in the immediatepostpartum is not followed by heavy bleeding what makes the diagnosischallenging. We report a rare case of iron-deficiency anemia in a multiparous29-year-old female patient two years after the last delivery. She sought medicalcare with clinical symptoms of anemia and recent menses alterations. Therewas no history of abortion. On gynecological examination, there was a twofoldenlarged uterus, and the pelvic ultrasound revealed an image compatible with anendometrial polyp. She underwent open hysterectomy because of uncontrollablebleeding followed by hypotension after curettage. The histolopathologicexamination revealed a partially hyalinized and necrotic placental polyp.

  16. 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....

  17. 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.

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

    Directory of Open Access Journals (Sweden)

    M Asgharnia

    2008-12-01

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

  19. Placental abruption possibly due to parvovirus B19 infection.

    Science.gov (United States)

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

    2016-01-01

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

  20. Increased placental nutrient transport in a novel mouse model of maternal obesity with fetal overgrowth.

    Science.gov (United States)

    Rosario, Fredrick J; Kanai, Yoshikatsu; Powell, Theresa L; Jansson, Thomas

    2015-08-01

    To identify possible mechanisms linking obesity in pregnancy to increased fetal adiposity and growth, a unique mouse model of maternal obesity associated with fetal overgrowth was developed, and the hypothesis that maternal obesity causes up-regulation of placental nutrient transporter expression and activity was tested. C57BL/6J female mice were fed a control (C) or a high-fat/high-sugar (HF/HS) pelleted diet supplemented by ad libitum access to sucrose (20%) solution, mated, and studied at embryonic day 18.5. HF/HS diet increased maternal fat mass by 2.2-fold (P Maternal circulating insulin, leptin, and cholesterol were increased (P maternal obesity. © 2015 The Obesity Society.

  1. 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.

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

    Science.gov (United States)

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

    2009-05-01

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

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

    Directory of Open Access Journals (Sweden)

    Marcos R Chiaratti

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

  4. Localization of the placental BCRP/ABCG2 transporter to lipid rafts: Role for cholesterol in mediating efflux activity.

    Science.gov (United States)

    Szilagyi, John T; Vetrano, Anna M; Laskin, Jeffrey D; Aleksunes, Lauren M

    2017-07-01

    The breast cancer resistance protein (BCRP/ABCG2) is an efflux transporter in the placental barrier. By transporting chemicals from the fetal to the maternal circulation, BCRP limits fetal exposure to a range of drugs, toxicants, and endobiotics such as bile acids and hormones. The purpose of the present studies was to 1) determine whether BCRP localizes to highly-ordered, cholesterol-rich lipid raft microdomains in placenta microvillous membranes, and 2) determine the impact of cholesterol on BCRP-mediated placental transport in vitro. BCRP expression was analyzed in lipid rafts isolated from placentas from healthy, term pregnancies and BeWo trophoblasts by density gradient ultracentrifugation. BeWo cells were also tested for their ability to efflux BCRP substrates after treatment with the cholesterol sequestrant methyl-β-cyclodextrin (MβCD, 5 mM, 1 h) or the cholesterol synthesis inhibitor pravastatin (200 μM, 48 h). BCRP was found to co-localize with lipid raft proteins in detergent-resistant, lipid raft-containing fractions from placental microvillous membranes and BeWo cells. Treatment of BeWo cells with MβCD redistributed BCRP protein into higher density non-lipid raft fractions. Repletion of the cells with cholesterol restored BCRP localization to lipid raft-containing fractions. Treatment of BeWo cells with MβCD or pravastatin increased cellular retention of two BCRP substrates, the fluorescent dye Hoechst 33342 and the mycotoxin zearalenone. Repletion with cholesterol restored BCRP transporter activity. Taken together, these data demonstrate that cholesterol may play a critical role in the post-translational regulation of BCRP in placental lipid rafts. Copyright © 2017 Elsevier Ltd. All rights reserved.

  5. 2011 and 2012 Early Careers Achievement Awards: Placental programming: how the maternal environment can impact placental function.

    Science.gov (United States)

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

    2013-06-01

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

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

    DEFF Research Database (Denmark)

    Mathiesen, Line

    2011-01-01

    be used as a negative control when adding a small amount to the fetal reservoir. To be able to detect any trace of dextran in the maternal reservoir in case of a leakage, the dextran is labeled with FITC and analyzed by fluorescence measurement (Paper I). Inter-laboratory comparisons have confirmed...... within two hours of perfusion with a fetal flow rate of 3 mL/min. Negative controls are added to ensure that substance transfer is not due to leakage, e.g. high molecular weight substances that only pass the placental barrier with bulk flow through a leakage in the fetal system. Dextran (40kD) can...

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

    Science.gov (United States)

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

    1998-01-01

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

  8. 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.

  9. Placentation in the plains zebra (Equus quagga).

    Science.gov (United States)

    Allen, W R Twink; Stansfield, Fiona; Wilsher, Sandra

    2017-10-01

    The placenta and fetal gonads of 12 pregnant plains zebra (Equus quagga), estimated to be between 81 and 239 days of gestation, were examined. The diffuse, microcotyledonary zebra placenta appeared, developmentally, to be 3-4 weeks behind its counterpart in horse pregnancy and this, together with the presence of small and long-lived endometrial cups, low levels of zebra chorionic gonadotrophin in maternal serum and few accessory corpora lutea in the maternal ovaries during the first half of gestation, made zebra pregnancy more similar to donkey than horse pregnancy. Zebra fetal gonads enlarged after 80 days of gestation and their interstitial cells stained positively for 3β hydroxysteroid dehydrogenase and 17,20 lyase steroid enzymes while the trophoblast stained for aromatase. This confirmed that zebra fetal gonads, like those of the horse and donkey, can synthesise C19 androgens, which can then be aromatised by the placenta to C18 oestrogens. It is remarkable that such unusual feto-placental mechanisms of production of gonadotrophic and steroid hormones has persisted unchanged within the genus Equus despite the many physical adaptations and the considerable loss of chromosomes that have occurred during the evolution of its member species.

  10. Placental transfer of iodine and iodine compounds

    International Nuclear Information System (INIS)

    Stieve, F.E.; Zemlin, G.; Griessl, I.

    1985-11-01

    The following topics are valid for man and mammalians with haemochorial placenta, which are examined up to now: Within several hours after injection of radioactive inorganic iodide-compounds activity can be realized in the fetus. The transfer occurs bidirectionally through the placenta. The concentration of radioactive iodide in the fetal serum exceeds that of the maternal one already a short time after application. Radioactive iodide accumulates in the fetus before its thyroid starts its function and is mainly concentrated in liver and intestine; after starting its function, the fetal thyroid, stores the radioactive iodide at a very high percent rate. During gestation the concentration of radioactive iodide in the fetal thyroid increases and at the end of gestation it can exceed by 3-10 fold that in the maternal thyroid. Single uptake of radioactive iodide leads to a higher activity than chronic uptake. No analogy can be found in the concentration of fetal and maternal radioactive thyroid hormon compounds. A placental permeability for T 4 and T 3 only exists to a very small extent. Resulting from radioactive iodide transfer examinations, good accordance can be found between the individual animal species and man, while data on the passage of radioactive thyroid hormones vary to a small extent between the animal species. (orig./MG) [de

  11. 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.

  12. Labor Inhibits Placental Mechanistic Target of Rapamycin Complex 1 Signaling

    Science.gov (United States)

    LAGER, Susanne; AYE, Irving L.M.H.; GACCIOLI, Francesca; RAMIREZ, Vanessa I.; JANSSON, Thomas; POWELL, Theresa L.

    2014-01-01

    Introduction Labor induces a myriad of changes in placental gene expression. These changes may represent a physiological adaptation inhibiting placental cellular processes associated with a high demand for oxygen and energy (e.g., protein synthesis and active transport) thereby promoting oxygen and glucose transfer to the fetus. We hypothesized that mechanistic target of rapamycin complex 1 (mTORC1) signaling, a positive regulator of trophoblast protein synthesis and amino acid transport, is inhibited by labor. Methods Placental tissue was collected from healthy, term pregnancies (n=15 no-labor; n=12 labor). Activation of Caspase-1, IRS1/Akt, STAT, mTOR, and inflammatory signaling pathways was determined by Western blot. NFκB p65 and PPARγ DNA binding activity was measured in isolated nuclei. Results Labor increased Caspase-1 activation and mTOR complex 2 signaling, as measured by phosphorylation of Akt (S473). However, mTORC1 signaling was inhibited in response to labor as evidenced by decreased phosphorylation of mTOR (S2448) and 4EBP1 (T37/46 and T70). Labor also decreased NFκB and PPARγ DNA binding activity, while having no effect on IRS1 or STAT signaling pathway. Discussion and conclusion Several placental signaling pathways are affected by labor, which has implications for experimental design in studies of placental signaling. Inhibition of placental mTORC1 signaling in response to labor may serve to down-regulate protein synthesis and amino acid transport, processes that account for a large share of placental oxygen and glucose consumption. We speculate that this response preserves glucose and oxygen for transfer to the fetus during the stressful events of labor. PMID:25454472

  13. Circulating microRNAs in breast cancer

    DEFF Research Database (Denmark)

    Hamam, Rimi; Hamam, Dana; Alsaleh, Khalid A

    2017-01-01

    Effective management of breast cancer depends on early diagnosis and proper monitoring of patients' response to therapy. However, these goals are difficult to achieve because of the lack of sensitive and specific biomarkers for early detection and for disease monitoring. Accumulating evidence in ...... circulating miRNAs as diagnostic, prognostic or predictive biomarkers in breast cancer management.......Effective management of breast cancer depends on early diagnosis and proper monitoring of patients' response to therapy. However, these goals are difficult to achieve because of the lack of sensitive and specific biomarkers for early detection and for disease monitoring. Accumulating evidence...... in the past several years has highlighted the potential use of peripheral blood circulating nucleic acids such as DNA, mRNA and micro (mi)RNA in breast cancer diagnosis, prognosis and for monitoring response to anticancer therapy. Among these, circulating miRNA is increasingly recognized as a promising...

  14. Regulation of pregnancy-associated plasma protein A2 (PAPPA2 in a human placental trophoblast cell line (BeWo

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    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

  15. 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.

  16. Associations of ACE Gene Insertion/Deletion Polymorphism, ACE Activity, and ACE mRNA Expression with Hypertension in a Chinese Population

    OpenAIRE

    He, Qingfang; Fan, Chunhong; Yu, Min; Wallar, Gina; Zhang, Zuo-Feng; Wang, Lixin; Zhang, Xinwei; Hu, Ruying

    2013-01-01

    Background The present study was designed to explore the association of angiotensin converting enzyme (ACE) gene insertion/deletion (I/D, rs4646994) polymorphism, plasma ACE activity, and circulating ACE mRNA expression with essential hypertension (EH) in a Chinese population. In addition, a new detection method for circulating ACE mRNA expression was explored. Methods The research was approved by the ethics committee of Zhejiang Provincial Center for Disease Prevention and Control. Written i...

  17. Placental FKBP5 genetic and epigenetic variation is associated with infant neurobehavioral outcomes in the RICHS cohort.

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    Alison G Paquette

    Full Text Available Adverse maternal environments can lead to increased fetal exposure to maternal cortisol, which can cause infant neurobehavioral deficits. The placenta regulates fetal cortisol exposure and response, and placental DNA methylation can influence this function. FK506 binding protein (FKBP5 is a negative regulator of cortisol response, FKBP5 methylation has been linked to brain morphology and mental disorder risk, and genetic variation of FKBP5 was associated with post-traumatic stress disorder in adults. We hypothesized that placental FKBP5 methylation and genetic variation contribute to gene expression control, and are associated with infant neurodevelopmental outcomes assessed using the Neonatal Intensive Care Unit (NICU Network Neurobehavioral Scales (NNNS. In 509 infants enrolled in the Rhode Island Child Health Study, placental FKBP5 methylation was measured at intron 7 using quantitative bisulfite pyrosequencing. Placental FKBP5 mRNA was measured in a subset of 61 infants by quantitative PCR, and the SNP rs1360780 was genotyped using a quantitative allelic discrimination assay. Relationships between methylation, expression and NNNS scores were examined using linear models adjusted for confounding variables, then logistic models were created to determine the influence of methylation on membership in high risk groups of infants. FKBP5 methylation was negatively associated with expression (P = 0.08, r = -0.22; infants with the TT genotype had higher expression than individuals with CC and CT genotypes (P = 0.06, and those with CC genotype displayed a negative relationship between methylation and expression (P = 0.06, r = -0.43. Infants in the highest quartile of FKBP5 methylation had increased risk of NNNS high arousal compared to infants in the lowest quartile (OR 2.22, CI 1.07-4.61. TT genotype infants had increased odds of high NNNS stress abstinence (OR 1.98, CI 0.92-4.26. Placental FKBP5 methylation reduces expression in

  18. A higher-level MRP supertree of placental mammals

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    Bininda-Emonds Olaf RP

    2006-11-01

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

  19. Fetal placental prostaglandin metabolism in the peripartum cow

    International Nuclear Information System (INIS)

    Gross, T.S.; Williams, W.F.; Lewis, G.S.

    1986-01-01

    Previous results demonstrate that fetal placental tissue synthesizes prostaglandin E (PGE) prior to parturition. When placental membranes do not separate postpartum, PGE synthesis is maintained, while prostaglandin F (PGF) synthesis predominates when the membranes separate. Concurrent with separation is a decline in fetal placental binucleate cell (BNC) numbers. These data suggest a fetal placental conversion of PGE to PGF. For this experiment, placentomes were collected at ten days prepartum (PRE, n=12) and within 1 hr postpartum. Nine of the postpartum animals had fetal membrane separation within 12 hr postpartum (S) and eight did not exhibit membrane separation (NS). For each placentome, fetal (villi) components were manually isolated and examined for the ability to interconvert 3 H labeled PGE 2 and PGF 2 . All villi were unable to convert PGE 2 to PGF 2 (P > .05). The PRE and NS villi were able to convert PGF 2 to PGE 2 (P 2 to PGE 2 (P 2 to PGE 2 also declines (P < .05). These data suggest that peripartum fetal placental tissue might synthesize PGF which is then converted to PGE. It is possible that the BNC are directly converting PGF to PGE or that they are modulating this conversion. Therefore, with a decline in BNC numbers, PGF synthesis would predominate

  20. Recurrent Placental Abruption with Methylenetetrahydrofolate Reductase C667t Heterozygosity: A Case Report

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    Ilgın Türkçüoğlu

    2007-12-01

    Risk of recurrence is high in patients with a history of placental abruption. Antenatal care and delivery after fetal lung maturation is advised since the perinatal mortality is high with placental abruption.

  1. Effects of vitamin C, vitamin E, and molecular hydrogen on the placental function in trophoblast cells.

    Science.gov (United States)

    Guan, Zhong; Li, Huai-Fang; Guo, Li-Li; Yang, Xiang

    2015-08-01

    This study aimed to investigate the effects of three different antioxidants, namely vitamin C, vitamin E, and molecular hydrogen, on cytotrophoblasts in vitro. Two trophoblast cell lines, JAR and JEG-3, were exposed to different concentrations of vitamin C (0, 25, 50, 100, 500, 1,000, 5,000 μmol/L), vitamin E (0, 25, 50, 100, 500, 1,000, 5,000 μmol/L), and molecular hydrogen (0, 25, 50, 100, 500 μmol/L) for 48 h. The cell viability was detected using the MTS assay. The secretion of human chorionic gonadotropin (hCG) and the tumor necrosis factor-α (TNF-α) were assessed and the expression of TNF-α mRNA was observed by real-time RT-PCR. Cell viability was significantly suppressed by 500 μmol/L vitamins C and E (P 0.05). The expression of TNF-α was increased by 100 μmol/L vitamin C and 50 μmol/L vitamins E, separately or combined (P vitamin C and E, separately or combined. High levels of antioxidant vitamins C and E may have significant detrimental effects on placental function, as reflected by decreased cell viability and secretion of hCG; and placental immunity, as reflected by increased production of TNF-a. Meanwhile hydrogen showed no such effects on cell proliferation and TNF-α expression, but it could affect the level of hCG, indicating hydrogen as a potential candidate of antioxidant in the management of preeclampsia (PE) should be further studied.

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

    DEFF Research Database (Denmark)

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

    2010-01-01

    Pregnant women are at increased malaria risk. The infections are characterized by placental accumulation of infected erythrocytes (IEs) with adverse consequences for mother and baby. Placental IE sequestration in the intervillous space is mediated by variant surface antigens (VSAs) selectively...... expressed in placental malaria (PM) and specific for chondroitin sulfate A (CSA). In Plasmodium falciparum, these VSA(PM) appear largely synonymous with the P. falciparum erythrocyte membrane protein 1 (PfEMP1) family variant VAR2CSA. As rodent malaria parasites do not possess PfEMP1 homologs......, the usefulness of experimental mouse PM models remains controversial. However, many features of murine and human PM are similar, including involvement of VSAs analogous to PfEMP1. It thus appears that rodent model studies can further the understanding of VSA-dependent malaria pathogenesis and immunity....

  3. 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...

  4. Intentional placental removal on suspicious placenta accreta spectrum: still prohibited?

    Science.gov (United States)

    Matsubara, Shigeki; Takahashi, Hironori

    2018-01-01

    Intentional placental removal for abnormally invasive placenta (AIP) is fundamentally abandoned at planned surgery for it. Whether this holds true even after recent introduction of various hemostatic procedures is unclear. We discussed on this issue based on our own experiences and also on the recent reports on various hemostatic procedures. Studies directly answering this question have been lacking. We must weigh the balance between the massive bleeding and possibility of uterus-preservation when intentional placental removal strategy is employed. An almost forgotten strategy, the "intentional placental removal" for planned AIP surgery may regain its position when appropriate hemostatic procedures are concomitantly used depending on the situation. Even employing this strategy, quick decision to perform hysterectomy under multidisciplinary team may be important.

  5. Placental weight and birth weight to placental weight ratio in monochorionic and dichorionic growth-restricted and non-growth-restricted twins

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    Mariângela Alves Souza

    Full Text Available OBJECTIVE: The aim of the present study was to compare the placental weight and birth weight/placental weight ratio for intrauterine growth-restricted and non-intrauterine growth-restricted monochorionic and dichorionic twins. METHODS: This was a retrospective analysis of placentas from twin pregnancies. Placental weight and the birth weight/placental weight ratio were compared in intrauterine growth-restricted and non-intrauterine growth-restricted monochorionic and dichorionic twins. The association between cord insertion type and placental lesions in intrauterine growth-restricted and non-intrauterine growth-restricted monochorionic and dichorionic twins was also investigated. RESULTS: A total of 105 monochorionic (intrauterine growth restriction=40; non-intrauterine growth restriction=65 and 219 dichorionic (intrauterine growth restriction=57; non-intrauterine growth restriction=162 placentas were analyzed. A significantly lower placental weight was observed in intrauterine growth-restricted monochorionic (p=0.022 and dichorionic (p<0.001 twins compared to non-intrauterine growth-restricted twins. There was no difference in the birth weight/placental weight ratio between the intrauterine growth restriction and non-intrauterine growth restriction groups for either monochorionic (p=0.36 or dichorionic (p=0.68 twins. Placental weight and the birth weight/placental weight ratio were not associated with cord insertion type or with placental lesions. CONCLUSION: Low placental weight, and consequently reduced functional mass, appears to be involved in fetal growth restriction in monochorionic and dichorionic twins. The mechanism by which low placental weight influences the birth weight/placental weight ratio in intrauterine growth-restricted monochorionic and dichorionic twins needs to be determined in larger prospective studies.

  6. Web-based education for placental complications of pregnancy.

    Science.gov (United States)

    Walker, Melissa G; Windrim, Catherine; Ellul, Katie N; Kingdom, John C P

    2013-04-01

    The objective of this study was to determine whether a web-based education strategy could improve maternal knowledge of placental complications of pregnancy and reduce maternal anxiety in high risk-pregnancies. Prospective study in the Placenta Clinic at Mount Sinai Hospital, Toronto, Ontario. Maternal demographics and Internet usage were recorded at the patient's baseline appointment. Placental knowledge was determined using structured verbal and illustrative assessments. The six-item State-Trait Anxiety Inventory (STAI) was administered to assess baseline maternal anxiety. Women were asked to visit the Placenta Clinic website for a minimum of 15 minutes before their follow-up appointment, at which time their placental knowledge and STAI assessments were repeated. Eighteen women were included in the study. Patient knowledge at the baseline appointment was generally poor (median score 10.5 out of a maximum score of 27, range 1 to 22), with major deficits in basic placental knowledge, placenta previa/increta, and preeclampsia. At the follow-up appointment, placental knowledge was significantly improved (median score 23, range 10 to 27; P Educational status (high school or less vs. college or more) had no effect on either baseline knowledge or knowledge improvement. Maternal anxiety at baseline (median score 12 out of a maximum score of 24, range 6 to 23) was significantly reduced at the follow-up appointment (median score 8.5, range 6 to 20; P = 0.005). Deficits in maternal knowledge of placental complications of pregnancy in high-risk pregnant women were substantial but easily rectified with a disease-targeted web-based educational resource. This intervention significantly improved patient knowledge and significantly reduced maternal anxiety.

  7. Oxygen and tissue culture affect placental gene expression.

    Science.gov (United States)

    Brew, O; Sullivan, M H F

    2017-07-01

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

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

    Directory of Open Access Journals (Sweden)

    Frederiksen Marie

    2010-07-01

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

  9. Correlation of ultrasound estimated placental volume and umbilical cord blood volume in term pregnancy.

    Science.gov (United States)

    Pannopnut, Papinwit; Kitporntheranunt, Maethaphan; Paritakul, Panwara; Kongsomboon, Kittipong

    2015-01-01

    To investigate the correlation between ultrasound measured placental volume and collected umbilical cord blood (UCB) volume in term pregnancy. An observational cross-sectional study of term singleton pregnant women in the labor ward at Maha Chakri Sirindhorn Medical Center was conducted. Placental thickness, height, and width were measured using two-dimensional (2D) ultrasound and calculated for placental volume using the volumetric mathematic model. After the delivery of the baby, UCB was collected and measured for its volume immediately. Then, birth weight, placental weight, and the actual placental volume were analyzed. The Pearson's correlation was used to determine the correlation between each two variables. A total of 35 pregnant women were eligible for the study. The mean and standard deviation of estimated placental volume and actual placental volume were 534±180 mL and 575±118 mL, respectively. The median UCB volume was 140 mL (range 98-220 mL). The UCB volume did not have a statistically significant correlation with the estimated placental volume (correlation coefficient 0.15; p=0.37). However, the UCB volume was significantly correlated with the actual placental volume (correlation coefficient 0.62; pcorrelation coefficient 0.38; p=0.02). The estimated placental volume by 2D ultrasound was not significantly correlated with the UCB volume. Further studies to establish the correlation between the UCB volume and the estimated placental volume using other types of placental imaging may be needed.

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

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    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

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

  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. 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

  14. Early studies of placental ultrastructure by electron microscopy

    DEFF Research Database (Denmark)

    Carter, A M; Enders, A C

    2016-01-01

    many other scientists to Washington University in St. Louis. Work on human placental ultrastructure was initiated at Cambridge and Kyoto whilst domestic animals were initially studied by Björkman in Stockholm and electron micrographs of bat placenta were published by Wimsatt of Cornell University......BACKGROUND: Transmission electron microscopy (TEM) was first applied to study placental ultrastructure in the 1950's. We review those early studies and mention the scientists that employed or encouraged the use of TEM. FINDINGS: Among the pioneers Edward W. Dempsey was a key figure who attracted...

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

    International Nuclear Information System (INIS)

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

    2015-01-01

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

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

    Science.gov (United States)

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

    2016-12-01

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

  17. Canine placental prostaglandin E2 synthase: expression, localization, and biological functions in providing substrates for prepartum PGF2alpha synthesis.

    Science.gov (United States)

    Gram, Aykut; Fox, Barbara; Büchler, Urs; Boos, Alois; Hoffmann, Bernd; Kowalewski, Mariusz P

    2014-12-01

    The prepartum output of PGF2alpha in the bitch is associated with increased placental PGE2-synthase (PTGES) mRNA levels. Contrasting with this is a decreased expression of PGF2alpha-synthase (PGFS/AKR1C3) in uteroplacental compartments during prepartum luteolysis, suggesting an involvement of alternative synthetic pathways in PGF2alpha synthesis, for example, conversion of PGE2 to PGF2alpha. However, because the expression and possible functions of the respective PTGES proteins remained unknown, no further conclusion could be drawn. Therefore, a canine-specific PTGES antibody was generated and used to investigate the expression, cellular localization, and biochemical activities of canine uteroplacental PTGES throughout pregnancy and at prepartum luteolysis. Additionally, the biochemical activities of these tissues involved in the conversion of PGE2 to PGF2alpha were investigated. The endometrial PTGES was localized in the uterine surface epithelium at preimplantation and in superficial and deep uterine glands, endothelial cells, and myometrium throughout pregnancy and at parturition. Placental signals were mostly in the trophoblast. The biochemical properties of recombinant PTGES protein were confirmed. Additionally, expression of two PGE2-receptors, PTGER2/EP2 and PTGER4/EP4, revealed their decreasing expression during luteolysis. In contrast, the uteroplacental expression of prostaglandin transporter (PGT) was strongly elevated prior to parturition. These localization patterns resembled that of PTGES. The increased expression of PTGES and PGT at parturition, together with the accompanying decreased levels of PGE2-receptors and the capability of canine uterine and placental homogenates to take part in the conversion of PGE2 to PGF2alpha, as found in this study, suggest that PGE2 could be used locally as a substrate for prepartum PGF2alpha synthesis in the dog. © 2014 by the Society for the Study of Reproduction, Inc.

  18. [The ratio birth-weight, placental weight and the term of delivery. A contribution to the problem of a relative placental insufficiency in late pregnancy (author's transl)].

    Science.gov (United States)

    Warkentin, B

    1976-12-10

    It is suggested, that a relative placental insufficiency in late pregnancy is one of the releasing factors of childbirth. Under this assumption 1027 deliveries in term pregnancy (266th-294th day of pregnancy) were inquired on the interrelationship between the ratio brith-weight: placental-weight and the duration of pregnancy. The average birth-weight increases slighly but significantly with the duration of pregnancy just as the average placental-weight. The average ratio birth-weight: placental-weight decreases significantly: The more unfavorable the ratio birth-weight: placental-weight is, the shorter remains the fetus in utero. This underlines the assumption of a relative placental insufficiency as one of the releasing factors of childbirth.

  19. Paraoxonase-2 and paraoxonase-3: comparison of mRNA expressions in the placentae of unexplained intrauterine growth restricted and noncomplicated pregnancies.

    Science.gov (United States)

    Dikbas, Levent; Yapca, Omer Erkan; Dikbas, Neslihan; Gundogdu, Cemal

    2017-05-01

    Recent evidence suggests that oxidative stress is involved in the pathophysiology of many human diseases. It has been demonstrated that oxidative stress is associated with intrauterine growth restriction (IUGR), and the depletion of placental antioxidant systems has been suggested as a key factor in this disease. Our aims were to explore the possible role of antioxidant paraoxonase-2 (PON2) and paraoxonase-3 (PON3) in the pathophysiology of unexplained IUGR. We have studied the expression of mRNA for PON2, PON3 in placental tissues by using RT-qPCR. Two groups, consisting of normal (n = 18) and unexplained IUGR pregnancies (n = 20) were compared. Our results demonstrated that there were no significant differences in the mRNA expressions of PON2, PON3 between the two groups (p = 0.28, p = 0.90, respectively). PON2 and PON3 were down-regulated in IUGR. Antenatal steroid therapy had no effect on the expression mRNA in placentae of unexplained IUGR pregnancies compared to non-treated group. These results suggest that PON2, PON3 mRNA levels were not changed significantly in placentae of IUGR when compared to normal pregnant women.

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

    Science.gov (United States)

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

    2018-04-01

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

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

    Directory of Open Access Journals (Sweden)

    Keisuke Nagao

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

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

    Science.gov (United States)

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

    2009-12-31

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

  3. Effects of aerobic exercise and medical nutrition intervention on endothelial injury and placental blood perfusion in patients with preeclampsia

    Directory of Open Access Journals (Sweden)

    Zhen-Ju Zhang1

    2017-06-01

    Full Text Available Objective: To study the effects of aerobic exercise and medical nutrition intervention on endothelial injury and placental blood perfusion in patients with preeclampsia. Methods: 72 cases of patients diagnosed with preeclampsia in Department of Obstetrics and Gynecology of Zigong Third People’s Hospital between January 2013 and August 2016 were selected randomly divided into two groups, the observation group received aerobic exercise, medical nutrition combined with routine intervention, and the control group received routine intervention. Before and after intervention, serum endothelial injury markers were detected. After delivery, the expression of apoptosis molecules and the contents of stress molecules caused by hypoxia in placenta were detected. Results: After intervention, serum AnnexinV, vWF, ET-1 and oxLDL contents of both groups were lower than those before intervention while NO, PLGF and ABCA1 contents were higher than those before intervention and serum AnnexinV, vWF, ET-1 and oxLDL contents of observation group were lower than those of control group while NO, PLGF and ABCA1 contents were higher than those of control group; after delivery, Bax, Fas, FasL and Caspase-3 mRNA expression as well as MDA, AOPP, CHOP and GRP78 protein contents in placenta of observation group were lower than those of control group. Conclusion: Aerobic exercise and medical nutrition intervention can reduce the endothelial injury and improve the placental hypoxia of preeclampsia.

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

    African Journals Online (AJOL)

    2016-02-16

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

  5. Placental transfer and distribution of 241Am in the rat

    International Nuclear Information System (INIS)

    Hisamatsu, S.; Takizawa, Y.

    1983-01-01

    The placental transfer and distribution of 241 Am in the feto-placental system were studied in pregnant rats. Rats were injected intravenously with 241 Am citrate at 15 or 18 days of gestation. Groups injected at 15 days of gestation were sacrificed 2, 24, 48, or 120 hr after injection, and the group injected at 18 days was sacrificed 24 hr after. The radioactivities of 241 Am in fetus, fetal membrane, and placenta were determined, and its distribution in the feto-placental system was investigated by high-speed autoradiography using a silver-activated zinc sulfide-coated membrane as an intensifying screen. The deposition of 241 Am in feto-placenta units increased with the number of days of gestation. Results of autoradiography revealed that major deposition sites of 241 Am in the fetus are the skeleton and liver. Heavy deposition of 241 Am in the yolksac splanchnopleure and its existence in the exocoelom strongly suggest that the yolk sac placenta plays an important role in the placental transfer of this nuclide

  6. 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...

  7. Placental telomere shortening in stillbirth: a sign of premature senescence?

    Science.gov (United States)

    Ferrari, Francesca; Facchinetti, Fabio; Saade, George; Menon, Ramkumar

    2016-01-01

    The objective of this study is to investigate placental telomere shortening in unexplained stillbirths (SBs) as an indication of premature senescence. Placentas were collected from 42 unexplained SB (>22 weeks), 43 term and 15 preterm live births, at the Policlinico Hospital of Modena (Italy). DNA extracted from placentae was studied for telomere length by real time PCR. Standard curves were generated for telomere lengths from single copy gene amplifications using a reference DNA. The telomere length for each sample was derived based on the ratio of telomere length between the sample and single copy gene standard (T/S ratio). The mean ratio of placental telomere in term live births was 5.181 ± 3.841. A twofold decrease in telomere length was seen in SBs (over all 2.455 ± 1.239; p PTBs) (6.382 ± 5.525; p < 0.01), whereas SBs telomere length were similar to those of preterm premature rupture of membranes (pPROM) (3.296 ± 3.599; p = ns). Substantial reduction in telomere length in SBs is indicative of placental senescence. These data provide mechanistic insights that premature aging may lead to placental dysfunction as an initiator of fetal demise in unexplained SBs.

  8. Diverse Placental Pathologies as the Main Causes of Fetal Death

    NARCIS (Netherlands)

    Korteweg, Fleurisca J.; Erwich, Jan Jaap H. M.; Holm, Jozien P.; Ravise, Joke M.; van der Meer, Jan; Veeger, Nic J. G. M.; Timmer, Albertus; van der, Meer J.

    2009-01-01

    OBJECTIVE: To estimate the occurrence of placental causes of fetal death in relation to different gestational ages and their clinical manifestations during pregnancy. METHODS: In a prospective cohort study conducted from 2002 to 2006, we studied 750 couples with singleton intrauterine fetal death

  9. Incidental placental choriocarcinoma in a term pregnancy: a case report

    Directory of Open Access Journals (Sweden)

    Chung Christopher

    2008-10-01

    Full Text Available Abstract Introduction Gestational choriocarcinoma occurs in 1 in 40,000 pregnancies. Of all forms of gestational choriocarcinoma, placental choriocarcinoma is the most rare. Maternal choriocarcinoma is usually diagnosed in symptomatic patients with metastases. The incidental finding of a choriocarcinoma confined to the placenta with no evidence of dissemination to the mother, or infant is the least common scenario. Case presentation The patient is an 18 year-old Gravida 1 Para 1 African American female who delivered a viable 3641 g female infant at 39 weeks gestation. Her pregnancy course was complicated by gestational hypertension during the third trimester. Her placenta revealed intraplacental choriocarcinoma. She was then followed closely by the Gynecologic Oncology service with a weekly serum beta human chorionic gonadotropin value. Beta human chorionic gonadotropin values dropped from 3070 mIU/ml to less than 2 mIU/ml two months post partum. No chemotherapy was initiated. Metastasis was ruled out by chest x-ray and whole body computed tomography scan. To date, both mother and baby are well. Conclusion Due to the potential fatal outcome of placental choriocarcinoma, careful evaluation of both mother and infant after the diagnosis is made is important. The incidence of placental choriocarcinoma may actually be higher than expected since it is not routine practice to send placentas for pathological evaluation after a normal spontaneous delivery. The obstetrician, pathologist, and pediatrician should have an increased awareness of placental choriocarcinoma and its manifestations.

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

    Science.gov (United States)

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

    2014-06-01

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

  11. 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 ...

  12. Ultrasound predictors of placental invasion: the Placenta Accreta Index.

    Science.gov (United States)

    Rac, Martha W F; Dashe, Jodi S; Wells, C Edward; Moschos, Elysia; McIntire, Donald D; Twickler, Diane M

    2015-03-01

    We sought to apply a standardized evaluation of ultrasound parameters for the prediction of placental invasion in a high-risk population. This was a retrospective review of gravidas with ≥1 prior cesarean delivery who received an ultrasound diagnosis of placenta previa or low-lying placenta in the third trimester at our institution from 1997 through 2011. Sonographic images were reviewed by an investigator blinded to pregnancy outcome and sonography reports. Parameters assessed included loss of retroplacental clear zone, irregularity and width of uterine-bladder interface, smallest myometrial thickness, presence of lacunar spaces, and bridging vessels. Diagnosis of placental invasion was based on histologic confirmation. Statistical analyses were performed using linear logistic regression and multiparametric analyses to generate a predictive equation evaluated using a receiver operating characteristic curve. Of 184 gravidas who met inclusion criteria, 54 (29%) had invasion confirmed on hysterectomy specimen. All sonographic parameters were associated with placental invasion (P placental location, yielded an area under the curve of 0.87 (95% confidence interval, 0.80-0.95). Using logistic regression, a predictive equation was generated, termed the "Placenta Accreta Index." Each parameter was weighted to create a 9-point scale in which a score of 0-9 provided a probability of invasion that ranged from 2-96%, respectively. Assignment of the Placenta Accreta Index may be helpful in predicting individual patient risk for morbidly adherent placenta. Copyright © 2015 Elsevier Inc. All rights reserved.

  13. Predictors of neonatal outcome in early-onset placental dysfunction

    NARCIS (Netherlands)

    Baschat, Ahmet A.; Cosmi, Erich; Bilardo, Catarina M.; Wolf, Hans; Berg, Christoph; Rigano, Serena; Germer, Ute; Moyano, Dolores; Turan, Sifa; Hartung, John; Bhide, Amarnath; Müller, Thomas; Bower, Sarah; Nicolaides, Kypros H.; Thilaganathan, Baskaran; Gembruch, Ulrich; Ferrazzi, Enrico; Hecher, Kurt; Galan, Henry L.; Harman, Chris R.

    2007-01-01

    To identify specific estimates and predictors of neonatal morbidity and mortality in early onset fetal growth restriction due to placental dysfunction. Prospective multicenter study of prenatally diagnosed growth-restricted liveborn neonates of less than 33 weeks of gestational age. Relationships

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

    African Journals Online (AJOL)

    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 ...

  15. Extracellular tumor-related mRNA in plasma of lymphoma patients and survival implications.

    Directory of Open Access Journals (Sweden)

    Vanesa Garcia

    Full Text Available BACKGROUND: We studied anomalous extracellular mRNAs in plasma from patients with diffuse large B-cell lymphoma (DLBCL and their survival implications. mRNAs studied have been reported in the literature as markers of poor (BCL2, CCND2, MYC and favorable outcome (LMO2, BCL6, FN1 in tumors. These markers were also analyzed in lymphoma tissues to test possible associations with their presence in plasma. METHODOLOGY/PRINCIPAL FINDINGS: mRNA from 42 plasma samples and 12 tumors from patients with DLBCL was analyzed by real-time PCR. Samples post-treatment were studied. The immunohistochemistry of BCL2 and BCL6 was defined. Presence of circulating tumor cells was determined by analyzing the clonality of the immunoglobulin heavy-chain genes by PCR. In DLBCL, MYC mRNA was associated with short overall survival. mRNA targets with unfavorable outcome in tumors were associated with characteristics indicative of poor prognosis, with partial treatment response and with short progression-free survival in patients with complete response. In patients with low IPI score, unfavorable mRNA targets were related to shorter overall survival, partial response, high LDH levels and death. mRNA disappeared in post-treatment samples of patients with complete response, and persisted in those with partial response or death. No associations were found between circulating tumor cells and plasma mRNA. Absence of BCL6 protein in tumors was associated with presence of unfavorable plasma mRNA. CONCLUSIONS/SIGNIFICANCE: Through a non-invasive procedure, tumor-derived mRNAs can be obtained in plasma. mRNA detected in plasma did not proceed from circulating tumor cells. In our study, unfavorable targets in plasma were associated with poor prognosis in B-cell lymphomas, mainly MYC mRNA. Moreover, the unfavorable targets in plasma could help us to classify patients with poor outcome within the good prognosis group according to IPI.

  16. Analysis of the original causes of placental oxidative stress in normal pregnancy and pre-eclampsia: a hypothesis.

    Science.gov (United States)

    Yang, Xiang; Guo, Lili; Li, Huaifang; Chen, Xinliang; Tong, Xiaowen

    2012-07-01

    Pre-eclampsia (PE) and eclampsia remain enigmatic despite intensive research. Growing evidence suggests that placental oxidative stress (OS) is involved in the etiopathogenesis of pre-eclampsia. Reduced perfusion as a result of abnormal placentation was proposed to be responsible for placental OS in PE. However, placental OS was also observed in normal pregnancy. The exact differences and correlation of placental OS in PE and normal pregnancy remain elusive. In this review, we attempted to link both normal pregnancy and PE on the causes of placental OS and proposed a hypothesis that placental OS in normal pregnancy, plus the exploration of other placental and/or maternal factors, could provide a novel explanation of that in PE. We concluded that pregnancy, placental abnormality and preexisting maternal constitutional conditions are three principle factors that could contribute to placental OS in PE. The specific causes in each clinical case could be heterogeneous, which requires individual analysis.

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

    Directory of Open Access Journals (Sweden)

    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

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

    Science.gov (United States)

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

    2018-01-01

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

  19. Microwave circulator design

    CERN Document Server

    Linkhart, Douglas K

    2014-01-01

    Circulator design has advanced significantly since the first edition of this book was published 25 years ago. The objective of this second edition is to present theory, information, and design procedures that will enable microwave engineers and technicians to design and build circulators successfully. This resource contains a discussion of the various units used in the circulator design computations, as well as covers the theory of operation. This book presents numerous applications, giving microwave engineers new ideas about how to solve problems using circulators. Design examples are provided, which demonstrate how to apply the information to real-world design tasks.

  20. Effects of maternal smoking on the placental expression of genes related to angiogenesis and apoptosis during the first trimester.

    Directory of Open Access Journals (Sweden)

    Akihiro Kawashima

    Full Text Available Maternal cigarette smoking is reportedly associated with miscarriage, fetal growth restriction and placental abruption, and is paradoxically associated with a decreased risk of developing preeclampsia. In the present study, we investigated the gene expression levels of villous tissues in early gestation. We compared the expression levels of the genes related to angiogenesis and apoptosis in the villous tissues obtained from smoking and non-smoking pregnant women.We collected villous tissue samples from 57 women requesting surgical termination due to non-medical reasons at 6-8 weeks of gestation. The maternal cigarette smoking status was evaluated by the level of serum cotinine and patients were divided into active smokers and non-smokers by the serum cotinine level. The placental levels of VEGFA, PGF, FLT1, HIF1A, TP53, BAX and BCL2 mRNA were quantified by real time PCR.The gene expression level of PGF and HIF1A in the active smoker group was significantly higher than that in the non-smoker group. We did not observe any significant differences in the VEGFA or FLT1 expression between the groups. In active smoker group, the gene expression levels of TP53 and BAX were significantly higher than those in the non-smoker group. The ratio of BAX/BCL2 mRNA in the active smoker group was significantly higher than that in the non-smoker group.Our findings revealed that smoking might affect the placenta during early pregnancy. Maternal cigarette smoking in early pregnancy may be associated with villus hypoxia, which may influence angiogenesis and apoptosis.

  1. Placentation in the colugos Cynocephalus volans and Galeopterus variegatus (Dermoptera) and the transition from labyrinthine to villous placentation in primates

    DEFF Research Database (Denmark)

    Carter, A. M.; Mess, A. M.

    2017-01-01

    Introduction Phylogenetics and genomics place colugos as the sister group to primates. Therefore their placentation is of interest in an evolutionary perspective. Previous accounts are fragmentary, not readily accessible and sometimes contradictory. Methods We have examined archival material...... placenta is intermediate between the labyrinthine placenta of rodents and the trabecular type of Neotropical primates....

  2. The importance of circulating tumor products as „liquid biopsies” in colorectal cancer

    Directory of Open Access Journals (Sweden)

    Alina Miscoci

    2018-04-01

    Full Text Available Liquid biopsies represent an array of plasma analysis tests that are studied to evaluate and identify circulating tumor products, especially circulating tumor cells (CTCs and circulating tumor DNA (ctDNA. Examining such biomarkers in the plasma of colorectal cancer patients has attracted attention due to its clinical significance in the treatment of malignant diseases. Given that tissue samples are sometimes challenging to procure or unsatisfactory for genomic profiling from patients with colorectal cancer, trustworthy biomarkers are mandatory for guiding treatment, monitoring therapeutic response, and detecting recurrence. This review considers the relevance of flowing tumor products like circulating tumor cells (CTCs, circulating tumor DNA (ctDNA, circulating messenger RNA (mRNA, circulating micro RNA (miRNA, circulating exosomes, and tumor educated platelets (TEPs for patients with colorectal cancer.

  3. Diagnostic comparison of malaria infection in peripheral blood, placental blood and placental biopsies in Cameroonian parturient women

    Directory of Open Access Journals (Sweden)

    Anchang-Kimbi Judith K

    2009-06-01

    Full Text Available Abstract Background In sub-Saharan Africa, Plasmodium falciparum malaria in pregnancy presents an enormous diagnostic challenge. The epidemiological and clinical relevance of the different types of malaria diagnosis as well as risk factors associated with malaria infection at delivery were investigated. Method In a cross-sectional survey, 306 women reporting for delivery in the Mutenegene maternity clinic, Fako division, South West province, Cameroon were screened for P. falciparum in peripheral blood, placental blood and placental tissue sections by microscopy. Information relating to the use of intermittent preventive treatment in pregnancy with sulphadoxine/pyrimethamine, history of fever attack, infant birth weights and maternal anaemia were recorded. Results Among these women, P. falciparum infection was detected in 5.6%, 25.5% and 60.5% of the cases in peripheral blood, placental blood and placental histological sections respectively. Placental histology was more sensitive (97.4% than placental blood film (41.5% and peripheral blood (8.0% microscopy. In multivariate analysis, age (≤ 20 years old (OR = 4.61, 95% CI = 1.47 – 14.70, history of fever attack (OR = 2.98, 95% CI = 1.58 – 5.73 were significant risk factors associated with microscopically detected parasitaemia. The use of ≥ 2 SP doses (OR = 0.18, 95% CI = 0.06 – 0.52 was associated with a significant reduction in the prevalence of microscopic parasitaemia at delivery. Age (>20 years (OR = 0.34, 95% CI = 0.15 – 0.75 was the only significant risk factor associated with parasitaemia diagnosed by histology only in univariate analysis. Microscopic parasitaemia (OR = 2.74, 95% CI = 1.33–5.62 was a significant risk factor for maternal anaemia at delivery, but neither infection detected by histology only, nor past infection were associated with increased risk of anaemia. Conclusion Placenta histological examination was the most sensitive indicator of malaria infection at

  4. Lower cerebrospinal fluid/plasma fibroblast growth factor 21 (FGF21 ratios and placental FGF21 production in gestational diabetes.

    Directory of Open Access Journals (Sweden)

    Bee K Tan

    Full Text Available OBJECTIVES: Circulating Fibroblast Growth Factor 21 (FGF21 levels are increased in insulin resistant states such as obesity, type 2 diabetes mellitus and gestational diabetes mellitus (GDM. In addition, GDM is associated with serious maternal and fetal complications. We sought to study human cerebrospinal fluid (CSF and corresponding circulating FGF21 levels in women with gestational diabetes mellitus (GDM and in age and BMI matched control subjects. We also assessed FGF21 secretion from GDM and control human placental explants. DESIGN: CSF and corresponding plasma FGF21 levels of 24 women were measured by ELISA [12 GDM (age: 26-47 years, BMI: 24.3-36.3 kg/m(2 and 12 controls (age: 22-40 years, BMI: 30.1-37.0 kg/m(2]. FGF21 levels in conditioned media were secretion from GDM and control human placental explants were also measured by ELISA. RESULTS: Glucose, HOMA-IR and circulating NEFA levels were significantly higher in women with GDM compared to control subjects. Plasma FGF21 levels were significantly higher in women with GDM compared to control subjects [234.3 (150.2-352.7 vs. 115.5 (60.5-188.7 pg/ml; P<0.05]. However, there was no significant difference in CSF FGF21 levels in women with GDM compared to control subjects. Interestingly, CSF/Plasma FGF21 ratio was significantly lower in women with GDM compared to control subjects [0.4 (0.3-0.6 vs. 0.8 (0.5-1.6; P<0.05]. FGF21 secretion into conditioned media was significantly lower in human placental explants from women with GDM compared to control subjects (P<0.05. CONCLUSIONS: The central actions of FGF21 in GDM subjects maybe pivotal in the pathogenesis of insulin resistance in GDM subjects. The significance of FGF21 produced by the placenta remains uncharted and maybe crucial in our understanding of the patho-physiology of GDM and its associated maternal and fetal complications. Future research should seek to elucidate these points.

  5. A novel glutamine-rich putative transcriptional adaptor protein (TIG-1), preferentially expressed in placental and bone-marrow tissues.

    Science.gov (United States)

    Abraham, S; Solomon, W B

    2000-09-19

    We used a subtractive hybridization protocol to identify novel expressed sequence tags (ESTs) corresponding to mRNAs whose expression was induced upon exposure of the human leukemia cell line K562 to the phorbol ester 12-O-tetradecanolyphorbol-13-acetate (TPA). The complete open reading frame of one of the novel ESTs, named TIG-1, was obtained by screening K562 cell and placental cDNA libraries. The deduced open reading frame of the TIG-1 cDNA encodes for a glutamine repeat-rich protein with a predicted molecular weight of 63kDa. The predicted open reading frame also contains a consensus bipartite nuclear localization signal, though no specific DNA-binding domain is found. The corresponding TIG-1 mRNA is ubiquitously expressed. Placental tissue expresses the TIG-1 mRNA 200 times more than the lowest expressing tissues such as kidney and lung. There is also preferential TIG-1 mRNA expression in cells of bone-marrow lineage.In-vitro transcription/translation of the TIG-1 cDNA yielded a polypeptide with an apparent molecular weight of 97kDa. Using polyclonal antibodies obtained from a rabbit immunized with the carboxy-terminal portion of bacterially expressed TIG-1 protein, a polypeptide with molecular weight of 97kDa was identified by Western blot analyses of protein lysates obtained from K562 cells. Cotransfection assays of K562 cells, using a GAL4-TIG-1 fusion gene and GAL4 operator-CAT, indicate that the TIG-1 protein may have transcriptional regulatory activity when tethered to DNA. We hypothesize that this novel glutamine-rich protein participates in a protein complex that regulates gene transcription. It has been demonstrated by Naar et al. (Naar, A.M., Beaurang, P.A., Zhou, S., Abraham, S., Solomon, W.B., Tjian, R., 1999, Composite co-activator ARC mediates chromatin-directed transcriptional activation. Nature 398, 828-830) that the amino acid sequences of peptide fragments obtained from a polypeptide found in a complex of proteins that alters chromatin

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

    International Nuclear Information System (INIS)

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

    2013-01-01

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

  7. Placental Growth Factor Promotes Ovarian Cancer Cell Invasion via ZEB2

    Directory of Open Access Journals (Sweden)

    Ning Song

    2016-01-01

    Full Text Available Background/Aims: The aggressive manner of ovarian cancer (OVC cells accounts for the majority of its lethality. Recently, we have shown that placental growth factor (PLGF promotes metastases of OVC cells through miR-543-regulated MMP7. In the current study, we analyzed the effects of PLGF on another cell invasion associated protein, ZEB2, in OVC cells. Methods: The PLGF and ZEB2 levels in OVC tissues were compared to the paired adjacent non-tumor ovary tissue. We modified ZEB2 levels in OVC cells, and examined its effects on PLGF mRNA and protein levels by RT-qPCR and by Western blot, respectively. We also modified PLGF levels in OVC cells, and examined its effects on ZEB2 mRNA and protein levels by RT-qPCR and by Western blot, respectively. Then, we examined the cell invasiveness in PLGF-modified OVC cells in a transwell cell invasion assay. Finally, we used specific signal pathway inhibitors to treat PLGF-modified OVC cells and examined the effects on ZEB2 activation. Results: PLGF and ZEB2 levels were both significantly increased in OVC tissues, compared to the paired adjacent non-tumor ovary tissue. The PLGF and ZEB2 levels were strongly correlated. ZEB2 modification did not alter PLGF levels. Overexpression of PLGF in OVC cells significantly increased ZEB2 levels and cell invasiveness, while PLGF depletion in OVC cells significantly decreased ZEB2 levels and cell invasiveness. Application of a specific MAPK-p38 inhibitor, but not application of specific inhibitors for MAPK-p42/p44, PI3k/Akt, or JNK signaling pathways, to PLGF-overexpressing OVC cells substantially abolished the PLGF-induced ZEB2 activation. Conclusion: PLGF enhances OVC cell invasion through MAPK-p38-dependent activation of ZEB2.

  8. Gestational exposure to titanium dioxide nanoparticles impairs the placentation through dysregulation of vascularization, proliferation and apoptosis in mice.

    Science.gov (United States)

    Zhang, Lu; Xie, Xingxing; Zhou, Yigang; Yu, Dainan; Deng, Yu; Ouyang, Jiexiu; Yang, Bei; Luo, Dan; Zhang, Dalei; Kuang, Haibin

    2018-01-01

    Titanium dioxide nanoparticles (TiO 2 NPs) have recently found applications in a wide variety of consumer goods. TiO 2 NPs exposure significantly increases fetal deformities and mortality. However, the potential toxicity of TiO 2 NPs on the growth and development of placenta has been rarely studied during mice pregnancy. The objective of this study was to investigate the effects of maternal exposure of TiO 2 NPs on the placentation. Mice were administered TiO 2 NPs by gavage at 0, 1 and 10 mg/kg/day from gestational day (GD) 1 to GD 13. Uteri and placentas from these mice were collected and counted the numbers of implanted and resorbed embryo and measured the placental weight on GD 13. Placental morphometry was observed by hematoxylin and eosin staining. The levels of Hand1, Esx1 , Eomes , Hand2 , Ascl2 and Fra1 mRNA were assessed by qRT-PCR. Uterine NK (uNK) cells were detected by using DBA lectin. Laminin immunohistochemical staining was to identify fetal vessels. Western blotting and transmission electron micrograph (TEM) were used to assess the apoptosis of placenta. No treatment-related difference was observed in the numbers of implanted and resorbed embryos and weight of placenta between the groups. However, 1 mg/kg/day TiO 2 NPs treatment significantly reduced the ratio of placenta/body weight on GD 13. The proportion of spongiotrophoblast in the 10 mg/kg/day dose group became higher than that in the control group, yet that of labyrinth was significantly lower in 10 mg/kg/day mice. The expression levels of Hand1 , Esx1 , Eomes , Hand2 , Ascl2 and Fra1 mRNA markedly decreased in TiO 2 NP treated placentas. Furthermore, TiO 2 NPs treatment impaired the formation of intricate networks of fetal vessels and reduced the number of uNK cells, and inhibited proliferation and induced apoptosis of placenta by nuclear pyknosis, the activation of caspase-3 and upregulation of Bax protein and downregulation of Bcl-2 protein on GD 13. Gestational exposure to TiO 2 NPs

  9. Circulation pump mounting

    International Nuclear Information System (INIS)

    Skalicky, A.

    1976-01-01

    The suspension is described of nuclear reactor circulating pumps enabling their dilatation with a minimum reverse force consisting of spacing rods supported with one end in the anchor joints and provided with springs and screw joints engaging the circulating pump shoes. The spacing rods are equipped with side vibration dampers anchored in the shaft side wall and on the body of the circulating pump drive body. The negative reverse force F of the spacing rods is given by the relation F=Q/l.y, where Q is the weight of the circulating pump, l is the spatial distance between the shoe joints and anchor joints, and y is the deflection of the circulating pump vertical axis from the mean equilibrium position. The described suspension is advantageous in that that the reverse force for the deflection from the mean equilibrium position is minimal, dynamic behaviour is better, and construction costs are lower compared to suspension design used so far. (J.B.)

  10. The endogenous retroviral locus ERVWE1 is a bona fide gene involved in hominoid placental physiology

    Science.gov (United States)

    Mallet, François; Bouton, Olivier; Prudhomme, Sarah; Cheynet, Valérie; Oriol, Guy; Bonnaud, Bertrand; Lucotte, Gérard; Duret, Laurent; Mandrand, Bernard

    2004-01-01

    The definitive demonstration of a role for a recently acquired gene is a difficult task, requiring exhaustive genetic investigations and functional analysis. The situation is indeed much more complicated when facing multicopy gene families, because most or portions of the gene are conserved among the hundred copies of the family. This is the case for the ERVWE1 locus of the human endogenous retrovirus W family (HERV-W), which encodes an envelope glycoprotein (syncytin) likely involved in trophoblast differentiation. Here we describe, in 155 individuals, the positional conservation of this locus and the preservation of the envelope ORF. Sequencing of the critical elements of the ERVWE1 provirus showed a striking conservation among the 48 alleles of 24 individuals, including the LTR elements involved in the transcriptional machinery, the splice sites involved in the maturation of subgenomic Env mRNA, and the Env ORF. The functionality and tissue specificity of the 5′ LTR were demonstrated, as well as the fusogenic activity of the envelope polymorphic variants. Such functions were also shown to be preserved in the orthologous loci isolated from chimpanzee, gorilla, orangutan, and gibbon. This functional preservation among humans and during evolution strongly argued for the involvement of this recently acquired retroviral envelope glycoprotein in hominoid placental physiology. PMID:14757826

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

    Science.gov (United States)

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

    2017-07-01

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

  12. 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.

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

    Directory of Open Access Journals (Sweden)

    Cécile Fanget

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

  14. Seasonal overturning circulation in the Red Sea: 2. Winter circulation

    KAUST Repository

    Yao, Fengchao; Hoteit, Ibrahim; Pratt, Lawrence J.; Bower, Amy S.; Kö hl, Armin; Gopalakrishnan, Ganesh; Rivas, David

    2014-01-01

    The shallow winter overturning circulation in the Red Sea is studied using a 50 year high-resolution MITgcm (MIT general circulation model) simulation with realistic atmospheric forcing. The overturning circulation for a typical year, represented

  15. Prenatal management and perinatal outcome in giant placental chorioangioma complicated with hydrops fetalis, fetal anemia and maternal mirror syndrome

    Directory of Open Access Journals (Sweden)

    García-Díaz Lutgardo

    2012-07-01

    Full Text Available Abstract Background Giant placental chorioangiomas have been associated with a number of severe fetal complications and high perinatal mortality. Case presentation We report a case of giant chorioangioma with fetal hydrops, additionally complicated by severe anemia, mild cardiomegaly with hyperdinamic heart circulation and maternal mirror syndrome. Intrauterine blood transfusion and amniodrainage was performed at 29 weeks. Worsening of the fetal and maternal condition prompted us to proceed with delivery at 29 + 5 weeks. The newborn died 3 hours later due to pulmonary hypoplasia and hemodynamic failure. Maternal course was favourable, mirror syndrome resolved in the second day and the patient was discharged four days following delivery. Conclusions In the case described here, fetal condition got worse despite of the anemia correction and amniodrainage. Our outcome raises the issue whether additional intrauterine clinical intervention, as intersticial laser, should have been performed to stop further deterioration of the fetal condition when progressive severe hydrops develops.

  16. 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.

  17. Placental transfer of the actinides and related heavy elements

    International Nuclear Information System (INIS)

    Sikov, M.R.

    1987-01-01

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

  18. Maternal Methadone Dose, Placental Methadone Concentrations, and Neonatal Outcomes

    Science.gov (United States)

    de Castro, Ana; Jones, Hendreé E.; Johnson, Rolley E.; Gray, Teresa R.; Shakleya, Diaa M.; Huestis, Marilyn A.

    2015-01-01

    BACKGROUND Few investigations have used placenta as an alternative matrix to detect in utero drug exposure, despite its availability at the time of birth and the large amount of sample. Methadone-maintained opioid-dependent pregnant women provide a unique opportunity to examine the placental disposition of methadone and metabolite [2-ethylidene-1,5-dimethyl-3,3-diphenylpyrrolidine (EDDP)], to explore their correlations with maternal methadone dose and neonatal outcomes, and to test the ability to detect in utero exposure to illicit drugs. METHODS We calculated the correlations of placental methadone and EDDP concentrations and their correlations with maternal methadone doses and neonatal outcomes. Cocaine- and opiate-positive placenta results were compared with the results for meconium samples and for urine samples collected throughout gestation. RESULTS Positive correlations were found between placental methadone and EDDP concentrations (r = 0.685), and between methadone concentration and methadone dose at delivery (r = 0.542), mean daily dose (r = 0.554), mean third-trimester dose (r = 0.591), and cumulative daily dose (r = 0.639). The EDDP/methadone concentration ratio was negatively correlated with cumulative daily dose (r = 0.541) and positively correlated with peak neonatal abstinence syndrome (NAS) score (r = 0.513). Placental EDDP concentration was negatively correlated with newborn head circumference (r = 0.579). Cocaine and opiate use was detected in far fewer placenta samples than in thrice-weekly urine and meconium samples, a result suggesting a short detection window for placenta. CONCLUSIONS Quantitative methadone and EDDP measurement may predict NAS severity. The placenta reflects in utero drug exposure for a shorter time than meconium but may be useful when meconium is unavailable or if documentation of recent exposure is needed. PMID:21245372

  19. 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.

  20. In vitro placental model optimization for nanoparticle transport studies

    DEFF Research Database (Denmark)

    Cartwright, Laura; Poulsen, Marie Sønnegaard; Nielsen, Hanne Mørck

    2012-01-01

    Background: 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...... 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...

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

    DEFF Research Database (Denmark)

    Carter, Anthony Michael

    2008-01-01

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

  2. Predisposing Factors to Abnormal First Trimester Placentation and the Impact on Fetal Outcomes

    Science.gov (United States)

    Kroener, Lindsay; Wang, Erica T.; Pisarska, Margareta D.

    2016-01-01

    Normal placentation during the first trimester sets the stage for the rest of pregnancy and involves a finely orchestrated cellular and molecular interplay of maternal and fetal tissues. The resulting intrauterine environment plays an important role in fetal programming and the future health of the fetus, and is impacted by multiple genetic and epigenetic factors. Abnormalities in placentation and spiral artery invasion can lead to ischemia, placental disease and adverse obstetrical outcomes including preeclampsia, intrauterine growth restriction, and placental abruption. Although first trimester placentation is affected my multiple factors, preconception environmental influences such as mode of conception, including assisted reproductive technologies which result in fertilization in vitro and intrauterine influences due to sex differences are emerging as potential significant factors impacting first trimester placentation. PMID:26696276

  3. Circulating microparticles: square the circle

    Science.gov (United States)

    2013-01-01

    Background The present review summarizes current knowledge about microparticles (MPs) and provides a systematic overview of last 20 years of research on circulating MPs, with particular focus on their clinical relevance. Results MPs are a heterogeneous population of cell-derived vesicles, with sizes ranging between 50 and 1000 nm. MPs are capable of transferring peptides, proteins, lipid components, microRNA, mRNA, and DNA from one cell to another without direct cell-to-cell contact. Growing evidence suggests that MPs present in peripheral blood and body fluids contribute to the development and progression of cancer, and are of pathophysiological relevance for autoimmune, inflammatory, infectious, cardiovascular, hematological, and other diseases. MPs have large diagnostic potential as biomarkers; however, due to current technological limitations in purification of MPs and an absence of standardized methods of MP detection, challenges remain in validating the potential of MPs as a non-invasive and early diagnostic platform. Conclusions Improvements in the effective deciphering of MP molecular signatures will be critical not only for diagnostics, but also for the evaluation of treatment regimens and predicting disease outcomes. PMID:23607880

  4. Effects of 60Co administration on early placental cells

    International Nuclear Information System (INIS)

    Honda, Jin

    1979-01-01

    The effects of 60 Co administration on early placental cells were studied. Placental tissue and embryo obtained by induced abortion (6 - 13 weeks gestational age) were placed in the minimal essential medium (MEM) and irradiated with various doses of 60 Co. After irradiation, the villi were cultured in a CO 2 incubater at 37 0 C. Cell growth process was observed every day with the phase-contrast microscope. Between 1 and 5 days epitheloid cells were dominant, but from about 7th day on fibroblastic cells dominated the culture. In placental tissue irradiated with 100, 200, 500 rad, fibroblastic cells began to grow earlier than in non-treated. Over 3000 rad 60 Co inhibited the growth of cells and a culture was impossible. For each dose, the tissue was incubated for various periods of time, exposed to tritiated thymidine for the last hour and autoradiogram was prepared by the dipping method. The labeling index of irradiated trophoblasts showed a significant decrease compared with controls. A chromosome study was made in irradiated in vitro cell lines of fetus and placenta. There was no significant difference between the two cell lines concerning the frequency of chromosome aberration, which tended to increase as the chromosome becomes longer. It is concluded that the trophoblast is highly radiosensitive and that irradiation early in pregnancy may damage DNA synthesis in the trophoblast, and induce abortion. (author)

  5. Identification of Novel Placentally Expressed Aspartic Proteinase in Humans

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    Marta Majewska

    2017-06-01

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

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

    Science.gov (United States)

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

    2014-06-01

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

  7. Placental Transfusion and Cardiovascular Instability in the Preterm Infant

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    Zbynĕk Straňák

    2018-02-01

    Full Text Available Postnatal adaptation in preterm newborn comprises complex physiological processes that involve significant changes in the circulatory and respiratory system. Increasing hemoglobin level and blood volume following placental transfusion may be of importance in enhancing arterial oxygen content, increasing cardiac output, and improving oxygen delivery. The European consensus on resuscitation of preterm infants recommends delayed cord clamping (DCC for at least 60 s to promote placenta–fetal transfusion in uncompromised neonates. Recently, published meta-analyses suggest that DCC is associated with fewer infants requiring transfusions for anemia, a lower incidence of intraventricular hemorrhage, and lower risk for necrotizing enterocolitis. Umbilical cord milking (UCM has the potential to avoid some disadvantages associated with DCC including the increased risk of hypothermia or delay in commencing manual ventilation. UCM represents an active form of blood transfer from placenta to neonate and may have some advantages over DCC. Moreover, both methods are associated with improvement in hemodynamic parameters and blood pressure within first hours after delivery compared to immediate cord clamping. Placental transfusion appears to be beneficial for the preterm uncompromised infant. Further studies are needed to evaluate simultaneous placental transfusion with resuscitation of deteriorating neonates. It would be of great interest for future research to investigate advantages of this approach further and to assess its impact on neonatal outcomes, particularly in extremely preterm infants.

  8. 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.

  9. 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.

  10. 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.

  11. Placental transport of radionuclides. Terminal report, May 1, 1973--July 31, 1975

    International Nuclear Information System (INIS)

    Kronfeld, D.S.

    1977-08-01

    Four successful experiments were conducted with tritiated water on pregnant sheep. This came into equilibrium between fetal and maternal circulations within 60 seconds after injection into the ewe or the fetus. The estimates of total water transport rate averaged 85% of the daily water intake. Six successful experiments were conducted with 3 H- and 14 C-glucose on pregnant ewes. The results for glucose space and transport rate in the ewes agree closely with previously published data. The fetal glucose pool size was large, presumably reflecting the relatively large volume of fetal-placental fluids in exchange with fetal blood. Six successful experiments were conducted with 45 Ca and 47 Ca for 5 days or more on pregnant ewes. The smallest compartment size of exchangeable calcium in mother and fetus were about 2 to 6 hours duration, and the net daily gain of calcium by the fetus was just slightly less in the chronic than in the acute experiments, 0.75 and 0.83 g/day respectively

  12. Stillbirth evaluation: a stepwise assessment of placental pathology and autopsy.

    Science.gov (United States)

    Miller, Emily S; Minturn, Lucy; Linn, Rebecca; Weese-Mayer, Debra E; Ernst, Linda M

    2016-01-01

    The American Congress of Obstetricians and Gynecologists places special emphasis on autopsy as one of the most important tests for evaluation of stillbirth. Despite a recommendation of an autopsy, many families will decline the autopsy based on religious/cultural beliefs, fear of additional suffering for the child, or belief that no additional information will be obtained or of value. Further, many obstetric providers express a myriad of barriers limiting their recommendation for a perinatal autopsy despite their understanding of its value. Consequently, perinatal autopsy rates have been declining. Without the information provided by an autopsy, many women are left with unanswered questions regarding cause of death for their fetus and without clear management strategies to reduce the risk of stillbirth in future pregnancies. To avoid this scenario, it is imperative that clinicians are knowledgeable about the benefit of autopsy so they can provide clear information on its diagnostic utility and decrease potential barriers; in so doing the obstetrician can ensure that each family has the necessary information to make an informed decision. We sought to quantify the contribution of placental pathologic examination and autopsy in identifying a cause of stillbirth and to identify how often clinical management is modified due to each result. This is a cohort study of all cases of stillbirth from 2009 through 2013 at a single tertiary care center. Records were reviewed in a stepwise manner: first the clinical history and laboratory results, then the placental pathologic evaluation, and finally the autopsy. At each step, a cause of death and the certainty of that etiology were coded. Clinical changes that would be recommended by information available at each step were also recorded. Among the 144 cases of stillbirth examined, 104 (72%) underwent autopsy and these cases constitute the cohort of study. The clinical and laboratory information alone identified a cause of death

  13. Creating a placental inflammatory composite index that has a high prognostic relevance to child morbidity.

    Science.gov (United States)

    Chen, Yan; Zou, Lile; Zhao, Yanjun; Wu, Ting; Ye, Jiangfeng; Zhang, Huijuan; Zhang, Jun

    2017-07-01

    Selecting pathologic measures of placental inflammation that affect pregnancy and childhood health is largely empirical. We aimed to systematically select several core inflammation-related placental measures to construct a novel placental inflammatory evaluation criterion with a high prognostic relevance to child morbidity. We used data from the US Collaborative Perinatal Project (1959-1976), a longitudinal birth cohort study that recruited women during pregnancy and followed the children until 7 years of age. Bootstrap resampling, least absolute shrinkage and selection operator, and receiver-operator curve were used to select placental pathologic measures that were closely related to child morbidity to form a placental inflammatory composite index. Twenty-six candidate placental inflammation-related measures were ranked based on their close association with adverse neonatal outcomes. The top five placental measures were: (i) neutrophilic infiltration in umbilical artery; (ii) placental weight-birthweight ratio; (iii) necrosis in decidua capsularis; (iv) bacterial colony in epithelium of amnion; and (v) opacity of membranes and fetal surface. Several composite indexes were constructed. A five-measure composite index that had the highest prognostic relevance was chosen. Compared with subjects without any of the five abnormal measures, those with any lesion ranging from 1 to 5 had a 1.2- to 4.6-fold risk of adverse child outcomes, respectively. Our composite index is simple, evidence-based, and has predictive value for child morbidity. It may be used as a novel placental inflammatory evaluation criterion. © 2017 Japan Society of Obstetrics and Gynecology.

  14. Identification of placental nutrient transporters associated with intrauterine growth restriction and pre-eclampsia.

    Science.gov (United States)

    Huang, Xiao; Anderle, Pascale; Hostettler, Lu; Baumann, Marc U; Surbek, Daniel V; Ontsouka, Edgar C; Albrecht, Christiane

    2018-03-02

    Gestational disorders such as intrauterine growth restriction (IUGR) and pre-eclampsia (PE) are main causes of poor perinatal outcomes worldwide. Both diseases are related with impaired materno-fetal nutrient transfer, but the crucial transport mechanisms underlying IUGR and PE are not fully elucidated. In this study, we aimed to identify membrane transporters highly associated with transplacental nutrient deficiencies in IUGR/PE. In silico analyses on the identification of differentially expressed nutrient transporters were conducted using seven eligible microarray datasets (from Gene Expression Omnibus), encompassing control and IUGR/PE placental samples. Thereby 46 out of 434 genes were identified as potentially interesting targets. They are involved in the fetal provision with amino acids, carbohydrates, lipids, vitamins and microelements. Targets of interest were clustered into a substrate-specific interaction network by using Search Tool for the Retrieval of Interacting Genes. The subsequent wet-lab validation was performed using quantitative RT-PCR on placentas from clinically well-characterized IUGR/PE patients (IUGR, n = 8; PE, n = 5; PE+IUGR, n = 10) and controls (term, n = 13; preterm, n = 7), followed by 2D-hierarchical heatmap generation. Statistical evaluation using Kruskal-Wallis tests was then applied to detect significantly different expression patterns, while scatter plot analysis indicated which transporters were predominantly influenced by IUGR or PE, or equally affected by both diseases. Identified by both methods, three overlapping targets, SLC7A7, SLC38A5 (amino acid transporters), and ABCA1 (cholesterol transporter), were further investigated at the protein level by western blotting. Protein analyses in total placental tissue lysates and membrane fractions isolated from disease and control placentas indicated an altered functional activity of those three nutrient transporters in IUGR/PE. Combining bioinformatic analysis

  15. Placental restriction of fetal growth reduces cutaneous responses to antigen after sensitization in sheep.

    Science.gov (United States)

    Wooldridge, Amy L; Bischof, Robert J; Meeusen, Els N; Liu, Hong; Heinemann, Gary K; Hunter, Damien S; Giles, Lynne C; Kind, Karen L; Owens, Julie A; Clifton, Vicki L; Gatford, Kathryn L

    2014-04-01

    Prenatal and early childhood exposures are implicated as causes of allergy, but the effects of intrauterine growth restriction on immune function and allergy are poorly defined. We therefore evaluated effects of experimental restriction of fetal growth on immune function and allergic sensitization in adolescent sheep. Immune function (circulating total red and white blood cells, neutrophils, lymphocytes, monocytes, eosinophils, and basophils, and the antibody response to Clostridial vaccination) and responses to house dust mite (HDM) allergen and ovalbumin (OVA) antigen sensitization (specific total Ig, IgG1, and IgE antibodies, and cutaneous hypersensitivity) were investigated in adolescent sheep from placentally restricted (PR, n = 23) and control (n = 40) pregnancies. Increases in circulating HDM-specific IgE (P = 0.007) and OVA-specific IgE (P = 0.038) were greater in PR than control progeny. PR did not alter total Ig, IgG1, or IgM responses to either antigen. PR increased OVA-specific but not HDM-specific IgA responses in females only (P = 0.023). Multiple birth increased Ig responses to OVA in a sex-specific manner. PR decreased the proportion of positive cutaneous hypersensitivity responders to OVA at 24 h (P = 0.030) but had no effect on cutaneous responses to HDM. Acute wheal responses to intradermal histamine correlated positively with birth weight in singletons (P = 0.023). Intrauterine growth restriction may suppress inflammatory responses in skin downstream of IgE induction, without impairment in antibody responses to a nonpolysaccharide vaccine. Discord between cutaneous and IgE responses following sensitization suggests new mechanisms for prenatal allergy programming.

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

    Energy Technology Data Exchange (ETDEWEB)

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

    2003-09-01

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

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

    Science.gov (United States)

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

    2016-02-01

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

  18. Interactions between the HIV-1 Unspliced mRNA and Host mRNA Decay Machineries

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    Daniela Toro-Ascuy

    2016-11-01

    Full Text Available The human immunodeficiency virus type-1 (HIV-1 unspliced transcript is used both as mRNA for the synthesis of structural proteins and as the packaged genome. Given the presence of retained introns and instability AU-rich sequences, this viral transcript is normally retained and degraded in the nucleus of host cells unless the viral protein REV is present. As such, the stability of the HIV-1 unspliced mRNA must be particularly controlled in the nucleus and the cytoplasm in order to ensure proper levels of this viral mRNA for translation and viral particle formation. During its journey, the HIV-1 unspliced mRNA assembles into highly specific messenger ribonucleoproteins (mRNPs containing many different host proteins, amongst which are well-known regulators of cytoplasmic mRNA decay pathways such as up-frameshift suppressor 1 homolog (UPF1, Staufen double-stranded RNA binding protein 1/2 (STAU1/2, or components of miRNA-induced silencing complex (miRISC and processing bodies (PBs. More recently, the HIV-1 unspliced mRNA was shown to contain N6-methyladenosine (m6A, allowing the recruitment of YTH N6-methyladenosine RNA binding protein 2 (YTHDF2, an m6A reader host protein involved in mRNA decay. Interestingly, these host proteins involved in mRNA decay were shown to play positive roles in viral gene expression and viral particle assembly, suggesting that HIV-1 interacts with mRNA decay components to successfully accomplish viral replication. This review summarizes the state of the art in terms of the interactions between HIV-1 unspliced mRNA and components of different host mRNA decay machineries.

  19. Association of chemerin mRNA expression in human epicardial adipose tissue with coronary atherosclerosis

    Directory of Open Access Journals (Sweden)

    Wang Linjie

    2011-10-01

    Full Text Available Abstract Background Growing evidence suggests that epicardial adipose tissue (EAT may play a key role in the pathogenesis and development of coronary artery disease (CAD by producing several inflammatory adipokines. Chemerin, a novel adipokine, has been reported to be involved in regulating immune responses and glucolipid metabolism. Given these properties, chemerin may provide an interesting link between obesity, inflammation and atherosclerosis. In this study, we sought to determine the relationship of chemerin expression in EAT and the severity of coronary atherosclerosis in Han Chinese patients. Methods Serums and adipose tissue biopsies (epicardial and thoracic subcutaneous were obtained from CAD (n = 37 and NCAD (n = 16 patients undergoing elective cardiac surgery. Gensini score was used to assess the severity of CAD. Serum levels of chemerin, adiponectin and insulin were measured by ELISA. Chemerin protein expression in adipose tissue was detected by immunohistochemistry. The mRNA levels of chemerin, chemR23, adiponectin and TNF-alpha in adipose tissue were detected by RT-PCR. Results We found that EAT of CAD group showed significantly higher levels of chemerin and TNF-alpha mRNA, and significantly lower level of adiponectin mRNA than that of NCAD patients. In CAD group, significantly higher levels of chemerin mRNA and protein were observed in EAT than in paired subcutaneous adipose tissue (SAT, whereas such significant difference was not found in NCAD group. Chemerin mRNA expression in EAT was positively correlated with Gensini score (r = 0.365, P P P P P P P > 0.05. Conclusions The expressions of chemerin mRNA and protein are significantly higher in EAT from patients with CAD in Han Chinese patients. Furthermore, the severity of coronary atherosclerosis is positive correlated with the level of chemerin mRNA in EAT rather than its circulating level.

  20. Self-amplifying mRNA vaccines.

    Science.gov (United States)

    Brito, Luis A; Kommareddy, Sushma; Maione, Domenico; Uematsu, Yasushi; Giovani, Cinzia; Berlanda Scorza, Francesco; Otten, Gillis R; Yu, Dong; Mandl, Christian W; Mason, Peter W; Dormitzer, Philip R; Ulmer, Jeffrey B; Geall, Andrew J

    2015-01-01

    This chapter provides a brief introduction to nucleic acid-based vaccines and recent research in developing self-amplifying mRNA vaccines. These vaccines promise the flexibility of plasmid DNA vaccines with enhanced immunogenicity and safety. The key to realizing the full potential of these vaccines is efficient delivery of nucleic acid to the cytoplasm of a cell, where it can amplify and express the encoded antigenic protein. The hydrophilicity and strong net negative charge of RNA impedes cellular uptake. To overcome this limitation, electrostatic complexation with cationic lipids or polymers and physical delivery using electroporation or ballistic particles to improve cellular uptake has been evaluated. This chapter highlights the rapid progress made in using nonviral delivery systems for RNA-based vaccines. Initial preclinical testing of self-amplifying mRNA vaccines has shown nonviral delivery to be capable of producing potent and robust innate and adaptive immune responses in small animals and nonhuman primates. Historically, the prospect of developing mRNA vaccines was uncertain due to concerns of mRNA instability and the feasibility of large-scale manufacturing. Today, these issues are no longer perceived as barriers in the widespread implementation of the technology. Currently, nonamplifying mRNA vaccines are under investigation in human clinical trials and can be produced at a sufficient quantity and quality to meet regulatory requirements. If the encouraging preclinical data with self-amplifying mRNA vaccines are matched by equivalently positive immunogenicity, potency, and tolerability in human trials, this platform could establish nucleic acid vaccines as a versatile new tool for human immunization. Copyright © 2015 Elsevier Inc. All rights reserved.

  1. Detection of suspected placental invasion by MRI: Do the results depend on observer’ experience?

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    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.

  2. Detection of suspected placental invasion by MRI: Do the results depend on observer’ experience?

    International Nuclear Information System (INIS)

    Alamo, Leonor; Anaye, Anass; Rey, Jannick; Denys, Alban; Bongartz, Georg; Terraz, Sylvain; Artemisia, Simona; Meuli, Reto; Schmidt, Sabine

    2013-01-01

    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 2 = 0.28), followed by focally interrupted myometrial border, infiltration of pelvic organs and tenting of the bladder (r 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

  3. Clinical significance of LUNX mRNA, CK19 mRNA, CEA mRNA expression in detecting micrometastasis from lung cancer

    International Nuclear Information System (INIS)

    Zhu Guangying; Liu Delin; Chen Jie

    2003-01-01

    Objective: To evaluate the sensitivity, specificity and clinical significance of CK19 mRNA, CEA mRNA and LUNX mRNA for detecting micrometastasis by sampling the peripheral blood and regional lymph nodes of lung cancer patients. Methods: Reverse transcriptase chain reaction (RT-PCR) was used to detect LUNX mRNA, CK19 mRNA, CEA mRNA for micrometastasis by sampling the peripheral blood of 48 lung cancer patients and 44 regional lymph nodes of such patients treated by curative resection. Peripheral blood of 30 patients with pulmonary benign lesions and 10 normal healthy volunteers and lymph nodes of 6 patients with benign pulmonary diseases served as control. Results: 1) LUNX mRNA, CK19 mRNA, CEA mRNA were expressed in all (35/35) lung cancer tissues. 2) In the peripheral blood from 48 lung cancer patients, 30 (62.5%) were positive for LUNX mRNA, 24 (50.0%) positive for CK19 mRNA and 32(66.7%) positive for CEA mRNA. The positive detection rates of micrometastasis in 44 lymph nodes from lung cancer patients were 36.4% (16 out of 44) for LUNX mRNA, 27.3% (12 out of 44) for CK19 mRNA and 40.9% (18 out of 44) for CEA mRNA. 3) In the 30 blood samples from patients with pulmonary benign diseases, 2 (6.7%) expressed CK19 mRNA, but none expressed LUNX mRNA or CEA mRNA. All the 3 molecular markers were negative in the 10 blood samples from healthy volunteers. In 11 lymph nodes from patients with pulmonary benign lesions, none was positive for any of the three markers. 4) In 44 regional lymph nodes from lung cancer patients, 6 (13.6%) were positive for metastasis by histopathological examination, with a positive rate significantly lower than that of the RT-PCR (P<0.05). 5) The micrometastatic positive rate in the peripheral blood of 40 non-small cell lung cancer (NSCLC) patients was significantly related to TNM stage (P=0.01). Conclusions: LUNX mRNA, CK19 MRNA, CEA mRNA are all appropriate target genes for the detection of micrometastasis from lung cancer. LUNX mRNA and CEA mRNA

  4. Let-7i-Induced Atg4B Suppression Is Essential for Autophagy of Placental Trophoblast in Preeclampsia.

    Science.gov (United States)

    Xu, Yinyan; Huang, Xinyan; Xie, Juan; Chen, Yanni; Fu, Jing; Wang, Li

    2017-09-01

    Autophagy, identified as type II programmed cell death, has already been known to be involved in the pathophysiology of preeclampsia (PE), which is a gestational disease with high morbidity. The present study aims to investigate the functional role of let-7i, a miRNA, in trophoblastic autophagy. Placental tissue used in this study was collected from patients with severe preeclampsia (SPE) or normal pregnant women. A decreased level of let-7i was found in placenta of SPE. In addition, autophagic vacuoles were observed in SPE and the expression of microtubule associated protein 1 light chain 3 (LC3) II/I was elevated. In vitro, let-7i mimics suppressed the autophagic activities in human HTR-8/SVneo trophoblast cell line (HTR-8) and human placental choriocarcinoma cell line JEG-3, whereas let-7i inhibitor enhanced the activities. As a potential target of let-7i, autophagy-related 4B cysteine peptidase (Atg4B) had an increased expression level in SPE. As expected, the increased expression of Atg4B was negatively regulated by let-7i using dual luciferase reporter assay. Furthermore, these trophoblast-like cells transfected with the let-7i mimic or inhibitors resulted in a significant change of Atg4B in both mRNA and protein level. More importantly, Atg4B overexpression could partly reverse let-7i mimic-reduced LC3II/I levels; whereas Atg4B silencing partly attenuated let-7i inhibitor-induced the level of LC3II/I expression. Taken together, these findings suggest that let-7i is able to regulate autophagic activity via regulating Atg4B expression, which might contribute to the pathogenesis of PE. J. Cell. Physiol. 232: 2581-2589, 2017. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

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

    DEFF Research Database (Denmark)

    Carlström, Mattias; Wentzel, Parri; Skøtt, Ole

    2009-01-01

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

  6. 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 ...

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

    Science.gov (United States)

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

    2017-08-29

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

  8. 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....

  9. 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

    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. A case control study was performed at the University

  10. Placental Malaria in Colombia: Histopathologic Findings in Plasmodium vivax and P. falciparum Infections

    Science.gov (United States)

    Carmona-Fonseca, Jaime; Arango, Eliana; Maestre, Amanda

    2013-01-01

    Studies on gestational malaria and placental malaria have been scarce in malaria-endemic areas of the Western Hemisphere. To describe the histopathology of placental malaria in Colombia, a longitudinal descriptive study was conducted. In this study, 179 placentas were studied by histologic analysis (112 with gestational malaria and 67 negative for malaria). Placental malaria was confirmed in 22.35%, 50.0% had previous infections, and 47.5% had acute infections. Typical malaria-associated changes were observed in 37%. The most common changes were villitis, intervillitis, deciduitis, increased fibrin deposition, increased syncytial knots, mononuclear (monocytes/macrophages and lymphocytes), polymorphonuclear cell infiltration, and trophozoites in fetal erythrocytes. No association was found between type of placental changes observed and histopathologic classification of placental malaria. The findings are consistent with those reported for placental malaria in other regions. Plasmodium vivax was the main parasite responsible for placental and gestational malaria, but its role in the pathogenesis of placental malaria was not conclusive. PMID:23546807

  11. A STUDY ON PLACENTAL MORPHOLOGY IN GESTATIONAL DIABETES

    Directory of Open Access Journals (Sweden)

    Katadi Venkata Sudha Madhuri

    2017-01-01

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

  12. A double antibody radioimmunoassay specific for placental alkaline phosphatase

    International Nuclear Information System (INIS)

    Dass, S.; Bagshawe, K.D.

    1984-01-01

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

  13. Extensive intron gain in the ancestor of placental mammals

    Science.gov (United States)

    2011-01-01

    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 reconstructing intron evolution. The

  14. Detection and clinical manifestation of placental malaria in southern Ghana

    Directory of Open Access Journals (Sweden)

    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.

  15. History of reptile placentology, part III: Giacomini's 1891 histological monograph on lizard placentation.

    Science.gov (United States)

    Blackburn, D G; Paulesu, L; Avanzati, A M; Roth, M

    2017-12-01

    By the 1890s, placental arrangements had been documented macroscopically in lizards and fishes, but placental studies on such species lagged far behind research on mammals. In 1891, the biologist Ercole Giacomini (at the University of Siena, Italy) published the first histological analysis of a reptile placenta. Focusing on a placentotrophic lizard (Chalcides chalcides) with a morphologically complex placenta, Giacomini documented the histological and cellular bases for placental nutrient transfer and gas exchange. In conjunction with a follow-up study in 1906, he demonstrated that placental structure is correlated with function and can vary dramatically between related species. Giacomini's work was highly influential in showing that placentation in lizards had converged evolutionarily on that of mammals, while establishing reptile placentology as a highly promising area for future research. Copyright © 2017 Elsevier Ltd. All rights reserved.

  16. The effect of Ramadan fasting and maternal hypoalbuminaemia on neonatal anthropometric parameters and placental weight.

    Science.gov (United States)

    Sakar, M N; Balsak, D; Verit, F F; Zebitay, A G; Buyuk, A; Akay, E; Turfan, M; Demir, S; Yayla, M

    2016-05-01

    In Islamic religion, daytime fasting during the month called Ramadan is an annual practice. In this study, we aimed to investigate the effect of Ramadan fasting and maternal hypoalbuminaemia on neonatal growth parameters. A prospective case-control study was conducted in Diyarbakir and Istanbul, Turkey. The sample size of fasting group was 168 and that of non-fasting group was 170. Demographic characteristics, obstetrics ultrasonographic findings and laboratory parameters of the participants were recorded. Neonatal anthropometric parameters and placental weight were noted. The mean placental weight was significantly higher in the fasting group (p = 0.037). Also, in the fasting group, pregnant women with hypoalbuminaemia had significantly higher placental weight (p = 0.009). In conclusion, the mean placental weight in the fasting group was significantly higher. Also a significant correlation between placental weight and maternal serum albumin level was observed in the fasting group.

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

    DEFF Research Database (Denmark)

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

    2016-01-01

    placental tissue. RESULTS: The ex vivo placental perfusion model was modified to study adhesion of infected erythrocytes binding to CSA, endothelial protein C receptor (EPCR) or a transgenic parasite where P. falciparum erythrocyte membrane protein 1 expression had been shut down. Infected erythrocytes......, such as binding to immunoglobulins. Furthermore, other parasite antigens have been associated with placental malaria. These findings have important implications for placental malaria vaccine design. The objective of this study was to adapt and describe a biologically relevant model of parasite adhesion in intact...... expressing VAR2CSA accumulated in perfused placental tissue whereas the EPCR binding and the transgenic parasite did not. Soluble CSA and antibodies specific against VAR2CSA inhibited binding of infected erythrocytes. CONCLUSION: The ex vivo model provides a novel way of studying receptor-ligand interactions...

  18. Protective antibodies against placental malaria and poor outcomes during pregnancy, Benin

    DEFF Research Database (Denmark)

    Ndam, Nicaise Tuikue; Denoeud-Ndam, Lise; Doritchamou, Justin

    2015-01-01

    Placental malaria is caused by Plasmodium falciparum-infected erythrocytes that bind to placental tissue. Binding is mediated by VAR2CSA, a parasite antigen coded by the var gene, which interacts with chondroitin sulfate A (CSA). Consequences include maternal anemia and fetal growth retardation....... Antibody-mediated immunity to placental malaria is acquired during successive pregnancies, but the target of VAR2CSA-specific protective antibodies is unclear. We assessed VAR2CSA-specific antibodies in pregnant women and analyzed their relationships with protection against placental infection, preterm...... birth, and low birthweight. Antibody responses to the N-terminal region of VAR2CSA during early pregnancy were associated with reduced risks for infections and low birthweight. Among women infected during pregnancy, an increase in CSA binding inhibition was associated with reduced risks for placental...

  19. Placental blood flow measurements with radioisotopes in the pregnant guinea pig

    International Nuclear Information System (INIS)

    Schmitt, R.; Giese, W.; Kurz, C.S.; Kuenzel, W.

    1976-01-01

    In 15 pregnant guinea pigs near term the blood flow (BF) of the myometrium and the placenta as well as the cardiac output were measured with 99 Tcsup(m)-labelled microspheres. In front of one placenta the clearance of 133 Xe was estimated in the same animal. For the 133 Xe measurement a theoretical concept is presented. The mean placental BF is 105ml/(minx100g)(SD:84) for 99 Tcsup(m) and 244(SD:80)ml/(minx100g) for 133 Xe. The difference in both flow values is assumed to be related to foetal placental BF. The placental blood flow is also related to the location of the placenta in the uterine horn. The ratio of myometrial blood flow to placental blood flow decreased with an increase in the mean arterial blood pressure. The measurements are a preliminary report of an attempt to compare two different methods in measuring placental blood flow. (author)

  20. Elevated utero/placental GR/NR3C1 is not required for the induction of parturition in the dog.

    Science.gov (United States)

    Gram, Aykut; Trachsel, Alexandra; Boos, Alois; Kowalewski, Mariusz P

    2016-10-01

    The endocrine mechanisms that lead to initiation of parturition in dogs are still not fully understood. The prepartum luteolysis is associated with increased prostaglandin (PG) F2α secretion; however, there is no pregnancy- or parturition-related increase in estrogens. Moreover, unlike in other mammalian species, in the dog, increased peripartum levels of cortisol measured sporadically in maternal peripheral blood are not mandatory for normal parturition. Nevertheless, auto/paracrine effects of cortisol at the placental feto-maternal level cannot be excluded. Therefore, the aim of this study was to investigate the expression and localization of glucocorticoid receptor (GR/NR3C1) in canine utero/placental (Ut/Pl) units and uterine interplacental sites at selected time points during pregnancy (pre-implantation, post-implantation and mid-gestation), and at normal and antigestagen-induced parturition. The Ut/Pl expression of GR/NR3C1 did not change significantly from pre-implantation until mid-gestation; however, it was strongly induced during the prepartum luteolysis. Within the interplacental samples, expression of GR/NR3C1-mRNA was greater post-implantation than pre-implantation and did not change afterward, i.e. toward mid-gestation. Compartmentalization studies within the Ut/Pl units, involving placenta, endometrium and myometrium separately, performed at the prepartum luteolysis revealed the highest GR/NR3C1-mRNA levels in placenta compared with endometrium and myometrium. Interestingly, in antigestagen-treated mid-pregnancy dogs, Ut/Pl and interplacental GR/NR3C1-mRNA expression remained unaffected. At the cellular level, placental GR/NR3C1 was clearly detectable in placenta fetalis, i.e. in trophoblast cells. In conclusion, increased expression of GR/NR3C1 during normal parturition, but not following antigestagen-treatment, suggest that it is not required for initiating the signaling cascade of PG synthesis leading to the induction of parturition in the dog.

  1. Epigenetic adaptation of the placental serotonin transporter gene (SLC6A4 to gestational diabetes mellitus.

    Directory of Open Access Journals (Sweden)

    Sofia Blazevic

    Full Text Available We tested the hypothesis that gestational diabetes mellitus (GDM alters the DNA methylation pattern of the fetal serotonin transporter gene (SLC6A4, and examined the functional relevance of DNA methylation for regulation of the SLC6A4 expression in the human placenta. The study included 50 mother-infant pairs. Eighteen mothers were diagnosed with GDM and 32 had normal glucose tolerance (NGT. All neonates were of normal birth weight and born at term by planned Cesarean section. DNA and RNA were isolated from samples of tissue collected from the fetal side of the placenta immediately after delivery. DNA methylation was quantified at 7 CpG sites within the SLC6A4 distal promoter region using PCR amplification of bisulfite treated DNA and subsequent DNA sequencing. SLC6A4 mRNA levels were measured by reverse transcription-quantitative PCR (RT-qPCR. Functional SLC6A4 polymorphisms (5HTTLPR, STin2, rs25531 were genotyped using standard PCR-based procedures. Average DNA methylation across the 7 analyzed loci was decreased in the GDM as compared to the NGT group (by 27.1%, p = 0.037 and negatively correlated, before and after adjustment for potential confounder/s, with maternal plasma glucose levels at the 24th to 28th week of gestation (p0.05. The results suggest that DNA methylation of the fetal SLC6A4 gene is sensitive to the maternal metabolic state in pregnancy. They also indicate a predominant role of epigenetic over genetic mechanisms in the regulation of SLC6A4 expression in the human placenta. Longitudinal studies in larger cohorts are needed to verify these results and determine to which degree placental SLC6A4 changes may contribute to long-term outcomes of infants exposed to GDM.

  2. Placental growth factor expression is reversed by antivascular endothelial growth factor therapy under hypoxic conditions.

    Science.gov (United States)

    Zhou, Ai-Yi; Bai, Yu-Jing; Zhao, Min; Yu, Wen-Zhen; Huang, Lv-Zhen; Li, Xiao-Xin

    2014-08-01

    Clinical trials have revealed that the antivascular endothelial growth factor (VEGF) therapies are effective in retinopathy of prematurity (ROP). But the low level of VEGF was necessary as a survival signal in healthy conditions, and endogenous placental growth factor (PIGF) is redundant for development. The purpose of this study was to elucidate the PIGF expression under hypoxia as well as the influence of anti-VEGF therapy on PIGF. CoCl2-induced hypoxic human umbilical vein endothelial cells (HUVECs) were used for an in vitro study, and oxygen-induced retinopathy (OIR) mice models were used for an in vivo study. The expression patterns of PIGF under hypoxic conditions and the influence of anti-VEGF therapy on PIGF were evaluated by quantitative reverse transcription-polymerase chain reaction (RTPCR). The retinal avascular areas and neovascularization (NV) areas of anti-VEGF, anti-PIGF and combination treatments were calculated. Retina PIGF concentration was evaluated by ELISA after treatment. The vasoactive effects of exogenous PIGF on HUVECs were investigated by proliferation and migration studies. PIGF mRNA expression was reduced by hypoxia in OIR mice, in HUVECs under hypoxia and anti-VEGF treatment. However, PIGF expression was reversed by anti-VEGF therapy in the OIR model and in HUVECs under hypoxia. Exogenous PIGF significantly inhibited HUVECs proliferation and migration under normal conditions, but it stimulated cell proliferation and migration under hypoxia. Anti-PIGF treatment was effective for neovascular tufts in OIR mice (P<0.05). The finding that PIGF expression is iatrogenically up-regulated by anti-VEGF therapy provides a consideration to combine it with anti-PIGF therapy.

  3. Arctic circulation regimes.

    Science.gov (United States)

    Proshutinsky, Andrey; Dukhovskoy, Dmitry; Timmermans, Mary-Louise; Krishfield, Richard; Bamber, Jonathan L

    2015-10-13

    Between 1948 and 1996, mean annual environmental parameters in the Arctic experienced a well-pronounced decadal variability with two basic circulation patterns: cyclonic and anticyclonic alternating at 5 to 7 year intervals. During cyclonic regimes, low sea-level atmospheric pressure (SLP) dominated over the Arctic Ocean driving sea ice and the upper ocean counterclockwise; the Arctic atmosphere was relatively warm and humid, and freshwater flux from the Arctic Ocean towards the subarctic seas was intensified. By contrast, during anticylonic circulation regimes, high SLP dominated driving sea ice and the upper ocean clockwise. Meanwhile, the atmosphere was cold and dry and the freshwater flux from the Arctic to the subarctic seas was reduced. Since 1997, however, the Arctic system has been under the influence of an anticyclonic circulation regime (17 years) with a set of environmental parameters that are atypical for this regime. We discuss a hypothesis explaining the causes and mechanisms regulating the intensity and duration of Arctic circulation regimes, and speculate how changes in freshwater fluxes from the Arctic Ocean and Greenland impact environmental conditions and interrupt their decadal variability. © 2015 The Authors.

  4. Plasma levels and placental expression of vaspin in pregnant women with diabetes mellitus

    Directory of Open Access Journals (Sweden)

    Y. Huo

    2015-03-01

    Full Text Available The present study aimed to investigate visceral adipose tissue-specific serpin (vaspin concentrations in serum and term placentas and relate these values to insulin resistance and lipid parameters in women with gestational diabetes mellitus (GDM. A total of 30 GDM subjects and 27 age-matched pregnant women with normal glucose tolerance (NGT, control were included. Serum glucose, glycated hemoglobin (HbA1c, lipid profile, insulin, and vaspin were measured at the end of pregnancy, and homeostasis model of assessment-insulin resistance (HOMA-IR values were calculated. Vaspin mRNA and protein levels in placentas were measured by real-time fluorescence quantitative reverse transcription polymerase chain reaction (RT-qPCR and Western blotting, respectively. Serum vaspin levels were significantly lower in the GDM group than in controls (0.49±0.24 vs 0.83±0.27 ng/mL, respectively; P<0.01. Three days after delivery, serum vaspin levels were significantly decreased in subjects with GDM (0.36±0.13 vs 0.49±0.24 ng/mL, P<0.01. However, in the GDM group, serum vaspin levels were not correlated with the parameters evaluated. In contrast, in the control group, serum vaspin levels were positively correlated with triglycerides (TG; r=0.45, P=0.02 and very low-density lipoprotein cholesterol (VLDL-C; r=0.42, P=0.03. Placental mRNA vaspin (0.60±0.32 vs 0.68±0.32, P=0.46 and protein (0.30±0.08 vs 0.39±0.26; P=0.33 levels in the GDM group did not differ significantly from those in the control group, but were negatively correlated with neonatal birth weight in the GDM group (r=-0.48, P=0.03; r=-0.88; P<0.01. Our findings indicated that vaspin may be an important adipokine involved in carbohydrate and lipid metabolism and may also play a role in fetal development.

  5. Effects of Assisted Reproduction Technology on Placental Imprinted Gene Expression

    Science.gov (United States)

    Katagiri, Yukiko; Aoki, Chizu; Tamaki-Ishihara, Yuko; Fukuda, Yusuke; Kitamura, Mamoru; Matsue, Yoichi; So, Akiko; Morita, Mineto

    2010-01-01

    We used placental tissue to compare the imprinted gene expression of IGF2, H19, KCNQ1OT1, and CDKN1C of singletons conceived via assisted reproduction technology (ART) with that of spontaneously conceived (SC) singletons. Of 989 singletons examined (ART n = 65; SC n = 924), neonatal weight was significantly lower (P < .001) in the ART group than in the SC group, but placental weight showed no significant difference. Gene expression analyzed by real-time PCR was similar for both groups with appropriate-for-date (AFD) birth weight. H19 expression was suppressed in fetal growth retardation (FGR) cases in the ART and SC groups compared with AFD cases (P < .02 and P < .05, resp.). In contrast, CDKN1C expression was suppressed in FGR cases in the ART group (P < .01), while KCNQ1OT1 expression was hyperexpressed in FGR cases in the SC group (P < .05). As imprinted gene expression patterns differed between the ART and SC groups, we speculate that ART modifies epigenetic status even though the possibilities always exist. PMID:20706653

  6. Placental methylome analysis from a prospective autism study.

    Science.gov (United States)

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

    2016-01-01

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

  7. Plutonium content of human placental tissues after occupational exposure

    International Nuclear Information System (INIS)

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

    2003-01-01

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

  8. Impact of placental insufficiency on fetal skeletal muscle growth

    Science.gov (United States)

    Hay, William W.

    2016-01-01

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

  9. Plutonium content of human placental tissues after occupational exposure

    Energy Technology Data Exchange (ETDEWEB)

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

    2003-07-01

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

  10. Downregulation of placental S100P is associated with cadmium exposure in Guiyu, an e-waste recycling town in China

    Energy Technology Data Exchange (ETDEWEB)

    Zhang, Qingying; Zhou, Taimei [Department of Preventive Medicine, Shantou University Medical College, Shantou, Guangdong 515041 (China); Xu, Xijin; Guo, Yongyong [Analytic Cytology Laboratory, Shantou University Medical College, Shantou, Guangdong 515041 (China); Zhao, Zhiguo; Zhu, Min [Department of Preventive Medicine, Shantou University Medical College, Shantou, Guangdong 515041 (China); Li, Weiqiu [Analytic Cytology Laboratory, Shantou University Medical College, Shantou, Guangdong 515041 (China); Yi, Deqing [Department of Preventive Medicine, Shantou University Medical College, Shantou, Guangdong 515041 (China); Huo, Xia, E-mail: xhuo@stu.edu.cn [Analytic Cytology Laboratory, Shantou University Medical College, Shantou, Guangdong 515041 (China)

    2011-12-01

    Excessive release of heavy metals, especially cadmium (Cd) and lead (Pb), results from primitive electronic waste (e-waste) recycling activities in Guiyu, China, and has adverse effects on the health of local infants and pregnant women. We investigated the expression of placental S100P, a Ca{sup 2+}-binding protein, as a biological indicator of heavy-metal environmental pollution in pregnant women involved in these activities and constantly exposed to Cd and Pb. We included 105 pregnant women in the study: 55 from Guiyu and 50 from Shantou, an area not involved in e-waste recycling. The placental concentrations of Cd and Pb (PCCd, PCPb) after birth were measured by graphite-furnace atomic-absorption spectrometry. S100P mRNA expression was determined by semi-quantitative RT-PCR and real-time quantitative PCR. S100P protein expression was examined by western blot analysis and immunohistochemistry. The expression of metallothionein (MT), previously found upregulated after heavy metal contamination, was used for comparison. Placentas from Guiyu women showed 62.8% higher Cd concentrations, higher MT levels, and lower S100P protein levels than placentas from Shantou women. Furthermore, PCCd was negatively correlated with S100P protein expression and positively with MT expression, with no correlation between PCPb and S100P or MT expression. The PCCd-associated downregulation of S100P in placentas from Guiyu women suggests that S100P might be an effective biological indicator in the placental response to Cd toxicity in areas of e-waste recycling.

  11. Downregulation of placental S100P is associated with cadmium exposure in Guiyu, an e-waste recycling town in China

    International Nuclear Information System (INIS)

    Zhang, Qingying; Zhou, Taimei; Xu, Xijin; Guo, Yongyong; Zhao, Zhiguo; Zhu, Min; Li, Weiqiu; Yi, Deqing; Huo, Xia

    2011-01-01

    Excessive release of heavy metals, especially cadmium (Cd) and lead (Pb), results from primitive electronic waste (e-waste) recycling activities in Guiyu, China, and has adverse effects on the health of local infants and pregnant women. We investigated the expression of placental S100P, a Ca 2+ -binding protein, as a biological indicator of heavy-metal environmental pollution in pregnant women involved in these activities and constantly exposed to Cd and Pb. We included 105 pregnant women in the study: 55 from Guiyu and 50 from Shantou, an area not involved in e-waste recycling. The placental concentrations of Cd and Pb (PCCd, PCPb) after birth were measured by graphite-furnace atomic-absorption spectrometry. S100P mRNA expression was determined by semi-quantitative RT-PCR and real-time quantitative PCR. S100P protein expression was examined by western blot analysis and immunohistochemistry. The expression of metallothionein (MT), previously found upregulated after heavy metal contamination, was used for comparison. Placentas from Guiyu women showed 62.8% higher Cd concentrations, higher MT levels, and lower S100P protein levels than placentas from Shantou women. Furthermore, PCCd was negatively correlated with S100P protein expression and positively with MT expression, with no correlation between PCPb and S100P or MT expression. The PCCd-associated downregulation of S100P in placentas from Guiyu women suggests that S100P might be an effective biological indicator in the placental response to Cd toxicity in areas of e-waste recycling.

  12. Single-cell mRNA cytometry via sequence-specific nanoparticle clustering and trapping

    Science.gov (United States)

    Labib, Mahmoud; Mohamadi, Reza M.; Poudineh, Mahla; Ahmed, Sharif U.; Ivanov, Ivaylo; Huang, Ching-Lung; Moosavi, Maral; Sargent, Edward H.; Kelley, Shana O.

    2018-05-01

    Cell-to-cell variation in gene expression creates a need for techniques that can characterize expression at the level of individual cells. This is particularly true for rare circulating tumour cells, in which subtyping and drug resistance are of intense interest. Here we describe a method for cell analysis—single-cell mRNA cytometry—that enables the isolation of rare cells from whole blood as a function of target mRNA sequences. This approach uses two classes of magnetic particles that are labelled to selectively hybridize with different regions of the target mRNA. Hybridization leads to the formation of large magnetic clusters that remain localized within the cells of interest, thereby enabling the cells to be magnetically separated. Targeting specific intracellular mRNAs enablescirculating tumour cells to be distinguished from normal haematopoietic cells. No polymerase chain reaction amplification is required to determine RNA expression levels and genotype at the single-cell level, and minimal cell manipulation is required. To demonstrate this approach we use single-cell mRNA cytometry to detect clinically important sequences in prostate cancer specimens.

  13. Lactate production and absence of gluconeogenesis from placental transferred substrates in fetuses from fed and 48-H starved rats

    Energy Technology Data Exchange (ETDEWEB)

    Palacin, M.; Lasuncion, M.A.; Herrera, E.

    1987-07-01

    Fed and 48-h starved rats were infused on day 21.5 of gestation for 20 min through the left uterine artery with (U-/sup 14/C-)-D-glucose, (U-/sup 14/C)-glycerol, or (U-/sup 14/C)-L-alanine. The mother and fetuses from both uterine horns were processed separately for radioactivity measurements in plasma and liver. Differences in radioactivity values between fetuses from the left and the right sides are used as indexes of placental transference of the infused tracers prior to their distribution and transformation in the maternal circulation. After infusion of (U-/sup 14/C)-D-glucose, (U-/sup 14/C)-glycerol, or (U-/sup 14/C)-L-alanine, plasma radioactivity values and specific activities corresponding to the respective infused tracer appeared much higher in fetuses from the left than the right uterine side. Plasma /sup 14/C-lactate values also were higher in the left than the right fetuses indicating that fetoplacental structures produced lactate from those placentally transferred /sup 14/C-metabolites. No difference in plasma /sup 14/C-glucose between left and right uterine horn fetuses was observed after maternal infusion with either (U-/sup 14/C)-glycerol or (U-/sup 14/C)-L-alanine, either in fed or 48-h starved rats. In the mother both (U-/sup 14/C)-glycerol and (U-/sup 14/C)-L-alanine were efficiently converted to /sup 14/C-glucose, and this process was significantly enhanced with starvation. /sup 14/C-fatty acids present in fetal liver after maternal infusions with either (U-/sup 14/C)-D-glucose or (U-/sup 14/C)-glycerol were decreased by starvation whereas no fatty acid synthesis from (U-/sup 14/C)-L-alanine was detected.

  14. Maternal Serum Lipid, Estradiol, and Progesterone Levels in Pregnancy, and the Impact of Placental and Hepatic Pathologies

    Science.gov (United States)

    Pecks, U.; Rath, W.; Kleine-Eggebrecht, N.; Maass, N.; Voigt, F.; Goecke, T. W.; Mohaupt, M. G.; Escher, G.

    2016-01-01

    Objective: Lipids and steroid hormones are closely linked. While cholesterol is the substrate for (placental) steroid hormone synthesis, steroid hormones regulate hepatic lipid production. The aim of this study was to quantify circulating steroid hormones and lipid metabolites, and to characterize their interactions in normal and pathological pregnancies with a focus on hepatic and placental pathologies. Methods: A total of 216 serum samples were analyzed. Group A consisted of 32 patients with uncomplicated pregnancies who were analyzed at three different time-points in pregnancy (from the first through the third trimester) and once post partum. Group B consisted of 36 patients (24th to 42nd week of gestation) with pregnancy pathologies (IUGR n = 10, preeclampsia n = 13, HELLP n = 6, intrahepatic cholestasis n = 7) and 31 controls with uncomplicated pregnancies. Steroid profiles including estradiol, progesterone, and dehydroepiandrosterone were measured by GC-MS and compared with lipid concentrations. Results: In Group A, cholesterol and triglycerides correlated positively with estradiol (cholesterol ρ = 0.50, triglycerides ρ = 0.57) and progesterone (ρ = 0.49, ρ = 0.53) and negatively with dehydroepiandrosterone (ρ = − 0.47, ρ = − 0.38). Smoking during pregnancy affected estradiol concentrations, leading to lower levels in the third trimester compared to non-smoking patients (p < 0.05). In Group B, cholesterol levels were found to be lower in IUGR pregnancies and in patients with HELLP syndrome compared to controls (p < 0.05). Steroid hormone concentrations of estradiol (p < 0.05) and progesterone (p < 0.01) were lower in pregnancies with IUGR. Discussion: Lipid and steroid levels were affected most in IUGR pregnancies, while only minor changes in concentrations were observed for other pregnancy-related disorders. Each of the analyzed entities displayed specific changes. However, since the

  15. Associations of ACE Gene Insertion/Deletion Polymorphism, ACE Activity, and ACE mRNA Expression with Hypertension in a Chinese Population

    Science.gov (United States)

    He, Qingfang; Fan, Chunhong; Yu, Min; Wallar, Gina; Zhang, Zuo-Feng; Wang, Lixin; Zhang, Xinwei; Hu, Ruying

    2013-01-01

    Background The present study was designed to explore the association of angiotensin converting enzyme (ACE) gene insertion/deletion (I/D, rs4646994) polymorphism, plasma ACE activity, and circulating ACE mRNA expression with essential hypertension (EH) in a Chinese population. In addition, a new detection method for circulating ACE mRNA expression was explored. Methods The research was approved by the ethics committee of Zhejiang Provincial Center for Disease Prevention and Control. Written informed consent was obtained prior to the investigation. 221 hypertensives (cases) and 221 normotensives (controls) were interviewed, subjected to a physical examination, and provided blood for biochemical and genetic tests. The ACE mRNA expression was analyzed by real time fluorescent quantitative Reverse Transcription PCR (FQ-RT-PCR). We performed logistic regression to assess associations of ACE I/D genotypes, ACE activity, and ACE mRNA expression levels with hypertension. Results The results of the multivariate logistic regression analysis showed that the additive model (ID, DD versus II) of the ACE genotype revealed an association with hypertension with adjusted OR of 1.43(95% CI: 1.04-1.97), and ACE ID genotype with adjusted OR of 1.72(95% CI: 1.01-2.92), DD genotype with adjusted OR of 1.94(95% CI: 1.01-3.73), respectively. In addition, our data also indicate that plasma ACE activity (adjusted OR was 1.13(95% CI: 1.08-1.18)) was significantly related to hypertension. However, the plasma ACE mRNA expressions were not different between the cases and controls. Conclusion ACE I/D polymorphism and ACE activity revealed significant influence on hypertension, while circulating ACE mRNA expression was not important factors associated with hypertension in this Chinese population. The detection of circulating ACE mRNA expression by FQ-RT-PCR might be a useful method for early screening and monitoring of EH. PMID:24098401

  16. Controlled humidity gas circulators

    International Nuclear Information System (INIS)

    Gruner, S.M.

    1981-01-01

    A programmable circulator capable of regulating the humidity of a gas stream over a wide range of humidity is described. An optical dew-point hygrometer is used as a feedback element to control the addition or removal of water vapor. Typical regulation of the gas is to a dew-point temperature of +- 0.2 0 C and to an accuracy limited by the dew-point hygrometer

  17. Fluid circulation control device

    International Nuclear Information System (INIS)

    Benard, Henri; Henocque, Jean.

    1982-01-01

    Horizontal fluid circulation control device, of the type having a pivoting flap. This device is intended for being fitted in the pipes of hydraulic installation, particularly in a bleed and venting system of a nuclear power station shifting radioactive or contaminated liquids. The characteristic of this device is the cut-out at the top of the flap to allow the air contained in the pipes to flow freely [fr

  18. Molecular evolution of adiponectin in Carnivora and its mRNA expression in relation to hepatic lipidosis.

    Science.gov (United States)

    Nieminen, Petteri; Rouvinen-Watt, Kirsti; Kapiainen, Suvi; Harris, Lora; Mustonen, Anne-Mari

    2010-09-15

    Adiponectin is a novel adipocyte-derived hormone with low circulating concentrations and/or mRNA expression in obesity and non-alcoholic fatty liver disease (NAFLD). The adiponectin mRNA of several Carnivora species was sequenced to enable further gene expression studies in this clade with potential experimental species to examine the connections of hypoadiponectinemia to hepatic lipidosis. In addition, adiponectin mRNA expression was studied in the retroperitoneal fat of the American mink (Neovison vison), as hepatic lipidosis with close similarities to NAFLD can be rapidly induced to the species by fasting. The mRNA expression was determined after overnight-7d of food deprivation and 28d of re-feeding and correlated to the liver fat %. The homologies between the determined carnivoran mRNA sequences and that of the domestic dog were 92.2-99.1%. As the mRNA expression was not affected by short-term fasting and did not correlate with the liver fat %, there seems to be no clear connection between adiponectin and the development of lipidosis in the American mink. In the future, the obtained sequences can be utilized in further studies of adiponectin expression in comparative endocrinology. Copyright (c) 2010 Elsevier Inc. All rights reserved.

  19. Maternal passive smoking and its effect on maternal, neonatal and placental parameters.

    Science.gov (United States)

    Ramesh, K N; Vidyadaran, M K; Goh, Y M; Nasaruddin, A A; Jammal, A B E; Zainab, S

    2005-08-01

    A study was undertaken to 1) determine the effects of tobacco smoke exposure on maternal and neonatal weight and body mass index (BMI) and placental weight, volume and surface area and 2) establish any correlations between the placental surface area, volume and weight with maternal and neonatal body weight and BMI in mothers exposed to cigarette smoke. A total of 154 full-term placentae, 65 from mothers exposed to tobacco smoke and 89 from non-exposed mothers were collected from Kuala Lumpur Maternity Hospital. The placental surface area was determined using a stereological grid, the volume by Scherle's method and the weight by using an electronic weighing machine. In general there were no differences in maternal, placental and neonatal parameters between the exposed and non-exposed groups. However, there were significant correlations between placental weight with maternal weight and maternal BMI in both exposed (r = 0.315; p = 0.013) and (r = 0.265; p = 0.038), and non-exposed (r = 0.224; p = 0.035) and (r = 0.241; p = 0.023) mothers. It was also found that the maternal weight on admission correlated significantly with placental weight in both Malay (r = 0.405; p = 0.020) and Indian (r = 0.553; p = 0.050) passive smokers. Correcting the placental parameters for the maternal weight had no effect on the results.

  20. We can Diagnose it if we Consider it. Diagnostic Pitfall for Placenta: Placental Mesenchymal Dysplasia

    Directory of Open Access Journals (Sweden)

    Havva Serap TORU

    2018-01-01

    Full Text Available Placental mesenchymal dysplasia is an increasingly recognizable abnormality. Early cases have been confused with partial hydatidiform mole. Placental mesenchymal dysplasia is probably under-diagnosed because of being an unfamiliar clinical entity and also mistaken for gestational trophoblastic disease due to the similar sonographic findings of two entities. In this report, we describe the clinical, gross, and histopathological findings of placental mesenchymal dysplasia in two cases. The 33-week-preterm baby of a 26-year-old woman with cardiovascular disease and 342 gram placenta and the 19-week fetus with trisomy 21 of a 40 year-old woman were terminated. Macroscopically thick-walled vessels and microscopically hydropic villous with peripherally localized thick-walled vessels without trophoblastic cell proliferation were observed in both cases. These two cases represent a rare placental anomaly that is benign but it is challenging to distinguish placental mesenchymal dysplasia from an incomplete mole. Placental mesenchymal dysplasia should be included in the differential diagnosis of sonographic findings that show a normal appearing fetus and a placenta with cystic lesions. Placental mesenchymal dysplasia is associated with pregnancy-related hypertension. In conclusion, the most important point is “you can diagnose it if you consider it”.

  1. Placental Oxidative Status throughout Normal Gestation in Women with Uncomplicated Pregnancies

    Directory of Open Access Journals (Sweden)

    Jayasri Basu

    2015-01-01

    Full Text Available The effects of gestational age on placental oxidative balance throughout gestation were investigated in women with uncomplicated pregnancies. Placental tissues were obtained from normal pregnant women who delivered at term or underwent elective pregnancy termination at 6 to 23 + 6 weeks of pregnancy. Placental tissues were analyzed for total antioxidant capacity (TAC and lipid peroxide (malondialdehyde, MDA levels using commercially available kits. Two hundred and one placental tissues were analyzed and the mean ± SD MDA (pmol/mg tissue and TAC (µmol Trolox equivalent/mg tissue levels for first, second, and third trimester groups were 277.01 ± 204.66, 202.66 ± 185.05, and 176.97 ± 141.61, P < 0.004 and 498.62 ± 400.74, 454.90 ± 374.44, and 912.19 ± 586.21, P < 0.0001 by ANOVA, respectively. Our data reflects an increased oxidative stress in the placenta in the early phase of normal pregnancy. As pregnancy progressed, placental antioxidant protective mechanisms increased and lipid peroxidation markers decreased resulting in diminution in oxidative stress. Our findings provide a biochemical support to the concept of a hypoxic environment in early pregnancy. A decrease in placental oxidative stress in the second and third trimesters appears to be a physiological phenomenon of normal pregnancy. Deviations from this physiological phenomenon may result in placental-mediated disorders.

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

    International Nuclear Information System (INIS)

    Myllynen, Paeivi; Pienimaeki, Paeivi; Vaehaekangas, Kirsi

    2005-01-01

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

  3. Prevalence, pattern, and determinants of placental malaria in a population of southeastern Nigerian parturients.

    Science.gov (United States)

    Ezebialu, Ifeanyichukwu U; Eke, Ahizechukwu C; Ezeagwuna, Dorothy A; Nwachukwu, Chukwuemeka E; Ifediata, Francis; Ezebialu, Chinenye U

    2012-12-01

    Placental malaria is a complication of malaria in pregnancy and is associated with adverse outcomes. Its burden is highest in Sub-Saharan Africa, but despite this, data based on histological analysis are scarce from this region. Questionnaires administered by the researchers were used to obtain information from parturients at a university teaching hospital in southeastern Nigeria between April and November 2010. Maternal blood and placental blood were collected for analysis. Placental blocks were taken for histological analysis. Statistical analyses were done using SPSS v. 17. Three hundred and sixty-five placentas were analyzed, out of which 254 showed histological evidence of malaria parasitization, giving a prevalence of 69.6%. Of the 254 placentas, 23 (9.0%) showed active infection and 196 (77.2%) showed active-on-past infection, while 35 (13.8%) showed past infection. Rural residence, hemoglobin genotype AA, not receiving intermittent preventive treatment in pregnancy (IPTp), and not sleeping under insecticide-treated bed nets (ITN) were significantly associated with placental malaria. Placental parasite density was inversely related to parity. This study showed that the prevalence of placental malaria in southeastern Nigeria is high, and demonstrated that the mean parasite density was inversely related to parity. Significant factors associated with placental malaria were also identified. Appreciation of these significant factors will assist program managers in implementing the strategies for the prevention of malaria in pregnancy. Copyright © 2012 International Society for Infectious Diseases. All rights reserved.

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

    Science.gov (United States)

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

    2014-01-01

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

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

    International Nuclear Information System (INIS)

    Salgado, S.S.; Pathmeswaran, A.

    2008-01-01

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

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

    Directory of Open Access Journals (Sweden)

    Kei Takahashi

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

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

    Science.gov (United States)

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

    2009-08-01

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

  9. Pregnant women carrying female fetuses are at higher risk of placental malaria infection.

    Directory of Open Access Journals (Sweden)

    Ishag Adam

    Full Text Available The pathophysiology of the placental malaria is not fully understood. If there is a fetal sex-specific susceptibility to malaria infection, this might add to the previous knowledge on the immunology, endocrinology and pathophysiology of placental malaria infections.This study was conducted to assess whether the sex of the fetus was associated with placental malaria infections.A cross-sectional study was performed including a secondary analysis of a cohort of women who were investigated for prevalence and risk factors (including fetal sex for placental malaria in eastern Sudan. Placental histology was used to diagnose placental malaria infections.Among 339 women enrolled, the mean (SD age was 25.8 (6.7 years and parity was 2.7 (2.2. Among the new born babies, 157 (46.3% were male and 182 (53.7% were female. Five (1.5%, 9 (2.7% and 103 (30.4% of the 339 placentas had active, active-chronic, past-chronic malaria infection on histopathology examination respectively, while 222 (65.5% of them showed no malaria infection. Logistic regression analyses showed no associations between maternal age or parity and placental malaria infections. Women who have blood group O (OR = 1.95, 95% CI = 1.19-3.10; P = 0.007 and women who had female new born were at higher risk for placental malaria infections (OR = 2.55, 95% CI = 1.57-4.13; P< 0.001.Fetal gender may be a novel risk factor for placental malaria. In this work the female placentas were at higher risk for malaria infections than the male placentas.

  10. Arachidonic acid metabolism by bovine placental tissue during the last month of pregnancy

    International Nuclear Information System (INIS)

    Hoedemaker, M.; Weston, P.G.; Wagner, W.C.

    1991-01-01

    Conversion of tritiated arachidonic acid (AA) into metabolites of the cyclo- and lipoxygenase pathways by bovine fetal placental tissue (200 mg) and fetal plus maternal placental tissue (400 mg) of Days 255, 265, 275 of gestation and at parturition (n = 5) during a 30 min incubation was measured using reverse-phase high pressure liquid chromatography. Fetal placental tissue produced 13,14-dihydro-15-keto-prostaglandin E2 (PGEM) as the major metabolite, the synthesis of which increased from Day 265 to Day 275 and parturition by 150% and 475%, respectively. In tissues collected at parturition, PGE2 synthesis was also detected. On Day 275 and at parturition fetal placental tissue synthesized the metabolite 12-hydroxyheptadecatrienoic acid (HHT), and throughout the experimental period the lipoxygenase product 15-HETE was detected with synthesis rates increasing over time of gestation. In addition, an unidentified metabolite was regularly found in the radiochromatograms which eluted at 1 h and 1 min (U101), between HHT and 15-HETE. The synthesis of this metabolite decreased as pregnancy progressed. Furthermore, various other polar and nonpolar metabolites pooled under the heading UNID were eluted, the production of which increased over time of gestation. The presence of maternal placental tissue did not influence the synthesis of PGEM, 15-HETE and U101, but the production of HHT was decreased when maternal tissue was present. Also, as pregnancy progressed, maternal placental tissue seemed to contribute to the pool of unidentified metabolites. In conclusion, fetal placental tissue seems to be the major source of the AA metabolites when compared with maternal placental tissue, and AA metabolism by bovine placental tissue is markedly increased throughout the last month of pregnancy, suggesting a role for AA metabolites in mechanisms controlling parturition

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

    Science.gov (United States)

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

    2018-07-01

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

  12. Effect of placental malaria on birth weight of babies in Nnewi, Anambra state, Nigeria.

    Science.gov (United States)

    Oraneli, Boniface U; Okeke, Ogochukwu C; Ubachukwu, Patience O

    2013-03-01

    In malaria-endemic countries, one adverse consequence of placental malaria on infants is low birth weight (LBW) caused by intra-uterine growth retardation and pre-term delivery. The effect of placental malaria on birth weight of babies was investigated in Nnamdi Azikiwe University Teaching Hospital (NAUTH), Nnewi, Anambra state, Nigeria. Placental blood was collected from 364 women who gave birth in NAUTH. Thin and thick placental blood smears were made and checked for the presence of malaria parasites. Plasmodium falciparum antigen rapid kit was used to confirm the presence of P. falciparum. New-borns were weighed and classified as normal birth weight (≥2500 g) or LBW (<2500 g). Analysis of variance (ANOVA), Student's t and Pearson chi-square tests were used to compare means and percentages. Risk factors for LBW were also determined. Placental malaria was found in 55.2% (n = 201) of the women. Placental malaria was associated with gravidity while age was not. In all the age groups, primigravidae and secundigravidae were mostly infected. Women with placental malaria delivered more LBW babies (32.1%) than their uninfected counterparts (5.5%), with primigravidae having more LBW babies. Similarly, weight of babies born by infected women was significantly different from that of uninfected women (p <0.0001). In multivariate analysis, placental malaria was associated with LBW (OR 0.1, 95% CI 0.06-0.17, p <0.0001). The result suggests a high prevalence of placental malaria and its close association with LBW in pregnant women attending antenatal clinic in NAUTH. It was also found that the percentage of LBW was highest in primigravidae.

  13. Placental transfer and metabolism of 17 alpha-ethynylestradiol-17 beta and estradiol-17 beta in the rhesus monkey

    International Nuclear Information System (INIS)

    Slikker, W. Jr.; Bailey, J.R.; Newport, D.; Lipe, G.W.; Hill, D.E.

    1982-01-01

    The synthetic estrogen component of many oral contraceptives, 17 alpha-ethynylestradiol-17 beta (EE2) and the naturally occurring estrogen, estradiol-17 beta (E2) were studied in four pregnant rhesus monkeys (71% term: 108-121 days gestational age). Under ketamine anesthesia, catheters were implanted in the maternal femoral artery and fetal interplacental artery. After simultaneous i.v. administration of [ 3 H]EE2-[ 14 C]E2 to the maternal animal, serial blood samples were drawn from both mother and fetus. The estrogens and metabolites were identified and quantified by the comigration of radioactivity with reference standards in several high-performance liquid chromatography systems and subsequent selective enzyme hydrolysis of the conjugates. Only estrone (E1), E1 sulfate, EE2 and EE2-3 sulfate were observed in the fetal circulation, whereas the major radiolabeled compounds in the maternal circulation consisted of the above plus E2, E1 glucuronide and EE2-3 glucuronide. In order to determine whether the placenta could convert E2 to its metabolite E1, the placentas of three term rhesus monkeys were perfused in situ via the umbilical artery with 120 ml (15 ml/min) of Hanks' balanced salt solution (pH 7.4) containing [ 3 H]E2. High-performance liquid chromatographic analysis of umbilical vein samples revealed that 96% of the E2 was metabolized to E1. These studies indicate that the placenta can metabolize the potent naturally occurring estrogen E2 to the less potent E1. In contrast, the synthetic estrogen EE2 does not undergo this placental metabolic conversion and thus enters the fetal circulation as the parent compound

  14. Placental mesenchymal dysplasia and intrauterine fetal growth restriction with doppler velocimetry alterations - a case report

    Directory of Open Access Journals (Sweden)

    Paula Vendruscolo Tozatti

    2014-06-01

    Full Text Available Placental mesenchymal dysplasia (PMD is a rare placental abnormality. We report a case of PMD associated with intrauterine growth restriction (IUGR, which was diagnosed by an ultrasound scan during the second trimester of pregnancy. A 36-year-old primiparous woman with signs of placental chorioangioma was referred to our hospital at the 23th gestational week. An ultrasonography revealed a small-for-gestational-age fetus with a large multicystic placenta. A serial Doppler sonographic assessment of umbilical and uterine artery blood flow showed a compromised fetus. A female, small-for-gestational-age baby was delivered by c-section at 28 weeks, and PMD was histopathologically confirmed.

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

    DEFF Research Database (Denmark)

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

    2017-01-01

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

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

    Science.gov (United States)

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

    2016-01-01

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

  17. Nonimmune immunoglobulin binding and multiple adhesion characterize Plasmodium falciparum-infected erythrocytes of placental origin

    DEFF Research Database (Denmark)

    Rasti, Niloofar; Namusoke, Fatuma; Chêne, Arnaud

    2006-01-01

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

  18. Clinical values of AFP, GPC3 mRNA in peripheral blood for prediction of hepatocellular carcinoma recurrence following OLT: AFP, GPC3 mRNA for prediction of HCC.

    Science.gov (United States)

    Wang, Yuliang; Shen, Zhongyang; Zhu, Zhijun; Han, Ruifa; Huai, Mingsheng

    2011-03-01

    Hepatocellular carcinoma (HCC) is one of the most common malignancies worldwide. Annually, about 200,000 patients died of HCC in China. Liver transplantation (LT) holds great theoretical appeal in treating HCC. However, the high recurrence rate after transplantation is the most important limiting factor for long-term survival. To assess the value of alpha-fetoprotein (AFP) messenger RNA (mRNA), Glypican-3 (GPC3) mRNA-expressing cells in the peripheral blood (PB) for prediction of HCC recurrence following orthotopic liver transplantation (OLT). 29 patients with HCC who underwent OLT with a minimum clinical follow-up of 12 months were included in this retrospective study. We detected AFP mRNA, GPC3 mRNA-expressing cells in the PB by TaqMan real-time reverse transcriptase-polymerase chain reaction (RT-PCR), pre-, intra- and post-operatively. The early recurrence of patients was evaluated. 8 (28%), 15 (52%), and 9 (31%) patients had AFP mRNA detected pre-, intra-, and post-operatively, respectively. With 12 months of follow-up, HCC recurred in 7 (24%) patients. Univariate analysis revealed that positive pre- and post-operative AFP mRNA, TNM stage as well as vascular invasion were significant predictors for the HCC recurrence. Multivariate analysis revealed that being positive for AFP mRNA pre-operatively remained a significant risk factor for HCC recurrence after OLT. GPC3 mRNA was expressed in all PB samples. There was no significant difference in the expression levels of GPC3 mRNA between the HCC and control groups. There were no significant differences in GPC3 mRNA expression values between those patients with and without tumor recurrence. The pre-operative detection of circulating AFP mRNA-expressing cells could be a useful predictor for HCC recurrence following OLT. GPC3 mRNA-expressing cells in PB seem to have no diagnostic value.

  19. Stimulation of monocytes by placental microparticles involves Toll-like receptors and nuclear factor kappa-light-chain-enhancer of activated B cells

    Directory of Open Access Journals (Sweden)

    Marianne Simone Joerger-Messerli

    2014-04-01

    Full Text Available Human pregnancy is accompanied by a mild systemic inflammatory response, which includes the activation of monocytes circulating in maternal blood. This response is exaggerated in preeclampsia, a placental-dependent disorder specific to human pregnancies. We and others showed that placental syncytiotrophoblast membrane microparticles (STBM generated in vitro from normal placentas stimulated peripheral blood monocytes, which suggests a contribution of STBM to the systemic maternal inflammation. Here, we analyzed the inflammatory potential of STBM prepared from preeclamptic placentas on primary monocytes and investigated the mode of action in vitro.STBM generated in vitro by placental villous explants of normal or preeclamptic placentas were co-incubated with human peripheral blood monocytes. In some cases, inhibitors of specific cellular functions or signaling pathways were used. The analysis of the monocytic response was performed by flow cytometry, enzyme-linked immunoassays, real-time PCR and fluorescence microscopy.STBM derived from preeclamptic placentas up-regulated the cell surface expression of CD54, and stimulated the secretion of the pro-inflammatory interleukin (IL-6 and IL-8 in a similar, dose-dependent manner as did STBM prepared from normal placentas. STBM bound to the cell surface of monocytes, but phagocytosis was not necessary for activation. STBM-induced cytokine secretion was impaired in the presence of inhibitors of toll-like receptor (TLR signaling or when nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB activation was blocked.Our results suggest that the inflammatory reaction in monocytes may be initiated by the interaction of STBM with TLRs, which in turn signal through NF-κB to mediate the transcription of genes coding for pro-inflammatory factors.

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

    Science.gov (United States)

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

    2000-01-01

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

  1. Pathologic evaluation of normal and perfused term placental tissue

    DEFF Research Database (Denmark)

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

    2014-01-01

    This study reports for the 1st time the incidence and interobserver variation of morphologic findings in a series of 34 term placentas from pregnancies with normal outcome used for perfusion studies. Histologic evaluation of placental tissue is challenging, especially when it comes to defining...... "normal tissue" versus "pathologic lesions." A scoring system for registration of abnormal morphologic findings was developed. Light microscopic examination was performed independently by 2 pathologists, and interobserver variation was analyzed. Findings in normal and perfused tissue were compared...... and selected findings were tested against success parameters from the perfusions. Finally, the criteria for frequent lesions with fair to poor interobserver variation in the nonperfused tissue were revised and reanalyzed. In the perfused tissue, the perfusion artefact "trophoblastic vacuolization," which...

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

    DEFF Research Database (Denmark)

    Brøgger, Torbjørn; Forman, Axel; Aalkjær, Christian

    2014-01-01

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

  3. 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...... parallel arrays of labyrinthine structures converging on a central spongy zone. At mid gestation, the arrays were composed of an inner cellular and outer syncytial trophoblast layer, the inner layer enclosing scant connective tissue and fetal capillaries. Maternal blood spaces coursed through the outer...... trophoblast and were lined by trophoblastic microvilli; the blood spaces were narrow in mid gestation but enlarged near term, while the inner trophoblast layer became thinner and seemed to be syncytial. These features were confirmed by transmission electron microscopy. The microvillous surfaces and dispersed...

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

    Directory of Open Access Journals (Sweden)

    M. V. Tulikov

    2013-01-01

    Full Text Available Neoangiogenesis in coronary heart disease is a protective reaction aimed to improve ischemic myocardial perfusion, by increasing the number and size of arterial collaterals. Placental growth factor (PlGF is one of the key peptides regulating angiogenic processes in atherosclerosis. In particular, a number of investigators have shown that injection of recombinant PlGF into the system or regional blood flow can stimulate neoangiogenesis. On the other hand, there is evidence confirming the involvement of PlGF in the progression of atherosclerosis and in the development of acute coronary syndrome. In this connection, the problem of investigating the efficiency and safety of possible use of PlGF preparations, as well as its place in the diagnosis of coronary heart disease and acute coronary syndrome remains urgent

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

    Science.gov (United States)

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

    2012-10-01

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

  6. Placental Chemokine Receptor D6 Is Functionally Impaired in Pre-Eclampsia.

    Directory of Open Access Journals (Sweden)

    Chiara Tersigni

    Full Text Available Pre-eclampsia (PE is a major cause of maternal and perinatal morbidity and mortality worldwide. It is defined by new onset of hypertension and proteinuria after the 20th week of gestation and characterized by systemic exaggerated inflammatory response. D6 is a chemokines scavenger receptor that binds with high affinity CC chemokines, internalizes and targets the ligands for degradation. It is expressed in trophoblast-derived tissues and prevents excessive placenta leukocyte infiltration.The aim of this study was to investigate the expression and function of D6 in human placentae from pre-eclamptic and healthy pregnant women.Plasma levels of D6-binding CC chemokines (CCL-2, CCL-3, CCL-4, CCL-7, CCL-11 and pro-inflammatory cytokines (IL-6, TNF-α, CRP were analyzed in 37 healthy pregnant women and 38 patients with PE by multiplex bead assay. Higher circulating levels of CCL7, CCL11, IL-6, (p<0.0001 and CRP (p<0.05 were observed in PE women compared to controls. Levels of circulating CCL4 were decreased in PE (p<0.001, while no significant differences of CCL2, CCL3 or TNF-α levels were detected. Immunofluorescent staining of placental sections showed higher expression of D6 receptor in the PE syncytiotrophoblast. Confocal and Western blot (WB analyses revealed a prevalent distribution of D6 in trophoblast cells membranes in PE. Increased activation of D6 intracellular pathway was observed by Western blot analyses of p-LIMK and p-cofilin in trophoblast cell lysates. D6 functional assays showed reduced scavenging of CCL2 in PE cells compared to controls. Since actin filaments spatial assembling is essential for D6 intracellular trafficking and scavenging activity, we investigated by confocal microscopy trophoblast cytoskeleton organization and we observed a dramatic disarrangement in PE compared to controls.our results suggest membrane distribution of D6 receptor on trophoblast cell membranes in PE, together with reduced functionality, probably due

  7. mRNA processing in yeast

    International Nuclear Information System (INIS)

    Stevens, A.

    1982-01-01

    Investigations in this laboratory center on basic enzymatic reactions of RNA. Still undefined are reactions involved in the conversion of precursors of mRA (pre-mRNA) to mRNA in eukaryotes. The pre-mRNA is called heterogeneous nuclear RNA and is 2 to 6 times larger than mRNA. The conversion, called splicing, involves a removal of internal sequences called introns by endoribonuclease action followed by a rejoining of the 3'- and 5'-end fragments, called exons, by ligating activity. It has not been possible yet to study the enzymes involved in vitro. Also undefined are reactions involved in the turnover or discarding of certain of the pre-mRNA molecules. Yeast is a simple eukaryote and may be expected to have the same, but perhaps simpler, processing reactions as the higher eukaryotes. Two enzymes involved in the processing of pre-mRNA and mRNA in yeast are under investigation. Both enzymes have been partially purified from ribonucleoprotein particles of yeast. The first is a unique decapping enzyme which cleaves [ 3 H]m 7 Gppp [ 14 C]RNA-poly (A) of yeast, yielding [ 3 H]m 7 GDP and is suggested by the finding that the diphosphate product, m 7 GpppA(G), and UDP-glucose are not hydrolyzed. The second enzyme is an endoribonuclease which converts both the [ 3 H] and [ 14 C] labels of [ 3 H]m 7 Gppp[ 14 C]RNA-poly(A) from an oligo(dT)-cellulose bound form to an unbound, acid-insoluble form. Results show that the stimulation involves an interaction of the labeled RNA with the small nuclear RNA. The inhibition of the enzyme by ethidium bromide and its stimulation by small nuclear RNA suggest that it may be a processing ribonuclease, requiring specific double-stranded features in its substrate. The characterization of the unique decapping enzyme and endoribonuclease may help to understand reactions involved in the processing of pre-mRNA and mRNA in eukaryotes

  8. Effect of polybrominated diphenyl ether congeners on placental cytokine production.

    Science.gov (United States)

    Arita, Yuko; Yeh, Corinne; Thoma, Theodosia; Getahun, Darios; Menon, Ramkumar; Peltier, Morgan R

    2018-02-01

    Polybrominated diphenyl ethers (PBDEs) are pollutants that may increase the risk of preterm birth. In previous studies, we found that a mixture of PBDEs altered the expression of biomarkers for preterm birth by the placenta. However, there are 209 different PBDE congeners with different tissue distributions. How these different congeners may alter the production of immunomodulators by the placenta that help to maintain the survival of the fetal allograft is unclear. Therefore, we compared the effects 5 common congeners on basal and bacteria-stimulated cytokine production by the placenta. Placental explant cultures were incubated with 20 μM of PBDE congeners 47, 99, 100, 153, 209 or vehicle in the presence and absence of Escherichia coli for 20 h. Conditioned medium was harvested and concentrations of IL-1β, TNF-α, IL-6, sgp130, HO-1, IL-10, BDNF, and 8-IsoP quantified. For unstimulated cultures, all congeners, except for PBDE-47, reduced the production of IL-1β and IL-6 production was enhanced by PBDE-153. BDNF concentrations tended to be reduced by most PBDE congeners and IL-10 production was enhanced by PBDE-99, -153, and -209. 8-IsoP production was enhanced by PBDE-153, but not the other congeners. For bacteria-stimulated cultures, PBDE-47 increased IL-1β production and PBDE-47, -153, and -209 tended to reduce TNF-α production. IL-6 production was enhanced by all PBDEs except 153. IL-10 production was enhanced by all congeners except for PBDE-47. All congeners significantly enhanced BDNF and 8-IsoP. These results suggest that PBDEs can alter the expression of placental biomarkers in a congener and infection-dependent manner. Copyright © 2018 Elsevier B.V. All rights reserved.

  9. PLACENTAL INSUFFICIENCY IN PREGNANCY AFTER 40th WEEK OF GESTATION

    Directory of Open Access Journals (Sweden)

    Vladimir Antic

    2007-12-01

    Full Text Available Pregnancy after the 40th week of gestation is often a great dilemma for obstetrician in diagnostic, therapeutic and in psychological terms as well. The aim of this study was to confirm the phenomenon of placental insufficiency in pregnancy after the 40th gestation week, the modality of delivery and perinatal outcome.The study comprised 3405 deliveries in a period of one year, 391 of which were terminated after the end of the 40th gestation week, including healthy pregnant women with singleton pregnancies. Control group included healthy pregnant women delivered between the 37th and 40th gestation week.The incidence of deliveries after the 40th week of gestation is 11.48%. Non-stress test was reactive in 99.65% of women in the study group. At the same time, CST (constriction– stress test was assessed as negative in 78.67% of cases. The pathological CST was found in only 1.33% of cases. Doppler ultrasound measurements showed the increased resistance in umbilical artery flow in 3% of cases. Vacuum extraction was used for 16.62%of deliveries in the study group, and 8.73% of deliveries in the control group (χ2=23.24;p<0.001. In the study group, Caesarean section was performed in 14.58% of cases, and in control group in 9.07% (χ2=11.09; p<0.001.Placental insufficiency induced by duration of pregnancy is a rear phenomenon in uncompromised pregnancy. There was no significant difference in the morbidity and mortality rates between the study and control group.

  10. Engine and radiator: fetal and placental interactions for heat dissipation.

    Science.gov (United States)

    Schröder, H J; Power, G G

    1997-03-01

    The 'engine' of fetal metabolism generates heat (3-4 W kg-1 in fetal sheep) which has to be dissipated to the maternal organism. Fetal heat may move through the amniotic/allantoic fluids to the uterine wall (conductive pathway; total conductance, 1.1 W degrees C-1 kg-1) and with the umbilical arterial blood flow (convective pathway) to the placenta. Because resistance to heat flow is larger than zero fetal temperature exceeds maternal temperature by about 0.5 degree C (0.3-1 degree C). Probably 85% of fetal heat is lost to the maternal organism through the placenta, which thus serves as the main 'radiator'. Placental heat conductivity appears to be extremely high and this may lead to impaired heat exchange (guinea-pig placenta). A computer simulation demonstrates that fetal temperature is essentially clamped to maternal temperature, and that fetal thermoregulatory efforts to gain thermal independence would be futile. Indeed, when the late gestational fetus in utero is challenged by cold stress, direct and indirect indicators of (non-shivering) thermogenesis (oxygen consumption, increase of plasma glycerol and free fatty acid levels) change only moderately. In prematurely delivered lambs, however, cold stress provokes summit metabolism and maximum heat production. Only when birth is imitated in utero (by cord clamping, external artificial lung ventilation and cooling) do thermogenic efforts approach levels typical of extra-uterine life. This suggests the presence of inhibitors of thermogenesis of placental origin, e.g. prostaglandins and adenosine. When the synthesis of prostaglandins is blocked by pretreatment with indomethacin, sheep fetuses react to intra-uterine cooling with vigorous thermogenic responses, which can be subdued by infusion of prostaglandin E2 (PGE2). Since the sheep placenta is known to produce sufficient amounts of PGE2, it seems that the placenta controls fetal thermogenic responses to some extent. This transforms the fetus into an ectothermic

  11. Good practices in collecting umbilical cord and placental blood.

    Science.gov (United States)

    Lopes, Lauren Auer; Bernardino, Elizabeth; Crozeta, Karla; Guimarães, Paulo Ricardo Bittencourt

    2016-08-18

    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. 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). 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. 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. identificar fatores relacionados à qualidade das amostras do sangue de cordão umbilical e placentário e definir boas práticas para sua coleta em um banco público de sangue de cordão umbilical e placentário. pesquisa descritiva, abordagem quantitativa, realizada em um banco público de sangue de cordão umbilical e placentário, desenvolvida em duas etapas: 1) verificação dos fatores obstétricos, neonatais e operacionais, obtidos por coleta em instrumento próprio e observação não participante; 2) definição das boas práticas, por meio do agrupamento de não-conformidades observadas antes, durante e após a coleta do sangue. Os dados foram analisados por meio da estatística descritiva, utilizando-se dos softwares Statistica(r) e R(r). houve

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

    Directory of Open Access Journals (Sweden)

    Svenja Rieke

    2014-09-01

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

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

    Directory of Open Access Journals (Sweden)

    Guo Yingqiang

    2010-05-01

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

  14. Circulating MicroRNAs as Potential Molecular Biomarkers in Pathophysiological Evolution of Pregnancy

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    Dragos Cretoiu

    2016-01-01

    Full Text Available MicroRNAs represent nonprotein coding small RNA molecules that are very stable to degradation and responsible for gene silencing in most eukaryotic cells. Increased evidence has been accumulating over the years about their potential value as biomarkers for several diseases. MicroRNAs were predicted to be involved in nearly all biological processes from development to oncogenesis. In this review, we address the importance of circulating microRNAs in different conditions associated with pregnancy starting with the implantation period to preeclampsia and we shortly describe the correlation between placental circulating miRNAs and pregnancy status. We also discuss the importance of microRNAs in recurrent abortion and ectopic pregnancy.

  15. Sex Differences in Placental Mitochondrial Function Associated with Ozone-Induced Fetal Growth Restriction

    Science.gov (United States)

    Fetal growth restriction is a major underlying cause of infant mortality worldwide. Despite knowledge of risk factors for adverse pregnancy outcomes, the mechanisms that drive compromised growth during pregnancy have not been well established. Placental maladaptation, particularl...

  16. Suppressed peripheral and placental blood lymphoproliferative responses in first pregnancies: relevance to malaria

    DEFF Research Database (Denmark)

    Rasheed, F N; Bulmer, J N; Dunn, D T

    1993-01-01

    protein derivative [PPD]) were examined in the peripheral and placental blood of 102 Gambian women at the time of delivery. The lymphoproliferative responses of placental cells were poor to all antigens compared with those of peripheral blood (Candida P PPD P ....003, and 190N P = 0.10). Reduced proliferative capacity of placental mononuclear cells may contribute to heavy parasite colonization of this organ. Proliferation to malarial and PPD but not Candida antigens was selectively suppressed in peripheral and placental blood of primiparae relative to multiparae (F32 P...... = 0.07, 190L P = 0.09, 190N P = 0.007, PPD P = 0.09). Autologous plasma contained factors that suppressed lymphoproliferative responses to the same series of antigens to which the primiparae responded poorly (F32 P PPD P = 0.03). Malarial antibody levels were...

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

    Energy Technology Data Exchange (ETDEWEB)

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

    1977-10-01

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

  18. 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.

  19. Twin-to-twin transfusion syndrome : from placental anastomoses to long-term outcome

    NARCIS (Netherlands)

    Lopriore, Enrico

    2006-01-01

    Twin-to-twin transfusion syndrome (TTTS) is a severe complication of monochorionic twin pregnancies associated with high perinatal mortality and morbidity rates. Placental vascular anastomoses, almost invariably present in monochorionic placentas, are the essential anatomical substrate for the

  20. 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 Nycteris...... placenta is endotheliochorial with a single layer of cytotrophoblast, the arborizing pattern of the maternal vessels and especially the extraordinary major placental artery differs from the placenta of the emballonurid bats to which this family is considered to be most closely related. The major placental...... other bat species. The paraplacenta is extensive with abundant fetal vessels underlying cytotrophoblast and syncytial trophoblast layers, fronting on an endometrium that largely lacks uterine epithelial cells but has large decidual cells and is poorly vascularized. The placenta of Nycteris lacks...

  1. Placenta and Placental Derivatives in Regenerative Therapies: Experimental Studies, History, and Prospects

    Directory of Open Access Journals (Sweden)

    Olena Pogozhykh

    2018-01-01

    Full Text Available Placental structures, capable to persist in a genetically foreign organism, are a natural model of allogeneic engraftment carrying a number of distinctive properties. In this review, the main features of the placenta and its derivatives such as structure, cellular composition, immunological and endocrine aspects, and the ability to invasion and deportation are discussed. These features are considered from a perspective that determines the placental material as a unique source for regenerative cell therapies and a lesson for immunological tolerance. A historical overview of clinical applications of placental extracts, cells, and tissue components is described. Empirically accumulated data are summarized and compared with modern research. Furthermore, we define scopes and outlooks of application of placental cells and tissues in the rapidly progressing field of regenerative medicine.

  2. Placenta and Placental Derivatives in Regenerative Therapies: Experimental Studies, History, and Prospects.

    Science.gov (United States)

    Pogozhykh, Olena; Prokopyuk, Volodymyr; Figueiredo, Constança; Pogozhykh, Denys

    2018-01-01

    Placental structures, capable to persist in a genetically foreign organism, are a natural model of allogeneic engraftment carrying a number of distinctive properties. In this review, the main features of the placenta and its derivatives such as structure, cellular composition, immunological and endocrine aspects, and the ability to invasion and deportation are discussed. These features are considered from a perspective that determines the placental material as a unique source for regenerative cell therapies and a lesson for immunological tolerance. A historical overview of clinical applications of placental extracts, cells, and tissue components is described. Empirically accumulated data are summarized and compared with modern research. Furthermore, we define scopes and outlooks of application of placental cells and tissues in the rapidly progressing field of regenerative medicine.

  3. Gestational age, gender and parity specific centile charts for placental weight for singleton deliveries in Aberdeen, UK.

    Science.gov (United States)

    Wallace, J M; Bhattacharya, S; Horgan, G W

    2013-03-01

    The weight of the placenta is a crude but useful proxy for its function in vivo. Accordingly extremes of placental weight are associated with adverse pregnancy outcomes while even normal variations in placental size may impact lifelong health. Centile charts of placental weight for gestational age and gender are used to identify placental weight extremes but none report the effect of parity. Thus the objective was to produce gender and gestational age specific centile charts for placental weight in nulliparous and multiparous women. Data was extracted from the Aberdeen Maternity and Neonatal Databank for all women delivering singleton babies in Aberdeen city and district after 24 weeks gestation. Gestational age specific centile charts for placental weight by gender and parity grouping (n = 88,649 deliveries over a 30 year period) were constructed using the LMS method after exclusion of outliers (0.63% of deliveries meeting study inclusion criteria). Tables and figures are presented for placental weight centiles according to gestational age, gender and parity grouping. Tables are additionally presented for the birth weight to placental weight ratio by gender. Placental weight and the fetal:placental weight ratio were higher in male versus female deliveries. Placental weight was greater in multiparous compared with nulliparous women. We present strong evidence that both gender and parity grouping influence placental weight centiles. The differences at any given gestational age are small and the effects of parity are greater overall than those of gender. In contrast the birth weight to placental weight ratio differs by gender only. These UK population specific centile charts may be useful in studies investigating the role of the placenta in mediating pregnancy outcome and lifelong health. Copyright © 2012 Elsevier Ltd. All rights reserved.

  4. Radiology of liver circulation

    International Nuclear Information System (INIS)

    Hermine, C.L.

    1985-01-01

    This book proposes that careful evaluation of the arterioportogram is the cornerstone in assessing portal flow obstruction, being the most consistent of all observations including liver histology, portal venous pressure, size and number of portosystemic collaterals, and wedged hepatic venous pressure. Very brief chapters cover normal hepatic circulation and angiographic methods. Contrast volumes and flow rates for celiac, hepatic, and superior mesenteric injection are given, with the timing for venous phase radiographs. In the main body of the text, portal obstruction is divided very simply into presinusoidal (all proximal causes) and postsinusoidal (all distal causes, including Budd-Chiari). Changes are discussed regarding the splenic artery and spleen; hepatic artery and its branches; portal flow rate and direction; and arterioportal shunting and portosystemic collateral circulation in minimal, moderate, severe, and very severe portal obstruction and in recognizable entities such as prehepatic portal and hepatic venous obstructions. The major emphasis in this section is the recognition and understanding of flow changes by which level and severity of obstruction are assessed (not simply the anatomy of portosystemic collateral venous flow). Excellent final chapters discuss the question of portal hypertension without obstruction, and the contribution of arterioportography to the treatment of portal hypertension, again with an emphasis on hemodynamics before and after shunt surgery. There is a fascinating final chapter on segmental intrahepatic obstruction without portal hypertension that explains much of the unusual contrast enhancement sometimes seen in CT scanning of hepatic mass lesions

  5. Circulation of Stars

    Science.gov (United States)

    Boitani, P.

    2016-01-01

    Since the dawn of man, contemplation of the stars has been a primary impulse in human beings, who proliferated their knowledge of the stars all over the world. Aristotle sees this as the product of primeval and perennial “wonder” which gives rise to what we call science, philosophy, and poetry. Astronomy, astrology, and star art (painting, architecture, literature, and music) go hand in hand through millennia in all cultures of the planet (and all use catasterisms to explain certain phenomena). Some of these developments are independent of each other, i.e., they take place in one culture independently of others. Some, on the other hand, are the product of the “circulation of stars.” There are two ways of looking at this. One seeks out forms, the other concentrates on the passing of specific lore from one area to another through time. The former relies on archetypes (for instance, with catasterism), the latter constitutes a historical process. In this paper I present some of the surprising ways in which the circulation of stars has occurred—from East to West, from East to the Far East, and from West to East, at times simultaneously.

  6. 3D Power Doppler ultrasound and computerised placental assessment in normal pregnancy

    International Nuclear Information System (INIS)

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

    2014-01-01

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

  7. Newborn body fat: associations with maternal metabolic state and placental size.

    Directory of Open Access Journals (Sweden)

    Camilla M Friis

    Full Text Available BACKGROUND: Neonatal body composition has implications for the health of the newborn both in short and long term perspective. The objective of the current study was first to explore the association between maternal BMI and metabolic parameters associated with BMI and neonatal percentage body fat and to determine to which extent any associations were modified if adjusting for placental weight. Secondly, we examined the relations between maternal metabolic parameters associated with BMI and placental weight. METHODS: The present work was performed in a subcohort (n = 207 of the STORK study, an observational, prospective study on the determinants of fetal growth and birthweight in healthy pregnancies at Oslo University Hospital, Norway. Fasting glucose, insulin, triglycerides, free fatty acids, HDL- and total cholesterol were measured at week 30-32. Newborn body composition was determined by Dual-Energy X-Ray Absorptiometry (DXA. Placenta was weighed at birth. Linear regression models were used with newborn fat percentage and placental weight as main outcomes. RESULTS: Maternal BMI, fasting glucose and gestational age were independently associated with neonatal fat percentage. However, if placental weight was introduced as a covariate, only placental weight and gestational age remained significant. In the univariate model, the determinants of placenta weight included BMI, insulin, triglycerides, total- and HDL-cholesterol (negatively, gestational weight gain and parity. In the multivariable model, BMI, total cholesterol HDL-cholesterol, gestational weight gain and parity remained independent covariates. CONCLUSION: Maternal BMI and fasting glucose were independently associated with newborn percentage fat. This effect disappeared by introducing placental weight as a covariate. Several metabolic factors associated with maternal BMI were associated with placental weight, but not with neonatal body fat. Our findings are consistent with a concept

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

    DEFF Research Database (Denmark)

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

    2015-01-01

    We here review the evolution of invasive placentation in primates towards the deep penetration of the endometrium and its arteries in hominoids. The strepsirrhine primates (lemurs and lorises) have non-invasive, epitheliochorial placentation, although this is thought to be derived from a more...... invasive type. In haplorhine primates, there is differentiation of trophoblast at the blastocyst stage into syncytial and cellular trophoblast. Implantation involves syncytiotrophoblast that first removes the uterine epithelium then consolidates at the basal lamina before continuing into the stroma...

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

    DEFF Research Database (Denmark)

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

    2014-01-01

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

  10. Placental share and hemoglobin level in relation to birth weight in twin anemia-polycythemia sequence.

    Science.gov (United States)

    Zhao, D; Slaghekke, F; Middeldorp, J M; Duan, T; Oepkes, D; Lopriore, E

    2014-12-01

    Twin anemia-polycythemia sequence (TAPS) is a newly described form of chronic twin transfusion. Previous observational studies noted a discordance between birth weight and individual placental share in TAPS. The purpose of this study was to investigate if fetal growth in monochorionic (MC) twins with TAPS is determined by placental share or by the net inter-twin blood transfusion. All consecutive MC twin placentas of live-born twin pairs with and without TAPS examined at our center between June 2002 and February 2014 were included in this study. Hemoglobin (Hb) levels and individual placental share were evaluated at birth and correlated with birth weight share. We excluded MC twin pregnancies with twin-twin transfusion syndrome. A total of 270 MC twin pregnancies (TAPS group, n = 20; control group without TAPS, n = 250) were included in this study. Donors with TAPS had a lower birth weight than recipients in 90% (18/20) of cases, but a larger placental share in 65% (13/20) of cases. In the TAPS group, birth weight share was positively correlated with Hb share at birth (P < 0.01) but not with placental share (P = 0.54). In the control group without TAPS, birth weight share was strongly correlated with placental share (P < 0.01) but not with Hb share (P = 0.14). A relatively larger placental share may enable the survival of the anemic twin in TAPS. In contrast with uncomplicated MC twins, fetal growth in MC twins with TAPS is determined primarily by the net inter-twin blood transfusion instead of placental share. Copyright © 2014 Elsevier Ltd. All rights reserved.

  11. Placental vascular complications in HIV-infected pregnant women: a case-control study

    OpenAIRE

    CANLORBE, Geoffroy

    2012-01-01

    Background: Data from international literature suggest a link between HIV infection and placental vascular complications during pregnancy. Current studies on the subject are conflicting.Objective: The aim of the study was to evaluate the incidence of placental vascular complications during pregnancy among HIV+ and HIV- patients.Study Design: It is a single-center case-control study comparing the rates of gestational hypertension, preeclampsia, eclampsia and vascular intrauterine growth retard...

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

    Science.gov (United States)

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

    2018-05-01

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

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

    Directory of Open Access Journals (Sweden)

    Marc-Jens Kleppa

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

  14. Placental lactogen secretion during prolonged-pregnancy in the rat: the ovary plays a pivotal role in the control of placental function.

    Science.gov (United States)

    Shiota, K; Furuyama, N; Takahashi, M

    1991-10-01

    The serum of rats at mid-pregnancy contains at least 2 distinct placental lactogen (PL)-like substances tentatively termed placental lactogen-alpha (PL-alpha) and placental lactogen-beta (PL-beta) (Endocrinol Japon 38: 533-540, 1991). We have investigated the secretory patterns of three placental lactogens (PL-alpha, PL-beta and placental lactogen-II) during normal pregnancy and in two prolonged-pregnancy models. Pregnancy was prolonged by the introduction of new corpora lutea by inducing ovulation on day 15 of pregnancy by successive treatments with PMSG (30 IU/rat, sc on day 12) and hCG (10 IU/rat, iv on day 14), and in the second model by progesterone implants on day 15 of pregnancy. During normal pregnancy, each of the 3 PLs exhibited only one secretory peak in the serum; PL-alpha and PL-beta on day 12 and placental lactogen II (PL-II) on day 20. Interestingly, in the rats with new sets of corpora lutea, serum PL-alpha and PL-beta levels began to increase again on day 18 and showed peaks on day 20 for PL-alpha and on day 22 for PL-beta. In this model, the initiation of PL-II secretion was not affected, but high levels were maintained until day 26, when parturition occurred. In rats receiving either PMSG or hCG, the secretory patterns of the PLs were similar to as those during normal pregnancy.(ABSTRACT TRUNCATED AT 250 WORDS)

  15. Principles of mRNA transport in yeast.

    Science.gov (United States)

    Heym, Roland Gerhard; Niessing, Dierk

    2012-06-01

    mRNA localization and localized translation is a common mechanism by which cellular asymmetry is achieved. In higher eukaryotes the mRNA transport machinery is required for such diverse processes as stem cell division and neuronal plasticity. Because mRNA localization in metazoans is highly complex, studies at the molecular level have proven to be cumbersome. However, active mRNA transport has also been reported in fungi including Saccharomyces cerevisiae, Ustilago maydis and Candida albicans, in which these events are less difficult to study. Amongst them, budding yeast S. cerevisiae has yielded mechanistic insights that exceed our understanding of other mRNA localization events to date. In contrast to most reviews, we refrain here from summarizing mRNA localization events from different organisms. Instead we give an in-depth account of ASH1 mRNA localization in budding yeast. This approach is particularly suited to providing a more holistic view of the interconnection between the individual steps of mRNA localization, from transcriptional events to cytoplasmic mRNA transport and localized translation. Because of our advanced mechanistic understanding of mRNA localization in yeast, the present review may also be informative for scientists working, for example, on mRNA localization in embryogenesis or in neurons.

  16. Self-reported smoking habits and serum cotinine levels in women with placental abruption.

    Science.gov (United States)

    Tikkanen, Minna; Surcel, Heljä-Marja; Bloigu, Aini; Nuutila, Mika; Ylikorkala, Olavi; Hiilesmaa, Vilho; Paavonen, Jorma

    2010-12-01

    smoking is an important risk factor for placental abruption with strong dose-dependency. Pregnant smokers often underreport tobacco use which can be objectively assessed by measuring serum cotinine levels. We examined the accuracy between self-reported smoking habits and early pregnancy serum cotinine levels in women with or without placental abruption. retrospective case-control study. university Hospital. a total of 175 women with placental abruption and 370 control women. serum samples collected during the first trimester were analyzed for serum cotinine levels. Cotinine concentration over 15 ng/ml was considered as the cutoff indicating active smoking. Smoking habits of the women and their partners were recorded at the same visit. placental abruption. of the cases of women with placental abruption, 27.4% reported smoking compared with 14.3% of the controls (p smoked daily correlated well with the cotinine levels (r = 0.68, p smoking habits correlate well with serum cotinine levels in Finland. Therefore, self-reported smoking can be considered as a risk marker for placental abruption.

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

    Directory of Open Access Journals (Sweden)

    Noura Abd Ellah

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

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

    Science.gov (United States)

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

    2015-06-18

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

  19. Assessment of placental stiffness using acoustic radiation force impulse elastography in pregnant women with fetal anomalies

    Energy Technology Data Exchange (ETDEWEB)

    Alan, Bircan; Goya, Cemil; Tunc, Senem; Teke, Memik; Hattapoglu, Salih [Dicle University Medical Faculty, Diyarbakir (Turkmenistan)

    2016-04-15

    We aimed to evaluate placental stiffness measured by acoustic radiation force impulse (ARFI) elastography in pregnant women in the second trimester with a normal fetus versus those with structural anomalies and non-structural findings. Forty pregnant women carrying a fetus with structural anomalies diagnosed sonographically at 18-28 weeks of gestation comprised the study group. The control group consisted of 34 healthy pregnant women with a sonographically normal fetus at a similar gestational age. Placental shear wave velocity (SWV) was measured by ARFI elastography and compared between the two groups. Structural anomalies and non-structural findings were scored based on sonographic markers. Placental stiffness measurements were compared among fetus anomaly categories. Doppler parameters of umbilical and uterine arteries were compared with placental SWV measurements. All placental SWV measurements, including minimum SWV, maximum SWV, and mean SWV were significantly higher in the study group than the control group ([0.86 ± 0.2, 0.74 ± 0.1; p < 0.001], [1.89 ± 0.7, 1.59 ± 0.5; p = 0.04], and [1.26 ± 0.4, 1.09 ± 0.2; p = 0.01]), respectively. Placental stiffness evaluated by ARFI elastography during the second trimester in pregnant women with fetuses with congenital structural anomalies is higher than that of pregnant women with normal fetuses.

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

    Directory of Open Access Journals (Sweden)

    Ronan M Doyle

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

  1. 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.

  2. Association between placental abruption and caesarean section among patients at Khyber teaching hospital Peshawar

    International Nuclear Information System (INIS)

    Gul, S.; Jamal, T.; Rana, G.E.; Majid, A.; Iqbal, M.; Abrar, S.

    2016-01-01

    Background: Ante partum haemorrhage remains to be a major cause of morbidity and mortality. 30 percentage of this haemorrhage is attributed to placental abruption. Along with other adverse maternal outcomes, it increases the risk of Caesarean sections in patients, which is a public health concern. This study was conducted to find out whether any significant association exists between placental abruption and C-section in our set up. Methods: A cross-sectional study was conducted from July 26th, 2011 to May 1st, 2013 (i.e., 21 months) in the Department of Obstetrics and Gynaecology, Khyber Teaching Hospital Peshawar on a sample of 334 patients who presented with antepartum haemorrhage after 28 weeks of gestation. All those patients with and without placental abruption were followed throughout pregnancy and labour to detect the risk of caesarean section. Results: Among study participants, parity had the highest dispersion while gestational age had the lowest. Caesarean section was performed on 26.3 percentage (95 percentage CI) of the study participants. Proportion of placental abruption among patients presenting with ante partum haemorrhage was 20.6 percentage, (95 percentage CI) out of which 7.5 percentage underwent C-section. Association between placental abruption and C-section was found significant at a=0.05 (ρ=0.03). Conclusion: Risk of caesarean section is increased in pregnancies complicated by placental abruption as compared to pregnancies complicated by other causes of ante partum haemorrhage. (author)

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

    International Nuclear Information System (INIS)

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

    2006-01-01

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

  4. A Single Center Experience on the Management of Placental Invasion Abnormalities

    Directory of Open Access Journals (Sweden)

    Alper Biler

    2016-03-01

    Full Text Available Objective: The aim of this study is to investigate our management of placental invasion abnormalities. Methods: A retrospective study was conducted on pa­tients admitted to a tertiary referral center with a diagno­sis of placental invasion abnormalities between 2011 and 2015. Risk factors and perinatal outcomes associated with placental invasion abnormalities were identified. Results: The overall incidence of placental invasion ab­normalities during the 5-year period was 8.3/10000 de­liveries, which showed an increasing trend. Ultrasonog­raphy and magnetic resonance imaging correctly identi­fied placental invasion abnormality in 36.7% and 68.7% cases, respectively. Majority of patients (55.1% with ad­herent placenta were diagnosed at the time of delivery. Of these patients, 22.4% underwent hysterectomy, 83.8% required at least one of the additional surgical procedures and 55% were transfused at least four units of packed red blood cell. Conclusion: Since placental invasion abnormalities are associated with significant morbidity, delivery should be scheduled in a tertiary center with appropriate expertise and facilities. J Clin Exp Invest 2016; 7 (1: 14-18

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

    Science.gov (United States)

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

    2011-12-01

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

  6. m-RNA mammaglobin expression in metastatic breast cancer patient at Medan city, Indonesia

    Science.gov (United States)

    Rimbun, S.; Siregar, Y.

    2018-03-01

    Breast cancer is the most common causes of women’s death in the world. Metastatic spread presents a major clinical problem in about 30% of the patients. The study aims to investigate the clinical reliability of mammaglobin mRNA as a marker of circulating cancer cells in breast cancer patients. The positivity of blood was analyzed in relation to clinical and pathological characteristics. This study was on 29 breast cancer patients (13 metastatic, 16 non- metastatic patients), where28 were invasive intraductal carcinoma type and 1 was invasive lobular carcinoma type. Breast cancer patients were according to the histologic grade into grade I (7 patients),grade II (6 patients) and grade III (15 patients). All individuals included in this study were subjected to detection of mammaglobin m-RNA of circulating tumor cells in peripheral blood using RT-PCR technique. Positivity for mammaglobin in blood samples was in 38% of patients with metastatic but not in the non-metastatic patients. The presence of mammaglobin correlated with metastatic tumor (P = 0.011). Mammaglobin overexpression in breast tissue was significantly positive in low-grade tumors (I and II).

  7. Matrotrophy and placentation in invertebrates: a new paradigm.

    Science.gov (United States)

    Ostrovsky, Andrew N; Lidgard, Scott; Gordon, Dennis P; Schwaha, Thomas; Genikhovich, Grigory; Ereskovsky, Alexander V

    2016-08-01

    histophagy are rarer, plausibly evolving through heterochronous development of the embryonic mouthparts and digestive system. During gestation, matrotrophic modes can shift, intergrade, and be performed simultaneously. Invertebrate matrotrophic adaptations are less complex structurally than in chordates, but they are more diverse, being formed either by a parent, embryo, or both. In a broad and still preliminary sense, there are indications of trends or grades of evolutionarily increasing complexity of nutritive structures: formation of (i) local zones of enhanced nutritional transport (placental analogues), including specialized parent-offspring cell complexes and various appendages increasing the entire secreting and absorbing surfaces as well as the contact surface between embryo and parent, (ii) compartmentalization of the common incubatory space into more compact and 'isolated' chambers with presumably more effective nutritional relationships, and (iii) internal secretory ('milk') glands. Some placental analogues in onychophorans and arthropods mimic the simplest placental variants in vertebrates, comprising striking examples of convergent evolution acting at all levels-positional, structural and physiological. © 2015 The Authors. Biological Reviews published by John Wiley & Sons Ltd on behalf of Cambridge Philosophical Society.

  8. Circulation Systems Past and Present

    Directory of Open Access Journals (Sweden)

    Maurice J. Freedman

    1981-01-01

    Full Text Available A review of the development of circulation systems shows two areas of change. The librarian's perception of circulation control has shifted from a broad service orientation to a narrow record-keeping approach and recently back again. The technological development of circulation sys-tems has evolved from manual systems to the online systems of today. The trade-offs and deficiencies of earlier systems in relation to the comprehensive services made possible by the online computer are detailed.

  9. The association between Placental T2* measured by MRI in dichorionic twin pregnancies and intertwin birth weight differences

    DEFF Research Database (Denmark)

    Sørensen, Anne Nødgaard Weidemann; Sinding, Marianne Munk; Peters, David Alberg

    ABSTRACT FINAL ID: P22.06 TITLE: The association between Placental T2* measured by MRI in dichorionic twin pregnancies and intertwin birth weight differences AUTHORS (FIRST NAME, LAST NAME): Anne Sørensen1, 2, Marianne Sinding1, David Peters3, Jens B. Frøkjær4, 2, Astrid Petersen6, Niels Uldbjerg5...... with an increased risk of adverse neonatal outcome, and new methods to predict the intertwin birth weight difference are highly clinical relevant. The Magnetic Resonance Imaging (MRI) variable placentalT2* reflects placental oxygenation and thereby placental function. Therefore, we aimed to investigate...... the association between the intertwin placental T2* difference and the intertwin birth weight difference Methods: A total of 21 dichorionic twin pregnancies (gestational age 20.1 – 34.1 weeks) were included in this study and placental T2* was measured using a gradient recalled echo MRI sequence with readout at 16...

  10. The ocean circulation inverse problem

    National Research Council Canada - National Science Library

    Wunsch, C

    1996-01-01

    .... This book addresses the problem of inferring the state of the ocean circulation, understanding it dynamically, and even forecasting it through a quantitative combination of theory and observation...

  11. Localization of glucocorticoid receptor mRNA in the male rat brain by in situ hybridization

    International Nuclear Information System (INIS)

    Aronsson, M.; Fuxe, K.; Dong, Y.; Agnati, L.F.; Okret, S.; Gustafsson, J.A.

    1988-01-01

    The localization and distribution of mRNA encoding the glucocorticoid receptor (GR) was investigated in tissue sections of the adult male rat brain by in situ hybridization and RNA blot analysis. GR mRNA levels were measured by quantitative autoradiography with 35S- and 32P-labeled RNA probes, respectively. Strong labeling was observed within the pyramidal nerve cells of the CA1 and CA2 areas of the hippocampal formation, in the granular cells of the dentate gyrus, in the parvocellular nerve cells of the paraventricular hypothalamic nucleus, and in the cells of the arcuate nucleus, especially the parvocellular part. Moderate labeling of a large number of nerve cells was observed within layers II, III, and VI of the neocortex and in many thalamic nuclei, especially the anterior and ventral nuclear groups as well as several midline nuclei. Within the cerebellar cortex, strong labeling was observed all over the granular layer. In the lower brainstem, strong labeling was found within the entire locus coeruleus and within the mesencephalic raphe nuclei rich in noradrenaline and 5-hydroxytryptamine cell bodies, respectively. A close correlation was found between the distribution of GR mRNA and the distribution of previously described GR immunoreactivity. These studies open the possibility of obtaining additional information on in vivo regulation of GR synthesis and how the brain may alter its sensitivity to circulating glucocorticoids

  12. Maternal circulating levels of activin A, inhibin A, sFlt-1 and endoglin at parturition in normal pregnancy and pre-eclampsia.

    Directory of Open Access Journals (Sweden)

    Aparna Reddy

    Full Text Available Maternal circulating levels of anti-angiogenic factors such as soluble fms-like tyrosine kinase-1 (sFlt-1, endoglin (sEng and placental proteins like activin A and inhibin A are increased before the onset of pre-eclampsia. There is evidence for oxidative stress in pre eclampsia. Recently it was shown that placental oxygen concentration is related to sFlt-1 and inhibin A. In addition it is reported that oxidative stress markers are increased in placental tissue delivered after labour. Therefore, the objective of this study is to investigate if these proteins are altered in maternal circulation of labouring pre-eclampsia and normal pregnancies.To assess the effects of labour, samples were taken from 10 normal pregnant (NP and 10 pre-eclamptic (PE women pre-labour, full dilation, placental delivery and 24 h. To assess the effects of placental delivery, plasma samples were taken from 10NP and 10PE women undergoing elective Caesarean section, pre-delivery, placental delivery and 10 min, 60 min and 24 h post delivery. SFlt-1 and sEng and activin A and inhibin A were measured using commercial and in house ELISA's respectively.The levels of sFlt-1 and sEng were significantly higher in PE compared to NP women in both groups. In labour, sFlt-1 levels increased significantly at full dilatation in PE women, before declining by 24 hr. However there was no significant rise in sEng levels in labour. Activin A and inhibin A levels declined rapidly with placental delivery in NP and PE pregnancies. There was a significant rise in activin A levels during labour in PE compared to pre labour, but inhibin levels did not increase.Labour in pre-eclamptic women increases the levels of sFlt-1 and activin A. This pilot data suggests that increase in the maternal levels of these factors in labour could predict and/or contribute to the maternal syndrome postpartum.

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

    Energy Technology Data Exchange (ETDEWEB)

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

    1971-02-15

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

  14. 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

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

    Science.gov (United States)

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

    2015-04-01

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

  16. The impact of ultrasonographic placental architecture on antenatal course, labor and delivery in a low-risk primigravid population.

    LENUS (Irish Health Repository)

    Cooley, Sharon M

    2012-02-01

    OBJECTIVE: To ascertain the impact of placental architecture on antenatal course and labor delivery in a low-risk primigravid population. METHODS: This study involves prospective recruitment of 1011 low-risk primigravids with placental ultrasound at 22?24 weeks and 36 weeks. Detailed postnatal review of all mothers and infants was undertaken. Retrospective analysis of ultrasound and clinical outcome data was performed. RESULTS: Eight hundred ten women with complete outcome data were available. Anterior placentation was statistically associated with intrauterine growth restriction (IUGR) and preterm birth and fundal placentation was significantly associated with a higher incidence of pregnancy-induced hypertension and infants with a birthweight less than the 9th centile. Placental infarcts in the third trimester was significantly increased in cases complicated by pre-eclampsia (PET) and in cases with fetal acidosis. Placental calcification was associated a 40-fold increase in the incidence of IUGR. Placental lakes in the second trimester were more prevalent in patients with threatened miscarriage. Increased placental thickness was associated with a higher rate of fetal acidosis. The Grannum grade of the placenta was higher with threatened first or second trimester loss, PET and in infants born less than 9th centile for gestation. CONCLUSION: Placental site and architecture impact on the incidence of maternal and fetal disease.

  17. Placental and lactating transfer of 147Pm in mice

    International Nuclear Information System (INIS)

    Tao Feng; Zhu Shoupeng

    1990-08-01

    The placental and lactating transfer of 147 Pm in late pregnant mice and lactating mice as well as the distribution of 147 Pm in some organs of mother mice were studied and compared. The pregnant mice and lactating mice had intravenous injection with 147 Pm nitrate at the 17th day of gestation and the next day of parturition respectively. The two groups were sacrified at the 1st, 4th, 9th, 14th and 21st day after the injection. The retentions of 147 Pm in the liver, right femur, uterus, spleen, placenta, fetal membrane and litter were determined by the method of liquid scintillation. The results showed that the amount of 147 Pm in litters of both groups was increasing with the days after injection. In the 1st and 4th day of injection the amount of 147 Pm in litters of lactating mice was 20 times higher than those in litters of pregnant mice. The amount of 147 Pm in livers and skeletons and the half-retention time of prenant and lactating dams were much greater than those of control group

  18. The roentgenographic study of placental calcifications in Korean pregnant

    International Nuclear Information System (INIS)

    Cho, Chung Che

    1980-01-01

    Calcifications in the placenta have been considered as a sign of the maturity because it is found frequently in variable degrees in full-term placentas. The placentas studied were those from deliveries at Chung-Ang University Hospital during the period of January 1978 to June 1980 and were excluded if their deliveries were by Caesarean section. Roentgenographic studies of placenta were performed postnatally in 135 cases delivered from normal pregnant. The results were as follows: 1. The incidence of calcification in the placenta was 53.3%. 2. The tendency of placenta calcification was increased as progress of maturity but not indicated as postmaturity. 3. Calcifications were less correlated with increasing gravidity or maternal age. 4. Calcifications occurred more frequently with increasing birth weight. 5. Calcifications in placentas were more frequently in the neonates with 10 scores of Apgar and normal level of maternal hemoglobin. 6. No significant correlation between incidence of calcification and maternal toxemia was observed. In the pregnant with an episode of previous abortion or S. P. R. M., incidence of calcification was apparently increased but statistically not significant. On the whole, placental calcifications are not harmful and identified as normal or proper aging process

  19. Radioimmunological assessment of placental lactogen concentrations in abortion risks

    International Nuclear Information System (INIS)

    Szymanski, W.; Przylepa, M.

    1981-01-01

    HPL concentrations in the blood serum were determined in 108 patients in the 6th to 16th week of gestation hospitalized for the risk of abortion, and in 12 women with normal pregnancy. The prognosis was based on clinical documentation and a questionnaire. The examinations performed showed that the mean HPL concentration in the serum in normal pregnancies increased from 93.5 ng/ml in the 6th to 7th weeks to 1461.7 ng/ml in the 15th to 16th weeks. In high-risk pregnancies, slightly lower values were found for the 8th to 14th week of pregnancy while the difference in concentrations in both groups only became statistically significant from the 14th week. An HPL concentration in the serum lower than 450 ng/ml from the 9th week onward indicated that the high-risk pregnancy would terminate by abortion. Careful determination of placental lactogen in the serum of pregnant women seems to be a good prognostic test of the viability of pregnancy. (author)

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

    Science.gov (United States)

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

    2010-01-01

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

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

    DEFF Research Database (Denmark)

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

    2012-01-01

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

  2. Ted (G.J.) Kloosterman: on intrauterine growth. The significance of prenatal care. Studies on birth weight, placental weight and placental index.

    Science.gov (United States)

    Bleker, O P; Buimer, M; van der Post, J A M; van der Veen, F

    2006-01-01

    In the last century, there was a heated debate on whether fetal growth retardation is caused by a small placenta or whether a placenta is small because the baby is small. One of the active participants in this debate was Kloosterman who studied 80,000 birth weights, and 30,000 placental weights, in relation to gestational age at birth, fetal sex, maternal parity, and perinatal mortality. He found that pregnancies related to heavier placentas last longer. He also found that, from about 32 weeks of gestation onwards, children from primiparous women as compared to those from multiparous women, like twin children as compared to singleton children, are relatively growth retarded, most likely related to prior relatively poor placental growth. He concluded that poor fetal growth is not the cause, but the result of poor placental growth. The clinical implication of all these is that future early detection of poor placental growth may prospect poor fetal growth, and may even allow for early interventions to improve fetal outcome.

  3. Ted (G.J.) Kloosterman: on intrauterine growth. The significance of prenatal care. Studies on birth weight, placental weight and placental index

    NARCIS (Netherlands)

    Bleker, O. P.; Buimer, M.; van der Post, J. A. M.; van der Veen, F.

    2006-01-01

    In the last century, there was a heated debate on whether fetal growth retardation is caused by a small placenta or whether a placenta is small because the baby is small. One of the active participants in this debate was Kloosterman who studied 80,000 birth weights, and 30,000 placental weights, in

  4. A web-database of mammalian morphology and a reanalysis of placental phylogeny

    Directory of Open Access Journals (Sweden)

    Asher Robert J

    2007-07-01

    Full Text Available Abstract Background Recent publications concerning the interordinal phylogeny of placental mammals have converged on a common signal, consisting of four major radiations with some ambiguity regarding the placental root. The DNA data with which these relationships have been reconstructed are easily accessible from public databases; access to morphological characters is much more difficult. Here, I present a graphical web-database of morphological characters focusing on placental mammals, in tandem with a combined-data phylogenetic analysis of placental mammal phylogeny. Results The results reinforce the growing consensus regarding the extant placental mammal clades of Afrotheria, Xenarthra, Euarchontoglires, and Laurasiatheria. Unweighted parsimony applied to all DNA sequences and insertion-deletion (indel characters of extant taxa alone support a placental root at murid rodents; combined with morphology this shifts to Afrotheria. Bayesian analyses of morphology, indels, and DNA support both a basal position for Afrotheria and the position of Cretaceous eutherians outside of crown Placentalia. Depending on treatment of third codon positions, the affinity of several fossils (Leptictis,Paleoparadoxia, Plesiorycteropus and Zalambdalestes vary, highlighting the potential effect of sequence data on fossils for which such data are missing. Conclusion The combined dataset supports the location of the placental mammal root at Afrotheria or Xenarthra, not at Erinaceus or rodents. Even a small morphological dataset can have a marked influence on the location of the root in a combined-data analysis. Additional morphological data are desirable to better reconstruct the position of several fossil taxa; and the graphic-rich, web-based morphology data matrix presented here will make it easier to incorporate more taxa into a larger data matrix.

  5. Maternal perception of reduced fetal movements is associated with altered placental structure and function.

    Directory of Open Access Journals (Sweden)

    Lynne K Warrander

    Full Text Available Maternal perception of reduced fetal movement (RFM is associated with increased risk of stillbirth and fetal growth restriction (FGR. DFM is thought to represent fetal compensation to conserve energy due to insufficient oxygen and nutrient transfer resulting from placental insufficiency. To date there have been no studies of placental structure in cases of DFM.To determine whether maternal perception of reduced fetal movements (RFM is associated with abnormalities in placental structure and function.Placentas were collected from women with RFM after 28 weeks gestation if delivery occurred within 1 week. Women with normal movements served as a control group. Placentas were weighed and photographs taken. Microscopic structure was evaluated by immunohistochemical staining and image analysis. System A amino acid transporter activity was measured as a marker of placental function. Placentas from all pregnancies with RFM (irrespective of outcome had greater area with signs of infarction (3.5% vs. 0.6%; p<0.01, a higher density of syncytial knots (p<0.001 and greater proliferation index (p<0.01. Villous vascularity (p<0.001, trophoblast area (p<0.01 and system A activity (p<0.01 were decreased in placentas from RFM compared to controls irrespective of outcome of pregnancy.This study provides evidence of abnormal placental morphology and function in women with RFM and supports the proposition of a causal association between placental insufficiency and RFM. This suggests that women presenting with RFM require further investigation to identify those with placental insufficiency.

  6. MRI of placenta percreta: differentiation from other entities of placental adhesive disorder.

    Science.gov (United States)

    Thiravit, Shanigarn; Lapatikarn, Sukanya; Muangsomboon, Kobkun; Suvannarerg, Voraparee; Thiravit, Phakphoom; Korpraphong, Pornpim

    2017-01-01

    To retrospectively review the MRI findings of placenta percreta and identify those helpful for differentiation from non-placenta percreta. The MRI images of 21 patients with a preliminary diagnosis of placental adhesive disorder scanned between 2005 and 2014 were evaluated. Radiologists blinded to the final diagnosis evaluated six previously described MRI findings of placenta adhesive disorder. The sensitivity, specificity, accuracy, negative predictive value (NPV), and positive predictive value (PPV) of MRI for the diagnosis of placenta percreta were also calculated. The study included 12 cases of placenta percreta and 9 cases of non-placenta percreta. Invasion of placental tissue outside the uterus was found only in placenta percreta (p = 0.045; sensitivity 41.7 %; specificity 100 %). All placenta percreta cases also had a moderate to marked degree of heterogeneous placental signal intensity (p = 0.063; sensitivity 100 %; specificity 33.3 %). The size of the dark bands on T2-weighted imaging, and the presence of disorganized intra-placental vessels, showed no statistically significant difference between placenta percreta and non-placenta percreta. The sensitivity, specificity, NPV, PPV, and accuracy of MRI for detection of placenta percreta were 91.7, 44, 80, 68, and 71.4 %, respectively. MRI is recommended for the evaluation of placenta percreta, with the most specific signs including the invasion of placental tissue outside the uterus on B-FFE sequences, and consideration of the degree of placental signal heterogeneity. The size of the T2 dark band alone, or bizarre disorganized intra-placental vessels, did not correlate with the severity of invasion.

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

    Science.gov (United States)

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

    2005-04-01

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

  8. Sino-Danish Brain Circulation

    DEFF Research Database (Denmark)

    Bertelsen, Rasmus Gjedssø; Du, Xiangyun; Søndergaard, Morten Karnøe

    2014-01-01

    China is faced with urgent needs to develop an economically and environmentally sustainable economy based on innovation and knowledge. Brain circulation and research and business investments from the outside are central for this development. Sino-American brain circulation and research...... and investment by overseas researchers and entrepreneurs are well described. In that case, the US is the center of global R&D and S&T. However, the brain circulation and research and investments between a small open Scandinavian economy, such as Denmark, and the huge developing economy of China are not well...... understood. In this case, Denmark is very highly developed, but a satellite in the global R&D and S&T system. With time and the growth of China as a R&D and S&T power house, both Denmark and China will benefit from brain circulation between them. Such brain circulation is likely to play a key role in flows...

  9. mRNA Cancer Vaccines-Messages that Prevail.

    Science.gov (United States)

    Grunwitz, Christian; Kranz, Lena M

    2017-01-01

    During the last decade, mRNA became increasingly recognized as a versatile tool for the development of new innovative therapeutics. Especially for vaccine development, mRNA is of outstanding interest and numerous clinical trials have been initiated. Strikingly, all of these studies have proven that large-scale GMP production of mRNA is feasible and concordantly report a favorable safety profile of mRNA vaccines. Induction of T-cell immunity is a multi-faceted process comprising antigen acquisition, antigen processing and presentation, as well as immune stimulation. The effectiveness of mRNA vaccines is critically dependent on making the antigen(s) of interest available to professional antigen-presenting cells, especially DCs. Efficient delivery of mRNA into DCs in vivo remains a major challenge in the mRNA vaccine field. This review summarizes the principles of mRNA vaccines and highlights the importance of in vivo mRNA delivery and recent advances in harnessing their therapeutic potential.

  10. Natural Circulation with Boiling

    Energy Technology Data Exchange (ETDEWEB)

    Mathisen, R P

    1967-09-15

    A number of parameters with dominant influence on the power level at hydrodynamic instability in natural circulation, two-phase flow, have been studied experimentally. The geometrical dependent quantities were: the system driving head, the boiling channel and riser dimensions, the single-phase as well as the two phase flow restrictions. The parameters influencing the liquid properties were the system pressure and the test section inlet subcooling. The threshold of instability was determined by plotting the noise characteristics in the mass flow records against power. The flow responses to artificially obtained power disturbances at instability conditions were also measured in order to study the nature of hydrodynamic instability. The results presented give a review over relatively wide ranges of the main parameters, mainly concerning the coolant performance in both single and parallel boiling channel flow. With regard to the power limits the experimental results verified that the single boiling channel performance was intimately related to that of the parallel channels. In the latter case the additional inter-channel factors with attenuating effects were studied. Some optimum values of the parameters were observed.

  11. CYP3A5 mRNA degradation by nonsense-mediated mRNA decay.

    Science.gov (United States)

    Busi, Florent; Cresteil, Thierry

    2005-09-01

    The total CYP3A5 mRNA level is significantly greater in carriers of the CYP3A5*1 allele than in CYP3A5*3 homozygotes. Most of the CYP3A5*3 mRNA includes an intronic sequence (exon 3B) containing premature termination codons (PTCs) between exons 3 and 4. Two models were used to investigate the degradation of CYP3A5 mRNA: a CYP3A5 minigene consisting of CYP3A5 exons and introns 3 to 6 transfected into MCF7 cells, and the endogenous CYP3A5 gene expressed in HepG2 cells. The 3'-untranslated region g.31611C>T mutation has no effect on CYP3A5 mRNA decay. Splice variants containing exon 3B were more unstable than wild-type (wt) CYP3A5 mRNA. Cycloheximide prevents the recognition of PTCs by ribosomes: in transfected MCF7 and HepG2 cells, cycloheximide slowed down the degradation of exon 3B-containing splice variants, suggesting the participation of nonsense-mediated decay (NMD). When PTCs were removed from pseudoexon 3B or when UPF1 small interfering RNA was used to impair the NMD mechanism, the decay of the splice variant was reduced, confirming the involvement of NMD in the degradation of CYP3A5 splice variants. Induction could represent a source of variability for CYP3A5 expression and could modify the proportion of splice variants. The extent of CYP3A5 induction was investigated after exposure to barbiturates or steroids: CYP3A4 was markedly induced in a pediatric population compared with untreated neonates. However, no effect could be detected in either the total CYP3A5 RNA, the proportion of splice variant RNA, or the protein level. Therefore, in these carriers, induction is unlikely to switch on the phenotypic CYP3A5 expression in carriers of CYP3A5*3/*3.

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

    Science.gov (United States)

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

    2016-03-01

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

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

    Directory of Open Access Journals (Sweden)

    Yong-Hong Zhang

    2015-05-01

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

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

    Science.gov (United States)

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

    2018-04-01

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

  15. Pre-delivery fibrinogen predicts adverse maternal or neonatal outcomes in patients with placental abruption.

    Science.gov (United States)

    Wang, Liangcheng; Matsunaga, Shigetaka; Mikami, Yukiko; Takai, Yasushi; Terui, Katsuo; Seki, Hiroyuki

    2016-07-01

    Placental abruption is a severe obstetric complication of pregnancy that can cause disseminated intravascular coagulation and progress to massive post-partum hemorrhage. Coagulation disorder due to extreme consumption of fibrinogen is considered the main pathogenesis of disseminated intravascular coagulation in patients with placental abruption. The present study sought to determine if the pre-delivery fibrinogen level could predict adverse maternal or neonatal outcomes in patients with placental abruption. This retrospective medical chart review was conducted in a center for maternal, fetal, and neonatal medicine in Japan with 61 patients with placental abruption. Fibrinogen levels prior to delivery were collected and evaluated for the prediction of maternal and neonatal outcomes. The main outcome measures for maternal outcomes were disseminated intravascular coagulation and hemorrhage, and the main outcome measures for neonatal outcomes were Apgar score at 5 min, umbilical artery pH, and stillbirth. The receiver-operator curve and multivariate logistic regression analyses indicated that fibrinogen significantly predicted overt disseminated intravascular coagulation and the requirement of ≥6 red blood cell units, ≥10 fresh frozen plasma units, and ≥20 fresh frozen plasma units for transfusion. Moderate hemorrhage occurred in 71.5% of patients with a decrease in fibrinogen levels to 155 mg/dL. Fibrinogen could also predict neonatal outcomes. Umbilical artery pH neonatal outcomes with placental abruption. © 2016 Japan Society of Obstetrics and Gynecology. © 2016 Japan Society of Obstetrics and Gynecology.

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

    Science.gov (United States)

    Bonnin, A; Levitt, P

    2011-12-01

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

  17. The ability of computed tomography to diagnose placental abruption in the trauma patient.

    Science.gov (United States)

    Kopelman, Tammy R; Berardoni, Nicole E; Manriquez, Maria; Gridley, Daniel; Vail, Sydney J; Pieri, Paola G; O'Neill; Pressman, Melissa A

    2013-01-01

    Fetal demise following trauma remains a devastating complication largely owing to placental injury and abruption. Our objective was to determine if abdominopelvic computed tomographic (CT) imaging can assess for placental abruption (PA) when obtained to exclude associated maternal injuries. Retrospective review of pregnant trauma patients of 20-week gestation or longer presenting to a trauma center during a 7-year period who underwent CT imaging as part of their initial evaluation. Radiographic images were reviewed by a radiologist for evidence of PA and classified based on percentage of visualized placental enhancement. Blinded to CT results, charts were reviewed by an obstetrician for clinical evidence of PA and classified as strongly positive, possibly positive, or no evidence. A total of 176 patients met inclusion criteria. CT imaging revealed evidence of PA in 61 patients (35%). As the percentage of placental enhancement decreased, patients were more likely to have strong clinical manifestations of PA, reaching statistical significance when enhancement was less than 50%. CT imaging evidence of PA was apparent in all patients who required delivery for nonassuring fetal heart tones. CT imaging evaluation of the placenta can accurately identify PA and therefore can help stratify patients at risk for fetal complications. The likelihood of requiring delivery increased as placental enhancement declined to less than 25%. Diagnostic study, level III.

  18. A dating success story: genomes and fossils converge on placental mammal origins

    Directory of Open Access Journals (Sweden)

    Goswami Anjali

    2012-08-01

    Full Text Available Abstract The timing of the placental mammal radiation has been a source of contention for decades. The fossil record of mammals extends over 200 million years, but no confirmed placental mammal fossils are known prior to 64 million years ago, which is approximately 1.5 million years after the Cretaceous-Paleogene (K-Pg mass extinction that saw the end of non-avian dinosaurs. Thus, it came as a great surprise when the first published molecular clock studies suggested that placental mammals originated instead far back in the Cretaceous, in some cases doubling divergence estimates based on fossils. In the last few decades, more than a hundred new genera of Mesozoic mammals have been discovered, and molecular divergence studies have grown from simple clock-like models applied to a few genes to sophisticated analyses of entire genomes. Yet, molecular and fossil-based divergence estimates for placental mammal origins have remained remote, with knock-on effects for macro-scale reconstructions of mammal evolution. A few recent molecular studies have begun to converge with fossil-based estimates, and a new phylogenomic study in particular shows that the palaeontological record was mostly correct; most placental mammal orders diversified after the K-Pg mass extinction. While a small gap still remains for Late Cretaceous supraordinal divergences, this study has significantly improved the congruence between molecular and palaeontological data and heralds a broader integration of these fields of evolutionary science.

  19. Presence of albumin mRNA precursors in nuclei of analbuminemic rat liver lacking cytoplasmic albumin mRNA.

    OpenAIRE

    Esumi, H; Takahashi, Y; Sekiya, T; Sato, S; Nagase, S; Sugimura, T

    1982-01-01

    Analbuminemic rats, which lack serum albumin, were previously found to have no albumin mRNA in the cytoplasm of the liver. In the present study, the existence of nuclear albumin mRNA precursors in the liver of analbuminemic rats was examined by RNA X cDNA hybridization kinetics. Albumin mRNA precursors were present in the nuclei of analbuminemic rat liver at almost normal levels, despite the absence of albumin mRNA from the cytoplasm. Nuclear RNA of analbuminemic rat liver was subjected to el...

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

    Directory of Open Access Journals (Sweden)

    Terry M Mayhew

    2011-05-01

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

  1. Chlamydia pecorum: fetal and placental lesions in sporadic caprine abortion.

    Science.gov (United States)

    Giannitti, Federico; Anderson, Mark; Miller, Myrna; Rowe, Joan; Sverlow, Karen; Vasquez, Marce; Cantón, Germán

    2016-03-01

    Chlamydial abortion in small ruminants is usually associated with Chlamydia abortus infection. Although Chlamydia pecorum has been detected in aborted ruminants and epidemiological data suggests that C. pecorum is abortigenic in these species, published descriptions of lesions in fetuses are lacking. This work describes fetoplacental lesions in a caprine abortion with C. pecorum infection, and further supports the abortigenic role of C. pecorum in ruminants. A 16-month-old Boer goat aborted twin fetuses at ~130 days of gestation. Both fetuses (A and B) and the placenta of fetus A were submitted for postmortem examination and diagnostic workup. At autopsy, the fetuses had moderate anasarca, intermuscular edema in the hindquarters (A), and brachygnathia and palatoschisis (B). In the placenta, the cotyledons were covered by yellow fibrinosuppurative exudate that extended into the adjacent intercotyledonary areas. Histologically, there was severe suppurative and necrotizing placentitis with vasculitis (arteriolitis) and thrombosis, multifocal lymphohistiocytic and neutrophilic hepatitis (A), and fibrinosuppurative enteritis in both fetuses. Chlamydia antigen was detected in the placenta by the direct fluorescent antibody test and in fetal intestines by immunohistochemistry. Nested polymerase chain reaction of DNA extracted from formalin-fixed, paraffin-embedded sections of placenta and intestine amplified 400 bp of the Chlamydia 16S rRNA gene that was sequenced and found to be 99% identical to C. pecorum by BLAST analysis. Other known abortigenic infectious agents were ruled out by specific testing. It is concluded that C. pecorum infection is associated with fetoplacental lesions and sporadic abortion in goats. © 2015 The Author(s).

  2. Placental Growth Factor Promotes Cardiac Muscle Repair via Enhanced Neovascularization

    Directory of Open Access Journals (Sweden)

    Jianfeng Zhang

    2015-06-01

    Full Text Available Background/Aims: Transplantation of mesenchymal stem cells (MSCs improves post-injury cardiac muscle repair using ill-defined mechanisms. Recently, we have shown that production and secretion of placental growth factor (PLGF by MSCs play a critical role in the MSCs-mediated post-injury cardiac muscle repair. In this study, we addressed the underlying molecular mechanisms, focusing specifically on the interactions between MSCs, macrophages and endothelial cells. Methods: We isolated macrophages (BM-MΦ from mouse bone-marrow derived cells based on F4/80 expression by flow cytometry. BM-MΦ were treated with different doses of PLGF. Cell number was analyzed by a MTT assay. Macrophage polarization was examined based on CD206 expression by flow cytometry. PLGF levels in macrophage subpopulations were analyzed by RT-qPCR and ELISA. Effects of macrophages on vascularization were evaluated by a collagen gel assay using Human umbilical vein endothelial cells (HUVECs co-cultured with PLGF-treated macrophages. Results: PLGF did not increase macrophage number, but dose-dependently polarized macrophages into a M2 subpopulation. M2 macrophages expressed high levels of PLGF. PLGF-polarized M2 macrophages significantly increased tubular structures in the collagen gel assay. Conclusion: Our data suggest that MSCs-derived PLGF may induce macrophage polarization into a M2 subpopulation, which in turn releases more PLGF to promote local neovascularization for augmenting post-injury cardiac muscle repair. This study thus sheds novel light on the role of PLGF in cardiac muscle regeneration.

  3. Seasonal overturning circulation in the Red Sea: 2. Winter circulation

    Science.gov (United States)

    Yao, Fengchao; Hoteit, Ibrahim; Pratt, Larry J.; Bower, Amy S.; Köhl, Armin; Gopalakrishnan, Ganesh; Rivas, David

    2014-04-01

    The shallow winter overturning circulation in the Red Sea is studied using a 50 year high-resolution MITgcm (MIT general circulation model) simulation with realistic atmospheric forcing. The overturning circulation for a typical year, represented by 1980, and the climatological mean are analyzed using model output to delineate the three-dimensional structure and to investigate the underlying dynamical mechanisms. The horizontal model circulation in the winter of 1980 is dominated by energetic eddies. The climatological model mean results suggest that the surface inflow intensifies in a western boundary current in the southern Red Sea that switches to an eastern boundary current north of 24°N. The overturning is accomplished through a cyclonic recirculation and a cross-basin overturning circulation in the northern Red Sea, with major sinking occurring along a narrow band of width about 20 km along the eastern boundary and weaker upwelling along the western boundary. The northward pressure gradient force, strong vertical mixing, and horizontal mixing near the boundary are the essential dynamical components in the model's winter overturning circulation. The simulated water exchange is not hydraulically controlled in the Strait of Bab el Mandeb; instead, the exchange is limited by bottom and lateral boundary friction and, to a lesser extent, by interfacial friction due to the vertical viscosity at the interface between the inflow and the outflow.

  4. Toxicological Responses of Environmental Mixtures: Environmental Metals Mixtures Display Synergistic Induction of Metal-Responsive and Oxidative Stress Genes in Placental Cells

    Science.gov (United States)

    Adebambo, Oluwadamilare A.; Ray, Paul D.; Shea, Damian; Fry, Rebecca C.

    2016-01-01

    Exposure to elevated levels of the toxic metals inorganic arsenic (iAs) and cadmium (Cd) represents a major global health problem. These metals often occur as mixtures in the environment, creating the potential for interactive or synergistic biological effects different from those observed in single exposure conditions. In the present study, environmental mixtures collected from two waste sites in China and comparable mixtures prepared in the laboratory were tested for toxicogenomic response in placental JEG-3 cells. These cells serve as a model for evaluating cellular responses to exposures during pregnancy. One of the mixtures was predominated by iAs and one by Cd. Six gene biomarkers were measured in order to evaluate the effects from the metals mixtures using dose and time-course experiments including: heme oxygenase 1 (HO-1) and metallothionein isoforms (MT1A, MT1F and MT1G) previously shown to be preferentially induced by exposure to either iAs or Cd, and metal transporter genes aquaporin-9 (AQP9) and ATPase, Cu2+ transporting, beta polypeptide (ATP7B). There was a significant increase in the mRNA expression levels of ATP7B, HO-1, MT1A, MT1F, and MT1G in mixture-treated cells compared to the iAs or Cd only-treated cells. Notably, the genomic responses were observed at concentrations significantly lower than levels found at the environmental collection sites. These data demonstrate that metal mixtures increase the expression of gene biomarkers in placental JEG-3 cells in a synergistic manner. Taken together, the data suggest that toxic metals that co-occur may induce detrimental health effects that are currently underestimated when analyzed as single metals. PMID:26472158

  5. Placental cord insertion and birthweight discordance in twin pregnancies: results of the national prospective ESPRiT Study.

    Science.gov (United States)

    Kent, Etaoin M; Breathnach, Fionnuala M; Gillan, John E; McAuliffe, Fionnuala M; Geary, Michael P; Daly, Sean; Higgins, John R; Dornan, James; Morrison, John J; Burke, Gerard; Higgins, Shane; Carroll, Stephen; Dicker, Patrick; Manning, Fiona; Malone, Fergal D

    2011-10-01

    The purpose of this study was to evaluate the impact of noncentral placental cord insertion on birthweight discordance in twins. We performed a multicenter, prospective trial of twin pregnancies. Placental cord insertion was documented as central, marginal, or velamentous according to a defined protocol. Association of the placental cord insertion site with chorionicity, birthweight discordance, and growth restriction were assessed. Eight hundred sixteen twin pairs were evaluated; 165 pairs were monochorionic, and 651 pairs were dichorionic. Monochorionic twins had higher rates of marginal (P = .0068) and velamentous (P < .0001) placental cord insertion. Noncentral placental cord insertion was more frequent in smaller twins of discordant pairs than control pairs (29.8% vs 19.1%; P = .004). Velamentous placental cord insertion in monochorionic twins was associated significantly with birthweight discordance (odds ratio, 3.5; 95% confidence interval, 1.3-9.4) and growth restriction (odds ratio, 4; 95% confidence interval, 1.1-14.3). Noncentral placental cord insertion contributes to birthweight discordance in monochorionic twin pregnancies. Sonographic delineation of placental cord insertion may be of value in antenatal assessment of twin pregnancies. Copyright © 2011 Mosby, Inc. All rights reserved.

  6. ALTERED EXPRESSION OF SURFACE RECEPTORS AT EA.HY926 ENDOTHELIAL CELL LINE INDUCED WITH PLACENTAL SECRETORY FACTORS

    Directory of Open Access Journals (Sweden)

    O. I. Stepanova

    2012-01-01

    Full Text Available Abstract. Placental cell populations produce a great variety of angiogenic factors and cytokines than control angiogenesis in placenta. Functional regulation of endothelial cells proceeds via modulation of endothelial cell receptors for endogenous angiogenic and apoptotic signals. Endothelial phenotype alteration during normal pregnancy and in cases of preclampsia is not well understood. The goal of this investigation was to evaluate altered expression of angiogenic and cytokine receptors at EA.hy926 endothelial cells under the influence of placental tissue supernatants. Normal placental tissue supernatants from 1st and 3rd trimesters, and pre-eclamptic placental tissue supernatants (3rd trimester stimulated angiogenic and cytokine receptors expression by the cultured endothelial cells, as compared with their background expression. Tissue supernatants from placental samples of 3rd trimester caused a decreased expression of angiogenic and cytokine receptors by endothelial cells, thus reflecting maturation of placental vascular system at these terms. Supernatants from preeclamptic placental tissue induced an increase of CD119 expression, in comparison with normal placental supernatants from the 3rd trimester. This finding suggests that IFNγ may be a factor of endothelial activation in pre-eclampsia. The study was supported by grants ГК №02.740.11.0711, НШ-3594.2010.7., and МД-150.2011.7.

  7. Cervical Length & Leading Placental Edge to Internal OS Measurements - TA vs TV

    DEFF Research Database (Denmark)

    Westerway, Sue Campbell; Pedersen, Lars Henning; Hyett, Jon

    Brief Description of the Purpose of the Study: To compare cervical length/leading placental edge from the internal cervical os measurements obtained by both transabdominal (TA) and transvaginal (TV) approach and to assess intra / inter-observer variation for these measurements. Methods: Cross...... sectional study of 374 consecutive pregnancies with gestation 12 weeks to term. The cervical length was estimated as the distance from internal to external os, and the placenta / cervix distance as the leading placental edge to internal cervical os. Bland-Altman plots were used to evaluate the two methods....... Importance of the Conclusions: TA estimates of cervix and placental edge position did not reflect the estimates obtained by TV assessment. As both measures are important markers of pregnancy outcome and management, the transabdominal method in the present form is insuffi- cient in clinical management....

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

    DEFF Research Database (Denmark)

    Obel, E B; Madsen, Mette

    1980-01-01

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

  9. High avidity antibodies to full-length VAR2CSA correlate with absence of placental malaria

    DEFF Research Database (Denmark)

    Tutterrow, Yeung Lo; Salanti, Ali; Avril, Marion

    2012-01-01

    VAR2CSA mediates sequestration of Plasmodium falciparum-infected erythrocytes in the placenta, increasing the risk of poor pregnancy outcomes. Naturally acquired antibodies (Ab) to placental parasites at delivery have been associated with improved pregnancy outcomes, but Ab levels and how early...... in pregnancy Ab must be present in order to eliminate placental parasites before delivery remains unknown. Antibodies to individual Duffy-binding like domains of VAR2CSA have been studied, but the domains lack many of the conformational epitopes present in full-length VAR2CSA (FV2). Thus, the purpose...... of this study was to describe the acquisition of Ab to FV2 in women residing in high and low transmission areas and determine how Ab levels during pregnancy correlate with clearance of placental parasites. Plasma samples collected monthly throughout pregnancy from pregnant women living in high and low...

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

    Science.gov (United States)

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

    1994-01-01

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

  11. Uteroplacental blood flow measured by placental scintigraphy during epidural anaesthesia for caesarean section

    Energy Technology Data Exchange (ETDEWEB)

    Skjoeldebrand, A.; Eklund, J.; Johansson, H.; Lunell, N.-O.; Nylund, L.; Sarby, B.; Thornstroem, S. (Departments of Anaesthesiology, Obstetrics and Gynaecology and Medical Physics, Karolinska Institute at Huddinge University Hospital, Stockholm (Sweden))

    1990-01-01

    The uteroplacental blood flow was measured before and during epidural anaesthesia for caesarean section in 11 woman. The blood flow was measured with dynamic placental scintigraphy. After an i.v. injection of indium-113m chloride, the gamma radiation over the placenta was recorded with a computer-linked scintillation camera. The uteroplacental blood flow could be calculated from the isotope accumulation curve. The anaesthesia was performed with bupivacaine plain 0.5%, 18-22 ml and a preload of a balanced electrolyte solution 10 ml/kg b.w. was given. The placental blood flow decreased in eight patients and increased in three with a median change of -21%, not being statistically significant. No correlation between maternal blood pressure and placental blood flow was found. (author).

  12. Uteroplacental blood flow measured by placental scintigraphy during epidural anaesthesia for caesarean section

    International Nuclear Information System (INIS)

    Skjoeldebrand, A.; Eklund, J.; Johansson, H.; Lunell, N.-O.; Nylund, L.; Sarby, B.; Thornstroem, S.

    1990-01-01

    The uteroplacental blood flow was measured before and during epidural anaesthesia for caesarean section in 11 woman. The blood flow was measured with dynamic placental scintigraphy. After an i.v. injection of indium-113m chloride, the gamma radiation over the placenta was recorded with a computer-linked scintillation camera. The uteroplacental blood flow could be calculated from the isotope accumulation curve. The anaesthesia was performed with bupivacaine plain 0.5%, 18-22 ml and a preload of a balanced electrolyte solution 10 ml/kg b.w. was given. The placental blood flow decreased in eight patients and increased in three with a median change of -21%, not being statistically significant. No correlation between maternal blood pressure and placental blood flow was found. (author)

  13. Growth restriction in gastroschisis: quantification of its severity and exploration of a placental cause

    Directory of Open Access Journals (Sweden)

    Olsen Sam

    2011-10-01

    Full Text Available Abstract Background Gastroschisis patients are commonly small for gestational age (SGA, birth weight [BW] th centile. However, the extent, symmetry and causes of that growth restriction remain controversial. Methods We compared BW, crown-heel length (LT, occipitofrontal circumference (OFC and ponderal index (PI in 179 gastroschisis cases and 895 matched controls by univariate and multiple regression. Fetal ultrasounds (N = 80 were reviewed to determine onset of growth restriction. Placental histology was examined in 31 gastroschisis patients whose placental tissue was available and in 29 controls. Results Gastroschisis cases weighed less than controls (BW = 2400 ± 502 g vs. 2750 ± 532 g, p Conclusions Marked, relatively symmetric intrauterine growth restriction is an intrinsic part of gastroschisis. It begins early in the second trimester, and is associated with placental chorangiosis.

  14. Measurement of utero-placental blood flow with /sup 113m/In in diabetic pregnancy

    International Nuclear Information System (INIS)

    Semmler, K.; Kirsch, G.; Zoellner, P.; Fuhrmann, K.; Jutzi, E.; Ernst-Moritz-Arndt-Universitaet, Greifswald

    1985-01-01

    In 122 diabetic pregnancies the placental blood flow has been estimated determining the half-life of the activity inflow (2 MBq /sup 113m/In-transferrin) into the placenta. A highly sensitive detector (modified pinhole collimator) and a computer-supported evaluation were used. 259 flow measurements were compared to the risk of complication in the course of diabetic pregnancy. The half-life values in the diabetic group, calculated by a gamma camera computer system by means of an iterative regression analysis, were significantly different compared to a control group (12 pregnancies without risk.) Severe diabetic angiopathic complications (classes D, F, and R according to White) are accompanied by higher half-life values (placental blood flow reductions) and perinatal complications. Even in pregnant women with gestational diabetes of disturbances of the carbohydrate metabolism disturbed placental hemodynamics is to be found. (author)

  15. Measurement of utero-placental blood flow with /sup 113m/In in diabetic pregnancy

    Energy Technology Data Exchange (ETDEWEB)

    Semmler, K.; Kirsch, G.; Zoellner, P.; Fuhrmann, K.; Jutzi, E. (Zentralinstitut fuer Diabetes, Karlsburg (German Democratic Republic); Ernst-Moritz-Arndt-Universitaet, Greifswald (German Democratic Republic). Radiologische Klinik)

    1985-01-01

    In 122 diabetic pregnancies the placental blood flow has been estimated determining the half-life of the activity inflow (2 MBq /sup 113m/In-transferrin) into the placenta. A highly sensitive detector (modified pinhole collimator) and a computer-supported evaluation were used. 259 flow measurements were compared to the risk of complication in the course of diabetic pregnancy. The half-life values in the diabetic group, calculated by a gamma camera computer system by means of an iterative regression analysis, were significantly different compared to a control group (12 pregnancies without risk.) Severe diabetic angiopathic complications (classes D, F, and R according to White) are accompanied by higher half-life values (placental blood flow reductions) and perinatal complications. Even in pregnant women with gestational diabetes of disturbances of the carbohydrate metabolism disturbed placental hemodynamics is to be found.

  16. Diagnosis of abnormally invasive posterior placentation: the role of MR imaging.

    Science.gov (United States)

    Kocher, Madison R; Sheafor, Douglas H; Bruner, Evelyn; Newman, Charles; Mateus Nino, Julio Fernando

    2017-06-01

    Abnormally invasive placentation is becoming more common with a recent increase in cesarean sections and maternal age, among other risk factors. Ultrasonography is the first line-imaging, but it can be difficult to diagnose when limiting factors are present. Failure to recognize this serious placental abnormality precludes us from making the appropriate plan for the delivery and consequently can lead to fatal results. In this report, we present a case in which magnetic resonance imaging was used to diagnose posterior placenta increta missed by multiple sonographic examinations in a patient with previous myomectomies, and we also include a review of the literature on this topic. It is our conclusion that magnetic resonance imaging is superior to sonography to diagnose abnormally invasive placentation in cases of posterior placenta previa and high pretesting probability.

  17. Diagnosis of abnormally invasive posterior placentation: the role of MR imaging

    Directory of Open Access Journals (Sweden)

    Madison R. Kocher, BS

    2017-06-01

    Full Text Available Abnormally invasive placentation is becoming more common with a recent increase in cesarean sections and maternal age, among other risk factors. Ultrasonography is the first line-imaging, but it can be difficult to diagnose when limiting factors are present. Failure to recognize this serious placental abnormality precludes us from making the appropriate plan for the delivery and consequently can lead to fatal results. In this report, we present a case in which magnetic resonance imaging was used to diagnose posterior placenta increta missed by multiple sonographic examinations in a patient with previous myomectomies, and we also include a review of the literature on this topic. It is our conclusion that magnetic resonance imaging is superior to sonography to diagnose abnormally invasive placentation in cases of posterior placenta previa and high pretesting probability.

  18. Increased IL-10 mRNA and IL-23 mRNA expression in multiple sclerosis

    DEFF Research Database (Denmark)

    Krakauer, Martin; Sorensen, P; Khademi, M

    2008-01-01

    BACKGROUND: Interferon (IFN)-beta therapy in multiple sclerosis (MS) has been suggested to promote a deviation from T lymphocyte production of pathogenic Th1 cytokines to less detrimental Th2 cytokines, but this is still controversial. We studied patterns of in vivo blood mononuclear cell (MNC...... of any Th1 or Th2 cytokines. The largest changes in cytokine mRNA levels occurred early (~9-12 h) after an IFN-beta injection. CONCLUSION: We found no evidence of a Th1- or Th2-mRNA-promoting effect of IFN-beta therapy. The therapeutic effect of IFN-beta is more likely attributable to the induction...

  19. Toxicological responses of environmental mixtures: Environmental metal mixtures display synergistic induction of metal-responsive and oxidative stress genes in placental cells

    Energy Technology Data Exchange (ETDEWEB)

    Adebambo, Oluwadamilare A. [Department of Biological Sciences, North Carolina State University (United States); Ray, Paul D. [Department of Environmental Sciences and Engineering, Gillings School of Global Public Health, University of North Carolina, Chapel Hill (United States); Shea, Damian [Department of Biological Sciences, North Carolina State University (United States); Fry, Rebecca C., E-mail: rfry@unc.edu [Department of Environmental Sciences and Engineering, Gillings School of Global Public Health, University of North Carolina, Chapel Hill (United States)

    2015-12-15

    Exposure to elevated levels of the toxic metals inorganic arsenic (iAs) and cadmium (Cd) represents a major global health problem. These metals often occur as mixtures in the environment, creating the potential for interactive or synergistic biological effects different from those observed in single exposure conditions. In the present study, environmental mixtures collected from two waste sites in China and comparable mixtures prepared in the laboratory were tested for toxicogenomic response in placental JEG-3 cells. These cells serve as a model for evaluating cellular responses to exposures during pregnancy. One of the mixtures was predominated by iAs and one by Cd. Six gene biomarkers were measured in order to evaluate the effects from the metal mixtures using dose and time-course experiments including: heme oxygenase 1 (HO-1) and metallothionein isoforms (MT1A, MT1F and MT1G) previously shown to be preferentially induced by exposure to either iAs or Cd, and metal transporter genes aquaporin-9 (AQP9) and ATPase, Cu{sup 2+} transporting, beta polypeptide (ATP7B). There was a significant increase in the mRNA expression levels of ATP7B, HO-1, MT1A, MT1F, and MT1G in mixture-treated cells compared to the iAs or Cd only-treated cells. Notably, the genomic responses were observed at concentrations significantly lower than levels found at the environmental collection sites. These data demonstrate that metal mixtures increase the expression of gene biomarkers in placental JEG-3 cells in a synergistic manner. Taken together, the data suggest that toxic metals that co-occur may induce detrimental health effects that are currently underestimated when analyzed as single metals. - Highlights: • Toxicogenomic responses of environmental metal mixtures assessed • Induction of ATP7B, HO-1, MT1A, MT1F and MT1G by metal mixtures observed in placental cells • Higher gene induction in response to metal mixtures versus single metal treatments.

  20. Toxicological responses of environmental mixtures: Environmental metal mixtures display synergistic induction of metal-responsive and oxidative stress genes in placental cells

    International Nuclear Information System (INIS)

    Adebambo, Oluwadamilare A.; Ray, Paul D.; Shea, Damian; Fry, Rebecca C.

    2015-01-01

    Exposure to elevated levels of the toxic metals inorganic arsenic (iAs) and cadmium (Cd) represents a major global health problem. These metals often occur as mixtures in the environment, creating the potential for interactive or synergistic biological effects different from those observed in single exposure conditions. In the present study, environmental mixtures collected from two waste sites in China and comparable mixtures prepared in the laboratory were tested for toxicogenomic response in placental JEG-3 cells. These cells serve as a model for evaluating cellular responses to exposures during pregnancy. One of the mixtures was predominated by iAs and one by Cd. Six gene biomarkers were measured in order to evaluate the effects from the metal mixtures using dose and time-course experiments including: heme oxygenase 1 (HO-1) and metallothionein isoforms (MT1A, MT1F and MT1G) previously shown to be preferentially induced by exposure to either iAs or Cd, and metal transporter genes aquaporin-9 (AQP9) and ATPase, Cu 2+ transporting, beta polypeptide (ATP7B). There was a significant increase in the mRNA expression levels of ATP7B, HO-1, MT1A, MT1F, and MT1G in mixture-treated cells compared to the iAs or Cd only-treated cells. Notably, the genomic responses were observed at concentrations significantly lower than levels found at the environmental collection sites. These data demonstrate that metal mixtures increase the expression of gene biomarkers in placental JEG-3 cells in a synergistic manner. Taken together, the data suggest that toxic metals that co-occur may induce detrimental health effects that are currently underestimated when analyzed as single metals. - Highlights: • Toxicogenomic responses of environmental metal mixtures assessed • Induction of ATP7B, HO-1, MT1A, MT1F and MT1G by metal mixtures observed in placental cells • Higher gene induction in response to metal mixtures versus single metal treatments

  1. Prognostic impact of clinical course-specific mRNA expression profiles in the serum of perioperative patients with esophageal cancer in the ICU: a case control study

    Directory of Open Access Journals (Sweden)

    Oshima Yoshiaki

    2010-10-01

    Full Text Available Abstract Background We previously reported that measuring circulating serum mRNAs using quantitative one-step real-time RT-PCR was clinically useful for detecting malignancies and determining prognosis. The aim of our study was to find crucial serum mRNA biomarkers in esophageal cancer that would provide prognostic information for post-esophagectomy patients in the critical care setting. Methods We measured serum mRNA levels of 11 inflammatory-related genes in 27 post-esophagectomy patients admitted to the intensive care unit (ICU. We tracked these levels chronologically, perioperatively and postoperatively, until the two-week mark, investigating their clinical and prognostic significance as compared with clinical parameters. Furthermore, we investigated whether gene expression can accurately predict clinical outcome and prognosis. Results Circulating mRNAs in postoperative esophagectomy patients had gene-specific expression profiles that varied with the clinical phase of their treatment. Multivariate regression analysis showed that upregulation of IL-6, VWF and TGF-β1 mRNA in the intraoperative phase (p = 0.016, 0.0021 and 0.009 and NAMPT and MUC1 mRNA on postoperative day 3 (p ®, Ono Pharmaceutical Co., Ltd. significantly correlated with MUC1 and NAMPT mRNA expression (p = 0.048 and 0.045. IL-6 mRNA correlated with hypercytokinemia and recovery from hypercytokinemia (sensitivity 80.9% and was a significant biomarker in predicting the onset of severe inflammatory diseases. Conclusion Chronological tracking of postoperative mRNA levels of inflammatory-related genes in esophageal cancer patients may facilitate early institution of pharamacologic therapy, prediction of treatment response, and prognostication during ICU management in the perioperative period.

  2. Even a Chronic Mild Hyperglycemia Affects Membrane Fluidity and Lipoperoxidation in Placental Mitochondria in Wistar Rats

    Science.gov (United States)

    Figueroa-García, María del Consuelo; Espinosa-García, María Teresa; Martinez-Montes, Federico; Palomar-Morales, Martín; Mejía-Zepeda, Ricardo

    2015-01-01

    It is known the deleterious effects of diabetes on embryos, but the effects of diabetes on placenta and its mitochondria are still not well known. In this work we generated a mild hyperglycemia model in female wistar rats by intraperitoneal injection of streptozotocin in 48 hours-old rats. The sexual maturity onset of the female rats was delayed around 6–7 weeks and at 16 weeks-old they were mated, and sacrificed at day 19th of pregnancy. In placental total tissue and isolated mitochondria, the fatty acids composition was analyzed by gas chromatography, and lipoperoxidation was measured by thiobarbituric acid reactive substances. Membrane fluidity in mitochondria was measured with the excimer forming probe dipyrenylpropane and mitochondrial function was measured with a Clark-type electrode. The results show that even a chronic mild hyperglycemia increases lipoperoxidation and decreases mitochondrial function in placenta. Simultaneously, placental fatty acids metabolism in total tissue is modified but in a different way than in placental mitochondria. Whereas the chronic mild hyperglycemia induced a decrease in unsaturated to saturated fatty acids ratio (U/S) in placental total tissue, the ratio increased in placental mitochondria. The measurements of membrane fluidity showed that fluidity of placenta mitochondrial membranes increased with hyperglycemia, showing consistency with the fatty acids composition through the U/S index. The thermotropic characteristics of mitochondrial membranes were changed, showing lower transition temperature and activation energies. All of these data together demonstrate that even a chronic mild hyperglycemia during pregnancy of early reproductive Wistar rats, generates an increment of lipoperoxidation, an increase of placental mitochondrial membrane fluidity apparently derived from changes in fatty acids composition and consequently, mitochondrial malfunction. PMID:26630275

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

    Science.gov (United States)

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

    2018-02-01

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

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

    Science.gov (United States)

    McCormack, Shelley A; Best, Brookie M

    2014-11-01

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

  5. Clinical significance of the molecular detection of melanoma cells circulating in the peripheral blood in melanoma patients.

    Science.gov (United States)

    Konstantopoulos, K; Psatha, M; Kalotychou, V; Frangia, N; Ioannovits, I; Meletis, I; Loukopoulos, D

    2001-06-01

    Blood circulating melanoma cells may be important for the spread of the disease. The current methods are not sensitive in detecting micro metastases. Tyrosinase mRNA can be detected in peripheral blood by a molecular test. As tyrosinase is expressed only in melanocytes and melanocytes normally do not circulate in the blood, the test may prove reliable in detecting circulating melanoma cells. we used a reverse-transcription polymerase chain reaction (RT-PCR) detecting tyrosinase mRNA in the blood. A prospective investigation in melanoma patients undergoing surgery was conducted; follow-up duration was 12 months. University Department Laboratory and Melanoma Clinic of a Tertiary Hospital. a total of 27 Greek patients with a diagnosis of malignant melanoma at different stages of the disease; 12 months follow-up after surgery. Samples form 12 healthy volunteers and 13 patients with chronic myelogenous leukemia served as controls. none. none. We detected mRNA tyrosinase in the peripheral blood in 16 out of 27 melanoma patients studied. No tyrosinase mRNA was detected in any of the 25 samples from the controls. Two of the 16 positive cases developed a metastasis within the next 12 months following testing. The other 14 positive cases remain metastasis free for this period, as also did the test negative cases. Detection of blood circulating melanoma cells by a RT-PCR technique, may be helpful in defining melanoma patients who are at risk for the spread of the disease.

  6. Maternal factors associated with fetal growth and birthweight are independent determinants of placental weight and exhibit differential effects by fetal sex.

    Directory of Open Access Journals (Sweden)

    Marie Cecilie Paasche Roland

    Full Text Available INTRODUCTION: Maternal nutritional and metabolic factors influence the developmental environment of the fetus. Virtually any nutritional factor in the maternal blood has to pass the placental membranes to reach the fetal blood. Placental weight is a commonly used measure to summarize placental growth and function. Placental weight is an independent determinant of fetal growth and birthweight and modifies the associations between maternal metabolic factors and fetal growth. We hypothesized that maternal factors known to be related to fetal growth, newborn size and body composition are determinants of placental weight and that effects of maternal metabolic factors on placental weight differ between the genders. METHODS: The STORK study is a prospective longitudinal study including 1031 healthy pregnant women of Scandinavian heritage with singleton pregnancies. Maternal determinants (parity, body mass index, gestational weight gain and fasting plasma glucose of placental weight were explored by linear regression models, stratified by fetal sex. RESULTS: Parity, maternal BMI, gestational weight gain and fasting glucose had positive effects on placental weight. There was a sex specific effect in these associations. Fasting glucose was significantly associated with placental weight in females but not in males. CONCLUSION: Maternal factors known to influence fetal growth, birthweight and neonatal body composition are determinants of placental weight. The effect of maternal factors on placental weight is influenced by sex as illustrated in the relation between maternal glucose and placental weight.

  7. Prediction of low birth weight: the placental T2* estimated by MRI versus the uterine artery pulsatility index

    DEFF Research Database (Denmark)

    Sinding, Marianne Munk; Peters, David Alberg; Frøkjær, Jens Brøndum

    (MRI) variable T2* reflects the placental oxygenation and thereby placental function. Therefore, we aimed to evaluate the performance of placental T2* in the prediction of low birth weight using the uterine artery (UtA) pulsatility index (PI) as gold standard. Methods: The study population......CONTROL ID: 2516296 ABSTRACT FINAL ID: P22.05 TITLE: Prediction of low birth weight: the placental T2* estimated by MRI versus the uterine artery pulsatility index AUTHORS (FIRST NAME, LAST NAME): Marianne Sinding1, David Peters2, Jens B. Frøkjær3, 4, Ole B. Christiansen1, 4, Astrid Petersen5...... had an EFW T2* was measured by MRI at 1.5T. A gradient recalled echo MRI sequence with readout at 16 echo times was used, and the placental T2* value was obtained by fitting the signal intensity as a function of the echo times...

  8. Tumor placentário diagnosticado durante a gravidez: relato de caso Placental tumor diagnosed in pregnancy: a case report

    Directory of Open Access Journals (Sweden)

    Francisco Mauad Filho

    2002-08-01

    Full Text Available O tumor não trofoblástico placentário encontrado com maior freqüência é o corioangioma, com incidência de aproximadamente 1%. Quando são pequenos, geralmente não levam a alterações fetais, mas quando são grandes, podem levar a restrição de crescimento intra-útero, poliidrâmnio, trabalho de parto prematuro, insuficiência cardíaca congestiva e morte fetal. Os autores relatam um caso de corioangioma em uma paciente de 28 anos, diagnosticado em exame ultra-sonográfico de rotina, com idade gestacional de 32 semanas. O diagnóstico foi confirmado pelo exame anatomopatológico. As avaliações ultra-sonográficas revelaram a presença de sofrimento fetal crônico, que levou à interrupção da gestação com 36 semanas. Os resultados neonatais foram satisfatórios, com Apgar de 9-10 e peso fetal de 2.460 gramas.The most frequently nontrophoblastic tumor of the placenta found is chorioangioma, with an incidence of about 1%. When they are small, they do not significantly affect the fetus, but the large ones can cause intrauterine growth restriction, polyhydramnios, premature delivery, congestive heart failure and fetal death. The authors report a case of chorioangioma in a 28-year-old woman, second gestation, whose diagnosis was established at the 32nd week by ultrasound and confirmed by the anatomopathological examination. Ultrasonography evaluations showed chronic fetal distress and the delivery was performed at 36 weeks. The newborn results were satisfactory with Apgar 9-10 and fetal weight 2.460 g.

  9. The effects of air pollution and smoking on placental cadmium, zinc concentration and metallothionein expression

    International Nuclear Information System (INIS)

    Sorkun, Hulya Cetin; Bir, Ferda; Akbulut, Metin; Divrikli, Umit; Erken, Gulten; Demirhan, Huriye; Duzcan, Ender; Elci, Latif; Celik, Ismail; Yozgatli, Unsal

    2007-01-01

    This study is designed to determine the placental zinc (Zn) and cadmium (Cd) levels in mothers who were smokers, mothers who were thought to be exposed to air pollution, and mothers who were non-smokers and to investigate the relationship between the expression of placental metallothionein (MT) binding these metals and blood progesterone level. Placental Zn and Cd levels were measured by atomic absorption spectrometry. Presence of placental MT was determined immunohistochemically. Placental changes were examined by light microscope after H and E and PAS staining. Immunohistochemical MT staining of syncytiotrophoblastic and villous interstitial cells were scored as positive or negative. Among the 92 mothers included in the study, 33 were smokers (Group I), 29 had been exposed to air pollution (Group II) and 30 were non-smoker rural residents who had never been exposed to air pollution (Group III). Mean off-spring birth weight of 3198.62 ± 380.01 g and mean placenta weight of 561.38 ± 111.55 g of Group II were lower when compared with those of other two groups. In Group I, mean placental Cd and Zn were 0.063 ± 0.022 μg/g and 39.84 ± 15.5 μg/g, res