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Sample records for endocrinologically active trophoblast

  1. Y-27632 enhances differentiation of blastocyst like cystic human embryoid bodies to endocrinologically active trophoblast cells on a biomimetic platform

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    Totey Satish M

    2009-09-01

    Full Text Available Abstract Trophoblast differentiation and formation of the placenta are important events linked to post-implantation embryonic development. Models mimicking the biology of trophoblast differentiation in a post-implantation maternal microenvironment are needed for understanding disorders like placental-ischemia or for applications in drug-screening, and would help in overcoming the ethical impasse on using human embryos for such research. Here we attempt to create such a model by using embryoid bodies (EBs and a biomimetic platform composed of a bilayer of fibronectin and gelatin on top of low-melting agarose. Using this model we test the hypothesis that cystic-EBs (day 30 that resemble blastocysts morphologically, are better sources as compared to noncytic EBs (day 10, for functional trophoblast differentiation; and that the Rho kinases inhibitor Y27632 can enhance this differentiation. Non/cytic EBs with/out Y27632 were grown on this platform for 28 days, and screened from secretion and expression of trophoblast and other lineage markers using ECLIA, RT-PCR, and Immunofluorescence. All EBs attached on this surface and rapidly proliferated into hCG and progesterone (P2 secreting functional trophoblast cells. However, the cells derived from cytic-EBs and cytic-EBs+ Y27632 showed the maximum secretion of these hormones and expressed IGF2, supporting our hypothesis. Also Y27632 reduced extraembryonic endoderm and trophoblast lineage differentiation from early noncystic-EBs, whereas, it specifically enhanced the induction of trophoblast and multinucleated syncitiotrophoblast differentiation from late cystic-EBs. In vivo trophoblast differentiation can be replicated in fibronectin based biomaterials, using cytic-EBs and by maneuvering the Rho-ROCK pathways. Response of EBs to a compound may vary temporally, and determination of their right stage is crucial for applications in directed-differentiation or drug-screening.

  2. Leukemia inhibitory factor promote trophoblast invasion via urokinase-type plasminogen activator receptor in preeclampsia.

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    Zheng, Qin; Dai, Kuixing; Cui, Xinyuan; Yu, Ming; Yang, Xuesong; Yan, Bin; Liu, Shuai; Yan, Qiu

    2016-05-01

    Preeclampsia is a pregnancy-related syndrome which can cause perinatal mortality and morbidity. Inadequate invasion by trophoblast cells may lead to poor perfusion of the placenta, even result in preeclampsia. Understanding the molecular mechanisms underlying placentation facilitates the better intervention of preeclampsia. Urokinase-type plasminogen activator receptor (uPAR) is involved in the physiological and pathological processes. Leukemia inhibitory factor (LIF) is an important regulator in the establishment of pregnancy. However, the expression of uPAR in preeclamptic patients and its relationship with LIF remains unclear. In the current study, we found that the level of uPAR was relatively lower in the placentas from preeclamptic patients as compared with normal pregnant women. LIF promoted trophoblast cell outgrowth by upregulating uPAR in an explants culture, and LIF also enhanced migration and invasion potential through uPAR in trophoblast JAR and JEG-3 cell lines, and with increased gelatinolytic activities of matrix metalloproteinase 2 (MMP-2). The effect of LIF and uPAR on trophoblast migration and invasion was mediated by PI3K/AKT signaling pathway. Our data indicates the roles of LIF in promoting trophoblast migration and invasion through uPAR and suggest that abnormal expression of uPAR might be associated with the etiology of preeclampsia. Copyright © 2016 Elsevier Masson SAS. All rights reserved.

  3. HCG-Activated Human Peripheral Blood Mononuclear Cells (PBMC Promote Trophoblast Cell Invasion.

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    Nan Yu

    Full Text Available Successful embryo implantation and placentation depend on appropriate trophoblast invasion into the maternal endometrial stroma. Human chorionic gonadotropin (hCG is one of the earliest embryo-derived secreted signals in the peripheral blood mononuclear cells (PBMC that abundantly expresses hCG receptors. The aims of this study were to estimate the effect of human embryo-secreted hCG on PBMC function and investigate the role and underlying mechanisms of activated PBMC in trophoblast invasion. Blood samples were collected from women undergoing benign gynecological surgery during the mid-secretory phase. PBMC were isolated and stimulated with or without hCG for 0 or 24 h. Interleukin-1β (IL-1β and leukemia inhibitory factor (LIF expressions in PBMC were detected by enzyme-linked immunosorbent assay and real-time polymerase chain reaction (PCR. The JAR cell line served as a model for trophoblast cells and was divided into four groups: control, hCG only, PBMC only, and PBMC with hCG. JAR cell invasive and proliferative abilities were detected by trans-well and CCK8 assays and matrix metalloproteinase (MMP-2 (MMP-2, MMP-9, vascular endothelial growth factor (VEGF, tissue inhibitor of metalloproteinase (TIMP-1, and TIMP-2 expressions in JAR cells were detected by western blotting and real-time PCR analysis. We found that hCG can remarkably promote IL-1β and LIF promotion in PBMC after 24-h culture. PBMC activated by hCG significantly increased the number of invasive JAR cells in an invasion assay without affecting proliferation, and hCG-activated PBMC significantly increased MMP-2, MMP-9, and VEGF and decreased TIMP-1 and TIMP-2 expressions in JAR cells in a dose-dependent manner. This study demonstrated that hCG stimulates cytokine secretion in human PBMC and could stimulate trophoblast invasion.

  4. Knockdown of Heparanase Suppresses Invasion of Human Trophoblasts by Activating p38 MAPK Signaling Pathway

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    Guanglu Che

    2018-01-01

    Full Text Available Preeclampsia is a pregnancy-related disease with increasing maternal and perinatal morbidity and mortality worldwide. Defective trophoblast invasion is considered to be a major factor in the pathophysiological mechanism of preeclampsia. Heparanase, the only endo-β-glucuronidase in mammalian cells, has been shown to be abnormally expressed in the placenta of preeclampsia patients in our previous study. The biological role and potential mechanism of heparanase in trophoblasts remain unclear. In the present study, stably transfected HTR8/SVneo cell lines with heparanase overexpression or knockdown were constructed. The effect of heparanase on cellular proliferation, apoptosis, invasion, tube formation, and potential pathways in trophoblasts was explored. Our results showed that overexpression of heparanase promoted proliferation and invasion. Knockdown of heparanase suppressed proliferation, invasion, and tube formation but induced apoptosis. These findings reveal that downregulation of heparanase may contribute to defective placentation and plays a crucial role in the pathogenesis of preeclampsia. Furthermore, increased activation of p38 MAPK in heparanase-knockdown HTR8/SVneo cell was shown by MAPK pathway phosphorylation array and Western blotting assay. After pretreatment with 3 specific p38 MAPK inhibitors (BMS582949, SB203580, or BIRB796, inadequate invasion in heparanase-knockdown HTR8/SVneo cell was rescued. That indicates that knockdown of heparanase decreases HTR8/SVneo cell invasion through excessive activation of the p38 MAPK signaling pathway. Our study suggests that heparanase can be a potential predictive biomarker for preeclampsia at an early stage of pregnancy and represents a promising therapeutic target for the treatment of preeclampsia.

  5. IL-27 Activates Human Trophoblasts to Express IP-10 and IL-6: Implications in the Immunopathophysiology of Preeclampsia

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    Nanlin Yin

    2014-01-01

    Full Text Available Purpose. To investigate the effects of IL-27 on human trophoblasts and the underlying regulatory signaling mechanisms in preeclampsia. Methods. The expression of IL-27 and IL-27 receptor (WSX-1 was studied in the placenta or sera from patients with preeclampsia. In vitro, we investigated the effects of IL-27 alone or in combination with inflammatory cytokine tumor necrosis factor (TNF-α on the proinflammatory activation of human trophoblast cells (HTR-8/SVneo and the underlying intracellular signaling molecules. Results. The expression of IL-27 and IL-27 receptor α (WSX-1 was significantly elevated in the trophoblastic cells from the placenta of patients with preeclampsia compared with control specimens. In vitro, IL-27 could induce the expression of inflammatory factors IFN-γ-inducible protein 10 (CXCL10/IP-10 and IL-6 in trophoblasts, and a synergistic effect was observed in the combined treatment of IL-27 and TNF-α on the release of IP-10 and IL-6. Furthermore, the production of IP-10 and IL-6 stimulated by IL-27 was differentially regulated by intracellular activation of phosphatidylinositol 3-OH kinase-AKT, p38MAPK, and JAK/STAT pathways. Conclusions. These results provide a new insight into the IL-27-activated immunopathological effects mediated by distinct intracellular signal transduction molecules in preeclampsia.

  6. Outer Membrane Protein 25 of Brucella Activates Mitogen-Activated Protein Kinase Signal Pathway in Human Trophoblast Cells

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    Jing Zhang

    2017-12-01

    Full Text Available Outer membrane protein 25 (OMP25, a virulence factor from Brucella, plays an important role in maintaining the structural stability of Brucella. Mitogen-activated protein kinase (MAPK signal pathway widely exists in eukaryotic cells. In this study, human trophoblast cell line HPT-8 and BALB/c mice were infected with Brucella abortus 2308 strain (S2308 and 2308ΔOmp25 mutant strain. The expression of cytokines and activation of MAPK signal pathway were detected. We found that the expressions of tumor necrosis factor-α, interleukin-1, and interleukin-10 (IL-10 were increased in HPT-8 cells infected with S2308 and 2308ΔOmp25 mutant. S2308 also activated p38 phosphorylation protein, extracellular-regulated protein kinases (ERK, and Jun-N-terminal kinase (JNK from MAPK signal pathway. 2308ΔOmp25 could not activate p38, ERK, and JNK branches. Immunohistochemistry experiments showed that S2308 was able to activate phosphorylation of p38 and ERK in BABL/c mice. However, 2308ΔOmp25 could weakly activate phosphorylation of p38 and ERK. These results suggest that Omp25 played an important role in the process of Brucella activation of the MAPK signal pathway.

  7. Conservation endocrinology

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    McCormick, Stephen; Romero, L. Michael

    2017-01-01

    Endocrinologists can make significant contributions to conservation biology by helping to understand the mechanisms by which organisms cope with changing environments. Field endocrine techniques have advanced rapidly in recent years and can provide substantial information on the growth, stress, and reproductive status of individual animals, thereby providing insight into current and future responses of populations to changes in the environment. Environmental stressors and reproductive status can be detected nonlethally by measuring a number of endocrine-related endpoints, including steroids in plasma, living and nonliving tissue, urine, and feces. Information on the environmental or endocrine requirements of individual species for normal growth, development, and reproduction will provide critical information for species and ecosystem conservation. For many taxa, basic information on endocrinology is lacking, and advances in conservation endocrinology will require approaches that are both “basic” and “applied” and include integration of laboratory and field approaches.

  8. Sphingosine-1-phosphate promotes extravillous trophoblast cell invasion by activating MEK/ERK/MMP-2 signaling pathways via S1P/S1PR1 axis activation.

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    Yang, Weiwei; Li, Qinghua; Pan, Zhifang

    2014-01-01

    Successful placentation depends on the proper invasion of extravillous trophoblast (EVT) cells into maternal tissues. Previous reports demonstrated that S1P receptors are expressed in the EVT cells and S1P could regulate migration and function of trophoblast cells via S1P receptors. However, little is known about roles of S1P in the invasion of EVT cells. Our study was performed to investigate S1P effect on the invasion of EVT cells. We used the extravillous trophoblast cell line HTR8/SVneo cells to evaluate the effect. In vitro invasion assay was employed to determine the invasion of HTR8/SVneo cells induced by S1P. MMP-2 enzyme activity and relative level in the supernatants of HTR8/SVneo was assessed by gelatin zymography and western blot. Based on the above, siRNA and specific inhibitors were used for the intervention and study of potential signal pathways, and Real-time qPCR and western blot were used to test the mRNA and protein level of potential signal targets. We found that S1P could promote HTR8/SVneo cell invasion and upregulates activity and level of MMP-2. The promotion requires activation of MEK-ERK and is dependent on the axis of S1P/S1PR1. Our investigation of S1P may provide new insights into the molecular mechanisms of EVT invasion.

  9. Antiphospholipid antibody-induced miR-146a-3p drives trophoblast interleukin-8 secretion through activation of Toll-like receptor 8.

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    Gysler, Stefan M; Mulla, Melissa J; Guerra, Marta; Brosens, Jan J; Salmon, Jane E; Chamley, Lawrence W; Abrahams, Vikki M

    2016-07-01

    What is the role of microRNAs (miRs) in antiphospholipid antibody (aPL)-induced trophoblast inflammation? aPL-induced up-regulation of trophoblast miR-146a-3p is mediated by Toll-like receptor 4 (TLR4), and miR-146a-3p in turn drives the cells to secrete interleukin (IL)-8 by activating the RNA sensor, TLR8. Obstetric antiphospholipid syndrome (APS) is an autoimmune disorder characterized by circulating aPL and an increased risk of pregnancy complications. We previously showed that aPL recognizing beta2 glycoprotein I (β2GPI) elicit human first trimester trophoblast secretion of IL-8 by activating TLR4. Since some miRs control TLR responses, their regulation in trophoblast cells by aPL and functional role in the aPL-mediated inflammatory response was investigated. miRs can be released from cells via exosomes, and therefore, miR exosome expression was also examined. A panel of miRs was selected based on their involvement with TLR signaling: miR-9; miR-146a-5p and its isomiR, miR-146a-3p; miR-155, miR-210; and Let-7c. Since certain miRs can activate the RNA sensor, TLR8, this was also investigated. For in vitro studies, the human first trimester extravillous trophoblast cell line, HTR8 was studied. HTR8 cells transfected to express a TLR8 dominant negative (DN) were also used. Plasma was evaluated from pregnant women who have aPL, either with or without systemic lupus erythematous (SLE) (n = 39); SLE patients without aPL (n = 30); and healthy pregnant controls (n = 20). Trophoblast HTR8 wildtype and TLR8-DN cells were incubated with or without aPL (mouse anti-human β2GPI mAb) for 48-72 h. HTR8 cells were also treated with or without aPL in the presence and the absence of a TLR4 antagonist (lipopolysaccharide from Rhodobacter sphaeroides; LPS-RS), specific miR inhibitors or specific miR mimics. miR expression levels in trophoblast cells, trophoblast-derived exosomes and exosomes isolated from patient plasma were measured by qPCR. Trophoblast IL-8 secretion was

  10. Ets-2 and p53 mediate cAMP-induced MMP-2 expression, activity and trophoblast invasion

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    Goldman Shlomit

    2009-11-01

    Full Text Available Abstract Background We have previously shown that Matrix metalloproteinase (MMP -2 is a key-enzyme in early trophoblast invasion and that Protein Kinase A (PKA increases MMP-2 expression and trophoblast invasion. The aim of this study was to examine MMP -2 regulation by PKA in invasive trophoblasts: JAR choriocarcinoma cell-line and 6-8 w first trimester trophoblasts. Methods The effect of Forskolin (PKA on MMP-2 expression was assessed by Northern Blot and RT-PCR. Possible transcription factors binding to consensus MMP-2 promoter sequences in response to Forskolin, were detected by EMSA binding assay and their expression assessed by western blot analysis. Antisense transfection of relevant transcription factors was performed and the inhibitory effect assessed on MMP-2 expression (RT-PCR, secretion (zymography and trophoblast invasiveness (transwell migration assay. Results We found that Forskolin increased MMP-2 mRNA in JAR cells within 24 hours, and induced binding to p53, Ets, C/EBP and AP-2. Transcription factors Ets-2, phospho- p53, C/EBP epsilon, C/EBP lambda and AP-2 alpha bound to their respective binding sequences in response to Forskolin and the expressions of these transcription factors were all elevated in Forskolin- treated cells. Inhibition of Ets-2 and p53 reduced MMP-2 expression, secretion and invasiveness of Forskolin treated cells. Conclusion MMP-2 is regulated by PKA through several binding sites and transcription factors including Ets-2, p53, C/EBP, C/EBP lambda and AP-2 alpha. Ets-2 and p53 mediate cAMP- induced trophoblast invasiveness, through regulation of MMP-2.

  11. Pediatric Endocrinology Nurses Society

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    ... Join Now International Welcome to PENS The Pediatric Endocrinology Nursing Society (PENS) is committed to the development ... nurses in the art and science of pediatric endocrinology nursing. Learn More Text1 2018 PENS Call for ...

  12. [Trophoblast: conductor of the maternal immune tolerance].

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    Mesdag, V; Salzet, M; Vinatier, D

    2014-11-01

    Pregnancy is a temporary semi-allograft that survives for nine months. The importance of this event for the survival of the species justifies several tolerance mechanisms that are put into place at the beginning of pregnancy, some of which occur even at the time of implantation. The description of these mechanisms underlines the leadership of the trophoblast. The trophoblast is the conductor of the events, protects himself by expressing specific antigens and regulates the environment of the decidua according to the calendar of the events of the pregnancy The trophoblast and the decidual environment attract the effectors of immunity, almost all present in the decidua. The immunological atmosphere of the decidua evolves during the pregnancy modulating the level of activation of the immunological cells and adapting the level of activation to the stage of the pregnancy. Copyright © 2014 Elsevier Masson SAS. All rights reserved.

  13. Computerized tomography in endocrinology

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    Kurtz, B.; Schmiedl, U.; Huebener, K.H.

    1987-01-05

    The role of CT in the evaluation of endocrinologic disorders is discussed and typical CT-findings in disease of the hypophysis, the thyroid, the parathyroid, the thymus and the pancreas are shown. Special interest is laid on adrenal disorders. This survey informs the clinician about the diagnostic value of CT in endocrinology.

  14. Computerized tomography in endocrinology

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    Kurtz, B.; Schmiedl, U.; Huebener, K.H.

    1987-01-01

    The role of CT in the evaluation of endocrinologic disorders is discussed and typical CT-findings in disease of the hypophysis, the thyroid, the parathyroid, the thymus and the pancreas are shown. Special interest is laid on adrenal disorders. This survey informs the clinician about the diagnostic value of CT in endocrinology. (orig.) [de

  15. Gestational Trophoblastic Disease -Choriocarcinoma

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    Bozik, M.

    2011-01-01

    Gestational trophoblastic tumors are a group of a diseases from the benign hydatidiform mole, through the invasive mole to the highly malignant form of a choriocarcinoma. Choriocarcinoma is a rare tumor and it is the most malignant and aggressive neoplasm of all the gestational trophoblastic diseases. It grows rapidly and metastasizes to the lung, liver, and, less frequently, to the brain. The author presents the case of a 26-year-old woman who is indicated to the CT examination for suspected brain tumor based on the previous examinations. The patient was diagnosed with metastatic choriocarcinoma to the brain, kidney and adrenal gland on the basis of an anamnesis by her husband, a high value of beta-hCG and a gynecological examination. (author)

  16. Thyrotropic Activity of Various Adenohypophyseal Hormones of the Bullfrog(Endocrinology)

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    MAKOTO, SAKAI; YOICHI, HANAOKA; SHIGEYASU, TANAKA; HIROAKI, HAYASHI; SAKAE, KIKUYAMA; Department of Biology, School of Education, Waseda University; Institute of Endocrinology, Gunma University; Institute of Endocrinology, Gunma University; Institute of Endocrinology, Gunma University; Department of Biology, School of Education, Waseda University

    1991-01-01

    The effects of adenohypophyseal hormones of the bullfrog (Rana catesbeiana) origin on the in vitro release of thyroxine (T_4) from the thyroid of prometamorphic larvae were studied. The bullfrog thyrotropin (TSH) preparation was 4 times as potent as bovine TSH in this model. Bullfrog luteinizing hormones (LHS) (I-IV) and follicle-stimulating hormones (FSHS) (I-IV), which were classified according to their isoelectric points, were tested for their thyrotropic activity and demons-trated about 1...

  17. Brucella suis vaccine strain 2 induces endoplasmic reticulum stress that affects intracellular replication in goat trophoblast cells in vitro

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    Xiangguo eWang

    2016-02-01

    Full Text Available Brucella has been reported to impair placental trophoblasts, a cellular target where Brucella efficiently replicates in association with the endoplasmic reticulum (ER, and ultimately trigger abortion in pregnant animals. However, the precise effects of Brucella on trophoblast cells remain unclear. Here, we describe the infection and replication of Brucella suis vaccine strain 2 (B.suis.S2 in goat trophoblast cells (GTCs and the cellular and molecular responses induced in vitro. Our studies demonstrated that B.suis.S2 was able to infect and proliferate to high titers, hamper the proliferation of GTCs and induce apoptosis due to ER stress. Tunicamycin (Tm, a pharmacological chaperone that strongly mounts ER stress-induced apoptosis, inhibited B.suis.S2 replication in GTCs. In addition, 4 phenyl butyric acid (4-PBA, a pharmacological chaperone that alleviates ER stress-induced apoptosis, significantly enhanced B.suis.S2 replication in GTCs. The Unfolded Protein Response (UPR chaperone molecule GRP78 also promoted B.suis.S2 proliferation in GTCs by inhibiting ER stress-induced apoptosis. We also discovered that the IRE1 pathway, but not the PERK or ATF6 pathway, was activated in the process. However, decreasing the expression of phosphoIRE1α and IRE1α proteins with Irestatin 9389 (IRE1 antagonist in GTCs did not affect the proliferation of B.suis.S2. Although GTC implantation was not affected upon B.suis.S2 infection, progesterone secretion was suppressed, and prolactin and estrogen secretion increased; these effects were accompanied by changes in the expression of genes encoding key steroidogenic enzymes. This study systematically explored the mechanisms of abortion in Brucella infection from the viewpoint of pathogen invasion, ER stress and reproductive endocrinology. Our findings may provide new insight for understanding the mechanisms involved in goat abortions caused by Brucella infection.

  18. A Rare Gestational Trophoblastic Disease: Placental Site Trophoblastic Tumor

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    Senem Yaman Tunç

    2016-12-01

    PSTT is a rare tumor. In contrast to other trophoblastic tumors, PSTT produces a small amount of ß-HCG and it is relatively insensitive to chemotherapy. Adjuvant chemotherapy is suggested to follow surgical treatment in the cases with metastasis.

  19. Find an Endocrinology - Thyroid Specialist

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    ... History Resource Center Patients Thyroid Information Find an Endocrinology – Thyroid Specialist Patient Support Links Clinical Thyroidology for ... Access Thyroid Online Access Clinical Thyroidology Online Video Endocrinology Donate Give Online Research Accomplishments Ridgway Legacy Fund ...

  20. Gestational trophoblastic neoplasms

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    Demas, B.E.; Hricak, H.; Braga, C.

    1988-01-01

    Twenty-four women with suspected gestational trophoblastic neoplasms were evaluated prospectively to identify imaging algorithms optimal for treatment planning. All underwent chest radiography, chest CT, hepatic and cranial CT or MR imaging, and pelvic MR imaging. Ten also underwent pelvic CT, 13 pelvic US. The most sensitive imaging combination was chest CT, hepatic and cranial CT or MR imaging, and pelvic MR imaging. However, correct assignment to ACOG therapeutic categories was achieved by means of history, physical examination, beta subunit of human chorionic gonadotropin measurements, and chest radiography in 81% of patients. Hepatic and cranial imaging defined the need for radiation therapy. Chest CT was needed only when chest radiographs were negative. Pelvic imaging aided diagnosis but did not assist in treatment planning

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

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    Martin eKnöfler

    2013-09-01

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

  2. Endocrinology in the Ramayana

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    Sanjay Kalra

    2016-01-01

    Full Text Available This article is one of a series of publications which highlight the possible endocrine conditions and interventions listed in the ancient texts. This compendium lists episodes from the Indian epic Ramayana and from the associated genealogy of Lord Rama′s dynasty, the Suryavanshis. These episodes are chosen for their relevance to endocrinology and are listed in a gland-based order. It is hoped that this communication will encourage further work on endocrine literary forensics.

  3. Alteration of Pituitary Tumor Transforming Gene-1 Regulates Trophoblast Invasion via the Integrin/Rho-Family Signaling Pathway.

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    Seung Mook Lim

    Full Text Available Trophoblast invasion ability is an important factor in early implantation and placental development. Recently, pituitary tumor transforming gene 1 (PTTG1 was shown to be involved in invasion and proliferation of cancer. However, the role of PTTG1 in trophoblast invasion remains unknown. Thus, in this study we analyzed PTTG1 expression in trophoblasts and its effect on trophoblast invasion activity and determined the mechanism through which PTTG1 regulates trophoblast invasion. Trophoblast proliferation and invasion abilities, regardless of PTTG1 expression, were analyzed by quantitative real-time polymerase chain reaction, fluorescence-activated cell sorting analysis, invasion assay, western blot, and zymography after treatment with small interfering RNA against PTTG1 (siPTTG1. Additionally, integrin/Rho-family signaling in trophoblasts by PTTG1 alteration was analyzed. Furthermore, the effect of PTTG1 on trophoblast invasion was evaluated by microRNA (miRNA mimic and inhibitor treatment. Trophoblast invasion was significantly reduced through decreased matrix metalloproteinase (MMP-2 and MMP-9 expression when PTTG1 expression was inhibited by siPTTG1 (p < 0.05. Furthermore, knockdown of PTTG1 increased expression of integrin alpha 4 (ITGA4, ITGA5, and integrin beta 1 (ITGB1; otherwise, RhoA expression was significantly decreased (p < 0.05. Treatment of miRNA-186-5p mimic and inhibitor controlled trophoblast invasion ability by altering PTTG1 and MMP expression. PTTG1 can control trophoblast invasion ability via regulation of MMP expression through integrin/Rho-family signaling. In addition, PTTG1 expression and its function were regulated by miRNA-186-5p. These results help in understanding the mechanism through which PTTG1 regulates trophoblast invasion and thereby implantation and placental development.

  4. miR-518b Enhances Human Trophoblast Cell Proliferation Through Targeting Rap1b and Activating Ras-MAPK Signal

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    Ming Liu

    2018-03-01

    Full Text Available Preeclampsia is a pregnancy-specific complication defined as newly onset gestational hypertension and proteinuria. Deficiency in placental development is considered as the predominant cause of preeclampsia. Our previous study found that the expression of miR-518b increased significantly in the preeclamptic placentas, indicating the potential participation of this small RNA in the occurrence of preeclampsia. In this study, data analysis using multiple databases predicted Rap1b as a candidate target of miR-518b. An evident decrease in Rap1b expression was observed in preeclamptic placentas when compared with the control placentas, which was negatively correlated with the level of miR-518b. Based on the data of in situ hybridization and immunohistochemistry showing that Rap1b exhibited similar localization with miR-518b in villous cytotrophoblast cells and column trophoblasts, we further explored their function in regulating trophoblast cell proliferation. In HTR8/SVneo cells, exogenous transfection of miR-518b reduced the expression of Rap1b, and dual-luciferase reporter assay validated Rap1b as the direct target of miR-518b. The small RNA could increase the BrdU incorporation and the ratio of cells at S phase, and enhance the phosphorylation of Raf-1 and ERK1/2. Such growth-promoting effect could be efficiently reversed by Rap1b overexpression. The data indicate that miR-518b can promote trophoblast cell proliferation via Rap1b–Ras–MAPK pathway, and the aberrant upregulation of miR-518b in preeclamptic placenta may contribute to the excessive trophoblast proliferation. The study provides new evidence to further understand the etiology of preeclampsia.

  5. HTR8/SVneo cells display trophoblast progenitor cell-like characteristics indicative of self-renewal, repopulation activity, and expression of "stemness-" associated transcription factors.

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    Weber, Maja; Knoefler, Ilka; Schleussner, Ekkehard; Markert, Udo R; Fitzgerald, Justine S

    2013-01-01

    JEG3 is a choriocarcinoma--and HTR8/SVneo a transformed extravillous trophoblast--cell line often used to model the physiologically invasive extravillous trophoblast. Past studies suggest that these cell lines possess some stem or progenitor cell characteristics. Aim was to study whether these cells fulfill minimum criteria used to identify stem-like (progenitor) cells. In summary, we found that the expression profile of HTR8/SVneo (CDX2+, NOTCH1+, SOX2+, NANOG+, and OCT-) is distinct from JEG3 (CDX2+ and NOTCH1+) as seen only in human-serum blocked immunocytochemistry. This correlates with HTR8/SVneo's self-renewal capacities, as made visible via spheroid formation and multi-passagability in hanging drops protocols paralleling those used to maintain embryoid bodies. JEG3 displayed only low propensity to form and reform spheroids. HTR8/SVneo spheroids migrated to cover and seemingly repopulate human chorionic villi during confrontation cultures with placental explants in hanging drops. We conclude that HTR8/SVneo spheroid cells possess progenitor cell traits that are probably attained through corruption of "stemness-" associated transcription factor networks. Furthermore, trophoblastic cells are highly prone to unspecific binding, which is resistant to conventional blocking methods, but which can be alleviated through blockage with human serum.

  6. Generation of Elf5-Cre knockin mouse strain for trophoblast-specific gene manipulation.

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    Kong, Shuangbo; Liang, Guixian; Tu, Zhaowei; Chen, Dunjin; Wang, Haibin; Lu, Jinhua

    2018-04-01

    Placental development is a complex and highly controlled process during which trophoblast stem cells differentiate to various trophoblast subtypes. The early embryonic death of systemic gene knockout models hampers the investigation of these genes that might play important roles during placentation. A trophoblast specific Cre mouse model would be of great help for dissecting out the potential roles of these genes during placental development. For this purpose, we generate a transgenic mouse with the Cre recombinase inserted into the endogenous locus of Elf5 gene that is expressed specifically in placental trophoblast cells. To analyze the specificity and efficiency of Cre recombinase activity in Elf5-Cre mice, we mated Elf5-Cre mice with Rosa26 mT/mG reporter mice, and found that Elf5-Cre transgene is expressed specifically in the trophoectoderm as early as embryonic day 4.5 (E4.5). By E12.5, the activity of Elf5-Cre transgene was detected exclusively in all derivatives of trophoblast lineages, including spongiotrophoblast, giant cells, and labyrinth trophoblasts. In addition, Elf5-Cre transgene was also active during spermatogenesis, from spermatids to mature sperms, which is consistent with the endogenous Elf5 expression in testis. Collectively, our results provide a unique tool to delete specific genes selectively and efficiently in trophoblast lineage during placentation. © 2018 Wiley Periodicals, Inc.

  7. Notch signaling activation in human embryonic stem cells is required for embryonic but not trophoblastic lineage commitment

    OpenAIRE

    Yu, Xiaobing; Zou, Jizhong; Ye, Zhaohui; Hammond, Holly; Chen, Guibin; Tokunaga, Akinori; Mali, Prashant; Li, Yue-Ming; Civin, Curt; Gaiano, Nicholas; Cheng, Linzhao

    2008-01-01

    The Notch signaling pathway plays important roles in cell fate determination during embryonic development and adult life. In this study, we focus on the role of Notch signaling in governing cell fate choices in human embryonic stem (hES) cells. Using genetic and pharmacological approaches, we achieved both blockade and conditional activation of Notch signaling in several hES cell lines. We report here that activation of Notch signaling is required for undifferentiated hES cells to form the pr...

  8. Primary Cilium-Regulated EG-VEGF Signaling Facilitates Trophoblast Invasion.

    Science.gov (United States)

    Wang, Chia-Yih; Tsai, Hui-Ling; Syu, Jhih-Siang; Chen, Ting-Yu; Su, Mei-Tsz

    2017-06-01

    Trophoblast invasion is an important event in embryo implantation and placental development. During these processes, endocrine gland-derived vascular endothelial growth factor (EG-VEGF) is the key regulator mediating the crosstalk at the feto-maternal interface. The primary cilium is a cellular antenna receiving environmental signals and is crucial for proper development. However, little is known regarding the role of the primary cilium in early human pregnancy. Here, we demonstrate that EG-VEGF regulates trophoblast cell invasion via primary cilia. We found that EG-VEGF activated ERK1/2 signaling and subsequent upregulation of MMP2 and MMP9, thereby facilitating cell invasion in human trophoblast HTR-8/SVneo cells. Inhibition of ERK1/2 alleviated the expression of MMPs and trophoblast cell invasion after EG-VEGF treatment. In addition, primary cilia were observed in all the trophoblast cell lines tested and, more importantly, in human first-trimester placental tissue. The receptor of EG-VEGF, PROKR1, was detected in primary cilia. Depletion of IFT88, the intraflagellar transporter required for ciliogenesis, inhibited primary cilium growth, thereby ameliorating ERK1/2 activation, MMP upregulation, and trophoblast cell invasion promoted by EG-VEGF. These findings demonstrate a novel function of primary cilia in controlling EG-VEGF-regulated trophoblast invasion and reveal the underlying molecular mechanism. J. Cell. Physiol. 232: 1467-1477, 2017. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

  9. Immunomodulator expression in trophoblasts from the feline immunodeficiency virus (FIV-infected cat

    Directory of Open Access Journals (Sweden)

    Donaldson Janet R

    2011-07-01

    Full Text Available Abstract Background FIV infection frequently compromises pregnancy under experimental conditions and is accompanied by aberrant expression of some placental cytokines. Trophoblasts produce numerous immunomodulators that play a role in placental development and pregnancy maintenance. We hypothesized that FIV infection may cause dysregulation of trophoblast immunomodulator expression, and aberrant expression of these molecules may potentiate inflammation and compromise pregnancy. The purpose of this project was to evaluate the expression of representative pro-(TNF-α, IFN-γ, IL-1β, IL-2, IL-6, IL-12p35, IL-12p40, IL-18, and GM-CSF and anti-inflammatory cytokines (IL-4, IL-5, and IL-10; CD134, a secondary co-stimulatory molecule expressed on activated T cells (FIV primary receptor; the chemokine receptor CXCR4 (FIV co-receptor; SDF-1α, the chemokine ligand to CXCR4; and FIV gag in trophoblasts from early-and late-term pregnancy. Methods We used an anti-cytokeratin antibody in immunohistochemistry to identify trophoblasts selectively, collected these cells using laser capture microdissection, and extracted total RNA from the captured cell populations. Real time, reverse transcription-PCR was used to quantify gene expression. Results We detected IL-4, IL-5, IL-6, IL-1β, IL-12p35, IL-12p40, and CXCR4 in trophoblasts from early-and late-term pregnancy. Expression of cytokines increased from early to late pregnancy in normal tissues. A clear, pro-inflammatory microenvironment was not evident in trophoblasts from FIV-infected queens at either stage of pregnancy. Reproductive failure was accompanied by down-regulation of both pro-and anti-inflammatory cytokines. CD134 was not detected in trophoblasts, and FIV gag was detected in only one of ten trophoblast specimens collected from FIV-infected queens. Conclusion Feline trophoblasts express an array of pro-and anti-inflammatory immunomodulators whose expression increases from early to late pregnancy in

  10. Differential Effects of Sodium Butyrate and Lithium Chloride on Rhesus Monkey Trophoblast Differentiation.

    Directory of Open Access Journals (Sweden)

    Priyadarsini Kumar

    Full Text Available Trophoblast differentiation during early placental development is critical for successful pregnancy and aberrant differentiation causes preeclampsia and early pregnancy loss. During the first trimester, cytotrophoblasts are exposed to low oxygen tension (equivalent to~2%-3% O2 and differentiation proceeds along an extravillous pathway (giving rise to invasive extravillous cytotrophoblasts and a villous pathway (giving rise to multinucleated syncytiotrophoblast. Interstitial extravillous cytotrophoblasts invade the decidua, while endovascular extravillous cytotrophoblasts are involved in re-modelling uterine spiral arteries. We tested the idea that sodium butyrate (an epigenetic modulator induces trophoblast differentiation in early gestation rhesus monkey trophoblasts through activation of the Wnt/β-catenin pathway. The results show that syncytiotrophoblast formation was increased by butyrate, accompanied by nuclear accumulation of β-catenin, and increased expression of EnvV2 and galectin-1 (two factors thought to be involved in trophoblast fusion. Surprisingly, the expression of GCM1 and syncytin-2 was not affected by sodium butyrate. When trophoblasts were incubated with lithium chloride, a GSK3 inhibitor that mimics Wnt activation, nuclear accumulation of β-catenin also occurred but differentiation into syncytiotrophoblast was not observed. Instead the cells differentiated to mononucleated spindle-shaped cells and showed molecular and behavioral characteristics of endovascular trophoblasts. Another highly specific inhibitor of GSK3, CHIR99021, failed to induce endovascular trophoblast characteristics. These observations suggest that activation of the Wnt/β-catenin pathway correlates with both trophoblast differentiation pathways, but that additional factors determine specific cell fate decisions. Other experiments suggested that the differential effects of sodium butyrate and lithium chloride might be explained by their effects on TNF

  11. Elsevier Trophoblast Research Award lecture: Molecular mechanisms underlying estrogen functions in trophoblastic cells--focus on leptin expression.

    Science.gov (United States)

    Gambino, Y P; Maymó, J L; Pérez Pérez, A; Calvo, J C; Sánchez-Margalet, V; Varone, C L

    2012-02-01

    The steroid hormone 17β-estradiol is an estrogen that influences multiple aspects of placental function and fetal development in humans. During early pregnancy it plays a role in the regulation of blastocyst implantation, trophoblast differentiation and invasiveness, remodeling of uterine arteries, immunology and trophoblast production of hormones such as leptin. Estradiol exerts some effects through the action of classical estrogen receptors ERα and ERβ, which act as ligand-activated transcription factors and regulate gene expression. In addition, estradiol can elicit rapid responses from membrane-associated receptors, like activation of protein-kinase pathways. Thus, the cellular effects of estradiol will depend on the specific receptors expressed and the integration of their signaling events. Leptin, the 16,000MW protein product of the obese gene, was originally considered an adipocyte-derived signaling molecule for the central control of metabolism. However, pleiotropic effects of leptin have been identified in reproduction and pregnancy. The leptin gene is expressed in placenta, where leptin promotes proliferation and survival of trophoblastic cells. Expression of leptin in placenta is highly regulated by key pregnancy molecules as hCG and estradiol. The aim of this paper is to review the molecular mechanisms underlying estrogen functions in trophoblastic cells; focusing on mechanisms involved in estradiol regulation of placental leptin expression. Copyright © 2012 Elsevier Ltd. All rights reserved.

  12. The Mahabharata and reproductive endocrinology

    OpenAIRE

    Kalra, Bharti; Baruah, Manash P.; Kalra, Sanjay

    2016-01-01

    This communication approaches the Mahabharata through the prism of reproductive endocrinology. Descriptions of episodes related to reproduction are listed here, to provide fodder for the endocrinologically minded brain. The cases described here are perhaps, the first documented observations of fetal orgasm, pseudocyesis and assisted reproductive technology, including assisted insemination by donor, induction of ovulation, and in vitro fertilization as well as precocious growth and intersex. W...

  13. Reproductive endocrinology of vitamin D

    DEFF Research Database (Denmark)

    Lorenzen, Mette; Boisen, Ida Marie; Mortensen, Li Juel

    2017-01-01

    Vitamin D is a versatile hormone with several functions beyond its well-established role in maintenance of skeletal health and calcium homeostasis. The effects of vitamin D are mediated by the vitamin D receptor, which is expressed together with the vitamin D metabolizing enzymes in the reproduct...... suffering from reproductive problems and abnormal endocrinology research addressing the role of vitamin D in reproductive endocrinology may be of clinical importance....

  14. HTR8/SVneo Cells Display Trophoblast Progenitor Cell-Like Characteristics Indicative of Self-Renewal, Repopulation Activity, and Expression of “Stemness-” Associated Transcription Factors

    Directory of Open Access Journals (Sweden)

    Maja Weber

    2013-01-01

    Full Text Available Introduction. JEG3 is a choriocarcinoma—and HTR8/SVneo a transformed extravillous trophoblast—cell line often used to model the physiologically invasive extravillous trophoblast. Past studies suggest that these cell lines possess some stem or progenitor cell characteristics. Aim was to study whether these cells fulfill minimum criteria used to identify stem-like (progenitor cells. In summary, we found that the expression profile of HTR8/SVneo (CDX2+, NOTCH1+, SOX2+, NANOG+, and OCT- is distinct from JEG3 (CDX2+ and NOTCH1+ as seen only in human-serum blocked immunocytochemistry. This correlates with HTR8/SVneo’s self-renewal capacities, as made visible via spheroid formation and multi-passagability in hanging drops protocols paralleling those used to maintain embryoid bodies. JEG3 displayed only low propensity to form and reform spheroids. HTR8/SVneo spheroids migrated to cover and seemingly repopulate human chorionic villi during confrontation cultures with placental explants in hanging drops. We conclude that HTR8/SVneo spheroid cells possess progenitor cell traits that are probably attained through corruption of “stemness-” associated transcription factor networks. Furthermore, trophoblastic cells are highly prone to unspecific binding, which is resistant to conventional blocking methods, but which can be alleviated through blockage with human serum.

  15. TNF-α inhibits trophoblast integration into endothelial cellular networks.

    Science.gov (United States)

    Xu, B; Nakhla, S; Makris, A; Hennessy, A

    2011-03-01

    Preeclampsia has been linked to shallow trophoblast invasion and failure of uterine spiral artery transformation. Interaction between trophoblast cells and maternal uterine endothelium is critically important for this remodelling. The aim of our study was to investigate the effect of TNF-α on the interactions of trophoblast-derived JEG-3 cells into capillary-like cellular networks. We have employed an in vitro trophoblast-endothelial cell co-culture model to quantify trophoblast integration into endothelial cellular networks and to investigate the effects of TNF-α. Controlled co-cultures were also treated with anti-TNF-α antibody (5 μg/ml) to specifically block the effect of TNF-α. The invasion was evaluated by performing quantitative PCR (Q-PCR) to analyse gene expression of matrix metalloproteinases-2 (MMP-2), MMP-9, tissue inhibitor of matrix metalloproteinase (TIMP)-1, integrins (α(1)β(1) and α(6)β(4)), plasminogen activator inhibitor (PAI)-1, E-cadherin and VE-cadherin. JEG-3 cell integration into endothelial networks was significantly inhibited by exogenous TNF-α. The inhibition was observed in the range of 0.2-5 ng/ml, to a maximum 56% inhibition at the highest concentration. This inhibition was reversed by anti-TNF-α antibody. Q-PCR analysis showed that mRNA expression of integrins α(1)β(1) and MMP-2 was significantly decreased. VE-cadherin mRNA expression was significantly up-regulated (32-80%, p integration into maternal endothelial cellular networks, and this process involves the inhibition of MMP-2 and a failure of integrins switch from α(6)β(4) to α(1)β(1.) These molecular correlations reflect the changes identified in human preeclampsia. Copyright © 2011 Elsevier Ltd. All rights reserved.

  16. Function of caspase-14 in trophoblast differentiation

    Directory of Open Access Journals (Sweden)

    Charles Adrian K

    2009-09-01

    Full Text Available Abstract Background Within the human placenta, the cytotrophoblast consists of a proliferative pool of progenitor cells which differentiate to replenish the overlying continuous, multi-nucleated syncytiotrophoblast, which forms the barrier between the maternal and fetal tissues. Disruption to trophoblast differentiation and function may result in impaired fetal development and preeclampsia. Caspase-14 expression is limited to barrier forming tissues. It promotes keratinocyte differentiation by cleaving profilaggrin to stabilise keratin intermediate filaments, and indirectly providing hydration and UV protection. However its role in the trophoblast remains unexplored. Methods Using RNA Interference the reaction of control and differentiating trophoblastic BeWo cells to suppressed caspase-14 was examined for genes pertaining to hormonal, cell cycle and cytoskeletal pathways. Results Transcription of hCG, KLF4 and cytokeratin-18 were increased following caspase-14 suppression suggesting a role for caspase-14 in inhibiting their pathways. Furthermore, hCG, KLF4 and cytokeratin-18 protein levels were disrupted. Conclusion Since expression of these molecules is normally increased with trophoblast differentiation, our results imply that caspase-14 inhibits trophoblast differentiation. This is the first functional study of this unusual member of the caspase family in the trophoblast, where it has a different function than in the epidermis. This knowledge of the molecular underpinnings of trophoblast differentiation may instruct future therapies of trophoblast disease.

  17. Gestational Trophoblastic Disease—Health Professional Version

    Science.gov (United States)

    Gestational trophoblastic disease (GTD) is a broad term encompassing both benign and malignant growths arising from products of conception in the uterus. GTDs contain paternal chromosomes and are placental in origin. Find evidence-based information on gestational trophoblastic disease treatment.

  18. MTA3 regulates CGB5 and Snail genes in trophoblast

    Energy Technology Data Exchange (ETDEWEB)

    Chen, Ying [Department of Obstetrics, Gynecology and Reproductive Biology, Michigan State University, Grand Rapids, MI 49503 (United States); Miyazaki, Jun [Department of Obstetrics and Gynecology, Fujita Health University School of Medicine, Fujita Health University, Toyoake (Japan); Division of Molecular Genetics, Institute for Comprehensive Medical Science, Fujita Health University, Toyoake (Japan); Nishizawa, Haruki [Department of Obstetrics and Gynecology, Fujita Health University School of Medicine, Fujita Health University, Toyoake (Japan); Kurahashi, Hiroki [Division of Molecular Genetics, Institute for Comprehensive Medical Science, Fujita Health University, Toyoake (Japan); Leach, Richard, E-mail: Richard.Leach@hc.msu.edu [Department of Obstetrics, Gynecology and Reproductive Biology, Michigan State University, Grand Rapids, MI 49503 (United States); Department of Obstetrics, Gynecology and Women’s Health, Spectrum Health Medical Group, Grand Rapids, MI 49503 (United States); Wang, Kai, E-mail: Kai.Wang@hc.msu.edu [Department of Obstetrics, Gynecology and Reproductive Biology, Michigan State University, Grand Rapids, MI 49503 (United States)

    2013-04-19

    Highlights: •Impaired MTA3, raised CGB5 and Snail expression are associated with preeclampsia. •Knock-down of MTA3 causes up-regulation of CGB5 and Snail genes in BeWo cells. •MTA3 occupies CGB5 and Snail gene promoters in BeWo cells. -- Abstract: Secreted by the placental trophoblast, human chorionic gonadotropin (hCG) is an important hormone during pregnancy and is required for the maintenance of pregnancy. Previous studies have shown that dys-regulation of hCG expression is associated with preeclampsia. However, the exact relationship between altered hCG levels and development of preeclampsia is unknown. Metastasis associated protein 3 (MTA3), a chromatin remodeling protein, is abundantly expressed in the placental trophoblasts, but its function is unknown. In breast cancer, MTA3 has been shown to repress the expression of Snail and cell migration. However, whether MTA3 acts similarly in the trophoblast has not been investigated. In the present study, we examined the role of MTA3 in regulating the hCG β-subunit gene (gene name: CGB5) and Snail expression in the trophoblast cell line, BeWo, as well as its relevance to the high hCG expression levels seen in preeclampsia. First, we investigated MTA3 expression in preeclamptic placenta as compared to normal control placenta via gene expression microarray and qRT-PCR and found that MTA3 was significantly down-regulated, whereas both CGB5 and Snail were up-regulated in preeclamptic placenta. Secondly, we knocked down MTA3 gene in trophoblast cell line BeWo and found Snail and hCG were both up-regulated, suggesting that MTA3 represses Snail and hCG gene expression in trophoblasts. Next, we cloned the CGB5 and Snail promoters into the pGL3-basic vector individually and found that silencing of MTA3 by siRNA resulted in an increase of both CGB5 and Snail promoter activities. To confirm that this MTA3 inhibition is a direct effect, we performed a chromatin immune-precipitation (ChIP) assay and found that MTA3

  19. MTA3 regulates CGB5 and Snail genes in trophoblast

    International Nuclear Information System (INIS)

    Chen, Ying; Miyazaki, Jun; Nishizawa, Haruki; Kurahashi, Hiroki; Leach, Richard; Wang, Kai

    2013-01-01

    Highlights: •Impaired MTA3, raised CGB5 and Snail expression are associated with preeclampsia. •Knock-down of MTA3 causes up-regulation of CGB5 and Snail genes in BeWo cells. •MTA3 occupies CGB5 and Snail gene promoters in BeWo cells. -- Abstract: Secreted by the placental trophoblast, human chorionic gonadotropin (hCG) is an important hormone during pregnancy and is required for the maintenance of pregnancy. Previous studies have shown that dys-regulation of hCG expression is associated with preeclampsia. However, the exact relationship between altered hCG levels and development of preeclampsia is unknown. Metastasis associated protein 3 (MTA3), a chromatin remodeling protein, is abundantly expressed in the placental trophoblasts, but its function is unknown. In breast cancer, MTA3 has been shown to repress the expression of Snail and cell migration. However, whether MTA3 acts similarly in the trophoblast has not been investigated. In the present study, we examined the role of MTA3 in regulating the hCG β-subunit gene (gene name: CGB5) and Snail expression in the trophoblast cell line, BeWo, as well as its relevance to the high hCG expression levels seen in preeclampsia. First, we investigated MTA3 expression in preeclamptic placenta as compared to normal control placenta via gene expression microarray and qRT-PCR and found that MTA3 was significantly down-regulated, whereas both CGB5 and Snail were up-regulated in preeclamptic placenta. Secondly, we knocked down MTA3 gene in trophoblast cell line BeWo and found Snail and hCG were both up-regulated, suggesting that MTA3 represses Snail and hCG gene expression in trophoblasts. Next, we cloned the CGB5 and Snail promoters into the pGL3-basic vector individually and found that silencing of MTA3 by siRNA resulted in an increase of both CGB5 and Snail promoter activities. To confirm that this MTA3 inhibition is a direct effect, we performed a chromatin immune-precipitation (ChIP) assay and found that MTA3

  20. The Mahabharata and reproductive endocrinology

    Directory of Open Access Journals (Sweden)

    Bharti Kalra

    2016-01-01

    Full Text Available This communication approaches the Mahabharata through the prism of reproductive endocrinology. Descriptions of episodes related to reproduction are listed here, to provide fodder for the endocrinologically minded brain. The cases described here are perhaps, the first documented observations of fetal orgasm, pseudocyesis and assisted reproductive technology, including assisted insemination by donor, induction of ovulation, and in vitro fertilization as well as precocious growth and intersex. We do not presume to offer a definite explanation for these interesting episodes from the Mahabharata. We do, however, hope to stimulate interest in ancient Indian literature, and encourage a literary “forensic endocrine” analysis of events relevant to our specialty.

  1. 42 CFR 493.933 - Endocrinology.

    Science.gov (United States)

    2010-10-01

    ... 42 Public Health 5 2010-10-01 2010-10-01 false Endocrinology. 493.933 Section 493.933 Public... Proficiency Testing Programs by Specialty and Subspecialty § 493.933 Endocrinology. (a) Program content and frequency of challenge. To be approved for proficiency testing for endocrinology, a program must provide a...

  2. 42 CFR 493.1212 - Condition: Endocrinology.

    Science.gov (United States)

    2010-10-01

    ... 42 Public Health 5 2010-10-01 2010-10-01 false Condition: Endocrinology. 493.1212 Section 493.1212 Public Health CENTERS FOR MEDICARE & MEDICAID SERVICES, DEPARTMENT OF HEALTH AND HUMAN SERVICES....1212 Condition: Endocrinology. If the laboratory provides services in the subspecialty of Endocrinology...

  3. Drugs Approved for Gestational Trophoblastic Disease

    Science.gov (United States)

    This page lists cancer drugs approved by the Food and Drug Administration (FDA) for gestational trophoblastic disease. The list includes generic names and brand names. The drug names link to NCI's Cancer Drug Information summaries.

  4. Trophoblast lineage cells derived from human induced pluripotent stem cells

    Energy Technology Data Exchange (ETDEWEB)

    Chen, Ying, E-mail: ying.chen@hc.msu.edu [Department of Obstetrics, Gynecology and Reproductive Biology, Michigan State University, 333 Bostwick NE, Grand Rapids, MI 49503 (United States); Wang, Kai; Chandramouli, Gadisetti V.R. [Department of Obstetrics, Gynecology and Reproductive Biology, Michigan State University, 333 Bostwick NE, Grand Rapids, MI 49503 (United States); Knott, Jason G. [Developmental Epigenetics Laboratory, Department of Animal Science, Michigan State University (United States); Leach, Richard, E-mail: Richard.leach@hc.msu.edu [Department of Obstetrics, Gynecology and Reproductive Biology, Michigan State University, 333 Bostwick NE, Grand Rapids, MI 49503 (United States); Department of Obstetrics, Gynecology and Women’s Health, Spectrum Health Medical Group (United States)

    2013-07-12

    Highlights: •Epithelial-like phenotype of trophoblast lineage cells derived from human iPS cells. •Trophoblast lineage cells derived from human iPS cells exhibit trophoblast function. •Trophoblasts from iPS cells provides a proof-of-concept in regenerative medicine. -- Abstract: Background: During implantation, the blastocyst trophectoderm attaches to the endometrial epithelium and continues to differentiate into all trophoblast subtypes, which are the major components of a placenta. Aberrant trophoblast proliferation and differentiation are associated with placental diseases. However, due to ethical and practical issues, there is almost no available cell or tissue source to study the molecular mechanism of human trophoblast differentiation, which further becomes a barrier to the study of the pathogenesis of trophoblast-associated diseases of pregnancy. In this study, our goal was to generate a proof-of-concept model for deriving trophoblast lineage cells from induced pluripotency stem (iPS) cells from human fibroblasts. In future studies the generation of trophoblast lineage cells from iPS cells established from patient’s placenta will be extremely useful for studying the pathogenesis of individual trophoblast-associated diseases and for drug testing. Methods and results: Combining iPS cell technology with BMP4 induction, we derived trophoblast lineage cells from human iPS cells. The gene expression profile of these trophoblast lineage cells was distinct from fibroblasts and iPS cells. These cells expressed markers of human trophoblasts. Furthermore, when these cells were differentiated they exhibited invasive capacity and placental hormone secretive capacity, suggesting extravillous trophoblasts and syncytiotrophoblasts. Conclusion: Trophoblast lineage cells can be successfully derived from human iPS cells, which provide a proof-of-concept tool to recapitulate pathogenesis of patient placental trophoblasts in vitro.

  5. Trophoblast lineage cells derived from human induced pluripotent stem cells

    International Nuclear Information System (INIS)

    Chen, Ying; Wang, Kai; Chandramouli, Gadisetti V.R.; Knott, Jason G.; Leach, Richard

    2013-01-01

    Highlights: •Epithelial-like phenotype of trophoblast lineage cells derived from human iPS cells. •Trophoblast lineage cells derived from human iPS cells exhibit trophoblast function. •Trophoblasts from iPS cells provides a proof-of-concept in regenerative medicine. -- Abstract: Background: During implantation, the blastocyst trophectoderm attaches to the endometrial epithelium and continues to differentiate into all trophoblast subtypes, which are the major components of a placenta. Aberrant trophoblast proliferation and differentiation are associated with placental diseases. However, due to ethical and practical issues, there is almost no available cell or tissue source to study the molecular mechanism of human trophoblast differentiation, which further becomes a barrier to the study of the pathogenesis of trophoblast-associated diseases of pregnancy. In this study, our goal was to generate a proof-of-concept model for deriving trophoblast lineage cells from induced pluripotency stem (iPS) cells from human fibroblasts. In future studies the generation of trophoblast lineage cells from iPS cells established from patient’s placenta will be extremely useful for studying the pathogenesis of individual trophoblast-associated diseases and for drug testing. Methods and results: Combining iPS cell technology with BMP4 induction, we derived trophoblast lineage cells from human iPS cells. The gene expression profile of these trophoblast lineage cells was distinct from fibroblasts and iPS cells. These cells expressed markers of human trophoblasts. Furthermore, when these cells were differentiated they exhibited invasive capacity and placental hormone secretive capacity, suggesting extravillous trophoblasts and syncytiotrophoblasts. Conclusion: Trophoblast lineage cells can be successfully derived from human iPS cells, which provide a proof-of-concept tool to recapitulate pathogenesis of patient placental trophoblasts in vitro

  6. Progranulin shows cytoprotective effects on trophoblast cells in vitro but does not antagonize TNF-α-induced apoptosis.

    Science.gov (United States)

    Stubert, Johannes; Waldmann, Kathrin; Dieterich, Max; Richter, Dagmar-Ulrike; Briese, Volker

    2014-11-01

    The glycoprotein progranulin directly binds to TNF-receptors and thereby can antagonize the inflammatory effects of TNF-α. Here we analyzed the impact of both cytokines on cytotoxicity and viability of trophoblast cells. Isolated villous first trimester human trophoblast cells and the human choriocarcinoma cell line BeWo were treated with recombinant human progranulin and TNF-α. Analyses were performed by LDH- and MTT-assay and measurement of caspase-8-activity. Progranulin treatment showed some cytoprotective effects on isolated trophoblast cells. However, TNF-α-induced apoptosis was not antagonized by addition of progranulin. Effects were similar, but more pronounced in BeWo cells. The cytoprotective activity of progranulin on trophoblast cells in vitro was only weak and of doubtful biologic relevance. It was not able to antagonize TNF-α. Future studies should focus on possible paracrine activities of progranulin.

  7. Development of the Clinic of Endocrinology, diabetes and metabolic disorders.

    Science.gov (United States)

    Shubeska Stratrova, S

    2013-01-01

    The Clinic of Endocrinology, diabetes and metabolic disorders was founded in 1975 by Prof d-r Alexandar Plashevski. Healthcare, educational and scientific activities in the Clinic of Endocrinology are performed in its departments. The Department for hospitalized diabetic and endocrine patients consists of the metabolic and endocrine intensive care unit, the department for diagnosis and treatment of diabetics and endocrine patients, day hospital, the department for education of diabetic patients, and the national center for insulin pump therapy. The Center for Diabetes was established in 1972 by Prof d-r Dimitar Arsov. In 1975, Prof d-r Alexandar Plasheski broadened the activities of the Center for Diabetes. It was dislocated in 1980, with new accommodation outside the clinic. Since then the Center has consisted of several organized units: two specialist outpatient clinics for diabetic patients, biochemical and endocrine laboratory, sub-departments for: diabetic foot, cardiovascular diagnosis, ophthalmology, and urgent interventions. The Department of Endocrinology and Metabolic Disorders for outclinic endocrine patients was established in 1980, and it integrates the following sub-departments: thyrology, andrology, reproductive endocrinology, obesity and lipid disorders and sub-department for osteoporosis. The educational staff of the Clinic of Endocrinology organizes theoretical and practical education about Clinical Investigation and Internal Medicine with credit transfer system course of study of the Medical Faculty, Faculty of Stomatology, postgraduate studies, specializations and sub-specializations. Symposiums, 3 congresses, schools for diabetes and osteoporosis and continuous medical education were also organized. The Clinic of Endocrinology was initiator, organizer, founder and the seat of several medical associations.

  8. Pregnancy outcomes after chemotherapy for trophoblastic neoplasia.

    Science.gov (United States)

    Garcia, Mila Trementosa; Lin, Lawrence Hsu; Fushida, Koji; Francisco, Rossana Pulcineli Vieira; Zugaib, Marcelo

    2016-12-01

    The successful development of chemotherapy enabled a fertilitysparing treatment for patients with trophoblastic neoplasia. After disease remission, the outcome of a subsequent pregnancy becomes a great concern for these women. To analyze existing studies in the literature that describe the reproductive outcomes of patients with trophoblastic neoplasia treated with chemotherapy. Systematic review was performed searching for articles on Medline/ Pubmed, Lilacs and Cochrane Library databases, using the terms "gestational trophoblastic disease" and "pregnancy outcome". A total of 18 articles were included. No evidence of decreased fertility after chemotherapy for trophoblastic neoplasia was observed. The abortion rates in patients who conceived within 6 months after chemotherapy was higher compared to those who waited longer. Some studies showed increased rates of stillbirth and repeat hydatidiform moles. Only one work showed increased congenital abnormalities. The pregnancies conceived after chemotherapy for trophoblastic neoplasia should be followed with clinical surveillance due to higher rates of some pregnancy complications. However, studies in the literature provide reassuring data about reproductive outcomes of these patients.

  9. Pregnancy outcomes after chemotherapy for trophoblastic neoplasia

    Directory of Open Access Journals (Sweden)

    MILA TREMENTOSA GARCIA

    Full Text Available SUMMARY Introduction The successful development of chemotherapy enabled a fertilitysparing treatment for patients with trophoblastic neoplasia. After disease remission, the outcome of a subsequent pregnancy becomes a great concern for these women. Objective To analyze existing studies in the literature that describe the reproductive outcomes of patients with trophoblastic neoplasia treated with chemotherapy. Method Systematic review was performed searching for articles on Medline/ Pubmed, Lilacs and Cochrane Library databases, using the terms “gestational trophoblastic disease” and “pregnancy outcome”. Results A total of 18 articles were included. No evidence of decreased fertility after chemotherapy for trophoblastic neoplasia was observed. The abortion rates in patients who conceived within 6 months after chemotherapy was higher compared to those who waited longer. Some studies showed increased rates of stillbirth and repeat hydatidiform moles. Only one work showed increased congenital abnormalities. Conclusion The pregnancies conceived after chemotherapy for trophoblastic neoplasia should be followed with clinical surveillance due to higher rates of some pregnancy complications. However, studies in the literature provide reassuring data about reproductive outcomes of these patients.

  10. [Endocrinology 1999-2000].

    Science.gov (United States)

    Schreiber, V

    2001-02-15

    Long-lasting problem on the differentiation of adenohypophyseal cell, which prepares them for their specific tasks (somatotropic, lactotropic ect.), becomes elucidated after recognition of the differentiational effect of transcription factor Pit-1. Expression of that factor in somatotrops results in STH secretion, contrary to lactotrops producing prolactin. Subclinical hypothyreosis (increased TSH with normal T3 and T4) endangers vessel not because of hypercholesterolemia, but because of changes in the dynamics of the blood flow. The idea of cardiotropic effect of thyroidal hormones is supported by the finding that administration of trijodthyronine to children after the surgical correction of heart malformations (cardiopulmonary bypass) improves myocardial function--it elevates cardiac output and decreases requirements on the intensive care. Receptors for hormones in tissues are flexible, they can be "heterooligomers" for dopamine and somatostatin. Mutations of mineralocorticoid receptor may cause hypertension in pregnancy and progesterone receptors have several isoforms. Receptors can be also activated by short exposition to a hormone. Glucocorticoids have probably also membrane receptors. Diabetes mellitus "type I" needn't to be immunogenic and DM type II not only results from down-regulation of receptors and subsequent insulin resistance, but it can be also caused by defects in insulin secretion. Insulin has receptors in the brain and participates in the appetite regulation. The attempt to use "desensibilisation" by peroraly administered insulin in patients with immunogenic DM had no effect. Stress affects memory mechanisms, heavy emotional stress during gravidity can bring congenital malformations. The decrease of mental functions in aged women depends on the level of free estradiol (the fraction, which is not bound to plasma proteins). Activation of dopaminergic neurons can be achieved by neurotropic growth factors. Nesiritide is a recombinant brain

  11. Smolt physiology and endocrinology

    Science.gov (United States)

    McCormick, Stephen D.; McCormick, Stephen D.; Farrell, Anthony Peter; Brauner, Colin J.

    2013-01-01

    Hormones play a critical role in maintaining body fluid balance in euryhaline fishes during changes in environmental salinity. The neuroendocrine axis senses osmotic and ionic changes, then signals and coordinates tissue-specific responses to regulate water and ion fluxes. Rapid-acting hormones, e.g. angiotensins, cope with immediate challenges by controlling drinking rate and the activity of ion transporters in the gill, gut, and kidney. Slow-acting hormones, e.g. prolactin and growth hormone/insulin-like growth factor-1, reorganize the body for long-term acclimation by altering the abundance of ion transporters and through cell proliferation and differentiation of ionocytes and other osmoregulatory cells. Euryhaline species exist in all groups of fish, including cyclostomes, and cartilaginous and teleost fishes. The diverse strategies for responding to changes in salinity have led to differential regulation and tissue-specific effects of hormones. Combining traditional physiological approaches with genomic, transcriptomic, and proteomic analyses will elucidate the patterns and diversity of the endocrine control of euryhalinity.

  12. Microbial Endocrinology: An Ongoing Personal Journey.

    Science.gov (United States)

    Lyte, Mark

    2016-01-01

    The development of microbial endocrinology is covered from a decidedly personal perspective. Specific focus is given to the role of microbial endocrinology in the evolutionary symbiosis between man and microbe as it relates to both health and disease. Since the first edition of this book series 5 years ago, the role of microbial endocrinology in the microbiota-gut-brain axis is additionally discussed. Future avenues of research are suggested.

  13. Peptides and the new endocrinology

    Science.gov (United States)

    Schwyzer, Robert

    1982-01-01

    The discovery of regulatory peptides common to the nervous and the endocrine systems (brain, gut, and skin) has brought about a revolution in our concepts of endocrinology and neurology. We are beginning to understand some of the complex interrelationships between soma and psyche that might, someday, be important for an integrated treatment of diseases. Examples of the actions of certain peptides in the periphery and in the central nervous system are given, and their biosynthesis and molecular anatomy as carriers for information are discussed.

  14. Reproductive endocrinology of vitamin D.

    Science.gov (United States)

    Lorenzen, Mette; Boisen, Ida Marie; Mortensen, Li Juel; Lanske, Beate; Juul, Anders; Blomberg Jensen, Martin

    2017-09-15

    Vitamin D is a versatile hormone with several functions beyond its well-established role in maintenance of skeletal health and calcium homeostasis. The effects of vitamin D are mediated by the vitamin D receptor, which is expressed together with the vitamin D metabolizing enzymes in the reproductive tissues. The reproductive organs are therefore responsive to and able to metabolize vitamin D locally. The exact role remains to be clarified but several studies have suggested a link between vitamin D and production/release of reproductive hormones into circulation, which will be the main focus of this review. Current evidence is primarily based on small human association studies and rodent models. This highlights the need for randomized clinical trials, but also functional animal and human in vitro studies, and larger, prospective cohort studies are warranted. Given the high number of men and women suffering from reproductive problems and abnormal endocrinology research addressing the role of vitamin D in reproductive endocrinology may be of clinical importance. Copyright © 2017 Elsevier B.V. All rights reserved.

  15. 42 CFR 493.843 - Standard; Endocrinology.

    Science.gov (United States)

    2010-10-01

    ... 42 Public Health 5 2010-10-01 2010-10-01 false Standard; Endocrinology. 493.843 Section 493.843 Public Health CENTERS FOR MEDICARE & MEDICAID SERVICES, DEPARTMENT OF HEALTH AND HUMAN SERVICES... These Tests § 493.843 Standard; Endocrinology. (a) Failure to attain a score of at least 80 percent of...

  16. African Journal of Endocrinology and Metabolism

    African Journals Online (AJOL)

    The African Journal of Endocrinology and Metabolism (AJEM) is a biomedical peer-reviewed journal with international circulation. It publishes Reports of Original Work, preferably briefly described, in the fields of endocrinology, metabolism and related subjects. Reviews are authoritative, evidence-based articles on topical ...

  17. Persistent trophoblast disease following partial molar pregnancy.

    NARCIS (Netherlands)

    Wielsma, S.; Kerkmeijer, L.G.W.; Bekkers, R.L.M.; Pyman, J.; Tan, J.; Quinn, M.

    2006-01-01

    OBJECTIVE: Human chorionic gonadotrophin (hCG) follow-up data were analysed retrospectively in all patients registered in the Hydatidiform Mole Registry at the Royal Women's Hospital, Melbourne from January 1992 to January 2001 to determine the risk of persistent trophoblast disease following

  18. Gestational trophoblastic disease following complete hydatidiform ...

    African Journals Online (AJOL)

    Gestational trophoblastic disease following complete hydatidiform mole in Mulago Hospital, Kampala, Uganda. ... The main outcome measures were pre- and post-evacuation serum hCG levels and complications associated with oral methotrexate use. Results : The prevalence of CHM was 3.42 per 1,000 deliveries.

  19. [Endocrinology, what's new in 2016].

    Science.gov (United States)

    Mavromati, Maria; Philippe, Jacques

    2017-01-11

    The European Society of Endocrinology has published this year a series of guidelines for hypoparathyroidism, the management of adrenal incidentalomas as well as for the long-term follow-up of patients operated on for a phaeochromocytoma/paraganglioma (PPGL). For hypoparathyroidism, guidelines insist on screening for chronic complications and monitoring treatment with calcium and vitamin D; the use of recombinant PTH may provide new opportunities for the future. Concerning adrenal incidentalomas, the panel of the guidelines primarily recommends non contrast CT for the evaluation of the risk of malignancy. Patients operated on for a PPGL, should be offered an individualized follow-up plan based on assessment of their risk of tumor recurrence.

  20. Uterine Rupture Due to Invasive Metastatic Gestational Trophoblastic Neoplasm

    Science.gov (United States)

    Bruner, David I.; Pritchard, Amy M.; Clarke, Jonathan

    2013-01-01

    While complete molar pregnancies are rare, they are wrought with a host of potential complications to include invasive gestational trophoblastic neoplasia. Persistent gestational trophoblastic disease following molar pregnancy is a potentially fatal complication that must be recognized early and treated aggressively for both immediate and long-term recovery. We present the case of a 21-year-old woman with abdominal pain and presyncope 1 month after a molar pregnancy with a subsequent uterine rupture due to invasive gestational trophoblastic neoplasm. We will discuss the complications of molar pregnancies including the risks and management of invasive, metastatic gestational trophoblastic neoplasia. PMID:24106538

  1. Female Physicians and the Future of Endocrinology.

    Science.gov (United States)

    Pelley, Elaine; Danoff, Ann; Cooper, David S; Becker, Carolyn

    2016-01-01

    Given that approximately 70% of current endocrinology fellows are women, female physicians will compose the majority of the future endocrinology workforce. This gender shift partly reflects an apparent waning of interest in endocrinology among male trainees. It also coincides with a projected shortage of endocrinologists overall. Female physicians face unique challenges in the workplace. To continue to attract trainees to the specialty and support their success, it is imperative that these challenges be recognized, understood, and addressed. A PubMed search using the terms "female physician" and "physician gender" covering the years 2000-2015 was performed. Additional references were identified through review of the citations of the retrieved articles. The following topics were identified as key to understanding the impact of this gender shift: professional satisfaction, work-life balance, income, parenthood, academic success, and patient satisfaction. Several changes can be predicted to occur as endocrinology becomes a female-predominant specialty. Although professional satisfaction should remain stable, increased burnout rates are likely. Work-life balance challenges will likely be magnified. The combined effects of occupational gender segregation and a gender pay gap are predicted to negatively impact salaries of endocrinologists of both genders. The underrepresentation of women in academic leadership may mean a lesser voice for endocrinology in this arena. Finally, gender biases evident in patient satisfaction measures--commonly used as proxies for quality of care--may disproportionately impact endocrinology. Endocrinology is predicted to become the most female-predominant subspecialty of internal medicine. The specialty of endocrinology should take a lead role in advocating for changes that support the success of female physicians. Strengthening and supporting the physician workforce can only serve to attract talented physicians of both genders to the

  2. Suppression of STAT3 Signaling by Δ9-Tetrahydrocannabinol (THC) Induces Trophoblast Dysfunction.

    Science.gov (United States)

    Chang, Xinwen; Bian, Yiding; He, Qizhi; Yao, Julei; Zhu, Jingping; Wu, Jinting; Wang, Kai; Duan, Tao

    2017-01-01

    Marijuana is a widely used illicit drug and its consumption during pregnancy has been associated with adverse reproductive outcomes. The purpose of this study was to determine the effects of chronic intake of Δ9-tetrahydrocannabinol (THC), the major component of marijuana, on trophoblast function, placental development, and birth outcomes. The pathological characteristics and distribution of cannabinoid receptors in placenta were observed by immunohistochemical (IHC) staining. Cell migration in response to THC was measured by transwell assays. The levels of cannabinoid receptors and Signal Transducer and Activator of Transcription 3 (STAT3) were detected by western blot. We found the placenta expressed two main cannabinoid receptors, suggesting that THC induced biological responses in placental cells. Supporting this hypothesis, we observed dramatic alterations of placental morphology in marijuana users. Using THC and inhibitors of cannabinoid receptors, we demonstrated that THC impaired trophoblast cell migration and invasion partly via cannabinoid receptors. Additionally, pregnant mice injected with THC showed adverse reproductive events including reduced number of fetuses, lower maternal and placental weights. Mechanistically, STAT3 signaling pathway was involved in the THC-induced suppression of trophoblast cell motility and pregnancy outcomes. Our study indicates that the STAT3 signaling pathway plays a critical role in THC-induced trophoblast dysfunction. © 2017 The Author(s). Published by S. Karger AG, Basel.

  3. Synthesis and release of fatty acids by human trophoblast cells in culture

    International Nuclear Information System (INIS)

    Coleman, R.A.; Haynes, E.B.

    1987-01-01

    In order to determine whether placental cells can synthesize and release fatty acids, trophoblast cells from term human placentas were established in monolayer culture. The cells continued to secrete placental lactogen and progesterone and maintained specific activities of critical enzymes of triacylglycerol and phosphatidylcholine biosynthesis for 24 to 72 hr in culture. Fatty acid was rapidly synthesized from [ 14 C]acetate and released by the cells. Palmitoleic, palmitic, and oleic acids were the major fatty acids synthesized from [ 14 C]acetate and released. Small amounts of lauric, myristic, and stearic acids were also identified. [ 14 C]acetate was also incorporated into cellular triacylglycerol, phospholipid, and cholesterol, but radiolabeled free fatty acid did not accumulate intracellularly. In a pulse-chase experiment, cellular glycerolipids were labeled with [1- 14 C]oleate; trophoblast cells then released 14 C-labeled fatty acid into the media as the cellular content of labeled phospholipid and triacylglycerol decreased without intracellular accumulation of free fatty acid. Twenty percent of the 14 C-label lost from cellular glycerolipid could not be recovered as a chloroform-extractable product, suggesting that some of the hydrolyzed fatty acid had been oxidized. These data indicate that cultured placenta trophoblast cells can release fatty acids that have either been synthesized de novo or that have been hydrolyzed from cellular glycerolipids. Trophoblast cells in monolayer culture should provide an excellent model for molecular studies of placental fatty acid metabolism and release

  4. Oxygen Modulates Human Decidual Natural Killer Cell Surface Receptor Expression and Interactions with Trophoblasts1

    Science.gov (United States)

    Wallace, Alison E.; Goulwara, Sonu S.; Whitley, Guy S.; Cartwright, Judith E.

    2014-01-01

    Decidual natural killer (dNK) cells have been shown to both promote and inhibit trophoblast behavior important for decidual remodeling in pregnancy and have a distinct phenotype compared to peripheral blood NK cells. We investigated whether different levels of oxygen tension, mimicking the physiological conditions of the decidua in early pregnancy, altered cell surface receptor expression and activity of dNK cells and their interactions with trophoblast. dNK cells were isolated from terminated first-trimester pregnancies and cultured in oxygen tensions of 3%, 10%, and 21% for 24 h. Cell surface receptor expression was examined by flow cytometry, and the effects of secreted factors in conditioned medium (CM) on the trophoblast cell line SGHPL-4 were assessed in vitro. SGHPL-4 cells treated with dNK cell CM incubated in oxygen tensions of 10% were significantly more invasive (P cells treated with dNK cell CM incubated in oxygen tensions of 3% or 21%. After 24 h, a lower percentage of dNK cells expressed CD56 at 21% oxygen (P cells expressed NKG2D at 10% oxygen (P oxygen tensions, with large patient variation. This study demonstrates dNK cell phenotype and secreted factors are modulated by oxygen tension, which induces changes in trophoblast invasion and endovascular-like differentiation. Alterations in dNK cell surface receptor expression and secreted factors at different oxygen tensions may represent regulation of function within the decidua during the first trimester of pregnancy. PMID:25232021

  5. Formaldehyde Crosses the Human Placenta and Affects Human Trophoblast Differentiation and Hormonal Functions.

    Directory of Open Access Journals (Sweden)

    Guillaume Pidoux

    Full Text Available The chorionic villus of the human placenta is the source of specific endocrine functions and nutrient exchanges. These activities are ensured by the syncytiotrophobast (ST, which bathes in maternal blood. The ST arises and regenerates throughout pregnancy by fusion of underlying cytotrophoblasts (CT. Any anomaly of ST formation or regeneration can affect pregnancy outcome and fetal growth. Because of its direct interaction with maternal blood, the ST is sensitive to drugs, pollutants and xenohormones. Ex vivo assays of perfused cotyledon show that formaldehyde, a common pollutant present in furniture, paint and plastics, can accumulate in the human placenta and cross to the fetal compartment. By means of RT-qPCR, immunoblot and immunocytochemistry experiments, we demonstrate in vitro that formaldehyde exerts endocrine toxicity on human trophoblasts, including a decrease in the production of protein hormones of pregnancy. In addition, formaldehyde exposure triggered human trophoblast fusion by upregulating syncitin-1 receptor expression (ASC-type amino-acid transporter 2: ASCT2. Moreover, we show that formaldehyde-exposed trophoblasts present an altered redox status associated with oxidative stress, and an increase in ASCT2 expression intended to compensate for this stress. Finally, we demonstrate that the adverse effects of formaldehyde on trophoblast differentiation and fusion are reversed by N-acetyl-L-cysteine (Nac, an antioxidant.

  6. Suppression of STAT3 Signaling by Δ9-Tetrahydrocannabinol (THC Induces Trophoblast Dysfunction

    Directory of Open Access Journals (Sweden)

    Xinwen Chang

    2017-06-01

    Full Text Available Aims: Marijuana is a widely used illicit drug and its consumption during pregnancy has been associated with adverse reproductive outcomes. The purpose of this study was to determine the effects of chronic intake of Δ9-tetrahydrocannabinol (THC, the major component of marijuana, on trophoblast function, placental development, and birth outcomes. Methods: The pathological characteristics and distribution of cannabinoid receptors in placenta were observed by immunohistochemical (IHC staining. Cell migration in response to THC was measured by transwell assays. The levels of cannabinoid receptors and Signal Transducer and Activator of Transcription 3 (STAT3 were detected by western blot. Results: We found the placenta expressed two main cannabinoid receptors, suggesting that THC induced biological responses in placental cells. Supporting this hypothesis, we observed dramatic alterations of placental morphology in marijuana users. Using THC and inhibitors of cannabinoid receptors, we demonstrated that THC impaired trophoblast cell migration and invasion partly via cannabinoid receptors. Additionally, pregnant mice injected with THC showed adverse reproductive events including reduced number of fetuses, lower maternal and placental weights. Mechanistically, STAT3 signaling pathway was involved in the THC-induced suppression of trophoblast cell motility and pregnancy outcomes. Conclusion: Our study indicates that the STAT3 signaling pathway plays a critical role in THC-induced trophoblast dysfunction.

  7. AMERICAN ASSOCIATION OF CLINICAL ENDOCRINOLOGISTS, AMERICAN COLLEGE OF ENDOCRINOLOGY, AND ASSOCIAZIONE MEDICI ENDOCRINOLOGI MEDICAL GUIDELINES FOR CLINICAL PRACTICE FOR THE DIAGNOSIS AND MANAGEMENT OF THYROID NODULES - 2016 UPDATE

    DEFF Research Database (Denmark)

    Gharib, Hossein; Papini, Enrico; Garber, Jeffrey R

    2016-01-01

    by the American Association of Clinical Endocrinologists (AACE), American College of Endocrinology (ACE) and Associazione Medici Endocrinologi (AME). ABBREVIATIONS: AACE = American Association of Clinical Endocrinologists ACE = American College of Endocrinology AME = Associazione Medici Endocrinologi BEL = best...

  8. 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.

  9. 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.

  10. Vitamin D attenuates sphingosine-1-phosphate (S1P)-mediated inhibition of extravillous trophoblast migration.

    Science.gov (United States)

    Westwood, Melissa; Al-Saghir, Khiria; Finn-Sell, Sarah; Tan, Cherlyn; Cowley, Elizabeth; Berneau, Stéphane; Adlam, Daman; Johnstone, Edward D

    2017-12-01

    Failure of trophoblast invasion and remodelling of maternal blood vessels leads to the pregnancy complication pre-eclampsia (PE). In other systems, the sphingolipid, sphingosine-1-phosphate (S1P), controls cell migration therefore this study determined its effect on extravillous trophoblast (EVT) function. A transwell migration system was used to assess the behaviour of three trophoblast cell lines, Swan-71, SGHPL-4, and JEG3, and primary human trophoblasts in the presence or absence of S1P, S1P pathway inhibitors and 1,25(OH) 2 D 3 . QPCR and immunolocalisation were used to demonstrate EVT S1P receptor expression. EVTs express S1P receptors 1, 2 and 3. S1P inhibited EVT migration. This effect was abolished in the presence of the specific S1PR2 inhibitor, JTE-013 (p S1P alone) whereas treatment with the S1R1/3 inhibitor, FTY720, had no effect. In other cell types S1PR2 is regulated by vitamin D; here we found that treatment with 1,25(OH) 2 D 3 for 48 or 72 h reduces S1PR2 (4-fold; S1P did not inhibit the migration of cells exposed to 1,25(OH) 2 D 3 (p S1P receptor isoforms, S1P predominantly signals through S1PR2/Gα 12/13 to activate Rho and thereby acts as potent inhibitor of EVT migration. Importantly, expression of S1PR2, and therefore S1P function, can be down-regulated by vitamin D. Our data suggest that vitamin D deficiency, which is known to be associated with PE, may contribute to the impaired trophoblast migration that underlies this condition. Copyright © 2017 Elsevier Ltd. All rights reserved.

  11. Lysosomal degradation of receptor-bound urokinase-type plasminogen activator is enhanced by its inhibitors in human trophoblastic choriocarcinoma cells

    DEFF Research Database (Denmark)

    Jensen, Poul Henning; Christensen, Erik Ilsø; Ebbesen, P.

    1990-01-01

    We have studied the effect of plasminogen activator inhibitors PAI-1 and PAI-2 on the binding of urokinase-type plasminogen activator (u-PA) to its receptor in the human choriocarcinoma cell line JAR. With 125I-labeled ligands in whole-cell binding assays, both uncomplexed u-PA and u......, with the highest density of grains over the membrane at cell-cell interphases, but, after incubation at 37 degrees C, 17 and 27% of the grains for u-PA and u-PA-PAI-1 complexes, respectively, appeared over lysosomal-like bodies. These findings suggest that the u-PA receptor possesses a clearance function......-PA-inhibitor complexes bound to the receptor with a Kd of approximately 100 pM at 4 degrees C. Transferring the cells to 37 degrees C led to degradation to amino acids of up to 50% of the cell-bound u-PA-inhibitor complexes, whereas the degradation of uncomplexed u-PA was 15%; the remaining ligand was recovered...

  12. The use of noninvasive and minimally invasive methods in endocrinology for threatened mammalian species conservation.

    Science.gov (United States)

    Kersey, David C; Dehnhard, Martin

    2014-07-01

    Endocrinology is an indispensable tool in threatened species research. The study of endocrinology in threatened species not only advances knowledge of endocrine mechanism but also contributes to conservation efforts of studied species. To this end, endocrinology has been traditionally used to understand reproductive and adrenocortical endocrine axes by quantifying excreted steroid metabolites. From these studies a large body of knowledge was created that contributed to the field of endocrinology, aided conservation efforts, and created a template by which to validate and conduct this research for other species. In this regard noninvasive hormone monitoring has become a favored approach to study the basic endocrinology of wildlife species. Due to the increased understanding of endocrine physiology of threatened species, breeding rates of captive population have improved to levels allowing for reintroduction of species to restored natural ecosystems. Although these approaches are still employed, advances in biochemical, molecular, and genomic technologies are providing inroads to describe lesser known endocrine activity in threatened species. These new avenues of research will allow for growth of the field with greater depth and breadth. However, for all approaches to endocrinology, limitations on resources and access to animals will require innovation of current methodologies to permit broad application for use in threatened species research. Crown Copyright © 2014. Published by Elsevier Inc. All rights reserved.

  13. Is Doppler ultrasound useful for evaluating gestational trophoblastic disease?

    Directory of Open Access Journals (Sweden)

    Lawrence H. Lin

    Full Text Available Doppler ultrasound is a non-invasive method for evaluating vascularization and is widely used in clinical practice. Gestational trophoblastic neoplasia includes a group of highly vascularized malignancies derived from placental cells. This review summarizes data found in the literature regarding the applications of Doppler ultrasound in managing patients with gestational trophoblastic neoplasia. The PubMed/Medline, Web of Science, Cochrane and LILACS databases were searched for articles published in English until 2014 using the following keywords: “Gestational trophoblastic disease AND Ultrasonography, Doppler.” Twenty-eight articles met the inclusion criteria and were separated into the 4 following groups according to the aim of the study. (1 Doppler ultrasound does not seem to be capable of differentiating partial from complete moles, but it might be useful when evaluating pregnancies in which a complete mole coexists with a normal fetus. (2 There is controversy in the role of uterine artery Doppler velocimetry in the prediction of development of gestational trophoblastic neoplasia. (3 Doppler ultrasound is a useful tool in the diagnosis of gestational trophoblastic neoplasia because abnormal myometrial vascularization and lower uterine artery Doppler indices seem to be correlated with invasive disease. (4 Lower uterine artery Doppler indices in the diagnosis of gestational trophoblastic neoplasia are associated with methotrexate resistance and might play a role in prognosis. CONCLUSION: Several studies support the importance of Doppler ultrasound in the management of patients with gestational trophoblastic neoplasia, particularly the role of Doppler velocimetry in the prediction of trophoblastic neoplasia and the chemoresistance of trophoblastic tumors. Doppler findings should be used as ancillary tools, along with human chorionic gonadotropin assessment, in the diagnosis of gestational trophoblastic neoplasia.

  14. Is Doppler ultrasound useful for evaluating gestational trophoblastic disease?

    Science.gov (United States)

    Lin, Lawrence H; Bernardes, Lisandra S; Hase, Eliane A; Fushida, Koji; Francisco, Rossana P V

    2015-12-01

    Doppler ultrasound is a non-invasive method for evaluating vascularization and is widely used in clinical practice. Gestational trophoblastic neoplasia includes a group of highly vascularized malignancies derived from placental cells. This review summarizes data found in the literature regarding the applications of Doppler ultrasound in managing patients with gestational trophoblastic neoplasia. The PubMed/Medline, Web of Science, Cochrane and LILACS databases were searched for articles published in English until 2014 using the following keywords: "Gestational trophoblastic disease AND Ultrasonography, Doppler." Twenty-eight articles met the inclusion criteria and were separated into the 4 following groups according to the aim of the study. (1) Doppler ultrasound does not seem to be capable of differentiating partial from complete moles, but it might be useful when evaluating pregnancies in which a complete mole coexists with a normal fetus. (2) There is controversy in the role of uterine artery Doppler velocimetry in the prediction of development of gestational trophoblastic neoplasia. (3) Doppler ultrasound is a useful tool in the diagnosis of gestational trophoblastic neoplasia because abnormal myometrial vascularization and lower uterine artery Doppler indices seem to be correlated with invasive disease. (4) Lower uterine artery Doppler indices in the diagnosis of gestational trophoblastic neoplasia are associated with methotrexate resistance and might play a role in prognosis. Several studies support the importance of Doppler ultrasound in the management of patients with gestational trophoblastic neoplasia, particularly the role of Doppler velocimetry in the prediction of trophoblastic neoplasia and the chemoresistance of trophoblastic tumors. Doppler findings should be used as ancillary tools, along with human chorionic gonadotropin assessment, in the diagnosis of gestational trophoblastic neoplasia.

  15. PET-CT in endocrinology

    International Nuclear Information System (INIS)

    Parysow, O.; Jager, V.; Racioppi, S.; Mollerach, A.M.; Collaud, C.; Arma, I.

    2008-01-01

    PET/CT scans have reached an important place in the evaluation of endocrine tumors. The metabolic marker 18F-FDG is the most widespread over the world, and, for the time being, it is the only one available in our country. The limitations of this technique in Endocrinology include high differentiation and low aggressiveness of most endocrine tumors, and low detection rate for low cellularity and/or small lesions. Indications for PET/CT scan in these tumors should be precise, due to the fact that not all of these lesions are significantly glucose-avid and to extract the maximum diagnostic efficacy of this modality to achieve the optimum diagnostic accuracy. The most important indication is DTC with high Tg levels and negative 131-Iodine scans. It is advisable to indicate a PET/CT scan in patients with Tg > 10 ng/ml and stimulated TSH (endogenous or exogenous). The aim is to locate recurrences and metastases in order to remove them, either surgically or by any other therapy alternative to 131 I. Due to higher uptake in more aggressive lesions, this study has a high prognostic value. In patients with high Tg levels, negative 131 I scan, and abnormal FDG uptake, the practitioner must act more aggressively in order to remove the pathologic foci, while with a negative FDG -PET scan, the conduct can be expectant, with periodic follow-up. The introduction of other positron-emitting tracers like 124-Iodine, is likely to yield superior quality images and provide better diagnoses. FDG has a limited efficiency in neuroendocrine tumors, unless they show a significant level of dedifferentiation. The scan is indicated in MTC, when calcitonin levels are above 1000 pg/ml, in order to locate the tumor sites. With the introduction of more specific positron-emitting radiopharmaceuticals, such as 18F-DOPA, 68Ga DOTA, 11C methomidate, 11C-hydroxytryptophan and others, it will be possible to study the metabolic-molecular behavior of these tumors with a more accurate approach. (author) [es

  16. Gestational trophoblastic disease with hyperthyroidism: Anesthetic management

    Directory of Open Access Journals (Sweden)

    Puneet Khanna

    2012-01-01

    Full Text Available The coexistence of hyperthyroidism with gestational trophoblastic disease is a known albeit rare clinical condition. We herein report the successful anesthetic management of such a case in our institute. There are only few case reports in literature of this association. Often, the diagnosis of hyperthyroid state is retrospective one, as it can be missed in the emergency scenario of patient requiring molar evacuation. This case report highlights the perioperative management and optimization of hyperthyroid state prior to surgical evacuation of the invasive hydatidiform mole.

  17. Rac1/β-Catenin Signalling Pathway Contributes to Trophoblast Cell Invasion by Targeting Snail and MMP9

    Directory of Open Access Journals (Sweden)

    Minghua Fan

    2016-03-01

    Full Text Available Background/Aims: Preeclampsia is an idiopathic and serious complication during gestation in which placental trophoblast cells differentiate into several functional subtypes, including highly invasive extravillous trophoblasts (EVTs. Although the cause and pathogenesis of preeclampsia have remained unclear, numerous studies have suggested that the inadequacy of EVT invasion leads to imperfect uterine spiral artery remodelling, which plays a crucial role in the development of preeclampsia. Rac1, or Ras-related C3 botulinum toxin substrate 1, was found to be a key regulator of the migration, invasion uand apoptosis of various tumour cells. Because EVTs share similar invasive and migratory biological behaviours with malignant cells, this study aimed to determine whether the Rac1 signalling pathway affects trophoblast invasion and is thus involved in the pathogenesis of preeclampsia. Methods: We measured the activity of Rac1 and its downstream targets, β-catenin, Snail and MMP9 in placental tissues from patients experiencing a normal pregnancy and those with preeclampsia. Furthermore, we treated HTR-8/SVneo cells with a shRNA Rac1 vector and the β-catenin inhibitor IWP-2 and explored Rac1 signalling pathway activation as well as the effects of Snail and β-catenin on trophoblast invasion. Results: In placental samples from patients experiencing a normal pregnancy and those with preeclampsia, active Rac1 levels and MMP9 protein and mRNA levels were significantly decreased in term pregnancy samples compared to early pregnancy samples. Lower levels were found in preeclampsia samples than in normal term pregnancy samples, and these levels significantly declined in severe preeclampsia samples compared with mild preeclampsia samples. Further analyses demonstrated that both Rac1 shRNA and the β-catenin inhibitor significantly suppressed MMP9 and Snail activation in trophoblasts, thus impairing trophoblast invasion. Notably, silencing Rac1 down

  18. Minimally-aggressive gestational trophoblastic neoplasms.

    Science.gov (United States)

    Cole, Laurence A

    2012-04-01

    We have previously defined a new syndrome "Minimally-aggressive gestational trophoblastic neoplasms" in which choriocarcinoma or persistent hydatidiform mole has a minimal growth rate and becomes chemorefractory. Previously we described a new treatment protocol, waiting for hCG rise to >3000 mIU/ml and disease becomes more advanced, then using combination chemotherapy. Initially we found this treatment successful in 8 of 8 cases, here we find this protocol appropriate in a further 16 cases. Initially we used hyperglycosylated hCG, a limited availability test, to identify this syndrome. Here we propose also using hCG doubling rate to detect this syndrome. Minimally aggressive gestational trophoblastic disease can be detected by chemotherapy resistance or low hyperglycosylated hCG, disease by hyperglycosylated hCG and by hCG doubling test. All were recommended to hold off further chemotherapy until hCG >3000mIU/ml. One case died prior to the start of the study, one case withdrew because of a lung nodule and one withdrew refusing the suggested combination chemotherapy. The remaining 16 women were all successfully treated. A total of 8 plus 16 or 24 of 24 women were successfully treated using the proposed protocol, holding back on chemotherapy until hCG >3000mIU/ml. Copyright © 2011 Elsevier Inc. All rights reserved.

  19. Activation of PAR-1/NADPH oxidase/ROS signaling pathways is crucial for the thrombin-induced sFlt-1 production in extravillous trophoblasts: possible involvement in the pathogenesis of preeclampsia.

    Science.gov (United States)

    Huang, Qi-Tao; Chen, Jian-Hong; Hang, Li-Lin; Liu, Shi-San; Zhong, Mei

    2015-01-01

    Preeclampsia was characterized by excessive thrombin generation in placentas and previous researches showed that thrombin could enhance soluble Fms-like tyrosine kinase 1 (sFlt-1) expression in first trimester trophoblasts. However, the detailed mechanism for the sFlt-1 over-production induced by thrombin was largely unknown. The purpose of this study was to explore the possible signaling pathway of thrombin-induced sFlt-1 production in extravillous trophoblasts (EVT). An EVT cell line (HRT-8/SVneo) was treated with various concentrations of thrombin. The mRNA expression and protein secretion of sFlt-1 in EVT were detected with real-time polymerase chain reaction and ELISA, respectively. The levels of intracellular reactive oxygen species (ROS) production were determined by DCFH-DA. Exposure of EVT to thrombin induced increased intracellular ROS generation and overexpression of sFlt-1 at both mRNA and protein levels in a dose dependent manner. Short interfering RNA (siRNA) directed against PAR-1 or apocynin (an inhibitor of NADPH oxidase) could decrease the intracellular ROS generation and subsequently suppressed the production of sFlt-1 at mRNA and protein levels. Our results suggested that thrombin increased sFlt-1 production in EVT via the PAR-1 /NADPH oxidase /ROS signaling pathway. This also highlights the PAR-1 / NADPH oxidase / ROS pathway might be a potential therapeutic target for the prevention of preeclampsia in the future. © 2015 S. Karger AG, Basel.

  20. Decreased IL-33 Production Contributes to Trophoblast Cell Dysfunction in Pregnancies with Preeclampsia

    Directory of Open Access Journals (Sweden)

    Hong Chen

    2018-01-01

    Full Text Available Preeclampsia (PE is a life-threatening pregnancy complication which is related to aggradation of risk regarding fetal and maternal morbidity and mortality. Dysregulation of systemic inflammatory response and dysfunction of trophoblast cells have been proposed to be involved in the development and progression of PE. Some studies have demonstrated that interleukin-33 (IL-33 is an immunomodulatory cytokine that is associated with the immune regulation of tumor cells. However, little is known whether IL-33 and its receptor ST2/IL-1 R4 could regulate trophoblast cells, which are associated with the pathogenesis of PE. In this study, our target is to explore the impact of IL-33 on trophoblast cells and elucidate its underlying pathophysiological mechanisms. Placental tissues from the severe PE group (n=11 and the normotensive pregnant women’s group (n=11 were collected for the protein expression and distribution of IL-33 along with its receptor ST2/IL-1 R4 via Western blot analysis and immunohistochemistry, respectively. We discovered that the level of IL-33 was decreased in placental tissues of pregnant women with PE, while no distinction was observed in the expression of ST2/IL-1 R4. These results were further verified in villous explants which were treated with sodium nitroprusside with different concentrations, to simulate the pathological environment of PE. To investigate IL-33 effects on trophoblast cells separately, IL-33 shRNA was introduced into HTR8/SVneo cells and villi. IL-33 shRNA weakened the proliferation, migration, and invasion capacity of HTR8/SVneo cells. The migration distance of villous explants was also markedly decreased. The reduced invasion of trophoblast cells is a result of IL-33 knockdown which could be related to the decline of MMP2/9 activity and the increased utterance of TIMP1/2. Overall, our findings demonstrated that the reduction of IL-33 production was connected with the reduced functional capability of

  1. Reproductive endocrinology of llamas and alpacas.

    Science.gov (United States)

    Bravo, P W

    1994-07-01

    The physiology of reproduction with emphasis in endocrinology of llamas and alpacas is addressed. Basic concepts of ovarian follicular dynamics, endocrine events associated with induction of ovulation, corpus luteum formation, pregnancy, parturition, postpartum interval, puberty, and sexual behavior on the female are reviewed. Pathologic conditions of the reproductive process are also reviewed.

  2. Polycystic ovary syndrome | Maharaj | Journal of Endocrinology ...

    African Journals Online (AJOL)

    Polycystic ovary syndrome. ... Journal of Endocrinology, Metabolism and Diabetes of South Africa ... the disorder, that we now know as the polycystic ovary (or ovarian) syndrome (PCOS), in seven women with amenorrhoea, enlarged ovaries with multiple cysts and hirsutism.2 These patients were treated with ovarian wedge ...

  3. Trophoblast cell fusion and differentiation are mediated by both the protein kinase C and a pathways.

    Directory of Open Access Journals (Sweden)

    Waka Omata

    Full Text Available The syncytiotrophoblast of the human placenta is an epithelial barrier that interacts with maternal blood and is a key for the transfer of nutrients and other solutes to the developing fetus. The syncytiotrophoblast is a true syncytium and fusion of progenitor cytotrophoblasts is the cardinal event leading to the formation of this layer. BeWo cells are often used as a surrogate for cytotrophoblasts, since they can be induced to fuse, and then express certain differentiation markers associated with trophoblast syncytialization. Dysferlin, a syncytiotrophoblast membrane repair protein, is up-regulated in BeWo cells induced to fuse by treatment with forskolin; this fusion is thought to occur through cAMP/protein kinase A-dependent mechanisms. We hypothesized that dysferlin may also be up-regulated in response to fusion through other pathways. Here, we show that BeWo cells can also be induced to fuse by treatment with an activator of protein kinase C, and that this fusion is accompanied by increased expression of dysferlin. Moreover, a dramatic synergistic increase in dysferlin expression is observed when both the protein kinase A and protein kinase C pathways are activated in BeWo cells. This synergy in fusion is also accompanied by dramatic increases in mRNA for the placental fusion proteins syncytin 1, syncytin 2, as well as dysferlin. Dysferlin, however, was shown to be dispensable for stimulus-induced BeWo cell syncytialization, since dysferlin knockdown lines fused to the same extent as control cells. The classical trophoblast differentiation marker human chorionic gonadotropin was also monitored and changes in the expression closely parallel that of dysferlin in all of the experimental conditions employed. Thus different biochemical markers of trophoblast fusion behave in concert supporting the hypothesis that activation of both protein kinase C and A pathways lead to trophoblastic differentiation.

  4. Create new research directions in comparative endocrinology from Asia and Oceania.

    Science.gov (United States)

    Tsutsui, Kazuyoshi

    2013-01-15

    The Asia and Oceania Society for Comparative Endocrinology (AOSCE) was founded in 1987, when the first congress was held in Nagoya, Japan. The purpose of the AOSCE is to progress scientific activities in the field of comparative endocrinology in Asia and Oceania and to establish a deep relationship among the members. For this purpose, the AOSCE holds a congress or an intercongress symposium every 2 years, which organizes an attractive scientific program covering the latest progress in the broad aspect of comparative endocrinology. 2012 was the 25th anniversary of AOSCE. Our scientific activities have increased dramatically during the past 25 years. The 7th AOSCE congress was held in Kuala Lumpur, Malaysia in 2012. The theme of this congress was "Overcoming challenges in the 21st century". To overcome challenges in the 21st century, we further need to create new research directions in comparative endocrinology from Asia and Oceania. This paper describes a brief history of the AOSCE and also highlights the discovery of gonadotropin-inhibitory hormone (GnIH) and the progress of GnIH research as one of new research directions in comparative endocrinology. In 2000, GnIH was discovered in Japan and now more than 50 laboratories are working on GnIH in the world. The discovery of GnIH has changed our understanding about regulation of the reproductive axis drastically in the past decade. Copyright © 2012 Elsevier Inc. All rights reserved.

  5. lessons from a hybrid epithelioid trophoblastic tumor and chorio

    African Journals Online (AJOL)

    (36,900 mIU/ml) and examination showed a bleeding cervical mass. An initial ... characterized by abnormal proliferation of placental trophoblasts and include .... MRI is invaluable to assess extra uterine disease spread and complications.

  6. A five - year review of gestational trophoblastic diseases in Port ...

    African Journals Online (AJOL)

    Methods: A retrospective analysis of women treated for gestational ... persistent trophoblastic disease while 8(21.1%) had chemotherapy for choriocarcinoma. ... as well as proper counseling of patients treated on the benefits of follow up visits.

  7. Uterine Rupture Due to Invasive Metastatic Gestational Trophoblastic Neoplasm

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    David I Bruner

    2013-09-01

    Full Text Available While complete molar pregnancies are rare, they are wrought with a host of potential complications to include invasive gestational trophoblastic neoplasia. Persistent gestational trophoblastic disease following molar pregnancy is a potentially fatal complication that must be recognized early and treated aggressively for both immediate and long-term recovery. We present the case of a 21-year-old woman with abdominal pain and presyncope 1 month after a molar pregnancy with a subsequent uterine rupture due to invasive gestational trophoblastic neoplasm. We will discuss the complications of molar pregnancies including the risks and management of invasive, metastatic gestational trophoblastic neoplasia. [West J Emerg Med. 2013;14(5:444–447.

  8. Trophoblast cells of ruminant placentas - A mini review

    International Nuclear Information System (INIS)

    Igwebuike, U.M.

    2004-09-01

    Understanding of ruminant placental structure and function is essential for veterinarians and researchers. The ruminant placenta is classified as cotyledonary and synepitheliochorial on the bases of its gross anatomical features and histological characteristics respectively. The richly vascularized embryonic chorioallantois is lined on its outer surface by cells of the trophectodermal epithelium. These cells which assume specialized functions are referred to as trophoblast cells. Two morphologically and functionally distinct cell types have been recognized in the trophectoderm of the placenta of ruminant animals. These are the mononucleate trophoblast cells and the binucleate trophoblast cells. The occurrence, morphological characteristics, and specialized functions of these trophoblast cells, in relation to conceptus nutrition and survival in utero are discussed in this review. (author)

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

    Science.gov (United States)

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

    2017-09-01

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

  10. 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.

  11. Glucose metabolism in cultured trophoblasts from human placenta

    International Nuclear Information System (INIS)

    Moe, A.J.; Farmer, D.R.; Nelson, D.M.; Smith, C.H.

    1990-01-01

    The development of appropriate placental trophoblast isolation and culture techniques enables the study of pathways of glucose utilization by this important cell layer in vitro. Trophoblasts from normal term placentas were isolated and cultured 24 hours and 72 hours in uncoated polystyrene culture tubes or tubes previously coated with a fibrin matrix. Trophoblasts cultured on fibrin are morphologically distinct from those cultured on plastic or other matrices and generally resemble in vivo syncytium. Cells were incubated up to 3 hours with 14 C-labeled glucose and reactions were stopped by addition of perchloric acid. 14 CO 2 production by trophoblasts increased linearly with time however the largest accumulation of label was in organic acids. Trophoblasts cultured in absence of fibrin utilized more glucose and accumulated more 14 C in metabolic products compared to cells cultured on fibrin. Glucose oxidation to CO 2 by the phosphogluconate (PG) pathway was estimated from specific yields of 14 CO 2 from [1- 14 C]-D-glucose and [6- 14 C]-D-glucose. Approximately 6% of glucose oxidation was by the PG pathway when cells were cultured on fibrin compared to approximately 1% by cells cultured in the absence of fibrin. The presence of a fibrin growth matrix appears to modulate the metabolism of glucose by trophoblast from human placenta in vitro

  12. Activation of PAR-1/NADPH Oxidase/ROS Signaling Pathways is Crucial for the Thrombin-Induced sFlt-1 Production in Extravillous Trophoblasts: Possible Involvement in the Pathogenesis of Preeclampsia

    Directory of Open Access Journals (Sweden)

    Qi-tao Huang

    2015-03-01

    Full Text Available Backgrounds/Aims: Preeclampsia was characterized by excessive thrombin generation in placentas and previous researches showed that thrombin could enhance soluble Fms-like tyrosine kinase 1 (sFlt-1 expression in first trimester trophoblasts. However, the detailed mechanism for the sFlt-1 over-production induced by thrombin was largely unknown. The purpose of this study was to explore the possible signaling pathway of thrombin-induced sFlt-1 production in extravillous trophoblasts (EVT. Methods: An EVT cell line (HRT-8/SVneo was treated with various concentrations of thrombin. The mRNA expression and protein secretion of sFlt-1 in EVT were detected with real-time polymerase chain reaction and ELISA, respectively. The levels of intracellular reactive oxygen species (ROS production were determined by DCFH-DA. Results: Exposure of EVT to thrombin induced increased intracellular ROS generation and overexpression of sFlt-1 at both mRNA and protein levels in a dose dependent manner. Short interfering RNA (siRNA directed against PAR-1 or apocynin (an inhibitor of NADPH oxidase could decrease the intracellular ROS generation and subsequently suppressed the production of sFlt-1 at mRNA and protein levels. Conclusions: Our results suggested that thrombin increased sFlt-1 production in EVT via the PAR-1 /NADPH oxidase /ROS signaling pathway. This also highlights the PAR-1 / NADPH oxidase / ROS pathway might be a potential therapeutic target for the prevention of preeclampsia in the future.

  13. The psychoactive compound of Cannabis sativa, Δ(9)-tetrahydrocannabinol (THC) inhibits the human trophoblast cell turnover.

    Science.gov (United States)

    Costa, M A; Fonseca, B M; Marques, F; Teixeira, N A; Correia-da-Silva, G

    2015-08-06

    The noxious effects of cannabis consumption for fertility and pregnancy outcome are recognized for years. Its consumption during gestation is associated with alterations in foetal growth, low birth weight and preterm labor. The main psychoactive molecule of cannabis, Δ(9)-tetrahydrocannabinol (THC) impairs the production of reproductive hormones and is also able to cross the placenta barrier. However, its effect on the main placental cells, the trophoblasts, are unknown. Actually, the role of THC in cell survival/death of primary human cytotrophoblasts (CTs) and syncytiotrophoblasts (STs) and in the syncytialization process remains to be explored. Here, we show that THC has a dual effect, enhancing MTT metabolism at low concentrations, whereas higher doses decreased cell viability, on both trophoblast phenotypes, though the effects on STs were more evident. THC also diminished the generation of oxidative and nitrative stress and the oxidized form of glutathione, whereas the reduced form of this tripeptide was increased, suggesting that THC prevents ST cell death due to an antioxidant effect. Moreover, this compound enhanced the mitochondrial function of STs, as observed by the increased MTT metabolism and intracellular ATP levels. These effects were independent of cannabinoid receptors activation. Besides, THC impaired CT differentiation into STs, since it decreased the expression of biochemical and morphological biomarkers of syncytialization, through a cannabinoid receptor-dependent mechanism. Together, these results suggest that THC interferes with trophoblast turnover, preventing trophoblast cell death and differentiation, and contribute to disclose the cellular mechanisms that lead to pregnancy complications in women that consume cannabis-derived drugs during gestation. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

  14. Sildenafil Prevents Apoptosis of Human First-Trimester Trophoblast Cells Exposed to Oxidative Stress

    Science.gov (United States)

    Bolnick, Jay M.; Kilburn, Brian A.; Bolnick, Alan D.; Diamond, Michael P.; Singh, Manvinder; Hertz, Michael; Dai, Jing

    2015-01-01

    Human first-trimester trophoblast cells proliferate at low O2, but survival is compromised by oxidative stress, leading to uteroplacental insufficiency. The vasoactive drug, sildenafil citrate (Viagra, Sigma, St Louis, Missouri), has proven useful in reducing adverse pregnancy outcomes. An important biological function of this pharmaceutical is its action as an inhibitor of cyclic guanosine monophosphate (cGMP) phosphodiesterase type 5 activity, which suggests that it could have beneficial effects on trophoblast survival. To investigate whether sildenafil can prevent trophoblast cell death, human first-trimester villous explants and the HTR-8/SVneo cytotrophoblast cell line were exposed to hypoxia and reoxygenation (H/R) to generate oxidative stress, which induces apoptosis. Apoptosis was optimally inhibited during H/R by 350 ng/mL sildenafil. Sildenafil-mediated survival was reversed by l-NG-nitro-l-arginine methyl ester hydrochloride or cGMP antagonist, indicating a dependence on both nitric oxide (NO) and cGMP. Indeed, either a cGMP agonist or an NO generator was cytoprotective independent of sildenafil. These findings suggest a novel intervention route for patients with recurrent pregnancy loss or obstetrical placental disorders. PMID:25431453

  15. Identification of CD147 (basigin) as a mediator of trophoblast functions.

    Science.gov (United States)

    Lee, Cheuk-Lun; Lam, Maggie P Y; Lam, Kevin K W; Leung, Carmen O N; Pang, Ronald T K; Chu, Ivan K; Wan, Tiffany H L; Chai, Joyce; Yeung, William S B; Chiu, Philip C N

    2013-11-01

    Does CD147 regulate trophoblast functions in vitro? CD147 exists as a receptor complex on human trophoblast and regulates the implantation, invasion and differentiation of trophoblast. CD147 is a membrane protein implicated in a variety of physiological and pathological conditions due to its regulation of cell-cell recognition, cell differentiation and tissue remodeling. Reduced placental CD147 expression is associated with pre-eclampsia, but the mechanism of actions remains unclear. A loss of function approach or functional blocking antibody was used to study the function of CD147 in primary human cytotrophoblasts isolated from first trimester termination of pregnancy and/or in the BeWo cell line, which possesses characteristics of human cytotrophoblasts. CD147 expression was analyzed by immunofluorescence staining and western blotting. CD147-associated protein complex on plasma membrane were separated by blue native gel electrophoresis and identified by reversed-phase liquid chromatography coupled with quadrupole time-of-flight hybrid mass spectrometer. Cell proliferation and invasion were determined by fluorometric cell proliferation assays and transwell invasion assays, respectively. Matrix metalloproteinases (MMPs) and urokinase plasminogen activator (uPA) activities were measured by gelatin gel zymography and uPA assay kits, respectively. Cell migration was determined by wound-healing assays. Cell fusion was analyzed by immunocytochemistry staining of E-cadherin and 4',6-diamidino-2-phenylindole. The transcripts of matrix proteinases and trophoblast lineage markers were measured by quantitative PCR. Extracellular signal-regulated kinase (ERK) activation was analyzed by western blot using antibodies against ERKs. CD147 exists as protein complexes on the plasma membrane of primary human cytotrophoblasts and BeWo cells. Several known CD147-interacting partners, including integrin β1 and monocarboxylate transporter-1, were identified. Suppression of CD147 by si

  16. Localization of chondromodulin-I at the feto-maternal interface and its inhibitory actions on trophoblast invasion in vitro

    Directory of Open Access Journals (Sweden)

    Kondo Jun

    2011-08-01

    Full Text Available Abstract Background Chondromodulin-I (ChM-I is an anti-angiogenic glycoprotein that is specifically localized at the extracellular matrix of the avascular mesenchyme including cartilage and cardiac valves. In this study, we characterized the expression pattern of ChM-I during early pregnancy in mice in vivo and its effect on invasion of trophoblastic cells into Matrigel in vitro. Results Northern blot analysis clearly indicated that ChM-I transcripts were expressed in the pregnant mouse uterus at 6.5-9.5 days post coitum. In situ hybridization and immunohistochemistry revealed that ChM-I was localized to the mature decidua surrounding the matrix metalloproteinase-9 (MMP-9-expressing trophoblasts. Consistent with this observation, the expression of ChM-I mRNA was induced in decidualizing endometrial stromal cells in vitro, in response to estradiol and progesterone. Recombinant human ChM-I (rhChM-I markedly inhibited the invasion through Matrigel as well as the chemotactic migration of rat Rcho-1 trophoblast cells in a manner independent of MMP activation. Conclusions This study demonstrates the inhibitory action of ChM-I on trophoblast migration and invasion, implying the potential role of the ChM-I expression in decidual cells for the regulated tissue remodeling and angiogenesis at feto-maternal interface.

  17. Human monocytes undergo functional re-programming during differentiation to dendritic cell mediated by human extravillous trophoblasts.

    Science.gov (United States)

    Zhao, Lei; Shao, Qianqian; Zhang, Yun; Zhang, Lin; He, Ying; Wang, Lijie; Kong, Beihua; Qu, Xun

    2016-02-09

    Maternal immune adaptation is required for a successful pregnancy to avoid rejection of the fetal-placental unit. Dendritic cells within the decidual microenvironment lock in a tolerogenic profile. However, how these tolerogenic DCs are induced and the underlying mechanisms are largely unknown. In this study, we show that human extravillous trophoblasts redirect the monocyte-to-DC transition and induce regulatory dendritic cells. DCs differentiated from blood monocytes in the presence of human extravillous trophoblast cell line HTR-8/SVneo displayed a DC-SIGN(+)CD14(+)CD1a(-) phenotype, similar with decidual DCs. HTR8-conditioned DCs were unable to develop a fully mature phenotype in response to LPS, and altered the cytokine secretory profile significantly. Functionally, conditioned DCs poorly induced the proliferation and activation of allogeneic T cells, whereas promoted CD4(+)CD25(+)Foxp3(+) Treg cells generation. Furthermore, the supernatant from DC and HTR-8/SVneo coculture system contained significant high amount of M-CSF and MCP-1. Using neutralizing antibodies, we discussed the role of M-CSF and MCP-1 during monocyte-to-DCs differentiation mediated by extravillous trophoblasts. Our data indicate that human extravillous trophoblasts play an important role in modulating the monocyte-to-DC differentiation through M-CSF and MCP-1, which facilitate the establishment of a tolerogenic microenvironment at the maternal-fetal interface.

  18. [The current state and prospectives of military endocrinology].

    Science.gov (United States)

    Nagibovich, O A; Golota, A S; Krassiĭ, A B

    2014-10-01

    The article is dedicated to the current state and prospectives of military endocrinology demonstrated on the examples of the endocrinology services of armed forces of Serbia, Poland, France, and USA. It is shown that this branch of military healthcare receives much attention abroad. The prospectives of military endocrinology are demonstrated in the context of two nosological forms which dominate in this section of military medicine, namely, primary hypothyroidism an diabetes mellitus.

  19. Down-Regulation of Neuropathy Target Esterase in Preeclampsia Placenta Inhibits Human Trophoblast Cell Invasion via Modulating MMP-9 Levels

    Directory of Open Access Journals (Sweden)

    Ting Zhong

    2018-02-01

    Full Text Available Background/Aims: Neuropathy target esterase (NTE, also known as neurotoxic esterase is proven to deacylate phosphatidylcholine (PC to glycerophosphocholine as a phospholipase B. Recently; studies showed that artificial phosphatidylserine/PC microvesicles can induce preeclampsia (PE-like changes in pregnant mice. However, it is unclear whether NTE plays a key role in the pathology of PE, a pregnancy-related disease, which was characterized by deficient trophoblast invasion and reduced trophoblast-mediated remodeling of spiral arteries. The aim of this study was to investigate the expression pattern of NTE in the placenta from women with PE and normal pregnancy, and the molecular mechanism of NTE involved in the development of PE. Methods: NTE expression levels in placentas from 20 pregnant women with PE and 20 healthy pregnant women were detected using quantitative PCR and immunohistochemistry staining. The effect of NTE on trophoblast migration and invasion and the underlying mechanisms were examined in HTR-8/SVneo cell lines by transfection method. Results: NTE mRNA and protein expression levels were significantly decreased in preeclamptic placentas than normal control. Over-expression of NTE in HTR-8/SVneo cells significantly promoted trophoblast cells migration and invasion and was associated with increased MMP-9 levels. Conversely, shRNA-mediated down-regulation of NTE markedly inhibited the cell migration and invasion. In addition, silencing NTE reduced the MMP-9 activity and phosphorylated Erk1/2 and AKT levels. Conclusions: Our results suggest that the decreased NTE may contribute to the development of PE through impairing trophoblast invasion by down-regulating MMP-9 via the Erk1/2 and AKT signaling pathway.

  20. Historical view of development of comparative endocrinology in Japan.

    Science.gov (United States)

    Kikuyama, Sakae; Tsutsui, Kazuyoshi

    2011-04-01

    This article describing a brief history of development of comparative endocrinology in Japan is contributed to the journal General and Comparative Endocrinology, in commemoration of the 50th anniversary of its publication. It covers significant works in the field of comparative endocrinology that have been done by Japanese endocrinologists, focusing those achieved during the past 70 years. The contents were arranged according to the taxonomical order of the experimental animals with which individual researchers or research groups have contributed to the acquisition of important knowledge in comparative endocrinology. Copyright © 2011 Elsevier Inc. All rights reserved.

  1. Linguistic aspects of eponymic professional endocrinologic terminology

    Directory of Open Access Journals (Sweden)

    N.I. Bytsko

    2017-03-01

    Full Text Available Background. Special linguistic researches of terminological units of different branches of medicine allow analyzing in details the ways of creating the systems of clinical terminology from different aspects: historical, scientific, cultural, linguistic and semantic. There is a wide area of terminology related to the clinical and experimental endocrino­logy within general medical terminological system. The purpose of the study: to demonstrate the structure of endocrine medical terms — eponyms through the prism of systematization of methodological researches on eponymic vocabulary. Materials and methods. The actual material received as a result of a total choice of eponyms (there were 296 terms from the “Reference dictionary for endocrinologist”, which was composed by the scientists of V. Danilevsky Institute of Endocrine Pathology Problems and Kharkiv Medical Academy of Postgraduate education — A.V. Kozakov, N.A. Kravchun, I.M. Ilyina, M.I. Zubko, O.A. Goncharova, I.V. Cherniavska has 10,000 endocrine terms, the authors successfully streamlined medical terms of the clinical and experimental endocrinology into the vocabulary. The method of total choice of terms from professional literature, the descriptive method and distributive method were used in the study that allowed distinguishing lexical and semantic features of eponymic terms in the branch of endocrinology. Results. The obtained results point out to the modernity of studies in the field of clinical and experimental endocrinology, which is due to the fact that this is the oldest terminology, by the example of which it is possible to trace the ways of formation, development and improvement of terms, the realization of semantic processes, certain trends, ways and means of word formation. Conclusions. The results of the research on the above mentioned sublanguage of clinical medicine at the level of linguistic observations of the functio­ning in dictionaries and scientific works will

  2. TRANSFER FROM PEDIATRIC TO ADULT ENDOCRINOLOGY.

    Science.gov (United States)

    Jones, Marybeth R; Robbins, Brett W; Augustine, Marilyn; Doyle, Jackie; Mack-Fogg, Jean; Jones, Heather; White, Patience H

    2017-07-01

    Adult and pediatric endocrinologists share responsibility for the transition of youth with type 1 diabetes from pediatric to adult healthcare. This study aimed to increase successful transfers to adult care in subspecialty practices by establishing a systematic health care transition (HCT) process. Providers from the adult and pediatric endocrinology divisions at the University of Rochester Medical Center met monthly to customize and integrate the Six Core Elements (6CEs) of HCT into clinical workflows. Young adult patients with type 1 diabetes having an outpatient visit during a 34-month pre-post intervention period were eligible (N = 371). Retrospective chart review was performed on patients receiving referrals to adult endocrinology (n = 75) to obtain (1) the proportion of patients explicitly tracked during transfer from the pediatric to adult endocrinology practice, (2) the providers' documentation of the use of the 6CEs, and (3) the patients' diabetes control and healthcare utilization during the transition period. The percent of eligible patients with type 1 diabetes who were explicitly tracked in their transfer more than doubled compared to baseline (11% vs. 27% of eligible patients; P<.01). Pediatric providers started to use transition readiness assessments and create medical summaries, and adult providers increased closed-loop communication with pediatric providers after a patient's first adult visit. Glycemic control and healthcare utilization remained stable. Successful implementation of the 6CEs into pediatric and adult subspecialty practices can result in improvements of planned transfers of pediatric patients with type 1 diabetes to adult subspecialty providers. 6CEs = six core elements; AYA = adolescent and young adult; DKA = diabetic ketoacidosis; ED = emergency department; HbA1c = hemoglobin A1c; HCT = health care transition.

  3. Reproductive endocrinology and infertility fellowships: is the 'reproductive endocrinology' portion obsolete?

    Science.gov (United States)

    Omurtag, Kenan; Lebovic, Dan I

    2015-08-01

    To take inventory of the past and present and project the future direction of our field to help train the next generation of providers. Review the history of the subspecialty and factors contributing to its evolution. Reproductive endocrinology and infertility's in-vitro fertilization future is shaping the intellectual priorities and surgical skill requirements of the next generation.

  4. Role of Mass Spectrometry in Clinical Endocrinology.

    Science.gov (United States)

    Ketha, Siva S; Singh, Ravinder J; Ketha, Hemamalini

    2017-09-01

    The advent of mass spectrometry into the clinical laboratory has led to an improvement in clinical management of several endocrine diseases. Liquid chromatography tandem mass spectrometry found some of its first clinical applications in the diagnosis of inborn errors of metabolism, in quantitative steroid analysis, and in drug analysis laboratories. Mass spectrometry assays offer analytical sensitivity and specificity that is superior to immunoassays for many analytes. This article highlights several areas of clinical endocrinology that have witnessed the use of liquid chromatography tandem mass spectrometry to improve clinical outcomes. Copyright © 2017 Elsevier Inc. All rights reserved.

  5. The variation of estrus in endocrinological levels and behaviour in endocrinological ewes throughout the year

    International Nuclear Information System (INIS)

    Basaran, A.; Saban, E. D.

    2002-01-01

    An investigation was carried out to determine reproductive activity of endocrinological and behavior in Akkaraman sheep (n=20.25 years, 74±7.7 body weight) throughout the year in the Middle Anatolian (39 57 deg. N 32.53 deg. W). The onset of estrous was detected by using apron ram for 30-minute period twice a day. Blood samples collected twice a week were analyzed by Enzyme immunoassay for progesterone (p 4 ), by Radio immunoassay for estradiol. Estrus cycle lengths and estrous lengths were (mean±SD) 18.33±1.03 day, 35.16±5.95 hours, respectively. The breeding season lengths were 283±63.36 day and 229.64±63.74 day according to hormonal and behavior data, respectively (P≤0.0032). Frequency of occurrence estrus was high between August and March however the highest peak was in October. The lowest peaks were both in June and July. Plasma progesterone levels were changed between 0.01-9 ng/ml throughout the year and 0.2-0.16 ng/ml in anoestrus. P 4 level of 11-th day of luteal phase of estrus was 3.73±1.50 ng/ml (n=11). Plasma estradiol level was 8.42±2.51 pg/ml between of 1-st and 2-nd day and 3.50±1.50 pg/ml on day 15. Second peak of estradiol determined on day 11 of estrus cycle was 6.09±2.87 pg/ml (n=11)

  6. Bariatric Endocrinology: Principles of Medical Practice

    Science.gov (United States)

    Gonzalez-Campoy, J. Michael; Richardson, Bruce; Gonzalez-Cameron, David; Ebrahim, Ayesha; Strobel, Pamela; Martinez, Tiphani; Blaha, Beth; Ransom, Maria; Quinonez-Weislow, Jessica; Pierson, Andrea; Gonzalez Ahumada, Miguel

    2014-01-01

    Obesity, is a chronic, biological, preventable, and treatable disease. The accumulation of fat mass causes physical changes (adiposity), metabolic and hormonal changes due to adipose tissue dysfunction (adiposopathy), and psychological changes. Bariatric endocrinology was conceived from the need to address the neuro-endocrinological derangements that are associated with adiposopathy, and from the need to broaden the scope of the management of its complications. In addition to the well-established metabolic complications of overweight and obesity, adiposopathy leads to hyperinsulinemia, hyperleptinemia, hypoadiponectinemia, dysregulation of gut peptides including GLP-1 and ghrelin, the development of an inflammatory milieu, and the strong risk of vascular disease. Therapy for adiposopathy hinges on effectively lowering the ratio of orexigenic to anorexigenic signals reaching the the hypothalamus and other relevant brain regions, favoring a lower caloric intake. Adiposopathy, overweight and obesity should be treated indefinitely with the specific aims to reduce fat mass for the adiposity complications, and to normalize adipose tissue function for the adiposopathic complications. This paper defines the principles of medical practice in bariatric endocrinology—the treatment of overweight and obesity as means to treat adiposopathy and its accompanying metabolic and hormonal derangements. PMID:24899894

  7. Gastrointestinal Hormones Induced the Birth of Endocrinology.

    Science.gov (United States)

    Wabitsch, Martin

    2017-01-01

    The physiological studies by British physiologists William Maddock Bayliss and Ernest Henry Starling, at the beginning of the last century, demonstrated the existence of specific messenger molecules (hormones) circulating in the blood that regulate the organ function and physiological mechanisms. These findings led to the concept of endocrinology. The first 2 hormones were secretin, discovered in 1902, and gastrin, discovered in 1905. Both hormones that have been described are produced in the gut. This chapter summarizes the history around the discovery of these 2 hormones, which is perceived as the birth of endocrinology. It is noteworthy that after the discovery of these 2 gastrointestinal hormones, many other hormones were detected outside the gut, and thereafter gut hormones faded from both the clinical and scientific spotlight. Only recently, the clinical importance of the gut as the body's largest endocrine organ producing a large variety of hormones has been realized. Gastrointestinal hormones are essential regulators of metabolism, growth, development and behavior and are therefore the focus of a modern pediatric endocrinologist. © 2017 S. Karger AG, Basel.

  8. [Acne vulgaris: morphologic, endocrinologic and psychosomatic aspects].

    Science.gov (United States)

    Welp, K; Gieler, U

    1990-12-01

    25 male patients suffering from acne vulgaris were examined by means of endocrinological, morphological, and 5 psychometric procedures in order to check the correlations and interactions between the psychological and dermatological aspects of the disease. In comparison with a control group, the acne patients did not show any striking endocrinological abnormalities; we found no correlation between the extensiveness of the lesions and the level of DHEA sulphate. All the psychological tests yielded results deviating from those achieved by the representative controls, but they were comparable with those of other patients suffering from psychosomatic diseases. The individual feeling of being "disfigured" found its expression in self-consciousness, lack of trust in his/her own body, as well as the clinically relevant difference between his/her conception of self and the ideal of self. During times of enhanced psychosocial strains subjectively assumed by the patients, the lesions increased and the patients were disturbed in social interaction and communication. Surprisingly, we did not find any correlation between the clinical status and significant psychometric findings. Our results show that in acne vulgaris, the individual experience of wanting physical attractiveness, associated with a predominantly neurotic depressive personal structure, may play a central part in a disturbed process of interaction with the environment and suggest the influence of psychic factors in the pathogenesis of acne vulgaris.

  9. Diagnostics of trophoblast disease and the control of therapeutic efficiency based on definition of chorionic gonadotrapin and trophoblastic beta1-glycoprotein

    International Nuclear Information System (INIS)

    Yugrinova, L.G.; Olefirenko, G.A.; Dotsenko, Yu.S.

    1982-01-01

    A comparative estimation of markers of trophoblast disease, chorionic gonadotropin (CG) and trophoblastic beta 1 -glycoprotein defined by different methods is given. It is found that diagnostics and control of therapeutic efficiency for patients having trophoblast disease based on CG definition are possible. In 86% of cases the clinical diagnosis was confirmed by the immunoradioautography, and in 33% - by the immunodiffusion method. The dependence of marker detection frequency on the therapeutic efficiency is found

  10. TCDD Induces the Hypoxia-Inducible Factor (HIF-1α Regulatory Pathway in Human Trophoblastic JAR Cells

    Directory of Open Access Journals (Sweden)

    Tien-Ling Liao

    2014-09-01

    Full Text Available The exposure to dioxin can compromise pregnancy outcomes and increase the risk of preterm births. 2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD has been demonstrated to induce placental hypoxia at the end of pregnancy in a rat model, and hypoxia has been suggested to be the cause of abnormal trophoblast differentiation and placental insufficiency syndromes. In this study, we demonstrate that the non-hypoxic stimulation of human trophoblastic cells by TCDD strongly increased hypoxia inducible factor-1 alpha (HIF-1α stabilization. TCDD exposure induced the generation of reactive oxygen species (ROS and nitric oxide. TCDD-induced HIF-1α stabilization and Akt phosphorylation was inhibited by pretreatment with wortmannin (a phosphatidylinositol 3-kinase (PI3K inhibitor or N-acetylcysteine (a ROS scavenger. The augmented HIF-1α stabilization by TCDD occurred via the ROS-dependent activation of the PI3K/Akt pathway. Additionally, a significant increase in invasion and metallomatrix protease-9 activity was found in TCDD-treated cells. The gene expression of vascular endothelial growth factor and placental growth factor was induced upon TCDD stimulation, whereas the protein levels of peroxisome proliferator-activated receptor γ (PPARγ, PPARγ coactivator-1α, mitochondrial transcription factor, and uncoupling protein 2 were decreased. Our results indicate that an activated HIF-1α pathway, elicited oxidative stress, and induced metabolic stress contribute to TCDD-induced trophoblastic toxicity. These findings may provide molecular insight into the TCDD-induced impairment of trophoblast function and placental development.

  11. Chemotherapy for resistant or recurrent gestational trophoblastic neoplasia.

    LENUS (Irish Health Repository)

    Alazzam, Mo'iad

    2012-12-01

    Gestational trophoblastic neoplasia (GTN) is a highly curable group of pregnancy-related tumours; however, approximately 25% of GTN tumours will be resistant to, or will relapse after, initial chemotherapy. These resistant and relapsed lesions will require salvage chemotherapy with or without surgery. Various salvage regimens are used worldwide. It is unclear which regimens are the most effective and the least toxic.

  12. MR imaging of gestational trophoblastic tumor: role of gadolinium enhancement

    International Nuclear Information System (INIS)

    Choi, Si Young; Byun, Jae Young; Kim, Bum Su; Yun, Young Hyun; Mun, Kyung Mi; Park, Kyung Sin; Kim, Byung Kee; Bae, Seog Nyeon; Shinn, Kyung Sub.

    1997-01-01

    The purpose of this study is to investigate the role of gadolinium enhanced MR imaging in the evaluation of gestational trophoblastic tumors (invasive mole and choriocarcinoma). Pre-enhanced T1-and T2-weighted images and gadolinium enhanced T1-weighted images of 34 gestational trophoblastic tumors (15 choriocarcinomas, 19 invasive moles) were retrospectively evaluated and enhancement patterns were analyzed. Morphologica differences and structural characteristics were analyzed by the evaluation of tumor margin, patterns of hemorrhagic necroses, the development of intratumoral vascularity, and molar villi. Graded scores of MR findings between pre- and gadolinium enhanced images were based on the following criteria : 1) visualization of tumor margin 2) distinction between tumor necrosis and zone of trophoblastic proliferation ; and 3) molar villi. Statistical differences between graded scores of pre- and post-enhanced images were analyzed. Gadolinium enhanced MR imaging was helpful for the visualization of tumor characteristics in gestational trophoblastic tumors and in differential diagnosis between invasive mole and choriocarcinoma. (author). 16 refs., 4 tabs., 4 figs

  13. Monoclonal antibodies against human trophoblast in female infertility

    Czech Academy of Sciences Publication Activity Database

    Sedláková, Alena; Elzeinová, Fatima; Bukovský, A.; Madar, J.; Ulčová-Gallová, Z.; Pěknicová, Jana

    2005-01-01

    Roč. 54, č. 3 (2005), s. 159 ISSN 0271-7352. [European Congress of Reproductive Immunology /3./. 05.09.11-05.09.15, Essex] R&D Projects: GA MZd(CZ) NR7838 Institutional research plan: CEZ:AV0Z50520514 Keywords : monoclonal antibodies * female infertility * trophoblast Subject RIV: EB - Genetics ; Molecular Biology

  14. Auxo-Endocrinological Approach to Celiac Children

    Directory of Open Access Journals (Sweden)

    Mauro Bozzola

    2015-06-01

    Full Text Available Celiac disease is a permanent genetically determined intolerance to gluten that generally presents with gastrointestinal symptoms in young children and extraintestinal manifestations (endocrinological, dermatological, neurological, etc. later. Furthermore, many studies demonstrate the close association between celiac and endocrine diseases, including growth and pubertal disorders, type I diabetes mellitus and autoimmune thyroid diseases, probably due to the presence of a common genetic predisposition. Follow-up for celiac children after the start of gluten-free diet is mandatory to avoid complications such as growth hormone deficiency. The present review deals with the problem of the diagnosis of endocrine-associated diseases in celiac children and gives suggestions for correct management and follow-up of these patients.

  15. Molecular and cellular endocrinology of the testis

    International Nuclear Information System (INIS)

    Stefanini, M.; Conti, M.; Geremia, R.; Ziparo, E.

    1986-01-01

    This volume contains the Proceedings of the IV European Workshop on Molecular and Cellular Endocrinology of the Testis held in Capri (Italy) between the 9th and 12th April 1986. The workshop was organized in several symposia related to some of the most relevant aspects of the regulation of testicular function. Main topics were the role of cell interactions, the mechanisms of signal transduction, gene expression and metabolic response of somatic cells as well as differentiation of germ cells. One session was devoted to prostaglandins in the male reproductive system and to brief discussions on interstitial fluid and on antispermatogenic compounds. In this book only the main lectures and some selected short papers are presented. (Auth.)

  16. Waddlia chondrophila infects and multiplies in ovine trophoblast cells stimulating an inflammatory immune response.

    Directory of Open Access Journals (Sweden)

    Nick Wheelhouse

    Full Text Available Waddlia chondrophila (W. chondrophila is an emerging abortifacient organism which has been identified in the placentae of humans and cattle. The organism is a member of the order Chlamydiales, and shares many similarities at the genome level and in growth studies with other well-characterised zoonotic chlamydial abortifacients, such as Chlamydia abortus (C. abortus. This study investigates the growth of the organism and its effects upon pro-inflammatory cytokine expression in a ruminant placental cell line which we have previously utilised in a model of C. abortus pathogenicity.Using qPCR, fluorescent immunocytochemistry and electron microscopy, we characterised the infection and growth of W. chondrophila within the ovine trophoblast AH-1 cell line. Inclusions were visible from 6 h post-infection (p.i. and exponential growth of the organism could be observed over a 60 h time-course, with significant levels of host cell lysis being observed only after 36 h p.i. Expression of CXCL8, TNF-α, IL-1α and IL-1β were determined 24 h p.i. A statistically significant response in the expression of CXCL8, TNF-α and IL-1β could be observed following active infection with W. chondrophila. However a significant increase in IL-1β expression was also observed following the exposure of cells to UV-killed organisms, indicating the stimulation of multiple innate recognition pathways.W. chondrophila infects and grows in the ruminant trophoblast AH-1 cell line exhibiting a complete chlamydial replicative cycle. Infection of the trophoblasts resulted in the expression of pro-inflammatory cytokines in a dose-dependent manner similar to that observed with C. abortus in previous studies, suggesting similarities in the pathogenesis of infection between the two organisms.

  17. Waddlia chondrophila infects and multiplies in ovine trophoblast cells stimulating an inflammatory immune response.

    Science.gov (United States)

    Wheelhouse, Nick; Coyle, Christopher; Barlow, Peter G; Mitchell, Stephen; Greub, Gilbert; Baszler, Tim; Rae, Mick T; Longbottom, David

    2014-01-01

    Waddlia chondrophila (W. chondrophila) is an emerging abortifacient organism which has been identified in the placentae of humans and cattle. The organism is a member of the order Chlamydiales, and shares many similarities at the genome level and in growth studies with other well-characterised zoonotic chlamydial abortifacients, such as Chlamydia abortus (C. abortus). This study investigates the growth of the organism and its effects upon pro-inflammatory cytokine expression in a ruminant placental cell line which we have previously utilised in a model of C. abortus pathogenicity. Using qPCR, fluorescent immunocytochemistry and electron microscopy, we characterised the infection and growth of W. chondrophila within the ovine trophoblast AH-1 cell line. Inclusions were visible from 6 h post-infection (p.i.) and exponential growth of the organism could be observed over a 60 h time-course, with significant levels of host cell lysis being observed only after 36 h p.i. Expression of CXCL8, TNF-α, IL-1α and IL-1β were determined 24 h p.i. A statistically significant response in the expression of CXCL8, TNF-α and IL-1β could be observed following active infection with W. chondrophila. However a significant increase in IL-1β expression was also observed following the exposure of cells to UV-killed organisms, indicating the stimulation of multiple innate recognition pathways. W. chondrophila infects and grows in the ruminant trophoblast AH-1 cell line exhibiting a complete chlamydial replicative cycle. Infection of the trophoblasts resulted in the expression of pro-inflammatory cytokines in a dose-dependent manner similar to that observed with C. abortus in previous studies, suggesting similarities in the pathogenesis of infection between the two organisms.

  18. Evidence for Differential Glycosylation of Trophoblast Cell Types*

    Science.gov (United States)

    Chen, Qiushi; Pang, Poh-Choo; Cohen, Marie E.; Longtine, Mark S.; Schust, Danny J.; Haslam, Stuart M.; Blois, Sandra M.; Dell, Anne; Clark, Gary F.

    2016-01-01

    Human placental villi are surfaced by the syncytiotrophoblast (STB), with a layer of cytotrophoblasts (CTB) positioned just beneath the STB. STB in normal term pregnancies is exposed to maternal immune cells in the placental intervillous space. Extravillous cytotrophoblasts (EVT) invade the decidua and spiral arteries, where they act in conjunction with natural killer (NK) cells to convert the spiral arteries into flaccid conduits for maternal blood that support a 3–4 fold increase in the rate of maternal blood flow into the placental intervillous space. The functional roles of these distinct trophoblast subtypes during pregnancy suggested that they could be differentially glycosylated. Glycomic analysis of these trophoblasts has revealed the expression of elevated levels of biantennary N-glycans in STB and CTB, with the majority of them bearing a bisecting GlcNAc. N-glycans terminated with polylactosamine extensions were also detected at low levels. A subset of the N-glycans linked to these trophoblasts were sialylated, primarily with terminal NeuAcα2–3Gal sequences. EVT were decorated with the same N-glycans as STB and CTB, except in different proportions. The level of bisecting type N-glycans was reduced, but the level of N-glycans decorated with polylactosamine sequences were substantially elevated compared with the other types of trophoblasts. The level of triantennary and tetraantennary N-glycans was also elevated in EVT. The sialylated N-glycans derived from EVT were completely susceptible to an α2–3 specific neuraminidase (sialidase S). The possibility exists that the N-glycans associated with these different trophoblast subpopulations could act as functional groups. These potential relationships will be considered. PMID:26929217

  19. Evidence for Differential Glycosylation of Trophoblast Cell Types.

    Science.gov (United States)

    Chen, Qiushi; Pang, Poh-Choo; Cohen, Marie E; Longtine, Mark S; Schust, Danny J; Haslam, Stuart M; Blois, Sandra M; Dell, Anne; Clark, Gary F

    2016-06-01

    Human placental villi are surfaced by the syncytiotrophoblast (STB), with a layer of cytotrophoblasts (CTB) positioned just beneath the STB. STB in normal term pregnancies is exposed to maternal immune cells in the placental intervillous space. Extravillous cytotrophoblasts (EVT) invade the decidua and spiral arteries, where they act in conjunction with natural killer (NK) cells to convert the spiral arteries into flaccid conduits for maternal blood that support a 3-4 fold increase in the rate of maternal blood flow into the placental intervillous space. The functional roles of these distinct trophoblast subtypes during pregnancy suggested that they could be differentially glycosylated. Glycomic analysis of these trophoblasts has revealed the expression of elevated levels of biantennary N-glycans in STB and CTB, with the majority of them bearing a bisecting GlcNAc. N-glycans terminated with polylactosamine extensions were also detected at low levels. A subset of the N-glycans linked to these trophoblasts were sialylated, primarily with terminal NeuAcα2-3Gal sequences. EVT were decorated with the same N-glycans as STB and CTB, except in different proportions. The level of bisecting type N-glycans was reduced, but the level of N-glycans decorated with polylactosamine sequences were substantially elevated compared with the other types of trophoblasts. The level of triantennary and tetraantennary N-glycans was also elevated in EVT. The sialylated N-glycans derived from EVT were completely susceptible to an α2-3 specific neuraminidase (sialidase S). The possibility exists that the N-glycans associated with these different trophoblast subpopulations could act as functional groups. These potential relationships will be considered. © 2016 by The American Society for Biochemistry and Molecular Biology, Inc.

  20. Adiponectin inhibits insulin function in primary trophoblasts by PPARα-mediated ceramide synthesis.

    Science.gov (United States)

    Aye, Irving L M H; Gao, Xiaoli; Weintraub, Susan T; Jansson, Thomas; Powell, Theresa L

    2014-04-01

    Maternal adiponectin (ADN) levels are inversely correlated with birth weight, and ADN infusion in pregnant mice down-regulates placental nutrient transporters and decreases fetal growth. In contrast to the insulin-sensitizing effects in adipose tissue and muscle, ADN inhibits insulin signaling in the placenta. However, the molecular mechanisms involved are unknown. We hypothesized that ADN inhibits insulin signaling and insulin-stimulated amino acid transport in primary human trophoblasts by peroxisome proliferator-activated receptor-α (PPARα)-mediated ceramide synthesis. Primary human term trophoblast cells were treated with ADN and/or insulin. ADN increased the phosphorylation of p38 MAPK and PPARα. ADN inhibited insulin signaling and insulin-stimulated amino acid transport. This effect was dependent on PPARα, because activation of PPARα with an agonist (GW7647) inhibited insulin signaling and function, whereas PPARα-small interfering RNA reversed the effects of ADN on the insulin response. ADN increased ceramide synthase expression and stimulated ceramide production. C2-ceramide inhibited insulin signaling and function, whereas inhibition of ceramide synthase (with Fumonisin B1) reversed the effects of ADN on insulin signaling and amino acid transport. These findings are consistent with the model that maternal ADN limits fetal growth mediated by activation of placental PPARα and ceramide synthesis, which inhibits placental insulin signaling and amino acid transport, resulting in reduced fetal nutrient availability.

  1. Decidual Stromal Cell Response to Paracrine Signals from the Trophoblast: Amplification of Immune and Angiogenic Modulators

    DEFF Research Database (Denmark)

    Hess, AP; Hamilton, AE; Talbi, S

    2007-01-01

    During the invasive phase of implantation, trophoblasts and maternal decidual stromal cells secrete products that regulate trophoblast differentiation and migration into the maternal endometrium. Paracrine interactions between the extravillous trophoblast and the maternal decidua are important...... a functional genomics approach to investigate these paracrine interactions. Human endometrial stromal cells were decidualized with progesterone and were further treated with conditioned media (CM) from human trophoblasts (TCM) or, as a control, with conditioned media (CCM) from non-decidualized stromal cells...... regulated groups. The data demonstrate a significant induction of pro-inflammatory cytokines and chemokines, as well as angiogenic/static factors in decidualized endometrial stromal cells in response to trophoblast-secreted products. The data suggest that the trophoblast acts to alter the local immune...

  2. Comparative endocrinology in the 21st century

    Science.gov (United States)

    Denver, R.J.; Hopkins, P.M.; McCormick, S.D.; Propper, C.R.; Riddiford, L.; Sower, S.A.; Wingfield, J.C.

    2009-01-01

    Hormones coordinate developmental, physiological, and behavioral processes within and between all living organisms. They orchestrate and shape organogenesis from early in development, regulate the acquisition, assimilation, and utilization of nutrients to support growth and metabolism, control gamete production and sexual behavior, mediate organismal responses to environmental change, and allow for communication of information between organisms. Genes that code for hormones; the enzymes that synthesize, metabolize, and transport hormones; and hormone receptors are important targets for natural selection, and variation in their expression and function is a major driving force for the evolution of morphology and life history. Hormones coordinate physiology and behavior of populations of organisms, and thus play key roles in determining the structure of populations, communities, and ecosystems. The field of endocrinology is concerned with the study of hormones and their actions. This field is rooted in the comparative study of hormones in diverse species, which has provided the foundation for the modern fields of evolutionary, environmental, and biomedical endocrinology. Comparative endocrinologists work at the cutting edge of the life sciences. They identify new hormones, hormone receptors and mechanisms of hormone action applicable to diverse species, including humans; study the impact of habitat destruction, pollution, and climatic change on populations of organisms; establish novel model systems for studying hormones and their functions; and develop new genetic strains and husbandry practices for efficient production of animal protein. While the model system approach has dominated biomedical research in recent years, and has provided extraordinary insight into many basic cellular and molecular processes, this approach is limited to investigating a small minority of organisms. Animals exhibit tremendous diversity in form and function, life-history strategies, and

  3. Journal of Endocrinology, Metabolism and Diabetes of South Africa ...

    African Journals Online (AJOL)

    Journal of Endocrinology, Metabolism and Diabetes of South Africa. ... Management of diabetic ketoacidosis · EMAIL FREE FULL TEXT EMAIL FREE FULL TEXT ... Prediabetes: a focus on the role of diabetes education in prevention of type 2 ...

  4. Journal of Endocrinology, Metabolism and Diabetes of South Africa

    African Journals Online (AJOL)

    JEMDSA) is published by the South African Medical Association and publishes papers related to endocrinology, metabolism and diabetes. Other websites related to this journal: http://www.jemdsa.co.za ...

  5. Proceedings of the 16. Brazilian Congress of Endocrinology and Metabology

    International Nuclear Information System (INIS)

    1984-01-01

    Studies in endocrinology and metabolism are presented. The primordial role of the use of radioisotopes in diagnosis, treatment and research is emphasized. Subjects like adrenal, gonads, diabetes, hypothalamus, parathyroid and thyroid are discussed. (M.A.C.) [pt

  6. Roles of CDX2 and EOMES in human induced trophoblast progenitor cells

    Energy Technology Data Exchange (ETDEWEB)

    Chen, Ying, E-mail: ying.chen@hc.msu.edu [Department of Obstetrics, Gynecology and Reproductive Biology, College of Human Medicine, Michigan State University, Grand Rapids, MI 49503 (United States); Wang, Kai [Department of Obstetrics, Gynecology and Reproductive Biology, College of Human Medicine, Michigan State University, Grand Rapids, MI 49503 (United States); Gong, Yun Guo; Khoo, Sok Kean [Genomic Microarray Core Facility, Van Andel Research Institute, Grand Rapids, MI 49503 (United States); Leach, Richard, E-mail: Richard.Leach@hc.msu.edu [Department of Obstetrics, Gynecology and Reproductive Biology, College of Human Medicine, Michigan State University, Grand Rapids, MI 49503 (United States); Department of Obstetrics, Gynecology and Women’s Health, Spectrum Health Medical Group, Grand Rapids, MI 49503 (United States)

    2013-02-08

    Highlights: ► CDX2 and EOMES play critical roles in human induced trophoblast progenitors (iTP). ► iTP cells directly transformed from fibroblasts. ► Differentiation of iTP cells into extravillous trophoblasts and syncytiotrophoblasts. -- Abstract: Abnormal trophoblast lineage proliferation and differentiation in early pregnancy have been associated with the pathogenesis of placenta diseases of pregnancy. However, there is still a gap in understanding the molecular mechanisms of early placental development due to the limited primary trophoblast cultures and fidelity of immortalized trophoblast lines. Trophoblasts stem (TS) cells, an in vitro model of trophectoderm that can differentiate into syncytiotrophoblasts and extravillous trophoblasts, can be an attractive tool for early pregnancy research. TS cells are well established in mouse but not in humans due to insufficient knowledge of which trophoblast lineage-specific transcription factors are involved in human trophectoderm (TE) proliferation and differentiation. Here, we applied induced pluripotent stem cell technique to investigate the human trophoblast lineage-specific transcription factors. We established human induced trophoblast progenitor (iTP) cells by direct reprogramming the fibroblasts with a pool of mouse trophoblast lineage-specific transcription factors consisting of CDX2, EOMES, and ELF5. The human iTP cells exhibit epithelial morphology and can be maintained in vitro for more than 2 months. Gene expression profile of these cells was tightly clustered with human trophectoderm but not with human neuron progenitor cells, mesenchymal stem cells, or endoderm cells. These cells are capable of differentiating into cells with an invasive capacity, suggesting extravillous trophoblasts. They also form multi-nucleated cells which secrete human chorionic gonadotropin and estradiol, consistent with a syncytiotrophoblast phenotype. Our results provide the evidence that transcription factors CDX2 and

  7. miR-210 inhibits trophoblast invasion and is a serum biomarker for preeclampsia.

    Science.gov (United States)

    Anton, Lauren; Olarerin-George, Anthony O; Schwartz, Nadav; Srinivas, Sindhu; Bastek, Jamie; Hogenesch, John B; Elovitz, Michal A

    2013-11-01

    Preeclampsia is characterized by hypertension and proteinuria in pregnant women. Its exact cause is unknown. Preeclampsia increases the risk of maternal and fetal morbidity and mortality. Although delivery, often premature, is the only known cure, early targeted interventions may improve maternal and fetal outcomes. Successful intervention requires a better understanding of the molecular etiology of preeclampsia and the development of accurate methods to predict women at risk. To this end, we tested the role of miR-210, a miRNA up-regulated in preeclamptic placentas, in first-trimester extravillous trophoblasts. miR-210 overexpression reduced trophoblast invasion, a process necessary for uteroplacental perfusion, in an extracellular signal-regulated kinase/mitogen-activated protein kinase-dependent manner. Conversely, miR-210 inhibition promoted invasion. Furthermore, given that the placenta secretes miRNAs into the maternal circulation, we tested if serum expression of miR-210 was associated with the disease. We measured miR-210 expression in two clinical studies: a case-control study and a prospective cohort study. Serum miR-210 expression was significantly associated with a diagnosis of preeclampsia (P = 0.007, area under the receiver operator curves = 0.81) and was predictive of the disease, even months before clinical diagnosis (P preeclampsia that can help in identifying at-risk women for monitoring and treatment. Copyright © 2013 American Society for Investigative Pathology. Published by Elsevier Inc. All rights reserved.

  8. Transgender Health in Endocrinology: Current Status of Endocrinology Fellowship Programs and Practicing Clinicians.

    Science.gov (United States)

    Davidge-Pitts, Caroline; Nippoldt, Todd B; Danoff, Ann; Radziejewski, Lauren; Natt, Neena

    2017-04-01

    The transgender population continues to face challenges in accessing appropriate health care. Adequate training of endocrinologists in this area is a priority. Assess the status of transgender health care education in US endocrinology fellowship training programs and assess knowledge and practice of transgender health among practicing US endocrinologists. Mayo Clinic and the Endocrine Society developed and administered a Web-based anonymous survey to 104 endocrinology fellowship program directors (PDs; members of the Association of Program Directors in Endocrinology, Diabetes and Metabolism) and 6992 US medical doctor members of Endocrine Society. There were 54 total responses from 104 PDs (51.9%). Thirty-five of these 54 programs (72.2%) provide teaching on transgender health topics; however, 93.8% respondents indicated that fellowship training in this area is important. Barriers to provision of education included lack of faculty interest or experience. The most desired strategies to increase transgender-specific content included online training modules for trainees and faculty. Of 411 practicing clinician responders, almost 80% have treated a transgender patient, but 80.6% have never received training on care of transgender patients. Clinicians were very or somewhat confident in terms of definitions (77.1%), taking a history (63.3%), and prescribing hormones (64.8%); however, low confidence was reported outside of the hormonal realm. The most requested methods of education included online training modules and presentation of transgender topics at meetings. Confidence and competence in transgender health needs to increase among endocrinologists. Strategies include the development of online training modules, expansion of formal transgender curricula in fellowship programs, and presentations at national and international meetings. Copyright © 2017 by the Endocrine Society

  9. TROPHOBLASTIC β1 – GLYCOPROTEIN SYNTHESIS IN SEROPOSITIVE PREGNANT WOMEN

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    R. N. Bogdanovich

    2005-01-01

    Full Text Available Abstract. The level of trophoblastic β1 – glycoprotein (SP–1 was determined in the blood sera of 200 healthy pregnant women and 184 women with threatened abortions in term till 20 weeks of pregnancy. In group of women experiencing recurrent abortions in 38 % cases antibodies to chorionic gonadotropin, in 39,5 % cases antibodies to phospholipids, in 25,5 % – antibodies to tireoglobulin were revealed in significant amounts. In 20,65 % lupus anticoagulant was found. The majority of women in this group had changes in homeostasis. The presence of autoantibodies during pregnancy is the unfavourable factor in the development of placental insufficiency. This is proved by the decreased secretion of trophoblastic β1 – glycoprotein – a marker of the fetal part of placenta. (Med. Immunol., 2005, vol.7, № 1, pp. 85588

  10. Overexpression of Endogenous Anti-Oxidants with Selenium Supplementation Protects Trophoblast Cells from Reactive Oxygen Species-Induced Apoptosis in a Bcl-2-Dependent Manner.

    Science.gov (United States)

    Khera, Alisha; Vanderlelie, Jessica J; Holland, Olivia; Perkins, Anthony V

    2017-06-01

    The human placenta provides life support for the developing foetus, and a healthy placenta is a prerequisite to a healthy start to life. Placental tissue is subject to oxidative stress which can lead to pathological conditions of pregnancy such as preeclampsia, preterm labour and intrauterine growth restriction. Up-regulation of endogenous anti-oxidants may alleviate placental oxidative stress and provide a therapy for these complications of pregnancy. In this study, selenium supplementation, as inorganic sodium selenite (NaSel) or organic selenomethionine (SeMet), was used to increase the protein production and cellular activity of the important redox active proteins glutathione peroxidase (GPx) and thioredoxin reductase (Thx-Red). Placental trophoblast cell lines, BeWo, JEG-3 and Swan-71, were cultured in various concentrations of NaSel or SeMet for 24 h and cell extracts prepared for western blots and enzyme assays. Rotenone and antimycin were used to stimulate mitochondrial reactive oxygen species (ROS) production and induce apoptosis. Trophoblast cells supplemented with 100 nM NaSel and 500 nM SeMet exhibited significantly enhanced expression and activity of both GPx and Thx-Red. Antimycin and rotenone were found to generate ROS when measured by 2',7'-dichlorofluorescein diacetate (DCFDA) assay, and selenium supplementation was shown to reduce ROS production in a dose-dependent manner. Rotenone, 100 μM treatment for 4 h, caused trophoblast cell apoptosis as evidenced by increased Annexin V binding and decreased expression of Bcl-2. In both assays of apoptosis, selenium supplementation was able to prevent apoptosis, preserve Bcl-2 expression and protect trophoblast cells from mitochondrial oxidative stress. This data suggests that selenoproteins such as GPx and Thx-Red have an important role in protecting trophoblast cells from mitochondrial oxidative stress and that selenium supplementation may be important in treating some placental pathologies.

  11. MSX2 Induces Trophoblast Invasion in Human Placenta.

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    Hao Liang

    Full Text Available Normal implantation depends on appropriate trophoblast growth and invasion. Inadequate trophoblast invasion results in pregnancy-related disorders, such as early miscarriage and pre-eclampsia, which are dangerous to both the mother and fetus. Msh Homeobox 2 (MSX2, a member of the MSX family of homeobox proteins, plays a significant role in the proliferation and differentiation of various cells and tissues, including ectodermal organs, teeth, and chondrocytes. Recently, MSX2 was found to play important roles in the invasion of cancer cells into adjacent tissues via the epithelial-mesenchymal transition (EMT. However, the role of MSX2 in trophoblastic invasion during placental development has yet to be explored. In the present study, we detected MSX2 expression in cytotrophoblast, syncytiotrophoblast, and extravillous cytotrophoblast cells of first or third trimester human placentas via immunohistochemistry analysis. Furthermore, we found that the in vitro invasive ability of HTR8/SVneo cells was enhanced by exogenous overexpression of MSX2, and that this effect was accompanied by increased protein expression of matrix metalloproteinase-2 (MMP-2, vimentin, and β-catenin. Conversely, treatment of HTR8/SVneo cells with MSX2-specific siRNAs resulted in decreased protein expression of MMP-2, vimentin, and β-catenin, and reduced invasion levels in a Matrigel invasion test. Notably, however, treatment with the MSX2 overexpression plasmid and the MSX2 siRNAs had no effect on the mRNA expression levels of β-catenin. Meanwhile, overexpression of MSX2 and treatment with the MSX2-specific siRNA resulted in decreased and increased E-cadherin expression, respectively, in JEG-3 cells. Lastly, the protein expression levels of MSX2 were significantly lower in human pre-eclamptic placental villi than in the matched control placentas. Collectively, our results suggest that MSX2 may induce human trophoblast cell invasion, and dysregulation of MSX2 expression may

  12. Live cell imaging of in vitro human trophoblast syncytialization.

    Science.gov (United States)

    Wang, Rui; Dang, Yan-Li; Zheng, Ru; Li, Yue; Li, Weiwei; Lu, Xiaoyin; Wang, Li-Juan; Zhu, Cheng; Lin, Hai-Yan; Wang, Hongmei

    2014-06-01

    Human trophoblast syncytialization, a process of cell-cell fusion, is one of the most important yet least understood events during placental development. Investigating the fusion process in a placenta in vivo is very challenging given the complexity of this process. Application of primary cultured cytotrophoblast cells isolated from term placentas and BeWo cells derived from human choriocarcinoma formulates a biphasic strategy to achieve the mechanism of trophoblast cell fusion, as the former can spontaneously fuse to form the multinucleated syncytium and the latter is capable of fusing under the treatment of forskolin (FSK). Live-cell imaging is a powerful tool that is widely used to investigate many physiological or pathological processes in various animal models or humans; however, to our knowledge, the mechanism of trophoblast cell fusion has not been reported using a live- cell imaging manner. In this study, a live-cell imaging system was used to delineate the fusion process of primary term cytotrophoblast cells and BeWo cells. By using live staining with Hoechst 33342 or cytoplasmic dyes or by stably transfecting enhanced green fluorescent protein (EGFP) and DsRed2-Nuc reporter plasmids, we observed finger-like protrusions on the cell membranes of fusion partners before fusion and the exchange of cytoplasmic contents during fusion. In summary, this study provides the first video recording of the process of trophoblast syncytialization. Furthermore, the various live-cell imaging systems used in this study will help to yield molecular insights into the syncytialization process during placental development. © 2014 by the Society for the Study of Reproduction, Inc.

  13. Gestational trophoblastic neoplasia: A 6 year retrospective study

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    Sushruta Shrivastava

    2014-01-01

    Full Text Available Aims and Objectives: To study the clinical presentations of gestational trophoblastic neoplasia and its response to chemotherapy. Materials and Methods: This is a retrospective study of 28 women of gestational trophoblastic neoplasia evaluated over a period of 6 years from January 2004 to December 2009. Patients were evaluated on the basis of their age, number of deliveries, history of abortion or molar pregnancy, and the treatment received. All patients were scored on the basis of WHO scoring system. Patients with low risk (score /=7 received multiple agent chemotherapy with EMACO regimen. After completion of chemotherapy patients were followed for a minimum of 2 years. The response to treatment was evaluated during follow-up by clinical examination, beta hCG levels and imaging as and when required. Results: Out of 28 women only 27 could be evaluated, because 1 patient was lost to follow-up. Out of 27 patients, 18 patients (66.67% achieved complete remission with the first-line chemotherapy and additional 25.92% (7/27 achieved complete remission with second line chemotherapy resulting in complete remission of 92.5% (25/27. Conclusion: Gestational trophoblastic neoplasia is curable if patient is properly evaluated and scored. It shows good response to chemotherapy.

  14. Clinical and radiological correlations in patients with gestational trophoblastic disease

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    Lana de Lourdes Aguiar Lima

    Full Text Available Abstract Gestational trophoblastic disease is an abnormality of pregnancy that encompasses a group of diseases that differ from each other in their propensity for regression, invasion, metastasis, and recurrence. In the past, it was common for patients with molar pregnancy to present with marked symptoms: copious bleeding; theca lutein cysts; uterus larger than appropriate for gestational age; early preeclampsia; hyperemesis gravidarum; and hyperthyroidism. Currently, with early diagnosis made by ultrasound, most patients are diagnosed while the disease is still in the asymptomatic phase. In cases of progression to trophoblastic neoplasia, staging-typically with Doppler flow studies of the pelvis and chest X-ray, although occasionally with computed tomography or magnetic resonance imaging-is critical to the choice of an appropriate antineoplastic therapy regimen. Because it is an unusual and serious disease that affects women of reproductive age, as well as because its appropriate treatment results in high cure rates, it is crucial that radiologists be familiar with gestational trophoblastic disease, in order to facilitate its early diagnosis and to ensure appropriate follow-up imaging.

  15. Clinical and radiological correlations in patients with gestational trophoblastic disease

    International Nuclear Information System (INIS)

    Lima, Lana de Lourdes Aguiar; Parente, Raphael Camara Medeiros; Amim Junior, Joffre; Rezende Filho, Jorge Fonte de; Montenegro, Carlos Antonio Barbosa; Braga, Antonio; Maesta, Izildinha

    2016-01-01

    Gestational trophoblastic disease is an abnormality of pregnancy that encompasses a group of diseases that differ from each other in their propensity for regression, invasion, metastasis, and recurrence. In the past, it was common for patients with molar pregnancy to present with marked symptoms: copious bleeding; theca lutein cysts; uterus larger than appropriate for gestational age; early preeclampsia; hyperemesis gravidarum; and hyperthyroidism. Currently, with early diagnosis made by ultrasound, most patients are diagnosed while the disease is still in the asymptomatic phase. In cases of progression to trophoblastic neoplasia, staging-typically with Doppler flow studies of the pelvis and chest X-ray, although occasionally with computed tomography or magnetic resonance imaging-is critical to the choice of an appropriate antineoplastic therapy regimen. Because it is an unusual and serious disease that affects women of reproductive age, as well as because its appropriate treatment results in high cure rates, it is crucial that radiologists be familiar with gestational trophoblastic disease, in order to facilitate its early diagnosis and to ensure appropriate follow-up imaging. (author)

  16. Clinical and radiological correlations in patients with gestational trophoblastic disease

    Energy Technology Data Exchange (ETDEWEB)

    Lima, Lana de Lourdes Aguiar; Parente, Raphael Camara Medeiros; Amim Junior, Joffre; Rezende Filho, Jorge Fonte de; Montenegro, Carlos Antonio Barbosa; Braga, Antonio, E-mail: lanalima@hotmail.com [Universidade Federal do Rio de Janeiro (UFRJ), RJ (Brazil); Maesta, Izildinha [Universidade Estadual Paulista Julio de Mesquita Filho (UNESP), Botucatu, SP (Brazil). Faculdade de Medicina

    2016-07-15

    Gestational trophoblastic disease is an abnormality of pregnancy that encompasses a group of diseases that differ from each other in their propensity for regression, invasion, metastasis, and recurrence. In the past, it was common for patients with molar pregnancy to present with marked symptoms: copious bleeding; theca lutein cysts; uterus larger than appropriate for gestational age; early preeclampsia; hyperemesis gravidarum; and hyperthyroidism. Currently, with early diagnosis made by ultrasound, most patients are diagnosed while the disease is still in the asymptomatic phase. In cases of progression to trophoblastic neoplasia, staging-typically with Doppler flow studies of the pelvis and chest X-ray, although occasionally with computed tomography or magnetic resonance imaging-is critical to the choice of an appropriate antineoplastic therapy regimen. Because it is an unusual and serious disease that affects women of reproductive age, as well as because its appropriate treatment results in high cure rates, it is crucial that radiologists be familiar with gestational trophoblastic disease, in order to facilitate its early diagnosis and to ensure appropriate follow-up imaging. (author)

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

    Science.gov (United States)

    Aghababaei, Mahroo; Beristain, Alexander G

    2015-04-01

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

  18. Community health orientation of Indian Journal of Endocrinology and Metabolism: A bibliometric analysis of Indian Journal of Endocrinology and Metabolism

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    Kanica Kaushal

    2015-01-01

    Full Text Available Background: Endocrine and metabolic diseases especially diabetes have become focus areas for public health professionals. Indian Journal of Endocrinology and Metabolism (IJEM, a publication of Endocrine Society of India, is a peer-reviewed online journal, which covers technical and clinical studies related to health, ethical and social issues in field of diabetes, endocrinology and metabolism. This bibliometric analysis assesses the journal from a community health perspective. Materials and Methods: Every article published in IJEM over a period of 4 years (2011-2014 was accessed to review coverage of community health in the field of endocrinology. Results: Seven editorials, 30 review articles, 41 original articles, 12 brief communications, 20 letter to editors, 4 articles on guidelines and 2 in the section "endocrinology and gender" directly or indirectly dealt with community health aspects of endocrinology. Together these amounted to 17% of all articles published through these 4 years. There were 14 articles on general, 60 pertaining to pancreas and diabetes, 10 on thyroid, 7 on pituitary/adrenal/gonads, 21 on obesity and metabolism and 4 on parathyroid and bone; all community medicine related. Conclusion: Community health is an integral part of the modern endocrinology diabetology and metabolism practice and it received adequate journal space during the last 4 years. The coverage is broad based involving all the major endocrine disorders.

  19. Community health orientation of Indian Journal of Endocrinology and Metabolism: A bibliometric analysis of Indian Journal of Endocrinology and Metabolism

    Science.gov (United States)

    Kaushal, Kanica; Kalra, Sanjay

    2015-01-01

    Background: Endocrine and metabolic diseases especially diabetes have become focus areas for public health professionals. Indian Journal of Endocrinology and Metabolism (IJEM), a publication of Endocrine Society of India, is a peer-reviewed online journal, which covers technical and clinical studies related to health, ethical and social issues in field of diabetes, endocrinology and metabolism. This bibliometric analysis assesses the journal from a community health perspective. Materials and Methods: Every article published in IJEM over a period of 4 years (2011–2014) was accessed to review coverage of community health in the field of endocrinology. Results: Seven editorials, 30 review articles, 41 original articles, 12 brief communications, 20 letter to editors, 4 articles on guidelines and 2 in the section “endocrinology and gender” directly or indirectly dealt with community health aspects of endocrinology. Together these amounted to 17% of all articles published through these 4 years. There were 14 articles on general, 60 pertaining to pancreas and diabetes, 10 on thyroid, 7 on pituitary/adrenal/gonads, 21 on obesity and metabolism and 4 on parathyroid and bone; all community medicine related. Conclusion: Community health is an integral part of the modern endocrinology diabetology and metabolism practice and it received adequate journal space during the last 4 years. The coverage is broad based involving all the major endocrine disorders. PMID:25932398

  20. Comparative endocrinology of aging and longevity regulation

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    John eAllard

    2011-11-01

    Full Text Available Hormones regulate growth, development, metabolism, and other complex processes in multicellular animals. For many years it has been suggested that hormones may also influence the rate of the aging process. Aging is a multifactorial process that causes biological systems to break down and cease to function in adult organisms as time passes, eventually leading to death. The exact underlying causes of the aging process remain a topic for debate, and clues that may shed light on these causes are eagerly sought after. In the last two decades, gene mutations that result in delayed aging and extended longevity have been discovered, and many of the affected genes have been components of endocrine signaling pathways. In this review we summarize the current knowledge on the roles of endocrine signaling in the regulation of aging and longevity in various animals. We begin by discussing the notion that conserved systems, including endocrine signaling pathways, regulate the aging process. Findings from the major model organisms: worms, flies and rodents, are then outlined. Unique lessons from studies of non-traditional models: bees, salmon and naked mole rats, are also discussed. Finally, we summarize the endocrinology of aging in humans, including changes in hormone levels with age, and the involvement of hormones in aging-related diseases. The most well studied and widely conserved endocrine pathway that affects aging is the insulin/insulin-like growth factor system. Mutations in genes of this pathway increase the lifespan of worms, flies, and mice. Population genetic evidence also suggests this pathway’s involvement in human aging. Other hormones including steroids have been linked to aging only in a subset of the models studied. Because of the value of comparative studies, it is suggested that the aging field could benefit from adoption of additional model organisms.

  1. Efficacy of NETDC (New England Trophoblastic Disease Center prognostic index score to predict gestational trophoblastic tumor from hydatidiform mole

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    Khrismawan Khrismawan

    2004-03-01

    Full Text Available A prospective longitudinal analytic study assessing the efficacy of NETDC (New England Trophoblastic Disease Center prognostic index score in predicting malignancy after hydatidiform mole had been performed. Of the parameter evaluated; age of patients, type of hydatidiform mole, uterine enlargement, serum hCG level, lutein cyst, and presence of complicating factors were significant risk factors for malignancy after hydatidiform mole were evacuated (p<0.032. The study were done on 50 women diagnosed with hydatidiform mole with 1 year observation (January 2001-December 2002 at the Department of Obstetrics and Gynecology, Mohammad Hoesin Hospital, Palembang. The results showed that the NETDC prognostic index score predicted malignancy in 50% of high risk group and 10% in low risk group (p<0.05. This showed a higher number than that found by the WHO (19%-30%. The risk for incidence of  malignancy after hydatidiform mole in the high risk group is 9.0 times higher compared to that of the low risk group (CI: 1.769-45.786. (Med J Indones 2004; 13: 40-6 Keywords: New England Trophoblastic Disease Center (NETDC, gestational trophoblastic tumor, hydatidiform mole, high and low risk

  2. Quality of life of gestational trophoblastic neoplasia survivors: a study of patients at the Philippine General Hospital trophoblastic disease section.

    Science.gov (United States)

    Cagayan, M Stephanie Fay S; Llarena, Raquel T

    2010-01-01

    To evaluate the quality of life (QOL) of patients who were diagnosed with gestational trophoblastic neoplasia (GTN) at the Philippine General Hospital Trophoblastic Disease Section and who were in remission at the time of this study. A cross-sectional descriptive study designed to measure the QOL of all patients diagnosed as having GTN in remission and following up at the Philippine General Hospital Trophoblastic Disease Outpatient Clinic from May-August 2008 (N = 46). This study used the short form 12-question (SF-12) survey forms to evaluate the QOL of patients diagnosed with GTN. Scores from the SF-12 were analyzed using Pearson's correlation. Statistical significance was assumed for p values educational level and physical functioning. A negative correlation was found between the stage of GTN and patients' general health. In conclusion, the survivors' age, educational level and type of treatment had impact on the QOL among GTN survivors in terms of physical functioning. No relationship was established between the demographic variables and mental status. SF-12 appears to be a reliable instrument, suggesting its potential in measuring health status in GTN survivors. Age, educational attainment and type of treatment were shown to have an impact on the QOL of the surviving GTN patients.

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

    Science.gov (United States)

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

    2017-11-07

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

  4. Saturated fatty acids enhance TLR4 immune pathways in human trophoblasts.

    Science.gov (United States)

    Yang, Xiaohua; Haghiac, Maricela; Glazebrook, Patricia; Minium, Judi; Catalano, Patrick M; Hauguel-de Mouzon, Sylvie

    2015-09-01

    What are the effects of fatty acids on placental inflammatory cytokine with respect to toll-like receptor-4/nuclear factor-kappa B (TLR4/NF-kB)? Exogenous fatty acids induce a pro-inflammatory cytokine response in human placental cells in vitro via activation of TLR4 signaling pathways. The placenta is exposed to changes in circulating maternal fatty acid concentrations throughout pregnancy. Fatty acids are master regulators of innate immune pathways through recruitment of toll-like receptors and activation of cytokine synthesis. Trophoblast cells isolated from 14 normal term human placentas were incubated with long chain fatty acids (FA) of different carbon length and degree of saturation. The expression and secretion of interleukin-6 (IL-6), IL-8 and tumor necrosis factor-alpha (TNF-α) were measured by reverse transcription-polymerase chain reaction and enzyme-linked immunosorbent assay. Antibodies against TLR4 ligand binding domain, downstream signaling and anti-p65 NFkB-inhibitor were used to characterize the pathways of FA action. General approach used primary human term trophoblast cell culture. Methods and end-points used real-time quantitative PCR, cytokine measurements, immunohistochemistry, western blots. The long chain saturated fatty acids, stearic and palmitic (PA), stimulated the synthesis as well as the release of TNF-α, IL-6 and IL-8 by trophoblast cells (2- to 6-fold, P acids did not modify cytokine expression significantly. Palmitate-induced inflammatory effects were mediated via TLR4 activation, NF-kB phosphorylation and nuclear translocation. TNF-α protein level was close to the limit of detection in the culture medium even when cells were cultured with PA. These mechanisms open the way to a better understanding of how changes in maternal lipid homeostasis may regulate placental inflammatory status. X.Y. was recipient of fellowship award from West China Second University Hospital, Sichuan University (NIH HD 22965-19). The authors have nothing

  5. Extravillous trophoblast invasion in placenta accreta is associated with differential local expression of angiogenic and growth factors: a cross-sectional study.

    Science.gov (United States)

    Duzyj, C M; Buhimschi, I A; Laky, C A; Cozzini, G; Zhao, G; Wehrum, M; Buhimschi, C S

    2018-02-22

    Placenta accreta is clinically associated with maternal uterine scar. Our objective was to investigate the biochemical contribution of maternal scarring to hyperinvasive trophoblast. We hypothesised that trophoblast over-invasion in placenta accreta is associated with aberrant invasion-site signalling of growth and angiogenic factors known to be involved in wound healing and promotion of cell invasion through the epithelial to mesenchymal cellular programme. Cross-sectional series. Yale-New Haven Hospital. Women with histologically confirmed normal and abnormal placentation. Placental invasion site tissue sections were immunostained for endoglin and other angiogenic regulators, and transforming growth factor β (TGFβ) proteins. Maternal serum endoglin, and the vascular endothelial growth factor (VEGF) mediators hypoxia-inducible factor-1α (HIF1α) and endostatin, were assessed using immunoassay. Differences in median H-score by immunostaining and in mean serum level by immunoassay. By immunostaining, placenta accreta samples demonstrated intervillous endoglin shedding and increased trophoblast expression of its cleavage protein matrix metalloproteinase-14. Absent decidual HIF1α and endostatin were observed in areas of VEGF upregulation. TGFβ1 was present in myocytes but not in collagen bundles into which accreta trophoblast invaded. Maternal serum endoglin decreased in praevia and accreta when corrected for gestational age. Angiogenic and growth factors at the placental invasion site are altered in accreta, both by decidual absence and within myometrial scar. We postulate this promotes the invasive phenotype of placenta accreta by activating hyperinvasive trophoblast and by dysregulating placental vascular remodelling. Yale Department of Obstetrics, Gynecology and Reproductive Sciences funds. Placenta accreta histology shows dysregulation of angiogenic and growth factors. © 2018 Royal College of Obstetricians and Gynaecologists.

  6. miR-346 and miR-582-3p-regulated EG-VEGF expression and trophoblast invasion via matrix metalloproteinases 2 and 9.

    Science.gov (United States)

    Su, Mei-Tsz; Tsai, Pei-Yin; Tsai, Hui-Ling; Chen, Yi-Chi; Kuo, Pao-Lin

    2017-03-01

    Endocrine gland-derived vascular endothelial growth factor (EG-VEGF) is an important regulator for embryo implantation and placental development, and is clinically associated with several obstetric disorders related to insufficient or inappropriate trophoblast invasion, such as recurrent abortion, preeclampsia, and intrauterine fetal growth restriction. This study was performed to identify the microRNAs targeting EG-VEGF, and evaluate the regulatory effect on trophoblast biology. miR-346 and miR-582-3p were initially identified via bioinformatic tools, and their specific binding sites on the EG-VEGF 3'UTR were further confirmed using dual luciferase and a co-transfection assays. miR-346 and miR-582-3p were demonstrated not only to suppress EG-VEGF expression, but also inhibit trophoblast invasion and migration in the JAR and HTR-8/SVneo cell lines. We further evaluated the effect of microRNAs in HTR-8/SVneo cells coexpressing EG-VEGF and miR-346 or miR-582-3p on matrix metalloproteinase (MMP 2 and MMP 9) and the tissue inhibitors of metalloproteinase (TIMP 1 and TIMP 2) using RT-PCR, western blotting and gelatin zymography. TIMP 1 and TIMP 2 were not affected by the two microRNAs, whereas the expressions and activities of MMP 2 and MMP 9 were significantly downregulated, which in turn inhibited the invasion ability of trophoblasts. In conclusion, miR-346 and miR-582-3p regulate EG-VEGF-induced trophoblast invasion through repressing MMP 2 and MMP 9, and may become novel diagnostic biomarkers or therapeutic targets for EG-VEGF-related obstetric disorders. © 2016 BioFactors, 43(2):210-219, 2017. © 2016 International Union of Biochemistry and Molecular Biology.

  7. [Cells of immune system of mother and trophoblast cells: constructive cooperation for the sake of achievement of the joint purpose].

    Science.gov (United States)

    Aĭlamazian, E K; Stepanova, O I; Sel'kov, S A; Sokolov, D I

    2013-01-01

    In the present review modern data about change of morfo-functional properties of a trophoblast during pregnancy, and also about influence of the cytokines produced by cells of a microenvironment, including leucocytes of mother, on a functional state of trophoblast is cited. Features of interaction between trophoblast and immune cells of mother are described within physiological pregnancy and within pregnancy complicated by preeclampsia.

  8. Fellowship training and board certification in reproductive endocrinology and infertility.

    Science.gov (United States)

    Gambone, Joseph C; Segars, James H; Cedars, Marcelle; Schlaff, William D

    2015-07-01

    Reproductive endocrinology and infertility (REI) is one of the original officially recognized subspecialties in obstetrics and gynecology and among the earlier subspecialties in medicine. Recognized by the American Board of Obstetrics and Gynecology in 1972, fellowship programs are now 3 years in length following an obstetrics and gynecology residency. Originally focused on endocrine problems related to reproductive function, the assisted reproductive technologies (ART) have recently become the larger part of training during REI fellowships. It is likely that the subspecialty of REI strengthens the specialty of obstetrics and gynecology and enhances the educational experience of residents in the field. The value of training and certification in REI is most evident in the remarkable and consistent improvement in the success of ART procedures, particularly in vitro fertilization. The requirement for documented research activity during REI fellowships is likely to stimulate a more rapid adoption (translation) of newer research findings into clinical care after training. Although mandatory reporting of outcomes has been proposed as a reason for this improvement the rapid translation of reproductive research into clinical practice is likely to be a major cause. Looking forward, REI training should emphasize and strengthen education and research into the endocrine, environmental, and genetic aspects of female and male reproduction to improve the reproductive health and fertility of all women. Copyright © 2015 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.

  9. GATA-2 and GATA-3 regulate trophoblast-specific gene expression in vivo.

    NARCIS (Netherlands)

    G.T. Ma (Grace); M.E. Roth (Matthew); J.C. Groskopf (John); F.G. Grosveld (Frank); J.D. Engel (Douglas); D.I.H. Linzer (Daniel); F.Y. Tsai (Fong-Ying); S.H. Orkin (Stuart)

    1997-01-01

    textabstractWe previously demonstrated that the zinc finger transcription factors GATA-2 and GATA-3 are expressed in trophoblast giant cells and that they regulate transcription from the mouse placental lactogen I gene promoter in a transfected trophoblast cell line. We present evidence here that

  10. Feasibility of central co-ordinated EMA/CO for gestational trophoblastic disease in the Netherlands

    NARCIS (Netherlands)

    van der Houwen, Clasien; Rietbroek, Ron C.; Lok, Christianne A. R.; ten Kate-Booij, Marianne J.; Lammes, Frits B.; Ansink, Anca C.

    2004-01-01

    In the Netherlands, high risk gestational trophoblastic disease (GTD) patients are treated in different referral hospitals with a national working party on trophoblastic tumours having a co-ordinating function. Our purpose was to evaluate whether this policy is a satisfactory alternative to complete

  11. ECM-dependent HIF induction directs trophoblast stem cell fate via LIMK1-mediated cytoskeletal rearrangement.

    Directory of Open Access Journals (Sweden)

    Hwa J Choi

    Full Text Available The Hypoxia-inducible Factor (HIF family of transcriptional regulators coordinates the expression of dozens of genes in response to oxygen deprivation. Mammalian development occurs in a hypoxic environment and HIF-null mice therefore die in utero due to multiple embryonic and placental defects. Mouse embryonic stem cells do not differentiate into placental cells; therefore, trophoblast stem cells (TSCs are used to study mouse placental development. Consistent with a requirement for HIF activity during placental development in utero, TSCs derived from HIF-null mice exhibit severe differentiation defects and fail to form trophoblast giant cells (TGCs in vitro. Interestingly, differentiating TSCs induce HIF activity independent of oxygen tension via unclear mechanisms. Here, we show that altering the extracellular matrix (ECM composition upon which TSCs are cultured changes their differentiation potential from TGCs to multinucleated syncytiotropholasts (SynTs and blocks oxygen-independent HIF induction. We further find that modulation of Mitogen Activated Protein Kinase Kinase-1/2 (MAP2K1/2, MEK-1/2 signaling by ECM composition is responsible for this effect. In the absence of ECM-dependent cues, hypoxia-signaling pathways activate this MAPK cascade to drive HIF induction and redirect TSC fate along the TGC lineage. In addition, we show that integrity of the microtubule and actin cytoskeleton is critical for TGC fate determination. HIF-2α ensures TSC cytoskeletal integrity and promotes invasive TGC formation by interacting with c-MYC to induce non-canonical expression of Lim domain kinase 1-an enzyme that regulates microtubule and actin stability, as well as cell invasion. Thus, we find that HIF can integrate positional and metabolic cues from within the TSC niche to regulate placental development by modulating the cellular cytoskeleton via non-canonical gene expression.

  12. Optimizing bone morphogenic protein 4-mediated human embryonic stem cell differentiation into trophoblast-like cells using fibroblast growth factor 2 and transforming growth factor-β/activin/nodal signalling inhibition.

    Science.gov (United States)

    Koel, Mariann; Võsa, Urmo; Krjutškov, Kaarel; Einarsdottir, Elisabet; Kere, Juha; Tapanainen, Juha; Katayama, Shintaro; Ingerpuu, Sulev; Jaks, Viljar; Stenman, Ulf-Hakan; Lundin, Karolina; Tuuri, Timo; Salumets, Andres

    2017-09-01

    Several studies have demonstrated that human embryonic stem cells (hESC) can be differentiated into trophoblast-like cells if exposed to bone morphogenic protein 4 (BMP4) and/or inhibitors of fibroblast growth factor 2 (FGF2) and the transforming growth factor beta (TGF-β)/activin/nodal signalling pathways. The goal of this study was to investigate how the inhibitors of these pathways improve the efficiency of hESC differentiation when compared with basic BMP4 treatment. RNA sequencing was used to analyse the effects of all possible inhibitor combinations on the differentiation of hESC into trophoblast-like cells over 12 days. Genes differentially expressed compared with untreated cells were identified at seven time points. Additionally, expression of total human chorionic gonadotrophin (HCG) and its hyperglycosylated form (HCG-H) were determined by immunoassay from cell culture media. We showed that FGF2 inhibition with BMP4 activation up-regulates syncytiotrophoblast-specific genes (CGA, CGB and LGALS16), induces several molecular pathways involved in embryo implantation and triggers HCG-H production. In contrast, inhibition of the TGF-β/activin/nodal pathway decreases the ability of hESC to form trophoblast-like cells. Information about the conditions needed for hESC differentiation toward trophoblast-like cells helps us to find an optimal model for studying the early development of human trophoblasts in normal and in complicated pregnancy. Copyright © 2017 Reproductive Healthcare Ltd. Published by Elsevier Ltd. All rights reserved.

  13. Transition in endocrinology: induction of puberty.

    Science.gov (United States)

    Dunkel, Leo; Quinton, Richard

    2014-06-01

    flag' clinical features. These 'red flags' comprise findings indicating lack of prior 'mini-puberty' (such as cryptorchidism or micropenis), or the presence of non-reproductive congenital defects known to be associated with specific hypogonadal syndromes, e.g. anosmia, deafness, mirror movements, renal agenesis, dental/digital anomalies, clefting or coloboma would be compatible with Kallmann (or perhaps CHARGE) syndrome. In children, interventions (whether in the form or treatment or simple reassurance) have been historically directed at maximising height potential and minimising psychosocial morbidity, though issues of future fertility and bone density potential are now increasingly 'in the mix'. Apubertal adults almost invariably harbour organic hypogonadism, requiring sensitive acknowledgement of underlying personal issues and the timely introduction of sex hormone replacement therapy at more physiological doses. © 2014 European Society of Endocrinology.

  14. Unsaturated fatty acids protect trophoblast cells from saturated fatty acid-induced autophagy defects.

    Science.gov (United States)

    Hong, Ye-Ji; Ahn, Hyo-Ju; Shin, Jongdae; Lee, Joon H; Kim, Jin-Hoi; Park, Hwan-Woo; Lee, Sung Ki

    2018-02-01

    Dysregulated serum fatty acids are associated with a lipotoxic placental environment, which contributes to increased pregnancy complications via altered trophoblast invasion. However, the role of saturated and unsaturated fatty acids in trophoblastic autophagy has yet to be explored. Here, we demonstrated that prolonged exposure of saturated fatty acids interferes with the invasiveness of human extravillous trophoblasts. Saturated fatty acids (but not unsaturated fatty acids) inhibited the fusion of autophagosomes and lysosomes, resulting in the formation of intracellular protein aggregates. Furthermore, when the trophoblast cells were exposed to saturated fatty acids, unsaturated fatty acids counteracted the effects of saturated fatty acids by increasing degradation of autophagic vacuoles. Saturated fatty acids reduced the levels of the matrix metalloproteinases (MMP)-2 and MMP-9, while unsaturated fatty acids maintained their levels. In conclusion, saturated fatty acids induced decreased trophoblast invasion, of which autophagy dysfunction plays a major role. Copyright © 2017 Elsevier B.V. All rights reserved.

  15. Microbial endocrinology and the microbiota-gut-brain axis.

    Science.gov (United States)

    Lyte, Mark

    2014-01-01

    Microbial endocrinology is defined as the study of the ability of microorganisms to both produce and recognize neurochemicals that originate either within the microorganisms themselves or within the host they inhabit. As such, microbial endocrinology represents the intersection of the fields of microbiology and neurobiology. The acquisition of neurochemical-based cell-to-cell signaling mechanisms in eukaryotic organisms is believed to have been acquired due to late horizontal gene transfer from prokaryotic microorganisms. When considered in the context of the microbiota's ability to influence host behavior, microbial endocrinology with its theoretical basis rooted in shared neuroendocrine signaling mechanisms provides for testable experiments with which to understand the role of the microbiota in host behavior and as importantly the ability of the host to influence the microbiota through neuroendocrine-based mechanisms.

  16. Radiation endocrinology as science and its tasks in Republic Kazakhstan

    International Nuclear Information System (INIS)

    Abylaev, Zh.A.

    1997-01-01

    It is known, that radiation endocrinology as science was formed comparatively not long ago and it is developing at the turn of endocrinology, medical radiology, radiobiology and immunology. Tasks of clinic radiation endocrinology for scientists of Kazakhstan are related with following problems: - radiation effects in condition of Semipalatinsk test site (Semipalatinsk, Karaganda, Pavlodar, East-Kazakhstan regions); - with definition of radiation factors (related with nuclear explosions) in ecologic systems for solution of national problems; - with contamination of Kazakhstan territory, associated with industrial radioactive materials handling ; - with goiter enemy in districts with unfavorable radiation situation; - with mass character of injuries of both the radiation exposure and the iodine deficit on territory of Republic. It was emphasised, that there is principle problem of population rehabilitation through systems of mass measures including prevention of endocrine complication in late time

  17. [Services portfolio of a department of endocrinology and clinical nutrition].

    Science.gov (United States)

    Vicente Delgado, Almudena; Gómez Enterría, Pilar; Tinahones Madueño, Francisco

    2011-03-01

    Endocrinology and Clinical Nutrition are branches of Medicine that deal with the study of physiology of body glands and hormones and their disorders, intermediate metabolism of nutrients, enteral and parenteral nutrition, promotion of health by prevention of diet-related diseases, and appropriate use of the diagnostic, therapeutic, and preventive tools related to these disciplines. Development of Endocrinology and Clinical Nutrition support services requires accurate definition and management of a number of complex resources, both human and material, as well as adequate planning of the care provided. It is therefore essential to know the services portfolio of an ideal Department of Endocrinology and Clinical Nutrition because this is a useful, valid and necessary tool to optimize the available resources, to increase efficiency, and to improve the quality of care. Copyright © 2010 SEEN. Published by Elsevier Espana. All rights reserved.

  18. The Gestational Trophoblastic Diseases: A Ten Year Retrospective Study

    Directory of Open Access Journals (Sweden)

    Razieh Mohammadjafari

    2010-01-01

    Full Text Available Background: Gestational trophoblastic disease (GTD defines a heterogenenous group ofinterrelated lesions that arise from the trophoblastic epithelium of the placenta. There are severalhistologically distinct types of GTD: hydatiform mole (complete or partial, persistant/invasivegestational trophoblastic neoplasia (GTN, choriocarcinoma and placenta site trophoblastictumors. The aim of this study was to determine the frequency and risk factors of GTD amongwomen admitted to Imam Khomeini Hospital in Ahvaz, Iran.Materials and Methods: This was a cross-sectional study conducted at Imam KhomeiniHospital in Ahvaz, Iran. All hospital records related to GTD (132 from 1996 until 2006 werereviewed. Demographic and histo-pathologic characteristics were extracted. Chi-square andFisher-exact tests were used to analyze all variables. P ≤ 0.05 was considered statisticallysignificant. SPSS, version 11 was used for statistical analysis.Results: The mean age of patients was 27.6 years. Most patients who presented with GTDwere of ages 18-35 years (71.3%. There was no relationship between age and hydatiformmole during the reproductive years. There were 28 (18.9% patients over the age 40, of which18 (15.90% of these had a complete hydatiform mole. Within this group, 9 (6.8% changedto a persistent mole. There was a significant relationship between age over 40 and completemole (p<0.02. The percentage of patients with blood groups A and O was the same (37.9%.There was a significant relationship between blood groups (O+ and A+ and complete mole(p<0.05.Conclusion: The most common age range for hydatiform mole was 18-35 years. Women overthe age of 40 had a more complete hydatiform mole, which is similar to the other countries.Age and blood group are two risk factors for hydatiform mole.

  19. Human parvovirus B19 antibodies induce altered membrane protein expression and apoptosis of BeWo trophoblasts.

    Science.gov (United States)

    Tzang, Bor-Show; Chiang, Szu-Yi; Chan, Hsu-Chin; Liu, Chung-Hsien; Hsu, Tsai-Ching

    2016-11-01

    Human parvovirus B19 (B19) is harmful during pregnancy since it can be vertically transmitted to the developing fetus. In addition, the anti‑B19 antibodies induced by B19 infection are believed to have a cytopathic role in B19 transmission; however, knowledge regarding the effects of anti‑B19 antibodies during pregnancy is limited. To investigate the possible roles of anti‑B19 antibodies during pregnancy, the present study examined the effects of anti‑B19‑VP1 unique region (VP1u), anti‑B19‑VP2 and anti‑B19‑nonstructural protein 1 (NS1) immunoglobulin G (IgG) antibodies on BeWo trophoblasts. Briefly, BeWo trophoblasts were incubated with purified IgG against B19‑VP1u, B19‑VP2 and B19‑NS1. Subsequently, the expression of surface proteins and apoptotic molecules were assessed in BeWo trophoblasts using flow cytometry, ELISA and western blotting. The expression levels of human leukocyte antigen (HLA)‑G were significantly increased on BeWo trophoblasts treated with rabbit anti‑B19‑VP1u IgG, and were unchanged in those treated with rabbit anti‑B19‑NS1 and anti‑B19‑VP2 IgG, as compared with the control group. Furthermore, the expression levels of globoside (P blood group antigen) and cluster of differentiation (CD)29 (β1 integrin) were significantly increased in BeWo trophoblasts treated with rabbit anti‑B19‑NS1 and anti‑B19‑VP2 IgG, whereas only CD29 was also significantly increased in cells treated with anti‑B19‑VP1u IgG. In addition, the number of cells at sub‑G1 phase; caspase‑3 activity; and the expression of intrinsic and extrinsic apoptotic molecules, including Fas‑associated death domain protein, activated caspase‑8, activated caspase‑3, B‑cell lymphoma 2‑associated X protein, cytochrome c, apoptotic peptidase activating factor 1 and activated caspase‑9, were significantly increased in BeWo trophoblasts treated with anti‑B19‑VP1u and anti‑B19‑NS1 IgG. In conclusion, the present

  20. 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.

  1. The future endocrine patient. Reflections on the future of clinical endocrinology

    NARCIS (Netherlands)

    S.W.J. Lamberts (Steven); J.A. Romijn (Johannes); W.M. Wiersinga (Wilmar)

    2003-01-01

    textabstractIn recent years the future position of clinical endocrinology has been extensively discussed by Western European endocrine societies. Clinical endocrinology seems to suffer from being too intellectual, generating too little income, and lacking too few spectacular

  2. The invasive phenotype of placenta accreta extravillous trophoblasts associates with loss of E-cadherin.

    Science.gov (United States)

    Duzyj, C M; Buhimschi, I A; Motawea, H; Laky, C A; Cozzini, G; Zhao, G; Funai, E F; Buhimschi, C S

    2015-06-01

    Epithelial-to-mesenchymal transition (EMT) is a process of molecular and phenotypic epithelial cell alteration promoting invasiveness. Loss of E-cadherin (E-CAD), a transmembrane protein involved in cell adhesion, is a marker of EMT. Proteolysis into N- and C-terminus fragments by ADAM10 and presenilin-1 (PSEN-1) generates soluble (sE-CAD) and transcriptionally active forms. We studied the protein expression patterns of E-CAD in the serum and placenta of women with histologically-confirmed over-invasive placentation. The patterns of expression and levels of sE-CAD were analyzed by Western blot, immunoassay, and immunoprecipitation. Tissue immunostaining for E-CAD, cytokeratin-7 (epithelial marker), vimentin (mesenchymal marker), ADAM10, PSEN-1 and β-catenin expression were investigated in parallel. N-terminus cleaved 80 kDa sE-CAD fragments were present in serum of pregnant women with gestational age regulation of the circulatory levels. Women with advanced trophoblast invasion did not display circulatory levels of sE-CAD different from those of women with normal placentation. Histologically, extravillous trophoblasts (EVT) closer to the placental-myometrial interface demonstrated less E-CAD staining than those found deeper in the myometrium. These cells expressed both vimentin and cytokeratin, an additional feature of EMT. EVT of placentas with advanced invasion displayed intracellular E-CAD C-terminus immunoreactivity predominating over that of the extracellular N-terminus, a pattern consistent with preferential PSEN-1 processing. Local processing of E-CAD may be an important molecular mechanism controlling the invasive phenotype of accreta EVT. Copyright © 2015 Elsevier Ltd. All rights reserved.

  3. Immunochemical identification of human trophoblast membrane antigens using monoclonal antibodies

    Energy Technology Data Exchange (ETDEWEB)

    Brown, P J; Molloy, C M; Johnson, P M [Liverpool Univ. (UK). Dept. of Immunology

    1983-11-01

    Human trophoblast membrane antigens recognised by monoclonal antibodies (H310, H315, H316 and H317) have been identified using combinations of radioimmunoprecipitation, SDS-PAGE, electroblotting, chromatographic and ELISA-type techniques. H317 is known to identify heat-stable placental-type alkaline phosphatase and accordingly was shown to react with a protein of subunit Msub(r) of 68000. H310 and H316 both recognise an antigen with a subunit Msub(r) of 34000 under reducing conditions. In non-reducing conditions, the H310/316 antigen gave oligomers of a component of Msub(r) 62000. It is unknown whether this 62000 dalton component is a dimer of the 34000 dalton protein with either itself or a second protein chain of presumed Msub(r) around 28000. H315 recognises an antigen with subunit Msub(r) of 36000; in non-reducing conditions this component readily associates to oligomeric structures. The epitope recognised by H315 may be sensitive to SDS. The two proteins recognised by H310/316 and H315 have been termed the p34 and p36 trophoblast membrane proteins, respectively.

  4. Effects of Human Umbilical Cord Mesenchymal Stem Cells on Human Trophoblast Cell Functions In Vitro

    Directory of Open Access Journals (Sweden)

    Yajing Huang

    2016-01-01

    Full Text Available Trophoblast cell dysfunction is involved in many disorders during pregnancy such as preeclampsia and intrauterine growth restriction. Few treatments exist, however, that target improving trophoblast cell function. Human umbilical cord mesenchymal stem cells (hUCMSCs are capable of self-renewing, can undergo multilineage differentiation, and have homing abilities; in addition, they have immunomodulatory effects and paracrine properties and thus are a prospective source for cell therapy. To identify whether hUCMSCs can regulate trophoblast cell functions, we treated trophoblast cells with hUCMSC supernatant or cocultured them with hUCMSCs. Both treatments remarkably enhanced the migration and invasion abilities of trophoblast cells and upregulated their proliferation ability. At a certain concentration, hUCMSCs also modulated hCG, PIGF, and sEndoglin levels in the trophoblast culture medium. Thus, hUCMSCs have a positive effect on trophoblast cellular functions, which may provide a new avenue for treatment of placenta-related diseases during pregnancy.

  5. Development to term of sheep embryos reconstructed after inner cell mass/trophoblast exchange.

    Science.gov (United States)

    Loi, Pasqualino; Galli, Cesare; Lazzari, Giovanna; Matsukawa, Kazutsugu; Fulka, Josef; Goeritz, Frank; Hildebrandt, Thomas B

    2018-04-13

    Here we report in vitro and term development of sheep embryos after the inner cell mass (ICM) from one set of sheep blastocysts were injected into the trophoblast vesicles of another set. We also observed successful in vitro development of chimeric blastocysts made from sheep trophoblast vesicles injected with bovine ICM. First, we dissected ICMs from 35 sheep blastocysts using a stainless steel microblade and injected them into 29 re-expanded sheep trophoblastic vesicles. Of the 25 successfully micromanipulated trophoblastic vesicles, 15 (51.7%) re-expanded normally and showed proper ICM integration. The seven most well reconstructed embryos were transferred for development to term. Three ewes receiving manipulated blastocysts were pregnant at day 45 (42.8%), and all delivered normal offspring (singletons, two females and one male, average weight: 3.54 ± 0.358 kg). Next, we monitored in vitro development of sheep trophoblasts injected with bovine ICMs. Of 17 injected trophoblastic vesicles, 10 (58.8%) re-expanded after 4 h in culture, and four (40%) exhibited integrated bovine ICM. Our results indicate that ICM/trophoblast exchange is feasible, allowing full term development with satisfactory lambing rate. Therefore, ICM exchange is a promising approach for endangered species conservation.

  6. Early embryonic demise: no evidence of abnormal spiral artery transformation or trophoblast invasion.

    Science.gov (United States)

    Ball, E; Robson, S C; Ayis, S; Lyall, F; Bulmer, J N

    2006-03-01

    Invasion by extravillous trophoblast of uterine decidua and myometrium and the associated spiral artery 'transformation' are essential for the development of normal pregnancy. Small pilot studies of placental bed and basal plate tissues from miscarriages have suggested that impaired interstitial and endovascular trophoblast invasion may play a role in the pathogenesis of miscarriage. The hypothesis that early miscarriage is associated with reduced extravillous trophoblast invasion and spiral artery transformation was tested in a large series of placental bed biopsies containing decidua and myometrium and at least one spiral artery from early, karyotyped embryonic miscarriages (trophoblast (cytokeratin), myometrium and spiral artery medial smooth muscle (desmin), and endothelium (von Willebrand factor). Trophoblast invasion and individual features of spiral artery transformation were assessed histologically in spiral arteries of miscarriages (n = 176) and controls (n = 246) and analysed statistically using a logistic regression model. Trophoblast invasion of uterine tissues and spiral artery transformation did not differ between euploid and aneuploid early miscarriage and also did not differ significantly from normal pregnancy. These findings suggest that failed trophoblast invasion and spiral artery transformation do not have a pivotal role in the pathogenesis of early miscarriage.

  7. Gestational Trophoblastic Disease: A Multimodality Imaging Approach with Impact on Diagnosis and Management

    International Nuclear Information System (INIS)

    Dhanda, S.; Ramani, S.; Dhanda, S.; Ramani, S.; Thakur, M.

    2014-01-01

    Gestational trophoblastic disease is a condition of uncertain etiology, comprised of hydatiform mole (complete and partial), invasive mole, choriocarcinoma, and placental site trophoblastic tumor. It arises from abnormal proliferation of trophoblastic tissue. Early diagnosis of gestational trophoblastic disease and its potential complications is important for timely and successful management of the condition with preservation of fertility. Initial diagnosis is based on a multimodality approach: encompassing clinical features, serial quantitative β-hCG titers, and pelvic ultrasonography. Pelvic magnetic resonance imaging (MRI) is sometimes used as a problem-solving tool to assess the depth of myometrial invasion and extra uterine disease spread in equivocal and complicated cases. Chest radiography, body computed tomography (CT), and brain MRI have been recommended as investigative tools for overall disease staging. Angiography has a role in management of disease complications and metastases. Efficacy of PET (positron emission tomography) and PET/CT in the evaluation of recurrent or metastatic disease has not been adequately investigated yet. This paper discusses the imaging features of gestational trophoblastic disease on various imaging modalities and the role of different imaging techniques in the diagnosis and management of this entity. 1. Introduction Gestational trophoblastic disease (GTD) refers to an abnormal trophoblastic proliferation composed of a broad spectrum of lesions ranging from benign, albeit pre malignant hydatiform mole (complete and partial), through to the aggressive invasive mole, choriocarcinoma

  8. Aspects of ecological radiation endocrinology and occupational pathology

    International Nuclear Information System (INIS)

    Ajtbembetov, B.M.

    1997-01-01

    The collection consists of works on radiation endocrinology and occupational pathology in different branches of industry - petroleum, mining, cotton, non-ferrous metallurgy as well as agriculture. Collection is intended for endocrinologists and occupational pathologists, for specialists of labour protection and occupational safety, for doctors examining of industrial and agricultural workers (author)

  9. Important Literature in Endocrinology: Citation Analysis and Historial Methodology.

    Science.gov (United States)

    Hurt, C. D.

    1982-01-01

    Results of a study comparing two approaches to the identification of important literature in endocrinology reveals that association between ranking of cited items using the two methods is not statistically significant and use of citation or historical analysis alone will not result in same set of literature. Forty-two sources are appended. (EJS)

  10. Physiology and Endocrinology Symposium. Factors controlling puberty in beef heifers

    Science.gov (United States)

    The Physiology and Endocrinology Symposium on “Factors controlling puberty in beef heifers” was held at the joint annual meeting of the American Dairy Science Association and the American Society of Animal Science in New Orleans, Louisiana, USA, July 10 to 14, 2011. The objective of the symposium w...

  11. Microbial Endocrinology in the Pathogenesis of Infectious Disease.

    Science.gov (United States)

    Lyte, Mark

    2016-04-01

    Microbial endocrinology represents the intersection of two seemingly disparate fields, microbiology and neurobiology, and is based on the shared presence of neurochemicals that are exactly the same in host as well as in the microorganism. The ability of microorganisms to not only respond to, but also produce, many of the same neurochemicals that are produced by the host, such as during periods of stress, has led to the introduction of this evolutionary-based mechanism which has a role in the pathogenesis of infectious disease. The consideration of microbial endocrinology-based mechanisms has demonstrated, for example, that the prevalent use of catecholamine-based synthetic drugs in the clinical setting contributes to the formation of biofilms in indwelling medical devices. Production of neurochemicals by microorganisms most often employs the same biosynthetic pathways as those utilized by the host, indicating that acquisition of host neurochemical-based signaling system in the host may have been acquired due to lateral gene transfer from microorganisms. That both host and microorganism produce and respond to the very same neurochemicals means that there is bidirectionality contained with the theoretical underpinnings of microbial endocrinology. This can be seen in the role of microbial endocrinology in the microbiota-gut-brain axis and its relevance to infectious disease. Such shared pathways argue for a role of microorganism-neurochemical interactions in infectious disease.

  12. Mandibular atrophy and metabolic bone loss. Endocrinology, radiology and histomorphometry

    NARCIS (Netherlands)

    Habets, L. L.; Bras, J.; Borgmeyer-Hoelen, A. M.

    1988-01-01

    In 11 edentulous patients with a severe atrophy of the mandible and submitted for ridge augmentation, endocrinological, radiological and histomorphometrical studies were carried out. The results showed that metabolic bone loss, histologically in nearly all patients characterized as a disturbance in

  13. Preeclampsia: novel insights from global RNA profiling of trophoblast subpopulations.

    Science.gov (United States)

    Gormley, Matthew; Ona, Katherine; Kapidzic, Mirhan; Garrido-Gomez, Tamara; Zdravkovic, Tamara; Fisher, Susan J

    2017-08-01

    syncytiotrophoblast data highlighted the dysregulation of immune functions, morphogenesis, transport, and responses to vascular endothelial growth factor and progesterone. The invasive cytotrophoblast data provided evidence of alterations in cellular movement, which is consistent with the shallow invasion often associated with severe preeclampsia. Other dysregulated pathways included immune, lipid, oxygen, and transforming growth factor-beta responses. The data for endovascular cytotrophoblasts showed disordered metabolism, signaling, and vascular development. Additionally, the transcriptional data revealed the differential expression in severe preeclampsia of 2 classes of non-coding RNAs: long non-coding RNAs and small nucleolar RNAs. The long non-coding RNA, urothelial cancer associated 1, was the most highly up-regulated in this class. In situ hybridization confirmed severe preeclampsia-associated expression in syncytiotrophoblasts. The small nucleolar RNAs, which chemically modify RNA structure, also correlated with severe preeclampsia. Thus, we enumerated Cajal body foci, sites of small nucleolar RNA activity, in primary cytotrophoblasts that were isolated from control and severe preeclampsia placentas. In severe preeclampsia, cytotrophoblasts had approximately double the number of these foci as the control samples. A laser microdissection approach enabled the identification of novel messenger RNAs and non-coding RNAs that were misexpressed by various trophoblast subpopulations in severe preeclampsia. The results suggested new avenues of investigation, in particular, the roles of PRG2, Kell blood group determinants, and urothelial cancer associated 1 in syncytiotrophoblast diseases. Additionally, many of the newly identified dysregulated molecules might have clinical utility as biomarkers of severe preeclampsia. Copyright © 2017 The Author(s). Published by Elsevier Inc. All rights reserved.

  14. ADAM28 localizes to HLA-G+ trophoblasts and promotes column cell outgrowth.

    Science.gov (United States)

    De Luca, L C; Le, H T; Mara, D L; Beristain, A G

    2017-07-01

    Trophoblast progenitor cell differentiation towards the extravillous trophoblast (EVT) lineage initiates within proximal regions of anchoring columns of first trimester placental villi. While molecular processes controlling the initial stages of progenitor cell differentiation along the EVT pathway have been described, much remains unknown about factors important in distal column cell differentiation into invasive EVTs. ADAMs are proteases that regulate growth factor signaling, cell-matrix adhesion, and matrix proteolysis, and thus impact many processes relevant in placentation. Global gene expression studies identified the ADAM subtype, ADAM28, to be highly expressed in EVT-like trophoblasts, suggesting that it may play a role in EVT function. This study aims to test the functional importance of ADAM28 in column cell outgrowth and maintenance. ADAM28 mRNA levels and protein localization were determined by qPCR and immunofluorescence microscopy analyses in purified placental villi cell populations and tissues. ADAM28 function in trophoblast column outgrowth was examined using ADAM28-targetting siRNAs in Matrigel-imbedded placental explant cultures. Within placental villi, ADAM28 mRNA levels were highest in HLA-G + column trophoblasts, and consistent with this, ADAM28 was preferentially localized to HLA-G + trophoblasts within distal anchoring columns and decidual tissue. siRNA-directed loss of ADAM28 impaired trophoblast column outgrowth and resulted in increased apoptosis in matrix-invading trophoblasts. Our findings suggest that ADAM28 promotes column outgrowth by providing survival cues within anchoring column cells. This study also provides insight into a possible role for ADAM28 in driving differentiation of column trophoblasts into invasive HLA-G + EVT subsets. Copyright © 2017 Elsevier Ltd. All rights reserved.

  15. Historia de la Endocrinología en Colombia

    Directory of Open Access Journals (Sweden)

    Alfredo Jácome Roca

    2001-08-01

    Full Text Available

    La especialidad clínica de la endocrinología lleva ya más de medio siglo en nuestro país, y si nos ponemos a ver la actividad de algunos precursores, esta historia bien puede remontarse al siglo XIX.

    El académico Antonio Ucrós Cuellar se puso en la tarea de recopilar las actuaciones de los especialistas en problemas hormonales y en las actividades de las asociaciones científicas de este ramo de la medicina y para ello contó con la ayuda editorial de los endocrinólogos y discípulos suyos, Eric Hernández y Stella Acosta.

    Ucrós ha participado personalmente en el devenir histórico de la endocrinología en Colombia, como investigador de la problemática del bocio, como fundador de la Asociación Colombiana de Endocrinología y de la sección de endocrinología del Hospital de San José, que recientemente cumplió sus Bodas de Oro, y en la cual se han formado numerosos y distinguidos especialistas que ejercen en el país su profesión.

    Comentar esta obra viene como anillo al dedo en este número especial sobre endocrinología que publica la revista “Medicina” de la Academia. Este libro de 230 páginas recoge en su parte inicial los antecedentes históricos y los estudios sobre el bocio en el país que el autor tan elegantemente lideró, finaliza esta parte inicial con su propia versión de la endocrinología en Colombia, que comienza con él y otros eminentes especialistas como Hernán Mendoza Hoyos, Tomás Quintero, Alonso Gutiérrez, Jaime Cortázar, Efraím tero, Mario Sánchez Medina (en el campo de la diabetes, Iván Molina en Medellín, Alberto Jamis en Barranquilla, y el importante grupo de Cali donde figuraron entre otros Eduardo Gaitán, Heins Wahner (actualmente en la Clínica Mayo, William Jubiz y Matilde de Bernal, todos de talla internacional.

    Mi interés por la endocrinología se inició con las magistrales clases de Mendoza Hoyos en la Javeriana, sobre el tema de la Fisiología Endocrina

  16. Hepatitis C Virus Sensing by Human Trophoblasts Induces Innate Immune Responses and Recruitment of Maternal NK Cells: Potential Implications for Limiting Vertical Transmission.

    Science.gov (United States)

    Giugliano, Silvia; Petroff, Margaret G; Warren, Bryce D; Jasti, Susmita; Linscheid, Caitlin; Ward, Ashley; Kramer, Anita; Dobrinskikh, Evgenia; Sheiko, Melissa A; Gale, Michael; Golden-Mason, Lucy; Winn, Virginia D; Rosen, Hugo R

    2015-10-15

    Hepatitis C virus (HCV) is the world's most common blood-borne viral infection for which there is no vaccine. The rates of vertical transmission range between 3 and 6% with odds 90% higher in the presence of HIV coinfection. Prevention of vertical transmission is not possible because of lack of an approved therapy for use in pregnancy or an effective vaccine. Recently, HCV has been identified as an independent risk factor for preterm delivery, perinatal mortality, and other complications. In this study, we characterized the immune responses that contribute to the control of viral infection at the maternal-fetal interface (MFI) in the early gestational stages. In this study, we show that primary human trophoblast cells and an extravillous trophoblast cell line (HTR8), from first and second trimester of pregnancy, express receptors relevant for HCV binding/entry and are permissive for HCV uptake. We found that HCV-RNA sensing by human trophoblast cells induces robust upregulation of type I/III IFNs and secretion of multiple chemokines that elicit recruitment and activation of decidual NK cells. Furthermore, we observed that HCV-RNA transfection induces a proapoptotic response within HTR8 that could affect the morphology of the placenta. To our knowledge, for the first time, we demonstrate that HCV-RNA sensing by human trophoblast cells elicits a strong antiviral response that alters the recruitment and activation of innate immune cells at the MFI. This work provides a paradigm shift in our understanding of HCV-specific immunity at the MFI as well as novel insights into mechanisms that limit vertical transmission but may paradoxically lead to virus-related pregnancy complications. Copyright © 2015 by The American Association of Immunologists, Inc.

  17. Expression of urokinase receptors by human trophoblast. A histochemical and ultrastructural analysis

    DEFF Research Database (Denmark)

    Multhaupt, H A; Mazar, A; Cines, D B

    1994-01-01

    BACKGROUND: Through their ability to invade endometrium, remodel the uterine spiral arteries, and sustain placental blood fluidity, trophoblast cells play a central role in establishing and maintaining the integrity of the uteroplacental vasculature. The expression of urokinase receptors by troph......BACKGROUND: Through their ability to invade endometrium, remodel the uterine spiral arteries, and sustain placental blood fluidity, trophoblast cells play a central role in establishing and maintaining the integrity of the uteroplacental vasculature. The expression of urokinase receptors...... at the leading edge of migrating extravillous trophoblast cells. Receptors were also abundantly expressed during the first and second trimesters of gestation by villous trophoblast, where they were located on apical villous projections and within intracellular vacuoles, a subset of which were lysosomes...

  18. Gestational trophoblastic disease in Abuth Zaria, Nigeria: A 5‑year ...

    African Journals Online (AJOL)

    Gestational trophoblastic disease in Abuth Zaria, Nigeria: A 5‑year review. ... Abimbola O. Kolawole, John K. Nwajagu, Adekunle O. Oguntayo, Marliya S. ... The data obtained were expressed in percentages, means, and standard deviations.

  19. Comparative experimental infection of Listeria monocytogenes and Listeria ivanovii in bovine trophoblasts.

    Science.gov (United States)

    Rocha, Cláudia E; Mol, Juliana P S; Garcia, Luize N N; Costa, Luciana F; Santos, Renato L; Paixão, Tatiane A

    2017-01-01

    Listeria monocytogenes is a Gram-positive, facultative intracellular and invasive bacterium that has tropism to the placenta, and causes fetal morbidity and mortality in several mammalian species. While infection with L. monocytogenes and L. ivanovii are known as important causes of abortion and reproductive failure in cattle, the pathogenesis of maternal-fetal listeriosis in this species is poorly known. This study used the bovine chorioallantoic membrane explant model to investigate the kinetics of L. monocytogenes, L. ivanovii, and L. innocua infections in bovine trophoblastic cells for up to 8 h post infection. L. monocytogenes and L. ivanovii were able to invade and multiply in trophoblastic cells without causing cell death or inducing expression of pro-inflammatory genes. Although L. innocua was unable to multiply in bovine trophoblastic cells, it induced transcription of the pro-inflammatory mediator CXCL6. This study demonstrated for the first time the susceptibility of bovine trophoblastic cells to L. monocytogenes and L. ivanovii infection.

  20. Immunomodulator expression in trophoblasts from the feline immunodeficiency virus FIV infected cat

    Science.gov (United States)

    FIV infection frequently compromises pregnancy under experimental conditions and is accompanied by aberrant expression of some placental cytokines. Trophoblasts produce numerous immunomodulators that play a role in placental development and pregnancy maintenance. We hypothesized that FIV infection m...

  1. 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...

  2. Placental Trophoblast Responses to Porphyromonas gingivalis Mediated by Toll-like Receptor-2 and -4

    Directory of Open Access Journals (Sweden)

    Banun Kusumawardani

    2013-09-01

    Full Text Available Trophoblast participates in preventing allorecognition and controlling pathogens that compromise fetal wellbeing. Toll-like receptors recognize conserved sequences on the pathogens surface and trigger effector cell functions. Porphyromonas gingivalis is thought to spread to the umbilical cord and cause fetal growth restriction. Objective: To characterize expression and function of TLR-2 and TLR-4 in trophoblast cells from Porphyromonas gingivalisinfected pregnant rats. Methods: Live Porphyromonas gingivalis were challenged into the maxillary first molar subgingival sulcus of female rats before and/or during pregnancy and sacrified on gestational day (GD 14 and 20. Porphyromonas gingivalis was detected by API-ZYM system in the maternal blood of the retro-orbital venous plexus and the umbilical cord. TLR-2 and TLR-4 expressions in trophoblast cells was detected by immunohistochemistry. Results: Porphyromonas gingivalis was first detected in the maternal blood and finally spread to the umbilical cord. Syncytiotrophoblast, spongitrophoblast and trophoblastic giant cell in treated groups had significantly higher expression of TLR-2 and TLR-4 than control group (p<0.05. Conclusion: Syncytiotrophoblast, spongitrophoblast and trophoblastic giant cell are able to recognize Porphyromonas gingivalis through TLR-2 and TLR-4 expression. The ligation of TLR-2 and TLR-4 promoted cytokine production and induced trophoblast cell death. These findings strengthen links between periodontal disease and fetal growth restriction.DOI: 10.14693/jdi.v20i2.150

  3. Gestational trophoblastic disease: experience at a tertiary care hospital of sindh

    International Nuclear Information System (INIS)

    Khaskheli, M.; Imdad, A.; Baloch, S.

    2007-01-01

    To determine the frequency, clinical presentation and management outcomes of Gestational Trophoblastic Disease (GTD). The case records of all the gestational trophoblastic cases during study period were analyzed regarding their illness history, clinical examination, investigations, treatment and follow-up. The main outcomes were measured in terms of duration, antecedent pregnancy, investigations, treatment and the follow-up. There were a total of 1030 obstetric admissions during the study period, which included 23 cases of trophoblastic disease. Hence, frequency of GTD was 1 per 45 live births. Of these 23 cases, 19 (82.6%) patients had hydatidiform mole and 4 patients had malignant trophoblastic disease. Eight patients (34.7%) received chemotherapy while rest of the patients had suction evacuation and follow-up. Among all patients, 21 (91.3%) fully recovered and 2 (8.69%) died because of extensive disease; metastasis extending upto brain. Frequency of trophoblastic disease was high in this series compared to world and national literature. Therefore, emphasis should be on the early diagnosis of disease as proper management in the early stages strongly influences the outcome of disease. Suction evacuation and follow-up are ideal treatments for benign trophoblastic disease. (author)

  4. Gestational trophoblastic disease: experience at a tertiary care hospital of sindh

    Energy Technology Data Exchange (ETDEWEB)

    Khaskheli, M; Imdad, A; Baloch, S [Liaquat Univ. of Medical and Health Sciences, Jamshoro (Pakistan). Dept. of Obstetrics and Gynaecology

    2007-02-15

    To determine the frequency, clinical presentation and management outcomes of Gestational Trophoblastic Disease (GTD). The case records of all the gestational trophoblastic cases during study period were analyzed regarding their illness history, clinical examination, investigations, treatment and follow-up. The main outcomes were measured in terms of duration, antecedent pregnancy, investigations, treatment and the follow-up. There were a total of 1030 obstetric admissions during the study period, which included 23 cases of trophoblastic disease. Hence, frequency of GTD was 1 per 45 live births. Of these 23 cases, 19 (82.6%) patients had hydatidiform mole and 4 patients had malignant trophoblastic disease. Eight patients (34.7%) received chemotherapy while rest of the patients had suction evacuation and follow-up. Among all patients, 21 (91.3%) fully recovered and 2 (8.69%) died because of extensive disease; metastasis extending upto brain. Frequency of trophoblastic disease was high in this series compared to world and national literature. Therefore, emphasis should be on the early diagnosis of disease as proper management in the early stages strongly influences the outcome of disease. Suction evacuation and follow-up are ideal treatments for benign trophoblastic disease. (author)

  5. The role of Sep (O-phosphoserine) tRNA: Sec (selenocysteine) synthase (SEPSECS) in proliferation, apoptosis and hormone secretion of trophoblast cells.

    Science.gov (United States)

    Zhao, H-D; Zhang, W-G; Sun, M-N; Duan, Q-F; Li, F-L; Li, H

    2013-11-01

    To investigate whether Sep (O-phosphoserine) tRNA: Sec (selenocysteine) synthase (SEPSECS), which plays an essential role in the synthesis of selenoprotein, affects proliferation, apoptosis and hormone secretion of human trophoblast cells. Human trophoblast JEG-3 cells were divided into four groups: control group, SEPSECS silenced-expression group, empty vector group and SEPSECS over-expression group. Over-expression and silenced-expression were achieved by transfection with plasmid DNA or RNA oligonucleotide, respectively. 3-[4,5-dimethylthiazol-2-yl] -2,5-diphenyltetrazolium bromide (MTT) and colony formation assays were performed to investigate cell proliferation, while apoptosis was tested by annexin V-FITC, PI double staining and caspases-3 activation assays, enzyme-linked immunosorbent assay (ELISA) was used to determine the level of progesterone (PG) and human chorionic gonadotropin (hCG). SEPSECS silenced-expression clearly inhibited proliferation of JEG-3 cells (p < 0.05), significantly induced cell apoptosis (p < 0.01) and reduced the production of PG and hCG (p < 0.05). On the contrary, SEPSECS over-expression significantly promoted both cell proliferation (p < 0.01) and secretion of PG and hCG (p < 0.05). SEPSECS significantly affects proliferation, apoptosis and hormone secretion of human trophoblast cells, suggesting that a potential relationship exists among SEPSECS, cell proliferation, apoptosis and hormone production of human placental trophoblast cells. Furthermore, this may provide a clue to uncover the relationship between selenium and human placental in association with an emphasis on the importance of selenium adequacy during pregnancy. Copyright © 2013 Elsevier Ltd. All rights reserved.

  6. Syndecan-1 Acts as an Important Regulator of CXCL1 Expression and Cellular Interaction of Human Endometrial Stromal and Trophoblast Cells

    Directory of Open Access Journals (Sweden)

    Dunja Maria Baston-Buest

    2017-01-01

    Full Text Available Successful implantation of the embryo into the human receptive endometrium is substantial for the establishment of a healthy pregnancy. This study focusses on the role of Syndecan-1 at the embryo-maternal interface, the multitasking coreceptor influencing ligand concentration, release and receptor presentation, and cellular morphology. CXC motif ligand 1, being involved in chemotaxis and angiogenesis during implantation, is of special interest as a ligand of Syndecan-1. Human endometrial stromal cells with and without Syndecan-1 knock-down were decidualized and treated with specific inhibitors to evaluate signaling pathways regulating CXC ligand 1 expression. Western blot analyses of MAPK and Wnt members were performed, followed by analysis of spheroid interactions between human endometrial cells and extravillous trophoblast cells. By mimicking embryo contact using IL-1β, we showed less ERK and c-Jun activation by depletion of Syndecan-1 and less Frizzled 4 production as part of the canonical Wnt pathway. Additionally, more beta-catenin was phosphorylated and therefore degraded after depletion of Syndecan-1. Secretion of CXC motif ligand 1 depends on MEK-1 with respect to Syndecan-1. Regarding the interaction of endometrial and trophoblast cells, the spheroid center-to-center distances were smaller after depletion of Syndecan-1. Therefore, Syndecan-1 seems to affect signaling processes relevant to signaling and intercellular interaction at the trophoblast-decidual interface.

  7. Field endocrinology of nonhuman primates: past, present, and future.

    Science.gov (United States)

    Higham, James P

    2016-08-01

    In the past few decades, research on nonhuman primate endocrinology has moved from the lab to the field, leading to a huge increase in both the breadth and depth of primate field studies. Here, I discuss the past, present, and future of primate field endocrinology. I review the history of the field, and go on to discuss methodological developments and the issues that they sometimes entail. Next, I consider ways in which we might conceptualize the role of hormones, and focus on the need to distinguish proximate from ultimate levels of explanation. Current potentially problematic issues in the field include: 1) an inability to obtain noninvasive measurements of Central Nervous System (CNS) rather than peripheral hormone concentrations; 2) research questions that become stuck (e.g., questions regarding sexual swelling expression mechanisms); 3) data dredging and post-hoc linking of hormones to any plausible variable, leading to a lack of clarity on their role in animal ecology and behavior. I finish by discussing several unanswered questions that might benefit from further research. These are how we might: 1) best obtain measurements for CNS hormone concentrations non-invasively; 2) measure hormone receptor expression alongside hormone concentrations; 3) consider the human endocrinology literature more thoroughly and perhaps take more multimarker approaches; 4) better consider the social environment, including audience and dyadic familiarity effects; and 5) apply our findings to conservation issues. Copyright © 2016 Elsevier Inc. All rights reserved.

  8. Trophoblast retrieval and isolation from the cervix: origins of cervical trophoblasts and their potential value for risk assessment of ongoing pregnancies.

    Science.gov (United States)

    Moser, Gerit; Drewlo, Sascha; Huppertz, Berthold; Armant, D Randall

    2018-03-28

    Early during human development, the trophoblast lineage differentiates to commence placentation. Where the placenta contacts the uterine decidua, extravillous trophoblast (EVT) cells differentiate and invade maternal tissues. EVT cells, identified by expression of HLA-G, invade into uterine blood vessels (endovascular EVT), as well as glands (endoglandular EVT), and open such luminal structures towards the intervillous space of the placenta. Endoglandular invasion diverts the contents of uterine glands to the intervillous space, while glands near the margin of the placenta that also contain endoglandular EVT cells open into the reproductive tract. Cells of the trophoblast lineage have thus been recovered from the uterine cavity and endocervical canal. An emerging non-invasive technology [trophoblast retrieval and isolation from the cervix (TRIC)] isolates and examines EVT cells residing in the cervix to explore their origin, biology and relationship to pregnancy and fetal status. This review explores the origins and possible uses of trophoblast cells obtained during ongoing pregnancies (weeks 5-20) by TRIC. We hypothesize that endoglandular EVT cells at the margins of the expanding placenta enter the uterine cavity and are carried together with uterine secretion products to the cervix where they can be retrieved from a Papanicolaou (Pap) smear. The advantages of TRIC for investigation of human placentation and prenatal testing will be considered. Evidence from the literature, and from archived in utero placental histological sections, is presented to support these hypotheses. We used 52 out of 80 publications that appeared between 1966 and 2017 and were found by searching the PubMed and Google Scholar databases. The studies described trophoblast invasion of uterine vessels and glands, as well as trophoblast cells residing in the reproductive tract. This was supplemented with literature on human placental health and disease. The literature describes a variety of

  9. RISK FACTORS FOR GESTATIONAL TROPHOBLASTIC NEOPLASIA: A CASE CONTROL STUDY IN A TERTIARY HOSPITAL

    Directory of Open Access Journals (Sweden)

    Hema Sreedharan Nair

    2016-10-01

    Full Text Available BACKGROUND Gestational trophoblastic disease is a spectrum of proliferative abnormalities of the trophoblast. GTD represents a benign form of the disease while GTN is the malignant often metastatic lesion. 75-80 per cent of patients initially diagnosed as GTD will follow a benign course after dilatation and curettage. 15-20 per cent develop locally invasive disease and 3-5 per cent develop metastatic lesions. The study aims to assess the proportion of gestational trophoblastic neoplasia among women with gestational trophoblastic disease and identify the risk factors for chemotherapy in gestational trophoblastic neoplasia. MATERIALS AND METHODS This is a case-control study conducted in a tertiary hospital during a 5-year period. Cases are gestational trophoblastic neoplasia diagnosed by either rising beta-HCG levels or plateauing beta-HCG levels or by histological evidence of choriocarcinoma. Controls are cases of gestational trophoblastic disease post evacuation with normal HCG regression at 8 weeks. There were 306 controls and 57 cases. RESULTS Tabulated and analysed using SPSS package. Of the 363 patients of gestational trophoblastic disease, 57 (15.7% needed chemotherapy. 98.2% belonged to the age group of 20-35 years. 63% had gestational age of more than 12 weeks, 56.1% had pre-evacuation HCG of more than 40,000. 15.7% needed combination therapy. CONCLUSION 1. 83.1% of patients belonged to age group of 20-30 years. 2. Blood group distribution of patients with gestational trophoblastic disease did not show any significance. 3. 15.7% of total patients were diagnosed to have gestational trophoblastic neoplasia that necessitated chemotherapy. 4. When uterine size was more than 12 weeks, a statistically significant number of patients needed chemotherapy compared to non-chemotherapy group. 5. When BHCG values were more than 40,000, a statistically significant number of patients needed chemotherapy. 6. A risk score of seven or more was found to

  10. Adrenal incidentaloma in adults - management recommendations by the Polish Society of Endocrinology.

    Science.gov (United States)

    Bednarczuk, Tomasz; Bolanowski, Marek; Sworczak, Krzysztof; Górnicka, Barbara; Cieszanowski, Andrzej; Otto, Maciej; Ambroziak, Urszula; Pachucki, Janusz; Kubicka, Eliza; Babińska, Anna; Koperski, Łukasz; Januszewicz, Andrzej; Prejbisz, Aleksander; Górska, Maria; Jarząb, Barbara; Hubalewska-Dydejczyk, Alicja; Glinicki, Piotr; Ruchała, Marek; Kasperlik-Załuska, Anna

    2016-01-01

    A wide use of imaging techniques results in more frequent diagnosis of adrenal incidenataloma. To analyse the current state of knowledge on adrenal incidentaloma in adults in order to prepare practical management recommendations. Following a discussion, the Polish Society of Endocrinology expert working group have analysed the available data and summarised the analysis results in the form of recommendations. Unenhanced adrenal computed tomography (CT) may be recommended as an initial assessment examination helpful in the differentiation between adenomas and "non-adenomatous" lesions. In the case of density > 10 Hounsfield units, CT with contrast medium washout assessment or MRI are recommended. However, in all patients with adrenal incidentaloma, hormonal assessment is recommended in order to exclude pheochromocytoma and hypercortisolism, notwithstanding the clinical picture or concomitant diseases. In addition, examination to exclude primary hyperaldosteronism is suggested in patients with diagnosed hypertension or hypokalaemia. Surgical treatment should be recommended in patients with adrenal incidentaloma, where imaging examinations suggest a malignant lesion (oncological indication) or with confirmed hormonal activity (endocrinological indication). The basis of the surgical treatment is laparoscopic adrenalectomy. Patients with suspected pheochromocytoma must be pharmacologically prepared prior to surgery. In patients not qualified for surgery, control examinations (imaging and laboratory tests) should be established individually, taking into consideration such features as the size, image, and growth dynamics of the tumour, clinical symptoms, hormonal tests results, and concomitant diseases.

  11. Avian reproductive anatomy, physiology and endocrinology.

    Science.gov (United States)

    Pollock, Christal G; Orosz, Susan E

    2002-09-01

    Although many environmental cues influence reproductive activity, the seasonal breeder responds most strongly to long day length. THE MALE BIRD: Testicular interstitial cells secrete testosterone, which influences reproductive behavior such as territorial aggression and song. Other changes observed in seasonal breeders include testicular hypertrophy and enlargement of the ductus deferens and seminal glomus. THE FEMALE BIRD: Early changes associated with rising estrogen levels in the hen include osteomyelosclerosis and hypercalcemia. Ovulation is then induced by LH, which is followed by eggshell calcification, which is under the control of progesterone. Sources of calcium for shell production include intestinal absorption from the diet, renal control of calcium levels, and mobilization of bone calcium stores. During oviposition, PGF2 alpha and vasotocin stimulate powerful uterine contractions [32] in the presence of calcium. Incubation is associated with falling LH levels and rising prolactin levels. If the hen actually enters reproductive quiescence at this time, then molt will follow. Molt is associated with the total regression of the reproductive tract.

  12. Endocrinologic control of normal canine ovarian function.

    Science.gov (United States)

    Concannon, P W

    2009-07-01

    In dogs, the termination of the 3-10-month obligate anoestrus involves selection of a cohort of LH-sensitive follicles, presumably from a wave of dominant small antral follicles that would otherwise undergo atresia. The number and size of such follicles appears to increase, especially during the last 50 days of anoestrus when the already elevated concentrations of FSH become further elevated. The final selection and eventual terminal development of these follicles is caused by an increased frequency of high-amplitude LH pulses at the end of anoestrus. Concomitant increases in FSH are typically small or negligible. High concentrations of FSH in anoestrus are likely to be important in maintaining, if not stimulating, overlapping waves of dominant follicles throughout anoestrus, their expression of aromatase activity and basal oestradiol secretion sufficient to suppress LH by negative feedback. An attractive hypothesis is that late anoestrus increases in LH-stimulate synthesis of precursor androgen for already available FSH-dependent aromatase. After 7 or more days of elevated LH, and perhaps 2-5 days of semi-autonomous growth, with maximal oestradiol production reached, follicle capacity to further increase oestradiol becomes limited and excess progesterone becomes increasingly secreted. The pre-ovulatory LH surge and oestrus onset are then triggered - often synchronously and in concert with the terminal maturation of the follicles - by central effects of the large decrease in the oestrogen to progestin ratio. Follicular endocrine and paracrine events during and following the LH surge are likely similar to those reported for other species. The prolonged luteal phase lengths of 55-75 days in non-pregnant bitches bracket the 64 +/- 1 day in pregnancy and represent a genetically programmed luteal cell lifespan approximating gestation length as occurs in the luteal phase of hysterectomized animals of most polyoestrous artiodactyls and rodents. The 30-40-day slow

  13. Gestational Trophoblastic Disease: A Multimodality Imaging Approach with Impact on Diagnosis and Management

    Directory of Open Access Journals (Sweden)

    Sunita Dhanda

    2014-01-01

    Full Text Available Gestational trophoblastic disease is a condition of uncertain etiology, comprised of hydatiform mole (complete and partial, invasive mole, choriocarcinoma, and placental site trophoblastic tumor. It arises from abnormal proliferation of trophoblastic tissue. Early diagnosis of gestational trophoblastic disease and its potential complications is important for timely and successful management of the condition with preservation of fertility. Initial diagnosis is based on a multimodality approach: encompassing clinical features, serial quantitative β-hCG titers, and pelvic ultrasonography. Pelvic magnetic resonance imaging (MRI is sometimes used as a problem-solving tool to assess the depth of myometrial invasion and extrauterine disease spread in equivocal and complicated cases. Chest radiography, body computed tomography (CT, and brain MRI have been recommended as investigative tools for overall disease staging. Angiography has a role in management of disease complications and metastases. Efficacy of PET (positron emission tomography and PET/CT in the evaluation of recurrent or metastatic disease has not been adequately investigated yet. This paper discusses the imaging features of gestational trophoblastic disease on various imaging modalities and the role of different imaging techniques in the diagnosis and management of this entity.

  14. Quebec Trophoblastic Disease Registry: how to make an easy-to-use dynamic database.

    Science.gov (United States)

    Sauthier, Philippe; Breguet, Magali; Rozenholc, Alexandre; Sauthier, Michaël

    2015-05-01

    To create an easy-to-use dynamic database designed specifically for the Quebec Trophoblastic Disease Registry (RMTQ). It is now well established that much of the success in managing trophoblastic diseases comes from the development of national and regional reference centers. Computerized databases allow the optimal use of data stored in these centers. We have created an electronic data registration system by producing a database using FileMaker Pro 12. It uses 11 external tables associated with a unique identification number for each patient. Each table allows specific data to be recorded, incorporating demographics, diagnosis, automated staging, laboratory values, pathological diagnosis, and imaging parameters. From January 1, 2009, to December 31, 2013, we used our database to register 311 patients with 380 diseases and have seen a 39.2% increase in registrations each year between 2009 and 2012. This database allows the automatic generation of semilogarithmic curves, which take into account β-hCG values as a function of time, complete with graphic markers for applied treatments (chemotherapy, radiotherapy, or surgery). It generates a summary sheet for a synthetic vision in real time. We have created, at a low cost, an easy-to-use database specific to trophoblastic diseases that dynamically integrates staging and monitoring. We propose a 10-step procedure for a successful trophoblastic database. It improves patient care, research, and education on trophoblastic diseases in Quebec and leads to an opportunity for collaboration on a national Canadian registry.

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

    Science.gov (United States)

    Carter, Anthony M.; 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. In later stages of pregnancy, especially in Old World monkeys and apes, cytotrophoblast plays a greater role in the invasive process. Columns of trophoblast cells advance to the base of the implantation site where they spread out to form a cytotrophoblastic shell. In addition, cytotrophoblasts advance into the lumen of the spiral arteries. They are responsible for remodelling these vessels to form wide, low-resistance conduits. In human and great apes, there is additional invasion of the endometrium and its vessels by trophoblasts originating from the base of the anchoring villi. Deep trophoblast invasion that extends remodelling of the spiral arteries to segments in the inner myometrium evolved in the common ancestor of gorilla, chimp and human. PMID:25602074

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

    Science.gov (United States)

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

    2015-03-05

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

  17. Membrane Protected Apoptotic Trophoblast Microparticles Contain Nucleic Acids

    Science.gov (United States)

    Orozco, Aaron F.; Jorgez, Carolina J.; Horne, Cassandra; Marquez-Do, Deborah A.; Chapman, Matthew R.; Rodgers, John R.; Bischoff, Farideh Z.; Lewis, Dorothy E.

    2008-01-01

    Microparticles (MPs) that circulate in blood may be a source of DNA for molecular analyses, including prenatal genetic diagnoses. Because MPs are heterogeneous in nature, however, further characterization is important before use in clinical settings. One key question is whether DNA is either bound to aggregates of blood proteins and lipid micelles or intrinsically associated with MPs from dying cells. To test the latter hypothesis, we asked whether MPs derived in vitro from dying cells were similar to those in maternal plasma. JEG-3 cells model extravillous trophoblasts, which predominate during the first trimester of pregnancy when prenatal diagnosis is most relevant. MPs were derived from apoptosis and increased over 48 hours. Compared with necrotic MPs, DNA in apoptotic MPs was more fragmented and resistant to plasma DNases. Membrane-specific dyes indicated that apoptotic MPs had more membranous material, which protects nucleic acids, including RNA. Flow cytometry showed that MPs derived from dying cells displayed light scatter and DNA staining similar to MPs found in maternal plasma. Quantification of maternal MPs using characteristics defined by MPs generated in vitro revealed a significant increase of DNA+ MPs in the plasma of women with preeclampsia compared with plasma from women with normal pregnancies. Apoptotic MPs are therefore a likely source of stable DNA that could be enriched for both early genetic diagnosis and monitoring of pathological pregnancies. PMID:18974299

  18. Gestational trophoblastic neoplasia: efficacy of color doppler ultrasound

    International Nuclear Information System (INIS)

    Song, Sun Wha; Jee, Won Hee; Choe, Bo Young; Byun, Jae Young; Choi, Byung Gil; Shinn, Kyung Sub

    1997-01-01

    To evaluate the efficacy of color Doppler ultrasound (US) in the diagnosis of gestational trophoblastic neoplasia (GTN). Intralesional color flows and resistive index (RI) on color Doppler US were prospectively analyzed in 21 consecutive suspected GTN cases. RI of the intralesional artery was investigated on the basis of the presence or absence of mass and metastasis. Correlation between RI of intralesional artery and urinary β-hCG was also investigated. Intralesional color flows were identified in 15 patients with GTN. On operation, intralesional color flows were observed in one of two patients in whom the presence of completely necrotic tissue was confirmed. Intralesional color flows, however, were not detected in four patients who were proved not to be GTN sufferers. Sensitivity, specificity, accuracy, positive and negative predictive values, and accuracy were 100%, 83%, 95%, 94% and 100%, respectively. Significant correlation between RI of the intralesional artery and urinary β-hCG was not established (p=0.49, r=0.19). RI of this artery was not substantially different between groups with and without mass, and between groups with and without metastasis (p=0.32, p=0.82). The current study demonstrates that color Doppler US is a sensitive and useful method for the diagnosis of GTN

  19. Introduction: Training in reproductive endocrinology and infertility: meeting worldwide needs.

    Science.gov (United States)

    de Ziegler, Dominique; Meldrum, David R

    2015-07-01

    Training in reproductive endocrinology (REI) and its male variant, andrology, has been profoundly influenced by the central role captured by assisted reproductive technologies (ART). The marked differences in financial, regulatory, and societal/ethical restrictions on ART in different countries of the world also prominently influence the clinical management of infertility. Training should strive for comprehensive teaching of all medically indicated procedures, even if only to optimize cross-border care. Better international standardization of infertility practices and training would benefit worldwide infertility care and should be promoted by international societies. Copyright © 2015. Published by Elsevier Inc.

  20. The role of surgery in the management of gestational trophoblastic neoplasia.

    Science.gov (United States)

    Doll, Kemi M; Soper, John T

    2013-07-01

    Although sensitive human chorionic gonadotropin assays and advances in chemotherapy have assumed primary importance in the management of gestational trophoblastic neoplasia, surgery remains important in the overall care of these patients. Management of molar pregnancies consists of surgical evacuation and subsequent monitoring. Hysterectomy decreases the risk of post-molar trophoblastic disease in appropriate patients and, when incorporated to primary management of gestational trophoblastic neoplasia, can decrease the chemotherapy requirements of patients with low-risk disease. In patients with high-risk disease, surgical intervention is frequently required to control complications of disease or as therapy to stabilize patients during chemotherapy. Hysterectomy, thoracotomy, or other extirpative procedures may be integrated into the management of patients with chemorefractory disease. Interventional procedures are useful adjuncts to control bleeding from metastases.

  1. Rare diseases in clinical endocrinology: a taxonomic classification system.

    Science.gov (United States)

    Marcucci, G; Cianferotti, L; Beck-Peccoz, P; Capezzone, M; Cetani, F; Colao, A; Davì, M V; degli Uberti, E; Del Prato, S; Elisei, R; Faggiano, A; Ferone, D; Foresta, C; Fugazzola, L; Ghigo, E; Giacchetti, G; Giorgino, F; Lenzi, A; Malandrino, P; Mannelli, M; Marcocci, C; Masi, L; Pacini, F; Opocher, G; Radicioni, A; Tonacchera, M; Vigneri, R; Zatelli, M C; Brandi, M L

    2015-02-01

    Rare endocrine-metabolic diseases (REMD) represent an important area in the field of medicine and pharmacology. The rare diseases of interest to endocrinologists involve all fields of endocrinology, including rare diseases of the pituitary, thyroid and adrenal glands, paraganglia, ovary and testis, disorders of bone and mineral metabolism, energy and lipid metabolism, water metabolism, and syndromes with possible involvement of multiple endocrine glands, and neuroendocrine tumors. Taking advantage of the constitution of a study group on REMD within the Italian Society of Endocrinology, consisting of basic and clinical scientists, a document on the taxonomy of REMD has been produced. This document has been designed to include mainly REMD manifesting or persisting into adulthood. The taxonomy of REMD of the adult comprises a total of 166 main disorders, 338 including all variants and subtypes, described into 11 tables. This report provides a complete taxonomy to classify REMD of the adult. In the future, the creation of registries of rare endocrine diseases to collect data on cohorts of patients and the development of common and standardized diagnostic and therapeutic pathways for each rare endocrine disease is advisable. This will help planning and performing intervention studies in larger groups of patients to prove the efficacy, effectiveness, and safety of a specific treatment.

  2. [The and beginnings of Chilean endocrinology in the 1920s].

    Science.gov (United States)

    Sánchez Delgado, Marcelo

    2016-01-01

    Rejuvenation was a chapter of critical importance for the worldwide development of endocrinology in the 1920s. This work explores the acceptance of these techniques in Chile. Starting in the late 19th century, the Chilean Medical Journal (Revista Médica de Chile) incorporated references to experiments with endocrine gland preparations that were being conducted in Europe at the time. An appropriation of the experiments by the Austrian Eugen Steinach began in 1920, with prominent figures such as the Italian professor Juan Noe Crevani and the young Chilean student Ottmar Wilhelm. Between 1922 and 1924, Wilhelm developed a series of experiments on dogs, bulls, pigs, rats and Welfare Board patients through the so-called Steinach operation, which consisted of the sectioning of the efferent channel in one of the testicles. Professor Noe's scientific patronage policy and Wilhelm's strategy of succession in the field led the latter to hold a chair in the new School of Medicine of Universidad de Concepci6n at the age of 25. From this position, the. figure of Wilhelm was fundamental for the development of a line of endocrinological research that was able to position Universidad de Concepci6n as a scientific development centre, which was strengthened by the arrival of another disciple of Steinach in Chile, the Latvian professor Alejandro Lipschütz.

  3. [Potential role of the angiogenic factor "EG-VEGF" in gestational trophoblastic diseases].

    Science.gov (United States)

    Boufettal, H; Feige, J-J; Benharouga, M; Aboussaouira, T; Nadifi, S; Mahdaoui, S; Samouh, N; Alfaidy, N

    2013-10-01

    Gestational trophoblastic disease (MGT) includes a wide spectrum of pathologies of the placenta, ranging from benign precancerous lesions, with gestational trophoblastic tumors. Metastases are the leading causes of death as a result of this tumor. They represent a major problem for obstetrics and for the public health system. To date, there is no predictor of the progression of molar pregnancies to gestational trophoblastic tumor (GTT). Only an unfavorable plasma hCG monitoring after evacuation of hydatidiform mole is used to diagnose a TTG. The causes of the development of this cancer are still poorly understood. Increasing data in the literature suggests a close association between the development of this tumor and poor placental vascularization during the first trimester of pregnancy. The development of the human placenta depends on a coordination between the trophoblast and endothelial cells. A disruption in the expression of angiogenic factors could contribute to uterine or extra-uterine tissue invasion by extravillous trophoblast, contributing to the development of TTG. This review sheds lights on the phenomenon of angiogenesis during normal and abnormal placentation, especially during the MGT and reports preliminary finding concerning, the variability of expression of "Endocrine Gland-Derived Vascular Endothelial Growth Factor" (EG-VEGF), a specific placental angiogenic factor, in normal and molar placentas, and the potential role of differentiated expressions of the main placental angiogenic factors in the scalability of hydatidiform moles towards a recovery or towards the development of gestational trophoblastic tumor. Deciphering the mechanisms by which the angiogenic factor influences these processes will help understand the pathophysiology of MGT and to create opportunities for early diagnosis and treatment of the latter. Copyright © 2013 Elsevier Masson SAS. All rights reserved.

  4. Fifty-Five Years of Pediatric Endocrinology and 50 Years of the Department of Pediatric Endocrinology, Diabetes and Metabolic Diseases in Slovenia

    Science.gov (United States)

    BATTELINO, Tadej

    2015-01-01

    Paediatric endocrinology started its independent development early in the general development of this specialty, with a strong focus on research and clinical excellence. Slovenian paediatric endocrinology was an integral part of the European paediatric endocrinology from its beginnings and a founding member of the first ‘International Study Group for Diabetes in Children and Adolescents’. After the pioneering work of Prof. Lev Matajc, Prof. Ciril Kržišnik firmly integrated the Department of Pediatric Endocrinology, Diabetes and Metabolic Diseases at the University Children’s Hospital in Ljubljana in the international scientific community. In the last decade, the department participates in cutting-edge research and provides clinical services at highest international standards. PMID:27646909

  5. Advances in conservation endocrinology: the application of molecular approaches to the conservation of endangered species.

    Science.gov (United States)

    Tubbs, Christopher; McDonough, Caitlin E; Felton, Rachel; Milnes, Matthew R

    2014-07-01

    Among the numerous societal benefits of comparative endocrinology is the application of our collective knowledge of hormone signaling towards the conservation of threatened and endangered species - conservation endocrinology. For several decades endocrinologists have used longitudinal hormone profiles to monitor reproductive status in a multitude of species. Knowledge of reproductive status among individuals has been used to assist in the management of captive and free-ranging populations. More recently, researchers have begun utilizing molecular and cell-based techniques to gain a more complete understanding of hormone signaling in wildlife species, and to identify potential causes of disrupted hormone signaling. In this review we examine various in vitro approaches we have used to compare estrogen receptor binding and activation by endogenous hormones and phytoestrogens in two species of rhinoceros; southern white and greater one-horned. We have found many of these techniques valuable and practical in species where access to research subjects and/or tissues is limited due to their conservation status. From cell-free, competitive binding assays to full-length receptor activation assays; each technique has strengths and weaknesses related to cost, sensitivity, complexity of the protocols, and relevance to in vivo signaling. We then present a novel approach, in which receptor activation assays are performed in primary cell lines derived from the species of interest, to minimize the artifacts of traditional heterologous expression systems. Finally, we speculate on the promise of next generation sequencing and transcriptome profiling as tools for characterizing hormone signaling in threatened and endangered species. Copyright © 2014 Elsevier Inc. All rights reserved.

  6. Involvement of reactive oxygen species in brominated diphenyl ether-47-induced inflammatory cytokine release from human extravillous trophoblasts in vitro

    International Nuclear Information System (INIS)

    Park, Hae-Ryung; Kamau, Patricia W.; Loch-Caruso, Rita

    2014-01-01

    Polybrominated diphenyl ethers (PBDEs) are widely used flame retardant compounds. Brominated diphenyl ether (BDE)-47 is one of the most prevalent PBDE congeners found in human breast milk, serum and placenta. Despite the presence of PBDEs in human placenta, effects of PBDEs on placental cell function are poorly understood. The present study investigated BDE-47-induced reactive oxygen species (ROS) formation and its role in BDE-47-stimulated proinflammatory cytokine release in a first trimester human extravillous trophoblast cell line, HTR-8/SVneo. Exposure of HTR-8/SVneo cells for 4 h to 20 μM BDE-47 increased ROS generation 1.7 fold as measured by the dichlorofluorescein (DCF) assay. Likewise, superoxide anion production increased approximately 5 fold at 10 and 15 μM and 9 fold at 20 μM BDE-47 with a 1-h exposure, as measured by cytochrome c reduction. BDE-47 (10, 15 and 20 μM) decreased the mitochondrial membrane potential by 47–64.5% at 4, 8 and 24 h as assessed with the fluorescent probe Rh123. Treatment with 15 and 20 μM BDE-47 stimulated cellular release and mRNA expression of IL-6 and IL-8 after 12 and 24-h exposures: the greatest increases were a 35-fold increased mRNA expression at 12 h and a 12-fold increased protein concentration at 24 h for IL-6. Antioxidant treatments (deferoxamine mesylate, (±)α-tocopherol, or tempol) suppressed BDE-47-stimulated IL-6 release by 54.1%, 56.3% and 37.7%, respectively, implicating a role for ROS in the regulation of inflammatory pathways in HTR-8/SVneo cells. Solvent (DMSO) controls exhibited statistically significantly decreased responses compared with non-treated controls for IL-6 release and IL-8 mRNA expression, but these responses were not consistent across experiments and times. Nonetheless, it is possible that DMSO (used to dissolve BDE-47) may have attenuated the stimulatory actions of BDE-47 on cytokine responses. Because abnormal activation of proinflammatory responses can disrupt trophoblast functions

  7. Involvement of reactive oxygen species in brominated diphenyl ether-47-induced inflammatory cytokine release from human extravillous trophoblasts in vitro

    Energy Technology Data Exchange (ETDEWEB)

    Park, Hae-Ryung, E-mail: heaven@umich.edu; Kamau, Patricia W.; Loch-Caruso, Rita

    2014-01-15

    Polybrominated diphenyl ethers (PBDEs) are widely used flame retardant compounds. Brominated diphenyl ether (BDE)-47 is one of the most prevalent PBDE congeners found in human breast milk, serum and placenta. Despite the presence of PBDEs in human placenta, effects of PBDEs on placental cell function are poorly understood. The present study investigated BDE-47-induced reactive oxygen species (ROS) formation and its role in BDE-47-stimulated proinflammatory cytokine release in a first trimester human extravillous trophoblast cell line, HTR-8/SVneo. Exposure of HTR-8/SVneo cells for 4 h to 20 μM BDE-47 increased ROS generation 1.7 fold as measured by the dichlorofluorescein (DCF) assay. Likewise, superoxide anion production increased approximately 5 fold at 10 and 15 μM and 9 fold at 20 μM BDE-47 with a 1-h exposure, as measured by cytochrome c reduction. BDE-47 (10, 15 and 20 μM) decreased the mitochondrial membrane potential by 47–64.5% at 4, 8 and 24 h as assessed with the fluorescent probe Rh123. Treatment with 15 and 20 μM BDE-47 stimulated cellular release and mRNA expression of IL-6 and IL-8 after 12 and 24-h exposures: the greatest increases were a 35-fold increased mRNA expression at 12 h and a 12-fold increased protein concentration at 24 h for IL-6. Antioxidant treatments (deferoxamine mesylate, (±)α-tocopherol, or tempol) suppressed BDE-47-stimulated IL-6 release by 54.1%, 56.3% and 37.7%, respectively, implicating a role for ROS in the regulation of inflammatory pathways in HTR-8/SVneo cells. Solvent (DMSO) controls exhibited statistically significantly decreased responses compared with non-treated controls for IL-6 release and IL-8 mRNA expression, but these responses were not consistent across experiments and times. Nonetheless, it is possible that DMSO (used to dissolve BDE-47) may have attenuated the stimulatory actions of BDE-47 on cytokine responses. Because abnormal activation of proinflammatory responses can disrupt trophoblast functions

  8. An interactive E-Learning portal in pediatric endocrinology : Practical experience

    NARCIS (Netherlands)

    Kranenburg-van Koppen, L.J.C.; Grijpink-van den Biggelaar, K.; Drop, S.L.S.

    2013-01-01

    Based on educational considerations, the European Society for Paediatric Endocrinology (ESPE) e-learning portal has been developed, providing an interactive learning environment for up-to-date information in pediatric endocrinology. From March 2011 to January 2012, five small-scale pilot studies

  9. The future endocrine patient. Reflections on the future of clinical endocrinology

    NARCIS (Netherlands)

    Lamberts, S. W. J.; Romijn, J. A.; Wiersinga, W. M.

    2003-01-01

    In recent years the future position of clinical endocrinology has been extensively discussed by Western European endocrine societies. Clinical endocrinology seems to suffer from being too intellectual, generating too little income, and lacking too few spectacular interventions. In this manuscript we

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

    DEFF Research Database (Denmark)

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

    2011-01-01

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

  11. Postmolar gestational trophoblastic neoplasia: beyond the traditional risk factors.

    Science.gov (United States)

    Bakhtiyari, Mahmood; Mirzamoradi, Masoumeh; Kimyaiee, Parichehr; Aghaie, Abbas; Mansournia, Mohammd Ali; Ashrafi-Vand, Sepideh; Sarfjoo, Fatemeh Sadat

    2015-09-01

    To investigate the slope of linear regression of postevacuation serum hCG as an independent risk factor for postmolar gestational trophoblastic neoplasia (GTN). Multicenter retrospective cohort study. Academic referral health care centers. All subjects with confirmed hydatidiform mole and at least four measurements of β-hCG titer. None. Type and magnitude of the relationship between the slope of linear regression of β-hCG as a new risk factor and GTN using Bayesian logistic regression with penalized log-likelihood estimation. Among the high-risk and low-risk molar pregnancy cases, 11 (18.6%) and 19 cases (13.3%) had GTN, respectively. No significant relationship was found between the components of a high-risk pregnancy and GTN. The β-hCG return slope was higher in the spontaneous cure group. However, the initial level of this hormone in the first measurement was higher in the GTN group compared with in the spontaneous recovery group. The average time for diagnosing GTN in the high-risk molar pregnancy group was 2 weeks less than that of the low-risk molar pregnancy group. In addition to slope of linear regression of β-hCG (odds ratio [OR], 12.74, confidence interval [CI], 5.42-29.2), abortion history (OR, 2.53; 95% CI, 1.27-5.04) and large uterine height for gestational age (OR, 1.26; CI, 1.04-1.54) had the maximum effects on GTN outcome, respectively. The slope of linear regression of β-hCG was introduced as an independent risk factor, which could be used for clinical decision making based on records of β-hCG titer and subsequent prevention program. Copyright © 2015 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.

  12. Interleukin-1β inhibits insulin signaling and prevents insulin-stimulated system A amino acid transport in primary human trophoblasts.

    Science.gov (United States)

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

    2013-12-05

    Interleukin-1β (IL-1β) promotes insulin resistance in tissues such as liver and skeletal muscle; however the influence of IL-1β on placental insulin signaling is unknown. We recently reported increased IL-1β protein expression in placentas of obese mothers, which could contribute to insulin resistance. In this study, we tested the hypothesis that IL-1β inhibits insulin signaling and prevents insulin-stimulated amino acid transport in cultured primary human trophoblast (PHT) cells. Cultured trophoblasts isolated from term placentas were treated with physiological concentrations of IL-1β (10pg/ml) for 24h. IL-1β increased the phosphorylation of insulin receptor substrate-1 (IRS-1) at Ser307 (inhibitory) and decreased total IRS-1 protein abundance but did not affect insulin receptor β expression. Furthermore, IL-1β inhibited insulin-stimulated phosphorylation of IRS-1 (Tyr612, activation site) and Akt (Thr308) and prevented insulin-stimulated increase in PI3K/p85 and Grb2 protein expression. IL-1β alone stimulated cRaf (Ser338), MEK (Ser221) and Erk1/2 (Thr202/Tyr204) phosphorylation. The inflammatory pathways nuclear factor kappa B and c-Jun N-terminal kinase, which are involved in insulin resistance, were also activated by IL-1β treatment. Moreover, IL-1β inhibited insulin-stimulated System A, but not System L amino acid uptake, indicating functional impairment of insulin signaling. In conclusion, IL-1β inhibited the insulin signaling pathway by inhibiting IRS-1 signaling and prevented insulin-stimulated System A transport, thereby promoting insulin resistance in cultured PHT cells. These findings indicate that conditions which lead to increased systemic maternal or placental IL-1β levels may attenuate the effects of maternal insulin on placental function and consequently fetal growth. Published by Elsevier Ireland Ltd.

  13. [Endocrinology in Portugal - Census 2016. Board of the Portuguese College of Endocrinology and Nutrition of the Portuguese Medical Association].

    Science.gov (United States)

    Guimarães, Joana; Afonso, António; Carvalho, Davide; Marques, Ana Paula; Martins, Teresa; Mascarenhas, Mário Rui; Pereira, Conceição; Rodrigues, Dírcea; Saraiva, Catarina; Cardoso, Helena

    2017-09-29

    On September 2016, the Board of the College of Endocrinology and Nutrition of the Portuguese Medical Association carried out a national survey, about all Endocrinology, Diabetes and Metabolism Departments of the public hospitals included in the Portuguese National Health Service and a simplified version of this survey was sent to all endocrinologists working in Portugal and registered with the Portuguese Medical Association. Data related to organizational and human resources were collected, reporting the situation by the end of year 2015. The census registered 107 individuals and 27 Departments. The ratio of endocrinologists-population was 1.4, much lower than in the other European countries (varies between 2 to 4), resulting in alarming shortages of services in some areas of Portugal and in worse quality indicators. These data suggest that actions should be taken to increase the number of endocrinologists and departments in the country. In recent years, the number of residents has significantly increased, which will make it possible to correct this situation.

  14. Management of prediabetes: a comparison of the treatment approaches utilized by a family practice clinic and an internal medicine/endocrinology practice.

    Science.gov (United States)

    Anderson, Zachary L; Scopelliti, Emily M; Trompeter, Jessica M; Havrda, Dawn E

    2015-02-01

    To compare the management of prediabetes between a family practice clinic and internal medicine/endocrinology practice. A randomized, retrospective evaluation of the medical history in 168 eligible patients with a diagnosis of prediabetes or abnormal blood glucose (BG) at a family practice clinic (n = 78) and an internal medicine/endocrinology practice (n = 90). The internal medicine/endocrinology practice provided more counseling regarding lifestyle modifications (91.1% vs 76.9%, P = .039), specific physical activity recommendations (26.7% vs 7.7%, P = .003), and recommended more patients receive 150 minutes/week of moderate exercise (8.9% vs 1.3%, P = .038). The family practice clinic provided more written dietary information (16.9% vs 13.3%, P = .044) and specific weight loss goals (20.5% vs 6.7%, P = .015). The internal medicine/endocrinology practice initiated pharmacological therapy in more patients (51.1% vs 3.8%, P< .001) and had a significant decrease in fasting BG from baseline compared to the family practice clinic (-9.0 vs -5.6 mg/dL, P< .001). Providers are likely to initiate nonpharmacological therapy but may not provide specific education recommended by the American Diabetes Association. The integration of a multidisciplinary team to provide guideline-based nonpharmacologic counseling may be beneficial in improving outcomes in the management of prediabetes. © The Author(s) 2013.

  15. Shared decision making in endocrinology: present and future directions.

    Science.gov (United States)

    Rodriguez-Gutierrez, Rene; Gionfriddo, Michael R; Ospina, Naykky Singh; Maraka, Spyridoula; Tamhane, Shrikant; Montori, Victor M; Brito, Juan P

    2016-08-01

    In medicine and endocrinology, there are few clinical circumstances in which clinicians can accurately predict what is best for their patients. As a result, patients and clinicians frequently have to make decisions about which there is uncertainty. Uncertainty results from limitations in the research evidence, unclear patient preferences, or an inability to predict how treatments will fit into patients' daily lives. The work that patients and clinicians do together to address the patient's situation and engage in a deliberative dialogue about reasonable treatment options is often called shared decision making. Decision aids are evidence-based tools that facilitate this process. Shared decision making is a patient-centred approach in which clinicians share information about the benefits, harms, and burden of different reasonable diagnostic and treatment options, and patients explain what matters to them in view of their particular values, preferences, and personal context. Beyond the ethical argument in support of this approach, decision aids have been shown to improve patients' knowledge about the available options, accuracy of risk estimates, and decisional comfort. Decision aids also promote patient participation in the decision-making process. Despite accumulating evidence from clinical trials, policy support, and expert recommendations in endocrinology practice guidelines, shared decision making is still not routinely implemented in endocrine practice. Additional work is needed to enrich the number of available tools and to implement them in practice workflows. Also, although the evidence from randomised controlled trials favours the use of this shared decision making in other settings, populations, and illnesses, the effect of this approach has been studied in a few endocrine disorders. Future pragmatic trials are needed to explore the effect and feasibility of shared decision making implementation into routine endocrinology and primary care practice. With the

  16. Freqüência e atividade enzimática de Candida spp. na cavidade oral de pacientes diabéticos do serviço de endocrinologia de um hospital de Fortaleza-CE Frequency and enzymatic activity of Candida spp. oral cavity of diabetic patients of the service of endocrinology of a hospital of Fortaleza-CE

    Directory of Open Access Journals (Sweden)

    Everardo Albuquerque Menezes

    2007-08-01

    identified (Candida tropicalis, Candida guillermondii, Candida glabrata, Candida krusei. The objective of this work was to evaluate frequency and enzymatic activity of Candida spp. in the oral cavity of diabetic patients taken care in the service of endocrinology of the University Hospital Walter Cantídio of the Federal University of the Ceará. Samples had been collected of 48 diabetic patients, men and women, with various situations of glicemic control. Clinical materials had been collected with aid of swab and harvested in plates of Petri contend Sabouraud agar dextrose with cloranfenicol and incubated to 37°C. The grown were identified by the used classic tests in mycology. In the following, these Candida strains were submitted to tests to detect phospholipase and proteinase enzymes. Of these, 15 samples (31,35% presented positive culture for the genera Candida. The species more frequent was C. albicans with 80%, followed by C. tropicalis (13.3% and C. guilliermondii (6.7%. Asfor the research on the enzymatic activity of Candida sp. it was observed that 86.6% presented activity of proteinase and 80% of phospholipase. It was concluded with these results that C. albicans is more frequent and that Candida spp. isolated species have strong enzymatic activity.

  17. IFPA Meeting 2010 Workshops Report II: Placental pathology; trophoblast invasion; fetal sex; parasites and the placenta; decidua and embryonic or fetal loss; trophoblast differentiation and syncytialisation.

    Science.gov (United States)

    Al-Khan, A; Aye, I L; Barsoum, I; Borbely, A; Cebral, E; Cerchi, G; Clifton, V L; Collins, S; Cotechini, T; Davey, A; Flores-Martin, J; Fournier, T; Franchi, A M; Fretes, R E; Graham, C H; Godbole, G; Hansson, S R; Headley, P L; Ibarra, C; Jawerbaum, A; Kemmerling, U; Kudo, Y; Lala, P K; Lassance, L; Lewis, R M; Menkhorst, E; Morris, C; Nobuzane, T; Ramos, G; Rote, N; Saffery, R; Salafia, C; Sarr, D; Schneider, H; Sibley, C; Singh, A T; Sivasubramaniyam, T S; Soares, M J; Vaughan, O; Zamudio, S; Lash, G E

    2011-03-01

    Workshops are an important part of the IFPA annual meeting. At IFPA Meeting 2010 diverse topics were discussed in twelve themed workshops, six of which are summarized in this report. 1. The placental pathology workshop focused on clinical correlates of placenta accreta/percreta. 2. Mechanisms of regulation of trophoblast invasion and spiral artery remodeling were discussed in the trophoblast invasion workshop. 3. The fetal sex and intrauterine stress workshop explored recent work on placental sex differences and discussed them in the context of whether boys live dangerously in the womb.4. The workshop on parasites addressed inflammatory responses as a sign of interaction between placental tissue and parasites. 5. The decidua and embryonic/fetal loss workshop focused on key regulatory mediators in the decidua, embryo and fetus and how alterations in expression may contribute to different diseases and adverse conditions of pregnancy. 6. The trophoblast differentiation and syncytialisation workshop addressed the regulation of villous cytotrophoblast differentiation and how variations may lead to placental dysfunction and pregnancy complications. Copyright © 2011 Elsevier Ltd. All rights reserved.

  18. Endocrinology of human female sexuality, mating, and reproductive behavior.

    Science.gov (United States)

    Motta-Mena, Natalie V; Puts, David A

    2017-05-01

    Hormones orchestrate and coordinate human female sexual development, sexuality, and reproduction in relation to three types of phenotypic changes: life history transitions such as puberty and childbirth, responses to contextual factors such as caloric intake and stress, and cyclical patterns such as the ovulatory cycle. Here, we review the endocrinology underlying women's reproductive phenotypes, including sexual orientation and gender identity, mate preferences, competition for mates, sex drive, and maternal behavior. We highlight distinctive aspects of women's sexuality such as the possession of sexual ornaments, relatively cryptic fertile windows, extended sexual behavior across the ovulatory cycle, and a period of midlife reproductive senescence-and we focus on how hormonal mechanisms were shaped by selection to produce adaptive outcomes. We conclude with suggestions for future research to elucidate how hormonal mechanisms subserve women's reproductive phenotypes. Copyright © 2016 Elsevier Inc. All rights reserved.

  19. Routine and new techniques in nuclearmedicine and endocrinology

    Energy Technology Data Exchange (ETDEWEB)

    Galvan, G [Landeskrankenanstalten Salzburg (Austria). Inst. fuer Nuklear medizin und Endokrinologie

    1980-10-15

    Nuclear medicine: Scintiscanning of the kidneys and the renal clearance of radionuclides give us separate information about the function of each kidney. Scintiscanning of the lungs has become very important for the diagnosis of embolisms. Scintiscanning is also an important method for the diagnosis of skeletal diseases (inflamation of neoplasms, especially metastases) or for the diagnosis of introhepatic neoplasms. New nuclear methods evaluating dynamic processes in the cardiovascular system will become of clinical relevance. Endocrinology: A number of radioimmunoassays (especially of thyroxine, triiodthyronine, TSH, ACTH, cortisol, androgeus, estrogeus, progesterone, LH, FSH and prolaction) the isolation and synthesis of hypothalamic releasing hormones, scintiscanning of the thyreoid and the adrenal glands and computed tomography give us information about the endocrine system. In particular, the new radioimmunoassay of prolactin has taught us new aspects of the function of this hormone and the etiology of hyperprolactinemia.

  20. European Society of Endocrinology Clinical Guideline: Treatment of chronic hypoparathyroidism in adults.

    Science.gov (United States)

    Bollerslev, Jens; Rejnmark, Lars; Marcocci, Claudio; Shoback, Dolores M; Sitges-Serra, Antonio; van Biesen, Wim; Dekkers, Olaf M

    2015-08-01

    Hypoparathyroidism (HypoPT) is a rare (orphan) endocrine disease with low calcium and inappropriately low (insufficient) circulating parathyroid hormone levels, most often in adults secondary to thyroid surgery. Standard treatment is activated vitamin D analogues and calcium supplementation and not replacement of the lacking hormone, as in other hormonal deficiency states. The purpose of this guideline is to provide clinicians with guidance on the treatment and monitoring of chronic HypoPT in adults who do not have end-stage renal disease. We intend to draft a practical guideline, focusing on operationalized recommendations deemed to be useful in the daily management of patients. This guideline was developed and solely sponsored by The European Society of Endocrinology, supported by CBO (Dutch Institute for Health Care Improvement) and based on the Grading of Recommendations Assessment, Development and Evaluation (GRADE) principles as a methodological base. The clinical question on which the systematic literature search was based and for which available evidence was synthesized was: what is the best treatment for adult patients with chronic HypoPT? This systematic search found 1100 articles, which was reduced to 312 based on title and abstract. The working group assessed these for eligibility in more detail, and 32 full-text articles were assessed. For the final recommendations, other literature was also taken into account. Little evidence is available on how best to treat HypoPT. Data on quality of life and the risk of complications have just started to emerge, and clinical trials on how to optimize therapy are essentially non-existent. Most studies are of limited sample size, hampering firm conclusions. No studies are available relating target calcium levels with clinically relevant endpoints. Hence it is not possible to formulate recommendations based on strict evidence. This guideline is therefore mainly based on how patients are managed in clinical practice

  1. Inhibiting trophoblast PAR-1 overexpression suppresses sFlt-1-induced anti-angiogenesis and abnormal vascular remodeling: a possible therapeutic approach for preeclampsia.

    Science.gov (United States)

    Zhao, Yin; Zheng, YanFang; Liu, XiaoXia; Luo, QingQing; Wu, Di; Liu, XiaoPing; Zou, Li

    2018-03-01

    Is it possible to improve vascular remodeling by inhibiting the excessive expression of protease-activated receptor 1 (PAR-1) in trophoblast of abnormal placenta? Inhibition of trophoblast PAR-1 overexpression may promote placental angiogenesis and vascular remodeling, offering an alternative therapeutic approach for preeclampsia. PAR-1 is high-affinity receptor of thrombin. Thrombin increases sFlt-1 secretion in trophoblast via the activation of PAR-1. It is reported that the expression of both thrombin and PAR-1 expression are increased in placentas of preeclampsia patients compared with normal placentas. Trophoblast cells were transfected with PAR-1 short hairpin RNA (shRNA) or PAR-1 overexpression plasmids in vitro. Tube formation assays and a villus-decidua co-culture system were used to study the effect of PAR-1 inhibition on placental angiogenesis and vascular remodeling, respectively. Placentas from rats with preeclampsia were transfected with PAR-1 shRNA to confirm the effect of inhibiting PAR-1 overexpression in placenta. The trophoblast cell line HTR-8/SVneo was transfected with PAR-1 shRNA or PAR-1 overexpression plasmids. After 48 h, supernatant was collected and the level of sFlt-1 secretion was measured by ELISA. Human umbilical cord epithelial cells and a villus-decidua co-culture system were treated with conditioned media to study the effect of PAR-1 inhibition on tube formation and villi vascular remodeling. A preeclampsia rat model was established by intraperitoneal injection of L-NAME. Plasmids were injected into the placenta of the preeclampsia rats and systolic blood pressure was measured on Days 15 and 19. The effect of different treatments was evaluated by proteinuria, placental weights, fetal weights and fetal numbers in study and control groups. The level of serum sFlt-1 in rats with preeclampsia was also measured. Changes in the placenta microvessels were studied by histopathological staining. PAR-1 shRNA inhibited PAR-1 expression and

  2. 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.

  3. Lack of a Y-Chromosomal Complement in the Majority of Gestational Trophoblastic Neoplasms

    Directory of Open Access Journals (Sweden)

    Kai Lee Yap

    2010-01-01

    Full Text Available Gestational trophoblastic neoplasms (GTNs are a rare group of neoplastic diseases composed of choriocarcinomas, placental site trophoblastic tumors (PSTTs and epithelioid trophoblastic tumors (ETTs. Since these tumors are derivatives of fetal trophoblastic tissue, approximately 50% of GTN cases are expected to originate from a male conceptus and carry a Y-chromosomal complement according to a balanced sex ratio. To investigate this hypothesis, we carried out a comprehensive analysis by genotyping a relatively large sample size of 51 GTN cases using three independent sex chromosome genetic markers; Amelogenin, Protein Kinase and Zinc Finger have X and Y homologues that are distinguishable by their PCR product size. We found that all cases contained the X-chromosomal complement while only five (10% of 51 tumors harbored the Y-chromosomal complement. Specifically, Y-chromosomal signals were detected in one (5% of 19 choriocarcinomas, one (7% of 15 PSTTs and three (18% of 17 ETTs. The histopathological features of those with a Y-chromosome were similar to those without. Our results demonstrate the presence of a Y-chromosomal complement in GTNs, albeit a low 10% of cases. This shortfall of Y-chromosomal complements in GTNs may reinforce the notion that the majority of GTNs are derived from previous molar gestations.

  4. The curative effect of a second curettage in persistent trophoblastic disease: a retrospective cohort survey.

    NARCIS (Netherlands)

    Trommel, N.E. van; Massuger, L.F.A.G.; Verheijen, R.; Sweep, C.G.J.; Thomas, C.M.G.

    2005-01-01

    OBJECTIVE: To assess the curative effect of a second curettage in patients with low-risk Persistent Trophoblastic Disease (PTD) after molar pregnancy. METHODS: A retrospective cohort survey was performed on 2122 patients registered with the Dutch Central Registry for Hydatidiform Moles between 1987

  5. Pre-evacuation hCG glycoforms in uneventful complete hydatidiform mole and persistent trophoblastic disease.

    NARCIS (Netherlands)

    Thomas, C.M.G.; Kerkmeijer, L.G.W.; Ariaens, H.J.; Steen, R. van der; Massuger, L.F.A.G.; Sweep, F.C.

    2010-01-01

    OBJECTIVE: To investigate whether the glycoform distribution patterns of human chorionic gonadotropin (hCG) obtained by chromatofocusing in pre-evacuation serum are different for patients who will eventually develop into persistent trophoblastic disease in case of complete hydatidiform mole

  6. Imaging and Clinical Data of Placental Site Trophoblastic Tumor: A Case Report

    International Nuclear Information System (INIS)

    Niknejadi, Maryam; Ahmadi, Firoozeh; Akhbari, Farnaz

    2016-01-01

    Placental site trophoblastic tumor (PSTT) is a very rare variant of gestational trophoblastic tumor. It can occur after normal termination of pregnancy or spontaneous abortion and ectopic or molar pregnancy. There is a wide range of clinical manifestations from a benign condition to an aggressive disease with fatal outcome. One of the most important characteristics of PSTT, unlike other forms of gestational trophoblastic diseases (GTD) is the presence of low beta-subunit of human chorionic gonadotropin (β-hCG) levels because it is a neoplastic proliferation of intermediate trophoblastic cells. However, human placental lactogen (hPL) is increased on histologic section and in the serum of patients too. We present a case of PSTT and discuss the differential diagnosis in order to further familiarize physicians with the diagnosis and treatment of this disease. It has a varied clinical spectrum and usually presents with irregular vaginal bleeding or amenorrhea. Diagnosis is confirmed by dilatation and curettage (D and C) and hysterectomy. Because chemotherapy is not effective, surgery is the cornerstone of treatment. This case is presented because it is a rare neoplasm with different treatments and it should be differentiated from molar pregnancy

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

    DEFF Research Database (Denmark)

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

    2011-01-01

    In contrast to baboon or rhesus macaque, trophoblast invasion in the human placental bed occurs by the interstitial as well as the endovascular route and reaches as deep as the inner myometrium. We here describe two rare specimens of gorilla placenta. In the light of recent findings in the chimpa......In contrast to baboon or rhesus macaque, trophoblast invasion in the human placental bed occurs by the interstitial as well as the endovascular route and reaches as deep as the inner myometrium. We here describe two rare specimens of gorilla placenta. In the light of recent findings...... in the chimpanzee, we postulated the occurrence of deep invasion in gorilla pregnancy. Tissues were processed for histology (PAS, orcein), lectin staining (Ulex europaeus agglutinin 1) and immunohistochemistry (cytokeratin 7/17, α-actin). A specimen of young but undetermined gestational age included deep placental...... no definite conclusions about the origin of the intramural trophoblast and the time-course of spiral artery invasion. A different late second trimester placenta specimen showed scattered extravillous trophoblast in the basal plate and underlying decidua, as well as a remodelled spiral artery containing...

  8. Oxygen concentration modulates cellular senescence and autophagy in human trophoblast cells.

    Science.gov (United States)

    Seno, Kotomi; Tanikawa, Nao; Takahashi, Hironori; Ohkuchi, Akihide; Suzuki, Hirotada; Matsubara, Shigeki; Iwata, Hisataka; Kuwayama, Takehito; Shirasuna, Koumei

    2018-02-15

    We investigated the effect of oxygen concentrations on cellular senescence and autophagy and examined the role of autophagy in human trophoblast cells. Human first-trimester trophoblast cells (Sw.71) were incubated under 21%, 5%, or 1% O 2 concentrations for 24 hours. We examined the extent of senescence caused using senescence-associated β-galactosidase (SA-β-Gal) and senescence-associated secretory phenotype (SASP) as markers. Moreover, we examined the role of autophagy in causing cellular senescence using an autophagy inhibitor (3-methyladenine, 3MA). Physiological normoxia (5% O 2 ) decreased SA-β-Gal-positive cells and SASP including interleukin-6 (IL-6) and IL-8 compared with cultured cells in 21% O 2 . Pathophysiological hypoxia (1% O 2 ) caused cytotoxicity, including extracellular release of ATP and lactate dehydrogenase, and decreased senescence phenotypes. 3MA-treated trophoblast cells significantly suppressed senescence markers (SA-β-Gal-positive cells and SASP secretion) in O 2 -independent manner. We conclude that O 2 concentration modulates cellular senescence phenotypes regulating autophagy in the human trophoblast cells. Moreover, inhibiting autophagy suppresses cellular senescence, suggesting that autophagy contributes to oxygen stress-induced cellular senescence. © 2018 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  9. Application of monoclonal antibodies against trophoblastic cells to study female infertility

    Czech Academy of Sciences Publication Activity Database

    Sedláková, Alena; Elzeinová, Fatima; Bukovský, A.; Madar, J.; Ulčová-Gallová, Z.; Pěknicová, Jana

    2004-01-01

    Roč. 51, č. 6 (2004), s. 482-483 ISSN 1046-7408. [European congress of reproductive immunology. Plzeň, 30.06.2004-03.07.2004] R&D Projects: GA MŠk LN00B030 Keywords : trophoblast * monoclonal antibody * ELISA Subject RIV: EC - Immunology Impact factor: 1.808, year: 2004

  10. The ubiquitin ligase ASB4 promotes trophoblast differentiation through the degradation of ID2.

    Directory of Open Access Journals (Sweden)

    W H Davin Townley-Tilson

    Full Text Available Vascularization of the placenta is a critical developmental process that ensures fetal viability. Although the vascular health of the placenta affects both maternal and fetal well being, relatively little is known about the early stages of placental vascular development. The ubiquitin ligase Ankyrin repeat, SOCS box-containing 4 (ASB4 promotes embryonic stem cell differentiation to vascular lineages and is highly expressed early in placental development. The transcriptional regulator Inhibitor of DNA binding 2 (ID2 negatively regulates vascular differentiation during development and is a target of many ubiquitin ligases. Due to their overlapping spatiotemporal expression pattern in the placenta and contrasting effects on vascular differentiation, we investigated whether ASB4 regulates ID2 through its ligase activity in the placenta and whether this activity mediates vascular differentiation. In mouse placentas, ASB4 expression is restricted to a subset of cells that express both stem cell and endothelial markers. Placentas that lack Asb4 display immature vascular patterning and retain expression of placental progenitor markers, including ID2 expression. Using JAR placental cells, we determined that ASB4 ubiquitinates and represses ID2 expression in a proteasome-dependent fashion. Expression of ASB4 in JAR cells and primary isolated trophoblast stem cells promotes the expression of differentiation markers. In functional endothelial co-culture assays, JAR cells ectopically expressing ASB4 increased endothelial cell turnover and stabilized endothelial tube formation, both of which are hallmarks of vascular differentiation within the placenta. Co-transfection of a degradation-resistant Id2 mutant with Asb4 inhibits both differentiation and functional responses. Lastly, deletion of Asb4 in mice induces a pathology that phenocopies human pre-eclampsia, including hypertension and proteinuria in late-stage pregnant females. These results indicate that

  11. Downregulation of miR-29a/b/c in placenta accreta inhibits apoptosis of implantation site intermediate trophoblast cells by targeting MCL1.

    Science.gov (United States)

    Gu, Yongzhong; Bian, Yuehong; Xu, Xiaofei; Wang, Xietong; Zuo, Changting; Meng, Jinlai; Li, Hongyan; Zhao, Shigang; Ning, Yunnan; Cao, Yongzhi; Huang, Tao; Yan, Junhao; Chen, Zi-Jiang

    2016-12-01

    Placenta accreta is defined as abnormal adhesion of placental villi to the uterine myometrium. Although this condition has become more common as a result of the increasing rate of cesarean sections, the underlying causative mechanism(s) remain elusive. Because microRNA-29a/b/c (miR-29a/b/c) have been shown to play important roles in placental development, this study evaluated the roles of these microRNAs in placenta accreta. Expression of miR-29a/b/c and myeloid cell leukemia-1 (MCL1) were quantified in patient tissues and HTR8/SVneo trophoblast cells using the real-time quantitative polymerase chain reaction. Western blotting was used to analyze expression of the MCL1 protein in HTR8/SVneo trophoblast cells with altered expression of miR-29a/b/c. To determine their role in apoptosis, miR-29a/b/c were overexpressed in HTR-8/SVneo cells, and levels of apoptosis were analyzed by flow cytometry. Luciferase activity assays were used to determine whether MCL1 is a target gene of miR-29a/b/c. Expression of miR-29a/b/c was significantly lower in creta sites compared to noncreta sites (p = 0.018, 0.041, and 0.022, respectively), but expression of MCL1 was upregulated in creta sites (p = 0.039). MCL1 expression was significantly downregulated in HTR-8/SVneo cells overexpressing miR-29a/b/c (p = 0.002, 0.008, and 0.013, respectively). Luciferase activity assays revealed that miR-29a/b/c directly target the 3' untranslated region of MCL1 in 293T cells. Over-expression of miR-29a/b/c induced apoptosis in the HTR-8/SVneo trophoblast cell line. Moreover, histopathological evaluation revealed that the number of implantation site intermediate trophoblast (ISIT) cells was increased in creta sites and that these cells were positive for MCL1. Our results demonstrate that in placenta accreta, miR-29a/b/c inhibits apoptosis of ISIT cells by targeting MCL1. These findings provide new insights into the pathogenesis of placenta accreta. Copyright © 2016 Elsevier Ltd. All rights

  12. Indomethacin inhibits the uptake of 22sodium by ovine trophoblastic tissue in vitro

    International Nuclear Information System (INIS)

    Lewis, G.S.

    1986-01-01

    Blastocysts from several species synthesize prostaglandins in vitro, but the exact functions of the prostaglandins are unknown. The purpose of this study was to determine if indomethacin, an inhibitor of prostaglandin synthesis, would inhibit the uptake of 22sodium ([22Na]) by ovine trophoblastic tissue. To determine the concentration of indomethacin that would inhibit the synthesis of PGF2 alpha and 13,14-dihydro-15-keto-PGF2 alpha (PGFM) by blastocysts, blastocysts were collected from ewes 16 days after mating, sliced into pieces approximately 2 mm in length and incubated for 48 h at 37 degrees C in 2 ml of medium containing either 0, 0.2, 0.4, 0.8 or 1.6 mM of indomethacin. Concentrations of indomethacin greater than or equal to 0.2 mM reduced (P less than .01) trophoblastic release (ng/micrograms DNA) of PGF2 alpha from 205 +/- 71.2 to less than or equal to 3.3 +/- 0.2, reduced PGFM from 0.7 +/- 0.1 to less than or equal to 0.17 +/- 0.01, and inhibited formation of trophoblastic vesicles. In a second experiment, blastocysts were recovered from ewes 16 days after mating and pieces of trophoblast were incubated with [22Na] and either 0 or 0.4 mM of indomethacin. Indomethacin reduced the uptake of [22Na], which is an indirect measure of the transport of water across epithelia, from 3680 +/- 1118 to 934 +/- 248 cpm/micrograms DNA (P less than .03) and prevented formation of trophoblastic vesicles. Prostaglandins produced by ovine blastocysts might be involved in controlling uptake of water, which is essential for expansion of blastocysts

  13. Current situation of hospital-based endocrinology and clinical nutrition in Spain.

    Science.gov (United States)

    Angeles Gálvez Moreno, M

    2008-01-01

    In 2006, the Healthcare Commission of Spanish Society of Endocrinology and Nutrition did a survey in order to know the actual situation of endocrinology and clinical nutrition healthcare in Public Sanitary Systems in Spain. The survey has been more extensive than the last and it has taken up number and geographical distribution of specialists in Spain in addition to data about clinical assistance. The mean of public hospitals with endocrinologist participation has been 50%. Copyright © 2008 Sociedad Española de Endocrinología y Nutrición. Published by Elsevier Espana. All rights reserved.

  14. Effects of phytoestrogens genistein and daidzein on progesterone and estrogen (estradiol) production of human term trophoblast cells in vitro.

    Science.gov (United States)

    Richter, Dagmar Ulrike; Mylonas, Ioannis; Toth, Bettina; Scholz, Christoph; Briese, Volker; Friese, Klaus; Jeschke, Udo

    2009-01-01

    Phytoestrogens are a diverse group of nonsteroidal plant compounds that occur naturally in many plants. Because they possess a ring system similar to estrogens they are able to bind on estrogen receptors alpha and beta in humans. The effects of the phytoestrogens genistein and daidzein on the production of progesterone and estrogen in isolated human term trophoblast cells in vitro were tested in this study. Cytotrophoblast cells were isolated from human term placentas. Phytoestrogens genistein and daidzein were incubated in different concentrations with trophoblast cells. Untreated cells were used as controls. After 24 h aliquots were removed and tested for progesterone and estrogen production. The production of the steroid hormones progesterone and estrogen are influenced by phytoestrogens genistein and daidzein in human term trophoblast cells. A strong inhibition effect of both phytoestrogens tested in the production of progesterone was demonstrated. In addition, a significant stimulating effect on estrogen production by genistein and daidzein was observed. Results obtained with this study show that phytoestrogens (genistein and daidzein) sufficiently reduce progesterone production in human term trophoblast cells. Because blockade of progesterone is a possible mechanism involved in initiation of labor, we may speculate that high doses of phytoestrogens at the feto-maternal interphase could play a negative role in maintenance of pregnancy. Stimulation of estrogen production by genistein and daidzein in trophoblast cells is probably due to estrogen receptor blocking effects of both phytoestrogens. Trophoblast cells seem to compensate blocking of its estrogen receptors by higher estrogen production.

  15. Multiple steroid radioimmunoassays and automation. Versatile techniques for reproductive endocrinology

    International Nuclear Information System (INIS)

    Vihko, R.; Hammond, G.L.; Pakarinen, A.; Viinikka, L.

    1978-01-01

    The combination of the efficient steroid-separating properties of a lipophilic Sephadex derivative Lipidex-5000sup(TM) and the use of antibodies with carefully selected specificity allows the quantitative determination of pregnenolone, progesterone, 17α-hydroxyprogesterone, androstenedione, testosterone, 5α-dihydrotestosterone, 5α-androstanedione, androsterone and 5α-androstane-3α, 17β-diol in 1- to 2-ml samples of both blood serum and amniotic fluid as well as in 300- to 600-mg pieces of prostatic tissue. The adaptation of the pipetting unit and incubator of a discrete clinical chemical analyser, System Olli 3000, for the automation of the radioimmunoassays has resulted in a greatly increased through-put and has decreased the experimental error of the procedure. In studies on reproductive endocrinology, the methodology developed has allowed the detection of a sex difference in androgen composition of the amniotic fluid early in pregnancy. Further, it is very likely that the decline in steroid production by the testis seen during the first year of life and then in senescence is affected by basically different mechanisms. There are also important differences in the steroid content of normal, hyperplastic and carcinomatous prostate. (author)

  16. Multiple steroid radioimmunoassays and automation: versatile techniques for reproductive endocrinology

    International Nuclear Information System (INIS)

    Vihko, R.; Hammond, G.L.; Pakarinen, A.; Viinikka, L.

    1977-01-01

    The combination of the efficient steroid separating properties of a lipophilic Sephadex derivative Lipidex-5000sup(TM), with the use of antibodies with carefully selected specificity allows the quantitative determination of pregnenolone, progesterone, 17α-hydroxyprogesterone, androstenedione, testosterone, 5α-dihydrotestosterone, 5α-androstanedione, androsterone and 5α-androstane-3α, 17β-diol from 1-2 ml samples of blood serum, amniotic fluid or 300-600 mg pieces of prostatic tissue. The adaptation of the pipetting unit and incubator of a discrete clinical chemical analyzer, System Olli 3000, for the automation of the radioimmunoassays has resulted in a greatly increased through-put and decreased experimental error of the procedure. In studies on reproductive endocrinology, the methodology developed has allowed the detection of a sex difference in androgen composition of the amniotic fluid early in pregnancy. Further, it is very likely that the decline in steroid production by the testis seen during the first year of life and then in senescence is affected by basically different mechanisms. There are also important differences in the steroid content of normal, hyperplastic and carcinomatous prostate. (orig.) [de

  17. Blocking Epidermal Growth Factor Receptor Signaling in HTR-8/SVneo First Trimester Trophoblast Cells Results in Dephosphorylation of PKBα/AKT and Induces Apoptosis

    Directory of Open Access Journals (Sweden)

    J. Bolnick

    2011-01-01

    Full Text Available We identified a major peptide signaling target of EGF/EGFR pathway and explored the consequences of blocking or activating this pathway in the first trimester extravillous trophoblast cells, HTR-8/SVneo. A global analysis of protein phosphorylation was undertaken using novel technology (Kinexus Kinetworks that utilizes SDS-polyacrylamide minigel electrophoresis and multi-lane immunoblotting to permit specific and semiquantitative detection of multiple phosphoproteins. Forty-seven protein phosphorylation sites were queried, and the results reported based on relative phosphorylation at each site. EGF- and Iressa-(gefitinib, ZD1839, an inhibitor of EGFR treated HTR-8/SVneo cells were subjected to immunoblotting and flow cytometry to confirm the phosphoprotein screen and to assess the effects of EGF versus Iressa on cell cycle and apoptosis. EGFR mediates the phosphorylation of important signaling proteins, including PKBα/AKT. This pathway is likely to be central to EGFR-mediated trophoblast survival. Furthermore, EGF treatment induces proliferation and inhibits apoptosis, while Iressa induces apoptosis.

  18. Calbindin-D9k (CaBP9k) localization and levels of expression in trophoblast cells from human term placenta.

    Science.gov (United States)

    Belkacemi, Louiza; Gariépy, Gilles; Mounier, Catherine; Simoneau, Lucie; Lafond, Julie

    2004-01-01

    During pregnancy, the calcium (Ca(2+)) transport machinery of the placenta is solely responsible for the nutrient supply to the developing fetus, where active Ca(2+) transport occurs from the mother to the fetus. As part of a larger study to determine the role of Ca(2+) in placental transport in vivo, we questioned whether calbindin-D9k (CaBP9k), which is mainly expressed in duodenum, uterus, and placenta of several mammals, is present in cytotrophoblast cells and syncytiotrophoblasts of human term placenta. We were interested in this protein because of its potential importance in serving as an indicator of Ca(2+) availability and utilization in the placenta. Here, we demonstrated that CaBP9k transcript is present in both cell types, with a lower expression in cytotrophoblast cells as compared to syncytiotrophoblasts. Moreover, we showed by immunochemistry that CaBP9k protein was present in cytotrophoblast and syncytiotrophoblast placental tissue sections as well as in cultured cells. The occurrence of CaBP9k protein in trophoblast cells was further confirmed by Western blot analysis. Thus, these results indicate for the first time that CaBP9k is unequivocally expressed by trophoblast cells from human term placenta.

  19. In vitro effects of triiodothyronine on gene expression in mouse trophoblast cells.

    Science.gov (United States)

    Silva, J F; Ocarino, N M; Serakides, R

    2015-01-01

    The objective of the present study was to evaluate the effects of different doses of T3 (10(-4) M, 10(-7) M, 10(-9) M) on the in vitro gene expression of Tpbp, Prl3b1, VEGF, PGF, PL-1, and INFy in mouse trophoblast cells by real-time RT-PCR. Doses of 10(-7) and 10(-9) M T3 increased the mRNA levels of Tpbp, Pl3b1, VEGF, PGF, INFy and PL-1. In contrast, the dose of 10(-4) M reduced the gene expression of PL-1 and VEGF. T3 affected the gene expression of differentiation, hormonal, immune and angiogenic factors in mouse trophoblast cells. Copyright © 2014 Elsevier Ltd. All rights reserved.

  20. The risk of persistent trophoblastic disease after hydatidiform mole classified by morphology and ploidy

    DEFF Research Database (Denmark)

    Niemann, Isa; Hansen, Estrid S; Sunde, Lone

    2007-01-01

    classifications, and compared the ability of the two classifications to discriminate between patients with and without a substantial risk of persistent trophoblastic disease. METHODS: 294 cases of consecutively collected hydropic placentas clinically suspected of hydatidiform mole made the basis......OBJECTIVE: Hydatidiform mole can be classified by histopathologic characteristics and by genetic constitutions and most complete moles are diploid, whereas most partial moles are triploid. We investigated the concordance between these two classifications, characterized moles with conflicting......-molar miscarriage, 20 were triploids, 2 were diploid androgenetic and 2 were diploid biparental. In 23% of the conceptuses, the histopathologic and genetic classifications were conflicting. 5% of the patients with hydropic placentas classified as partial mole encountered persistent trophoblastic disease; however...

  1. Endoarterial pulmonary metastasis of malignant trophoblast associated with a term intrauterine pregnancy.

    Science.gov (United States)

    Carlson, J A; Day, T G; Kuhns, J G; Howell, R S; Masterson, B J

    1984-02-01

    A previously healthy gravida 4, para 3, developed preclampsia and progressive dyspnea at the 37th gestational week and had bilateral pulmonary infiltrates on chest roentgenogram. She delivered a healthy, term, male infant with a normal appearing placenta. Postpartum, her respiratory status gradually worsened. A lung biopsy on the 20th postpartum day revealed intravascular trophoblasts, diffuse arteriolar thrombosis with pulmonary infarction, and subacute interstitial pneumonitis. Combination chemotherapy was instituted, but the patient died from respiratory insufficiency.

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

    Directory of Open Access Journals (Sweden)

    Yahong Jiang

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

  3. Effect of proline rich 15-deficiency on trophoblast viability and survival.

    Directory of Open Access Journals (Sweden)

    Katherine C Gates

    Full Text Available Deviations from the normal program of gene expression during early pregnancy can lead to early embryonic loss as well as dysfunctional placentation, which can cause significant morbidity and mortality. Proline rich 15 (PRR15 is a low molecular weight nuclear protein expressed by the trophoblast during early gestation. Lentivirus-mediated knockdown of PRR15 mRNA in ovine trophectoderm led to demise of the embryo by gestational day 15, providing compelling evidence that PRR15 expression is critical during this precarious window of development. Our objective was to determine the effect of PRR15 knockdown on trophoblast gene expression, proliferation, and survival. The first-trimester human trophoblast cell line, ACH-3P, was infected with control lentivirus or a lentivirus expressing a short hairpin (shRNA to target PRR15 mRNA for degradation, resulting in a 68% reduction in PRR15 mRNA. Microarray analysis of these cell lines revealed differential expression of genes related to cancer, focal adhesion, and p53 signaling. These changes included significant up-regulation of GDF15, a cytokine increased in pregnancies with preeclampsia. Viability and proliferation decreased in PRR15-deficient cells, which was consistent with down-regulation of cell cycle-related genes CCND1 and CDK6 and an up-regulation of CCNG2 and CDKN1A in the PRR15-deficient cells. TNFSF10, a tumor necrosis factor superfamily member known to induce apoptosis increased significantly in the PRR15-deficient cells. Migration through a basement membrane matrix decreased and an increased population of apoptotic cells was present when treated with shRNA to target PRR15. These results suggest that PRR15 enhances trophoblast viability and survival during early implantation and placentation.

  4. First-line chemotherapy in low-risk gestational trophoblastic neoplasia.

    LENUS (Irish Health Repository)

    Alazzam, Mo'iad

    2012-01-01

    This is an update of a Cochrane review that was first published in Issue 1, 2009. Gestational trophoblastic neoplasia (GTN) is a rare but curable disease arising in the fetal chorion during pregnancy. Most women with low-risk GTN will be cured by evacuation of the uterus with or without single-agent chemotherapy. However, chemotherapy regimens vary between treatment centres worldwide and the comparable benefits and risks of these different regimens are unclear.

  5. Prophylactic chemotherapy for hydatidiform mole to prevent gestational trophoblastic neoplasia.

    Science.gov (United States)

    Wang, Qiuyi; Fu, Jing; Hu, Lina; Fang, Fang; Xie, Lingxia; Chen, Hengxi; He, Fan; Wu, Taixiang; Lawrie, Theresa A

    2017-09-11

    This is an update of the original Cochrane Review published in Cochrane Library, Issue 10, 2012.Hydatidiform mole (HM), also called a molar pregnancy, is characterised by an overgrowth of foetal chorionic tissue within the uterus. HMs may be partial (PM) or complete (CM) depending on their gross appearance, histopathology and karyotype. PMs usually have a triploid karyotype, derived from maternal and paternal origins, whereas CMs are diploid and have paternal origins only. Most women with HM can be cured by evacuation of retained products of conception (ERPC) and their fertility preserved. However, in some women the growth persists and develops into gestational trophoblastic neoplasia (GTN), a malignant form of the disease that requires treatment with chemotherapy. CMs have a higher rate of malignant transformation than PMs. It may be possible to reduce the risk of GTN in women with HM by administering prophylactic chemotherapy (P-Chem). However, P-Chem given before or after evacuation of HM to prevent malignant sequelae remains controversial, as the risks and benefits of this practice are unclear. To evaluate the effectiveness and safety of P-Chem to prevent GTN in women with a molar pregnancy. To investigate whether any subgroup of women with HM may benefit more from P-Chem than others. For the original review we performed electronic searches in the Cochrane Gynaecological Cancer Specialised Register, the Cochrane Central Register of Controlled Trials (CENTRAL, Issue 2, 2012), MEDLINE (1946 to February week 4, 2012) and Embase (1980 to 2012, week 9). We developed the search strategy using free text and MeSH. For this update we searched the Cochrane Central Register of Controlled Trials (CENTRAL, Issue 5, 2017), MEDLINE (February 2012 to June week 1, 2017) and Embase (February 2012 to 2017, week 23). We also handsearched reference lists of relevant literature to identify additional studies and searched trial registries. We included randomised controlled trials

  6. Gender-Dependent Survival of Allogeneic Trophoblast Stem Cells in Liver

    Science.gov (United States)

    Epple-Farmer, Jessica; Debeb, Bisrat G.; Smithies, Oliver; Binas, Bert

    2012-01-01

    In view of the well-known phenomenon of trophoblast immune privilege, trophoblast stem cells (TSCs) might be expected to be immune privileged, which could be of interest for cell or gene therapies. Yet in the ectopic sites tested so far, TSC transplants fail to show noticeable immune privilege and seem to lack physiological support. However, we show here that after portal venous injection, green fluorescent protein (GFP)-labeled TSCs survive for several months in the livers of allogeneic female but not male mice. Gonadectomy experiments revealed that this survival does not require the presence of ovarian hormones but does require the absence of testicular factors. By contrast, GFP-labeled allogeneic embryonic stem cells (ESCs) are reliably rejected; however, these same ESCs survive when mixed with unlabeled TSCs. The protective effect does not require immunological compatibility between ESCs and TSCs. Tumors were not observed in animals with either successfully engrafted TSCs or coinjected ESCs. We conclude that in a suitable hormonal context and location, ectopic TSCs can exhibit and confer immune privilege. These findings suggest applications in cell and gene therapy as well as a new model for studying trophoblast immunology and physiology. PMID:19523327

  7. Proportion hyperglycosylated hCG: a new test for discriminating gestational trophoblastic diseases.

    Science.gov (United States)

    Cole, Laurence A

    2014-11-01

    Hyperglycosylated human chorionic gonadotropin (hCG) is a variant of hCG with large oligosaccharide side chains. Although hCG is produced by syncytiotrophoblast cells, hyperglycosylated hCG marks cytotrophoblast cell. Hyperglycosylated hCG signals placental implantation. Total hCG in serum and urine is measured by the Siemens Immulite hCG pregnancy test; the result is in milli-international unit per milliliter. Hyperglycosylated hCG is determined by the B152 microtiter plate assay; the result is in nanogram per milliliter. Hyperglycosylated hCG results can be converted to milli-international unit per milliliter equivalents by multiplying by 11. The test measures proportion hyperglycosylated hCG, hyperglycosylated hCG / total hCG. Proportion hyperglycosylated hCG marks cases intent on developing persistent hydatidiform mole (68% detection at 17% false detection). Proportion hyperglycosylated hCG also marks persistent hydatidiform mole (100% detection at 5.1% false detection). Proportion hyperglycosylated hCG distinguishes choriocarcinoma and gestational trophoblastic neoplasm cases, absolutely discriminating aggressive cases and minimally aggressive cases. Proportion hyperglycosylated hCG identifies quiescent gestational trophoblastic disease cases. It recognizes quiescent cases that become persistent disease (100% detection at 0% false positive). Proportion hyperglycosylated hCG is an invaluable test for discriminating gestational trophoblastic diseases.

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

    Science.gov (United States)

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

    2017-01-27

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

  9. Trophoblastic progranulin expression is upregulated in cases of fetal growth restriction and preeclampsia.

    Science.gov (United States)

    Stubert, Johannes; Schattenberg, Florian; Richter, Dagmar-Ulrike; Dieterich, Max; Briese, Volker

    2012-05-13

    The expression of the anti-inflammatory glycoprotein progranulin and the hypoxia-induced transcription factor 1α (HIF-1α) in the villous trophoblast was compared between placentae from patients with preeclampsia (PE), fetal growth restriction (FGR), and normal controls. Matched pairs analysis of third trimester placentae specimens (mean gestational age 36+2) was performed by semiquantitative measurements of the immunohistochemical staining intensities for progranulin and HIF-1α expression (PE n=13, FGR n=9 and controls n=11). Further, placental progranulin mRNA expression was analyzed by qRT-PCR on term placentae (n=3 for each group). Compared to controls, villous trophoblast revealed a significantly higher expression of progranulin in cases of PE (Pprogranulin protein was not accompanied by an increase of the progranulin mRNA in term placentae. Increased expression of progranulin protein in villous trophoblast cells in cases of PE and FGR may result from disturbed placental development and, therefore, may be of pathogenetic importance. The increase was correlated to HIF-1α expression. Further evaluation of this potential mechanism of regulation is required.

  10. Feeder Cell Type Affects the Growth of In Vitro Cultured Bovine Trophoblast Cells

    Directory of Open Access Journals (Sweden)

    Islam M. Saadeldin

    2017-01-01

    Full Text Available Trophectoderm cells are the foremost embryonic cells to differentiate with prospective stem-cell properties. In the current study, we aimed at improving the current approach for trophoblast culture by using granulosa cells as feeders. Porcine granulosa cells (PGCs compared to the conventional mouse embryonic fibroblasts (MEFs were used to grow trophectoderm cells from hatched bovine blastocysts. Isolated trophectoderm cells were monitored and displayed characteristic epithelial/cuboidal morphology. The isolated trophectoderm cells expressed mRNA of homeobox protein (CDX2, cytokeratin-8 (KRT8, and interferon tau (IFNT. The expression level was higher on PGCs compared to MEFs throughout the study. In addition, primary trophectoderm cell colonies grew faster on PGCs, with a doubling time of approximately 48 hrs, compared to MEFs. PGCs feeders produced a fair amount of 17β-estradiol and progesterone. We speculated that the supplementation of sex steroids and still-unknown factors during the trophoblasts coculture on PGCs have helped to have better trophectoderm cell’s growth than on MEFs. This is the first time to use PGCs as feeders to culture trophectoderm cells and it proved superior to MEFs. We propose PGCs as alternative feeders for long-term culture of bovine trophectoderm cells. This model will potentially benefit studies on the early trophoblast and embryonic development in bovines.

  11. Morphologic and proteomic characterization of exosomes released by cultured extravillous trophoblast cells

    International Nuclear Information System (INIS)

    Atay, Safinur; Gercel-Taylor, Cicek; Kesimer, Mehmet; Taylor, Douglas D.

    2011-01-01

    Exosomes represent an important intercellular communication vehicle, mediating events essential for the decidual microenvironment. While we have demonstrated exosome induction of pro-inflammatory cytokines, to date, no extensive characterization of trophoblast-derived exosomes has been provided. Our objective was to provide a morphologic and proteomic characterization of these exosomes. Exosomes were isolated from the conditioned media of Swan71 human trophoblast cells by ultrafiltration and ultracentrifugation. These were analyzed for density (sucrose density gradient centrifugation), morphology (electron microscopy), size (dynamic light scattering) and protein composition (Ion Trap mass spectrometry and western immunoblotting). Based on density gradient centrifugation, microvesicles from Sw71 cells exhibit a density between 1.134 and 1.173 g/ml. Electron microscopy demonstrated that microvesicles from Sw71 cells exhibit the characteristic cup-shaped morphology of exosomes. Dynamic light scattering showed a bell-shaped curve, indicating a homogeneous population with a mean size of 165 nm ± 0.5 nm. Ion Trap mass spectrometry demonstrated the presence of exosome marker proteins (including CD81, Alix, cytoskeleton related proteins, and Rab family). The MS results were confirmed by western immunoblotting. Based on morphology, density, size and protein composition, we defined the release of exosomes from extravillous trophoblast cells and provide their first extensive characterization. This characterization is essential in furthering our understanding of 'normal' early pregnancy.

  12. Morphologic and proteomic characterization of exosomes released by cultured extravillous trophoblast cells

    Energy Technology Data Exchange (ETDEWEB)

    Atay, Safinur [Department of Microbiology and Immunology, University of Louisville School of Medicine, Louisville, KY (United States); Gercel-Taylor, Cicek [Obstetrics, Gynecology and Women' s Health, University of Louisville School of Medicine, Louisville, KY (United States); Kesimer, Mehmet [Department of Biochemistry and Biophysics, University of North Carolina at Chapel Hill, Chapel Hill, NC (United States); Taylor, Douglas D., E-mail: ddtaylor@louisville.edu [Department of Microbiology and Immunology, University of Louisville School of Medicine, Louisville, KY (United States); Obstetrics, Gynecology and Women' s Health, University of Louisville School of Medicine, Louisville, KY (United States)

    2011-05-01

    Exosomes represent an important intercellular communication vehicle, mediating events essential for the decidual microenvironment. While we have demonstrated exosome induction of pro-inflammatory cytokines, to date, no extensive characterization of trophoblast-derived exosomes has been provided. Our objective was to provide a morphologic and proteomic characterization of these exosomes. Exosomes were isolated from the conditioned media of Swan71 human trophoblast cells by ultrafiltration and ultracentrifugation. These were analyzed for density (sucrose density gradient centrifugation), morphology (electron microscopy), size (dynamic light scattering) and protein composition (Ion Trap mass spectrometry and western immunoblotting). Based on density gradient centrifugation, microvesicles from Sw71 cells exhibit a density between 1.134 and 1.173 g/ml. Electron microscopy demonstrated that microvesicles from Sw71 cells exhibit the characteristic cup-shaped morphology of exosomes. Dynamic light scattering showed a bell-shaped curve, indicating a homogeneous population with a mean size of 165 nm {+-} 0.5 nm. Ion Trap mass spectrometry demonstrated the presence of exosome marker proteins (including CD81, Alix, cytoskeleton related proteins, and Rab family). The MS results were confirmed by western immunoblotting. Based on morphology, density, size and protein composition, we defined the release of exosomes from extravillous trophoblast cells and provide their first extensive characterization. This characterization is essential in furthering our understanding of 'normal' early pregnancy.

  13. Studies on the physiology and endocrinology of reproduction of Helisoma duryi (Mollusca: Pulmonata)

    Energy Technology Data Exchange (ETDEWEB)

    Miksys, S.L.

    1987-01-01

    Helisoma duryi is a hermaphroditic, freshwater, pulmonate snail native to North America. It has been proposed as a biological control agent against snail intermediate hosts of Schistosoma sp., a parasitic trematode in man. Very little is known of the physiology and endocrinology of reproduction of H. duryi. This thesis investigates vitello-genesis, endocrine control of the synthesis of albumen, a nutrient-rich fluid catabolized by developing embryos, and the possible endocrine role of the gonad. Light and electron microscopy, chemical extraction, energy dispersive X-ray analysis, and radioimmunoassay are used to identify the yolk protein ferritin. It is proposed that ferritin synthesis, and its circulating levels, are regulated, probably indirectly, by a gonadal factor released into the blood. The rate of synthesis of albumen polysaccharides can be monitored in vitro by providing albumen gland explants with the precursor /sup 14/C-glucose and measuring /sup 14/C-polysaccharide produced. The basal synthetic activity of the gland reflects the reproductive activity of the snail.

  14. Forever young: Endocrinology of paedomorphosis in the Mexican axolotl (Ambystoma mexicanum).

    Science.gov (United States)

    De Groef, Bert; Grommen, Sylvia V H; Darras, Veerle M

    2018-05-16

    The Mexican axolotl (Ambystoma mexicanum) is a salamander species that does not undergo metamorphosis, resulting in the retention of juvenile characteristics in the mature breeding stage (paedomorphosis). Here we review the endocrinological studies investigating the proximate cause of axolotl paedomorphosis with a focus on the hypothalamo-pituitary-thyroid (HPT) axis. It is well established that axolotl paedomorphosis is a consequence of low activity of the HPT axis. The pituitary hormone thyrotropin (TSH) is capable of inducing metamorphosis in the axolotl, which indicates that all processes and interactions in the HPT axis below the pituitary level are functional, but that TSH release is impaired. In metamorphosing species, TSH secretion is largely controlled by the hypothalamic neuropeptide corticotropin-releasing hormone (CRH), which seems to have lost its thyrotropic activity in the axolotl. However, preliminary experiments have not yet confirmed a role for faulty CRH signalling in axolotl paedomorphosis. Other hypothalamic factors and potential pituitary inhibitors need to be investigated to identify their roles in amphibian metamorphosis and axolotl paedomorphosis. Copyright © 2018 Elsevier Inc. All rights reserved.

  15. Establishment and characterization of a spontaneously immortalized trophoblast cell line (HPT-8) and its hepatitis B virus-expressing clone.

    Science.gov (United States)

    Zhang, Lei; Zhang, Weilu; Shao, Chen; Zhang, Jingxia; Men, Ke; Shao, Zhongjun; Yan, Yongping; Xu, Dezhong

    2011-08-01

    Most trophoblast cell lines currently available to study vertical transmission of hepatitis B virus (HBV) are immortalized by viral transformation. Our goal was to establish and characterize a spontaneously immortalized human first-trimester trophoblast cell line and its HBV-expressing clone. Chorionic villi of Asian human first-trimester placentae were digested with trypsin and collagenase I to obtain the primary trophoblast cell culture. A spontaneously immortalized trophoblast cell line (HPT-8) was analyzed by scanning and transmission electron microscopy, cell cycle analysis, immunohistochemistry and immunofluorescence. HPT-8 cells were stably transfected with the adr subtype of HBV (HPT-8-HBV) and characterized by PCR and enzyme-linked immunosorbent assay. We obtained a clonal derivative of a spontaneously immortalized primary cell clone (HPT-8). HPT-8 cells were epithelioid and polygonal, and formed multinucleate, giant cells. They exhibited microvilli, distinct desmosomes between adjacent cells, abundant endoplasm, lipid inclusions and glycogen granules, which are all characteristic of cytotrophoblasts. HPT-8 cells expressed cytokeratin 7, cytokeratin 18, vimentin, cluster of differentiation antigen 9, epidermal growth factor receptor, stromal cell-derived factor 1 and placental alkaline phosphatase. They secreted prolactin, estradiol, progesterone and hCG, and were positive for HLA-G, a marker of extravillous trophoblasts. HPT-8-HBV cells were positive for HBV relaxed-circular, covalently closed circular DNA and pre-S sequence. HPT-8-HBV cells also produced and secreted HBV surface antigen and HBV e antigen. We established a trophoblast cell line, HPT-8 and its HBV-expressing clone which could be valuable in exploring the mechanism of HBV viral integration in human trophoblasts during intrauterine infection.

  16. Perceptions about Training during Endocrinology Residency Programs in India over the Years: A Cross-sectional Study (PEER India Study)

    Science.gov (United States)

    Khandelwal, Deepak; Dutta, Deep; Singla, Rajiv; Surana, Vineet; Aggarwal, Sameer; Gupta, Yashdeep; Kalra, Sanjay; Khadgawat, Rajesh; Tandon, Nikhil

    2017-01-01

    Background: Residents' perception on quality of endocrinology training in India is not known. This study aimed to evaluate the perceptions about endocrinology residency programs in India among current trainees as compared to practicing endocrinologists. Methods: Trainees attending a preconference workshop at the annual conference of Endocrine Society of India (ESI) were given a questionnaire designed to evaluate their perceptions on their training. These evaluated the reasons for choosing endocrinology, their experiences during residency, and career plans. Practicing endocrinologists attending ESICON with at least 5-year experience were evaluated as controls. Results: Questionnaires from 63 endocrine trainees and 78 practicing endocrinologists were analyzed. Endocrinology is perceived to be the super-specialty with the best quality of life (QOL) but fair with regard to financial remuneration. Among current trainees, 61.89%, 31.74%, and 34.91% are satisfied with training in clinical endocrinology, laboratory endocrinology, and clinical/translational research, respectively. The corresponding figures for practicing endocrinologists are 71.78%, 25.63%, and 30.75%, respectively. Exposure to national endocrinology conferences during their endocrinology residency was adequate. However, exposure to international endocrinology conferences, research publications, project writing, and grant application are limited. Laboratory endocrinology is rated as the most neglected aspect during endocrine residency. Most of the trainees want to establish their own clinical practice in the long run. Very few trainees (17.46%) wish to join the medical education services. Conclusion: There is a good perception of QOL in endocrinology in spite of average financial remuneration. There is dissatisfaction with the quality of training in laboratory endocrinology and clinical research. Very few endocrine trainees consider academics as a long-term career option in India. PMID:28459024

  17. Co-expression of cytokeratins and vimentin by highly invasive trophoblast in the white-winged vampire bat, Diaemus youngi, and the black mastiff bat, Molossus ater, with observations on intermediate filament proteins in the decidua and intraplacental trophoblast.

    Science.gov (United States)

    Badwaik, N K; Rasweiler, J J; Muradali, F

    1998-11-01

    Histological and immunocytochemical studies of gravid reproductive tracts obtained from the white-winged vampire bat (Diaemus youngi) and the black mastiff bat (Molossus ater) have established that both species develop unusually invasive trophoblast. This is released by the developing discoidal haemochorial placenta, expresses both cytokeratins and vimentin, and invades the myometrium and adjacent tissues (including the ovaries) via interstitial migration within the walls of maternal blood vessels. Hence, this trophoblast is noteworthy for the extent to which it undergoes an epithelial-mesenchymal transformation. In Molossus, it originates from the cytotrophoblastic shell running along the base of the placenta, is mononuclear, and preferentially invades maternal arterial vessels serving the discoidal placenta. This trophoblast may have a role in dilatation of these vessels when the discoidal placenta becomes functional. In Diaemus, the highly invasive trophoblast appears to originate instead from a layer of syncytiotrophoblast on the periphery of the placenta is multinucleated, and vigorously invades both arterial and venous vessels. During late pregnancy, it becomes extensively branched and sends attenuated processes around many of the myometrial smooth muscle fibres. In view of its distribution, this trophoblast could have important influences upon myometrial contractility and the function of blood vessels serving the gravid tract. Other aspects of intermediate filament expression in the uteri and placentae of these bats are also noteworthy. Many of the decidual giant cells in Molossus co-express cytokeratins and vimentin, while the syncytiotrophoblast lining the placental labyrinth in Diaemus late in pregnancy expresses little cytokeratin.

  18. Training in reproductive endocrinology and infertility and assisted reproductive technologies: options and worldwide needs.

    Science.gov (United States)

    de Ziegler, Dominique; de Ziegler, Nathalie; Sean, Sokteang; Bajouh, Osama; Meldrum, David R

    2015-07-01

    Standardized, high-quality training in reproductive endocrinology, infertility, and assisted reproductive technologies (REI-ART) faces challenges owing to the high-tech nature of ART and the important country-to-country differences in clinical practice and regulations overseeing training. Moreover, while the training capacity of the classical by-fellowship training platforms is shrinking, an increasing demand for REI-ART specialists is coming from emerging countries. To meet this expanding need for REI-ART specialists, we propose a novel by-network model linking a reference training center to satellite practical training sites. Simulation should be used more extensively to achieve competency before initiating live clinical experience, analogous to the highly effective training systems that have been used in aviation for decades. Large ART databases that exist because of obligations to report ART activity and results constitute unique yet so far untapped sources for developing by-scenario simulation training models. Online training materials incorporating these state-of-the-art information technology tools could be developed as a means of fulfilling training needs worldwide. Copyright © 2015. Published by Elsevier Inc.

  19. Gonadal Morphology, Histology, and Endocrinological Characteristics of Immature Female Whale Sharks, Rhincodon typus.

    Science.gov (United States)

    Nozu, Ryo; Murakumo, Kiyomi; Matsumoto, Rui; Nakamura, Masaru; Ueda, Keiichi; Sato, Keiichi

    2015-10-01

    Captive breeding of whale sharks is one of the great challenges for aquariums. However, there is limited information available related to reproductive physiology due to the difficulty of sampling and long-term observation. In the present report, we provide information on the reproductive physiology of female whale sharks, which were incidentally captured as bycatch in a set-net off the coast of Okinawa, Japan. Total lengths of three captured female whale sharks were 403, 665, and 761 cm, respectively, at the time of their death. Collected paired ovaries differed in size between right and left. However, it seems not to determine which side of ovary becomes developed. Histological observations revealed that oocytes surrounded by follicle cell layers localized in the developed ovary, and most developed oocytes exhibited yolk vesicle stage. Additionally, in the largest specimen, there were low levels of three steroid hormones (Testosterone, Dihydrotestosterone, and Estradiol-17ß) that did not show seasonal variation. The present results indicate that even the whale shark over 7 m in TL are still histologically and endocrinologically immature. We expect that the present data will provide fundamental information related to reproductive physiology of female whale sharks, and will contribute to protection activities and increased success in captive breeding of whale sharks.

  20. Trends in endocrinology related research articles in a medical journal from India

    Science.gov (United States)

    Kumar, K. V. S. H; Aravinda, Konidena

    2012-01-01

    Background: The details about the research productivity in the specialty of endocrinology from India is lacking. We plan to assess the publishing trends and the research productivity of Endocrinology related research articles published in the Journal of the Association of Physicians of India (JAPI). Materials and Methods: We carried the bibliometric analysis of endocrinology related articles from JAPI. The data were obtained from the JAPI website for the publications between 2000 and 2011. The articles were analyzed for the type (original article, case reports, correspondence, and pictorial image), subspecialty (diabetes, thyroid, etc.), and place of the research. Data were presented with descriptive statistics in numbers and percentages. Results: Out of a total 2977 articles published by JAPI, 312 articles belong to endocrine subspecialty. Endocrinology related articles constitute about 11.2%–23.2% of the published articles per year in JAPI and the percentage is increasing every year. Original articles (52%) and case reports (27%) constituite the majority, while the rest were letters to editor (9%) and pictorial images (12%). Diabetes (57%) and metabolic bone disorders (16%) lead the subspecialty articles, followed by thyroid (9%), adrenal and gonad (8%), and pituitary (8%). Chennai (20%), Mumbai (14%), and Delhi (9%) are the top 3 places contributing to the articles followed by Chandigarh and Varanasi. Conclusion: Majority of endocrinology related research productivity is seen in form of original articles and case reports. Diabetes is the leading disease with maximum research articles from Chennai and other glands are equally represented in the research productivity. PMID:23226637

  1. Worldwide research productivity in the field of endocrinology and metabolism--a bibliometric analysis.

    Science.gov (United States)

    Zhao, Xiyan; Ye, Ru; Zhao, Linhua; Lin, Yiqun; Huang, Wenjing; He, Xinhui; Lian, Fengmei; Tong, Xiaolin

    2015-01-01

    Recently, significant contributions to the study of endocrinology and metabolism have been made. The national contribution, however, has not been reported. The aim of this study was to assess national efforts in the field of endocrinology and metabolism. A Web of Science search was performed using subject categories "endocrinology & metabolism" to identify articles published from 2010 to 2014. The total and per capita numbers of articles and citations were analysed for different countries. A total of 79,394 articles were published on endocrinology and metabolism from 2010 to 2014. Most were published in North America, East Asia, and Europe. The majority (82.28%) were reported by authors in high-income countries, 17.64% were published in middle-income countries, and only 0.08% were published in low-income countries. Authors in the United States published the most articles (27.38%), followed by China (7.22%), Italy (5.70%), the United Kingdom (5.6%), and Japan (5.54%). Articles published by authors in the United States had the most citations (260,934). A positive correlation was found between the number of publications and population/gross domestic product (GDP; p endocrinology and metabolism articles were published by authors from high-income countries with few from low-income countries. The United States was the most productive country. However, when population size and GDP were considered, some European countries were ranked higher.

  2. Trends in endocrinology related research articles in a medical journal from India

    Directory of Open Access Journals (Sweden)

    K. V. S. Hari Kumar

    2012-01-01

    Full Text Available Background: The details about the research productivity in the specialty of endocrinology from India is lacking. We plan to assess the publishing trends and the research productivity of Endocrinology related research articles published in the Journal of the Association of Physicians of India (JAPI. Materials and Methods: We carried the bibliometric analysis of endocrinology related articles from JAPI. The data were obtained from the JAPI website for the publications between 2000 and 2011. The articles were analyzed for the type (original article, case reports, correspondence, and pictorial image, subspecialty (diabetes, thyroid, etc., and place of the research. Data were presented with descriptive statistics in numbers and percentages. Results: Out of a total 2977 articles published by JAPI, 312 articles belong to endocrine subspecialty. Endocrinology related articles constitute about 11.2%-23.2% of the published articles per year in JAPI and the percentage is increasing every year. Original articles (52% and case reports (27% constituite the majority, while the rest were letters to editor (9% and pictorial images (12%. Diabetes (57% and metabolic bone disorders (16% lead the subspecialty articles, followed by thyroid (9%, adrenal and gonad (8%, and pituitary (8%. Chennai (20%, Mumbai (14%, and Delhi (9% are the top 3 places contributing to the articles followed by Chandigarh and Varanasi. Conclusion: Majority of endocrinology related research productivity is seen in form of original articles and case reports. Diabetes is the leading disease with maximum research articles from Chennai and other glands are equally represented in the research productivity.

  3. Endocrinologic, neurologic, and visual morbidity after treatment for craniopharyngioma

    Science.gov (United States)

    Sughrue, Michael E.; Yang, Isaac; Kane, Ari J.; Fang, Shanna; Clark, Aaron J.; Aranda, Derrick; Barani, Igor J.

    2010-01-01

    Craniopharyngiomas are locally aggressive tumors which typically are focused in the sellar and suprasellar region near a number of critical neural and vascular structures mediating endocrinologic, behavioral, and visual functions. The present study aims to summarize and compare the published literature regarding morbidity resulting from treatment of craniopharyngioma. We performed a comprehensive search of the published English language literature to identify studies publishing outcome data of patients undergoing surgery for craniopharyngioma. Comparisons of the rates of endocrine, vascular, neurological, and visual complications were performed using Pearson’s chi-squared test, and covariates of interest were fitted into a multivariate logistic regression model. In our data set, 540 patients underwent surgical resection of their tumor. 138 patients received biopsy alone followed by some form of radiotherapy. Mean overall follow-up for all patients in these studies was 54 ± 1.8 months. The overall rate of new endocrinopathy for all patients undergoing surgical resection of their mass was 37% (95% CI = 33–41). Patients receiving GTR had over 2.5 times the rate of developing at least one endocrinopathy compared to patients receiving STR alone or STR + XRT (52 vs. 19 vs. 20%, χ2P < 0.00001). On multivariate analysis, GTR conferred a significant increase in the risk of endocrinopathy compared to STR + XRT (OR = 3.45, 95% CI = 2.05–5.81, P < 0.00001), after controlling for study size and the presence of significant hypothalamic involvement. There was a statistical trend towards worse visual outcomes in patients receiving XRT after STR compared to GTR or STR alone (GTR = 3.5% vs. STR 2.1% vs. STR + XRT 6.4%, P = 0.11). Given the difficulty in obtaining class 1 data regarding the treatment of this tumor, this study can serve as an estimate of expected outcomes for these patients, and guide decision making until these data are available. PMID

  4. Spanish language content on reproductive endocrinology and infertility practice websites.

    Science.gov (United States)

    Londra, Laura C; Tobler, Kyle J; Omurtag, Kenan R; Donohue, Michael B

    2014-11-01

    To analyze the use of Spanish language translation on the websites of reproductive endocrinology and infertility (REI) practices in the context of evidence of underuse of infertility services by minority populations. Cross-sectional survey of websites from REI practices. Not applicable. None. None. Assessment of the relationship between having a Spanish-translated website and REI practice characteristics. Variables included concurrent use of social media, size of the practice, Spanish-speaking practitioner in the practice, being a private or a university-based practice, being in a mandated insurance state, and being in an area with different levels of percentage of Hispanic population, adjusted for annual income levels of the population. Of the 376 REI practice websites analyzed, 101 (27%) offered at least some information in Spanish. We identified 97 Spanish-speaking practitioners at 71 REI practices. Having a Spanish-translated website was significantly associated with the practice's use of social media, having an international/out-of-town web page, and having a Spanish-speaking physician in the practice. The size of the practice, as measured in number of cycles reported per year, was not associated with having a translated website. In practices located in the top 60 metropolitan areas by Hispanic population, the odds of having a Spanish-translated website were only related to the percentage of Hispanic population after adjusting for state-mandated insurance and average annual income level of the Hispanic population. Sixty-six of the websites with Spanish-translated content had been automatically translated. An additional eight websites were partially translated automatically. REI practices in metropolitan areas with a higher percentage of Hispanics were more likely to reach out to this minority population by translating their website content into Spanish. These practices were also more likely to use social media. Future studies are needed to determine whether

  5. Immune modulatory mesenchymal stem cells derived from human embryonic stem cells through a trophoblast-like stage.

    Science.gov (United States)

    Wang, Xiaofang; Lazorchak, Adam S; Song, Li; Li, Enqin; Zhang, Zhenwu; Jiang, Bin; Xu, Ren-He

    2016-02-01

    Mesenchymal stem/stromal cells (MSCs) have great clinical potential in modulating inflammation and promoting tissue repair. Human embryonic stem cells (hESCs) have recently emerged as a potentially superior cell source for MSCs. However, the generation methods reported so far vary greatly in quality and efficiency. Here, we describe a novel method to rapidly and efficiently produce MSCs from hESCs via a trophoblast-like intermediate stage in approximately 11-16 days. We term these cells "T-MSCs" and show that T-MSCs express a phenotype and differentiation potential minimally required to define MSCs. T-MSCs exhibit potent immunomodulatory activity in vitro as they can remarkably inhibit proliferation of cocultured T and B lymphocytes. Unlike bone marrow MSCs, T-MSCs do not have increased expression of inflammatory mediators in response to IFNγ. Moreover, T-MSCs constitutively express a high level of the immune inhibitory ligand PD-L1 and elicit strong and durable efficacy in two distinct animal models of autoimmune disease, dextran sulfate sodium induced colitis, and experimental autoimmune encephalomyelitis, at doses near those approved for clinical trials. Together, we present a simple and fast derivation method to generate MSCs from hESCs, which possess potent immunomodulatory properties in vitro and in vivo and may serve as a novel and ideal candidate for MSC-based therapies. © 2015 AlphaMed Press.

  6. Enhancement of trophoblast differentiation and survival by low molecular weight heparin requires heparin-binding EGF-like growth factor.

    Science.gov (United States)

    Bolnick, Alan D; Bolnick, Jay M; Kohan-Ghadr, Hamid-Reza; Kilburn, Brian A; Pasalodos, Omar J; Singhal, Pankaj K; Dai, Jing; Diamond, Michael P; Armant, D Randall; Drewlo, Sascha

    2017-06-01

    Does low molecular weight heparin (LMWH) require heparin-binding epidermal growth factor (EGF)-like growth factor (HBEGF) signaling to induce extravillous trophoblast differentiation and decrease apoptosis during oxidative stress? LMWH increased HBEGF expression and secretion, and HBEGF signaling was required to stimulate trophoblast extravillous differentiation, increase invasion in vitro and reduce trophoblast apoptosis during oxidative stress. Abnormal trophoblast differentiation and survival contribute to placental insufficiency syndromes, including preeclampsia and intrauterine growth restriction. Preeclampsia often manifests as a pro-thrombotic state, with unsuccessful transformation of the spiral arteries that reduces oxygen supply and can produce placental infarction. LMWH improves placental function by increasing blood flow. Recent data suggest that the actions of LMWH transcend its anti-coagulative properties, but the molecular mechanism is unknown. There is evidence that LMWH alters the expression of human HBEGF in trophoblast cells, which regulates human trophoblast pathophysiology. HBEGF, itself, is capable of increasing trophoblast survival and invasiveness. First-trimester placental explants and the HTR-8/SVneo cell line, established using extravillous trophoblast outgrowths from first-trimester villous explants, were treated in vitro with LMWH to examine the effects on HBEGF signaling and trophoblast function under normal physiological and pathological conditions. A highly specific antagonist of HBEGF and other inhibitors of HBEGF downstream signaling were used to determine the relationship between LMWH treatment and HBEGF. Placental tissues (n = 5) were obtained with IRB approval and patient consent from first-trimester terminations. Placental explants and HTR-8/SVneo cells were cultured on plastic or Matrigel™ and treated with a therapeutic dose of LMWH (Enoxaparin; 10 IU/ml), with or without CRM197, pan Erb-B2 Receptor Tyrosine Kinase (ERBB

  7. Referring Quality Assessment of Primary Health Care for Endocrinology in Rio Grande do Sul, Brazil.

    Science.gov (United States)

    Monteiro Grendene, Gabriela; Szczecinski Rodrigues, Átila; Katz, Natan; Harzheim, Erno

    2015-01-01

    This paper presents results of an assessment of the quality research of endocrinology referrals in the public health system in the state of Rio Grande do Sul. From the analysis of 4,458 requests for endocrinology referrals, it was found that 15% of referrals had insufficient information for evaluation and 71% showed no clinical justification for authorization of referencing. The partial results of the study indicated that the lack of information makes it impossible to clinically regulate these requests. The use of referencing protocols associated with telemedicine tools can assist doctors in primary health care in the clinical management and make access to specialized services more equitable and timely.

  8. A Critical Role of TET1/2 Proteins in Cell-Cycle Progression of Trophoblast Stem Cells

    Directory of Open Access Journals (Sweden)

    Stephanie Chrysanthou

    2018-04-01

    Full Text Available Summary: The ten-eleven translocation (TET proteins are well known for their role in maintaining naive pluripotency of embryonic stem cells. Here, we demonstrate that, jointly, TET1 and TET2 also safeguard the self-renewal potential of trophoblast stem cells (TSCs and have partially redundant roles in maintaining the epithelial integrity of TSCs. For the more abundantly expressed TET1, we show that this is achieved by binding to critical epithelial genes, notably E-cadherin, which becomes hyper-methylated and downregulated in the absence of TET1. The epithelial-to-mesenchymal transition phenotype of mutant TSCs is accompanied by centrosome duplication and separation defects. Moreover, we identify a role of TET1 in maintaining cyclin B1 stability, thereby acting as facilitator of mitotic cell-cycle progression. As a result, Tet1/2 mutant TSCs are prone to undergo endoreduplicative cell cycles leading to the formation of polyploid trophoblast giant cells. Taken together, our data reveal essential functions of TET proteins in the trophoblast lineage. : TET proteins are well known for their role in pluripotency. Here, Hemberger and colleagues show that TET1 and TET2 are also critical for maintaining the epithelial integrity of trophoblast stem cells. TET1/2 ensure mitotic cell-cycle progression by stabilizing cyclin B1 and by regulating centrosome organization. These insights reveal the importance of TET proteins beyond their role in epigenome remodeling. Keywords: TET proteins, trophoblast stem cells, cell cycle, endoreduplication, self-renewal, mitosis, trophoblast giant cells, differentiation

  9. Role of HLA-G1 in trophoblast cell proliferation, adhesion and invasion

    Energy Technology Data Exchange (ETDEWEB)

    Jiang, Feng, E-mail: jiangfeng1161@163.com [Department of Gynecology and Obstetrics, Tangdu Hospital, The Fourth Military Medical University, 569 Xinsi Road, Baqiao District, Xi' an 710038 (China); Zhao, Hongxi [Department of Gynecology and Obstetrics, Tangdu Hospital, The Fourth Military Medical University, 569 Xinsi Road, Baqiao District, Xi' an 710038 (China); Wang, Li [Department of Gynecology and Obstetrics, The Chinese PLA General Hospital, 28 Fuxing Road, Haidian District, Beijing 100853 (China); Guo, Xinyu [Assisted Reproductive Center, General Hospital of Guangzhou Military Command, Guangzhou 510010 (China); Wang, Xiaohong; Yin, Guowu [Department of Gynecology and Obstetrics, Tangdu Hospital, The Fourth Military Medical University, 569 Xinsi Road, Baqiao District, Xi' an 710038 (China); Hu, Yunsheng [Department of Orthopedics, Tangdu Hospital, The Fourth Military Medical University, Xi' an 710038 (China); Li, Yi [Department of Gynecology and Obstetrics, Tangdu Hospital, The Fourth Military Medical University, 569 Xinsi Road, Baqiao District, Xi' an 710038 (China); Yao, Yuanqing, E-mail: yuanqingyaoxa@163.com [Department of Gynecology and Obstetrics, The Chinese PLA General Hospital, 28 Fuxing Road, Haidian District, Beijing 100853 (China)

    2015-02-27

    Trophoblast cells are important in embryo implantation and fetomaternal tolerance. HLA-G is specifically expressed at the maternal–fetal interface and is a regulator in pregnancy. The aim of the present study was to detect the effect of HLA-G1 on trophoblast cell proliferation, adhesion, and invasion. Human trophoblast cell lines (JAR and HTR-8/SVneo cells) were infected with HLA-G1-expressing lentivirus. After infection, HLA-G1 expression of the cells was detected by western blotting. Cell proliferation was detected by the BrdU assay. The cell cycle and apoptosis of JAR and HTR-8/SVneo cells was measured by flow cytometry (FCM). The invasion of the cells under different conditions was detected by the transwell invasion chamber assay. HLA-G1 didn't show any significant influence on the proliferation, apoptosis, adhesion, and invasion of trophocytes in normal culture conditions. However, HLA-G1 inhibited JAR and HTR-8/SVneo cells invasion induced by hepatocyte growth factor (HGF) under normal oxygen conditions. In conditions of hypoxia, HLA-G1 couldn't inhibit the induction of cell invasion by HGF. HLA-G1 is not an independent factor for regulating the trophocytes. It may play an indirect role in embryo implantation and formation of the placenta. - Highlights: • HLA-G1 could not influence trophocytes under normal conditions. • HLA-G1 inhibited cell invasion induced by HGF under normal oxygen condition. • HLA-G1 could not influence cell invasion under hypoxia conditions.

  10. Role of HLA-G1 in trophoblast cell proliferation, adhesion and invasion

    International Nuclear Information System (INIS)

    Jiang, Feng; Zhao, Hongxi; Wang, Li; Guo, Xinyu; Wang, Xiaohong; Yin, Guowu; Hu, Yunsheng; Li, Yi; Yao, Yuanqing

    2015-01-01

    Trophoblast cells are important in embryo implantation and fetomaternal tolerance. HLA-G is specifically expressed at the maternal–fetal interface and is a regulator in pregnancy. The aim of the present study was to detect the effect of HLA-G1 on trophoblast cell proliferation, adhesion, and invasion. Human trophoblast cell lines (JAR and HTR-8/SVneo cells) were infected with HLA-G1-expressing lentivirus. After infection, HLA-G1 expression of the cells was detected by western blotting. Cell proliferation was detected by the BrdU assay. The cell cycle and apoptosis of JAR and HTR-8/SVneo cells was measured by flow cytometry (FCM). The invasion of the cells under different conditions was detected by the transwell invasion chamber assay. HLA-G1 didn't show any significant influence on the proliferation, apoptosis, adhesion, and invasion of trophocytes in normal culture conditions. However, HLA-G1 inhibited JAR and HTR-8/SVneo cells invasion induced by hepatocyte growth factor (HGF) under normal oxygen conditions. In conditions of hypoxia, HLA-G1 couldn't inhibit the induction of cell invasion by HGF. HLA-G1 is not an independent factor for regulating the trophocytes. It may play an indirect role in embryo implantation and formation of the placenta. - Highlights: • HLA-G1 could not influence trophocytes under normal conditions. • HLA-G1 inhibited cell invasion induced by HGF under normal oxygen condition. • HLA-G1 could not influence cell invasion under hypoxia conditions

  11. MECHANISMS IN ENDOCRINOLOGY: Nutrition as a mediator of oxidative stress in metabolic and reproductive disorders in women.

    Science.gov (United States)

    Diamanti-Kandarakis, Evanthia; Papalou, Olga; Kandaraki, Eleni A; Kassi, Georgia

    2017-02-01

    Nutrition can generate oxidative stress and trigger a cascade of molecular events that can disrupt oxidative and hormonal balance. Nutrient ingestion promotes a major inflammatory and oxidative response at the cellular level in the postprandial state, altering the metabolic state of tissues. A domino of unfavorable metabolic changes is orchestrated in the main metabolic organs, including adipose tissue, skeletal muscle, liver and pancreas, where subclinical inflammation, endothelial dysfunction, mitochondrial deregulation and impaired insulin response and secretion take place. Simultaneously, in reproductive tissues, nutrition-induced oxidative stress can potentially violate delicate oxidative balance that is mandatory to secure normal reproductive function. Taken all the above into account, nutrition and its accompanying postprandial oxidative stress, in the unique context of female hormonal background, can potentially compromise normal metabolic and reproductive functions in women and may act as an active mediator of various metabolic and reproductive disorders. © 2017 European Society of Endocrinology.

  12. Rare Presentation of Metastatic Cystic Trophoblastic Tumor in a Patient Without Prior Chemotherapy

    Directory of Open Access Journals (Sweden)

    Michael L. Wang

    2017-07-01

    Full Text Available Cystic trophoblastic tumor (CTT is a rare testicular germ cell tumor (GCT predominantly seen in post-chemotherapy patients. It is prognostically similar to teratoma and requires no additional chemotherapy in the absence of a nonteratomatous GCT component. We report a case of metastatic CTT in a patient with primary testicular teratoma without prior chemotherapy. Retroperitoneal lymph node metastases contained teratoma, embryonal carcinoma, and CTT. The CTT was β-hCG positive and SALL4 negative by immunohistochemistry (IHC. CTT can arise in metastatic testicular GCT in treatment naïve patients. An important differential diagnosis is choriocarcinoma due to treatment implications, and SALL4 IHC may help.

  13. [Gestational trophoblastic diseases in cesarean scar: an analysis of 20 cases].

    Science.gov (United States)

    Zhang, Ge'er; Pan, Zimin

    2017-05-25

    To analyze the clinical features, diagnosis and treatment of gestational trophoblastic diseases in cesarean scar. Clinical data of three cases of gestational trophoblastic diseases in cesarean scar diagnosed in Women's Hospital, Zhejiang University School of Medicine during December 2011 and December 2016 were collected. And literature search was performed in Wanfang data, VIP, CNKI, PubMed, ISI Web of Knowledge and EMbase database. A total of 20 cases of gestational trophoblastic diseases were included in the analysis. Clinical features were mainly abnormal vaginal bleeding after menopause, artificial abortion or medical abortion, which might be accompanied by abdominal pain. Serum β-human chorionic gonadotropin (β-hCG) levels were increased in 19 patients. The sonographic features were increase of uterine volume, honeycomb-like abnormal intrauterine echo (or described as multiple cystic dark area, multiple anechoic area and multiple liquid dark area) or heterogeneity echo conglomeration, and no clear bound with muscular layer in some cases. There were abundant blood flow signals inside or around the lesions. The ultrasonography indicated that the lesions were located in the anterior side of the uterine isthmus with the involvement of cesarean section scar. In 12 cases with lesions in cesarean scar shown by preliminary diagnosis, 9 underwent uterine artery embolization (UAE) for pretreatment; the blood loss greater than 1500 mL was observed in only one case without UAE; no patient received hysterectomy. In 8 patients whose lesions were not shown in cesarean scar, only one case received UAE pretreatment, and hysterectomy was performed in 3 cases due to blood loss greater than 1500 mL. Two cases were lost in follow-up and no death was reported in remaining 18 cases. The serum β-hCG levels returned to normal or satisfactory level during the follow-up in 17 cases with increased β-hCG levels before treatment and no recurrence was observed. The misdiagnosis rate and

  14. Reactive Oxygen Stimulation of Interleukin-6 Release in the Human Trophoblast Cell Line HTR-8/SVneo by the Trichlorethylene Metabolite S-(1,2-Dichloro)-l-Cysteine.

    Science.gov (United States)

    Hassan, Iman; Kumar, Anjana M; Park, Hae-Ryung; Lash, Lawrence H; Loch-Caruso, Rita

    2016-09-01

    Trichloroethylene (TCE) is a common environmental pollutant associated with adverse reproductive outcomes in humans. TCE intoxication occurs primarily through its biotransformation to bioactive metabolites, including S-(1,2-dichlorovinyl)-l-cysteine (DCVC). TCE induces oxidative stress and inflammation in the liver and kidney. Although the placenta is capable of xenobiotic metabolism and oxidative stress and inflammation in placenta have been associated with adverse pregnancy outcomes, TCE toxicity in the placenta remains poorly understood. We determined the effects of DCVC by using the human extravillous trophoblast cell line HTR-8/SVneo. Exposure to 10 and 20 μM DCVC for 10 h increased reactive oxygen species (ROS) as measured by carboxydichlorofluorescein fluorescence. Moreover, 10 and 20 μM DCVC increased mRNA expression and release of interleukin-6 (IL-6) after 24-h exposure, and these responses were inhibited by the cysteine conjugate beta-lyase inhibitor aminooxyacetic acid and by treatments with antioxidants (alpha-tocopherol and deferoxamine), suggesting that DCVC-stimulated IL-6 release in HTR-8/SVneo cells is dependent on beta-lyase metabolic activation and increased generation of ROS. HTR-8/SVneo cells exhibited decreased mitochondrial membrane potential at 5, 10, and 20 μM DCVC at 5, 10, and 24 h, showing that DCVC induces mitochondrial dysfunction in HTR-8/Svneo cells. The present study demonstrates that DCVC stimulated ROS generation in the human placental cell line HTR-8/SVneo and provides new evidence of mechanistic linkage between DCVC-stimulated ROS and increase in proinflammatory cytokine IL-6. Because abnormal activation of cytokines can disrupt trophoblast functions necessary for placental development and successful pregnancy, follow-up investigations relating these findings to physiologic outcomes are warranted. © 2016 by the Society for the Study of Reproduction, Inc.

  15. TNF-α stimulates System A amino acid transport in primary human trophoblast cells mediated by p38 MAPK signaling.

    Science.gov (United States)

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

    2015-10-01

    Maternal obesity and gestational diabetes mellitus (GDM) increase the risk of delivering infants that are large for gestational age with greater adiposity, who are prone to the development of metabolic disease in childhood and beyond. These maternal conditions are also associated with increased levels of the proinflammatory cytokine TNF-α in maternal tissues and the placenta. Recent evidence suggests that changes in placental amino acid transport contribute to altered fetal growth. TNF-α was previously shown to stimulate System A amino acid transport in primary human trophoblasts (PHTs), however the molecular mechanisms remain unknown. In this study, we tested the hypothesis that TNF-α regulates amino acid uptake in cultured PHTs by a mitogen-activated protein kinase (MAPK)-dependent mechanism. Treatment of PHTs with TNF-α significantly increased System A amino acid transport, as well as Erk and p38 MAPK signaling. Pharmacological antagonism of p38, but not Erk MAPK activity, inhibited TNF-α stimulated System A activity. Silencing of p38 MAPK using siRNA transfections prevented TNF-α stimulated System A transport in PHTs. TNF-α significantly increased the protein expression of System A transporters SNAT1 and SNAT2, but did not affect their mRNA expression. The effects of TNF-α on SNAT1 and SNAT2 protein expression were reversed by p38 MAPK siRNA silencing. In conclusion, TNF-α regulates System A activity through increased SNAT1 and SNAT2 transporter protein expression in PHTs. These findings suggest that p38 MAPK may represent a critical mechanistic link between elevated proinflammatory cytokines and increased placental amino acid transport in obese and GDM pregnancies associated with fetal overgrowth. © 2015 The Authors. Physiological Reports published by Wiley Periodicals, Inc. on behalf of the American Physiological Society and The Physiological Society.

  16. OS041. Apolipoprotein A-I protects normal integration of the trophoblast into endothelial cellular networks in an in vitro model of preeclampsia.

    Science.gov (United States)

    Charlton, F; Xu, B; Makris, A; Hennessy, A; Rye, K-A

    2012-07-01

    Failure of the trophoblast to appropriately invade uterine spiral arteries is thought to be an initiating event in preeclampsia, a disorder associated with endothelial dysfunction. A dyslipidemia characterised by low plasma levels of high density lipoproteins (HDL) and elevated triglycerides has also been described in preeclampsia. The pro-inflammatory cytokine TNF-α inhibits trophoblast invasion of uterine endothelial cells. Previous work using an in vitro JEG-3 cell/Uterine endothelial cell co-culture model investigated the effect of apoliopoprotein A-I, the main apolipoprotein component of HDL, on trophoblast incorporation into endothelial tubules in the presence and absence of TNF-α. These effects are now investigated using the human invasive trophoblast cell line HTR-8/SVneo. This study asks if apoA-I, which has established anti-inflammatory properties, can protect against the deleterious effect of TNF-α on trophoblast-endothelial cell interactions. The in vitro trophoblast-uterine endothelial cell co-culture model was used to investigate the effect of apoA-I on trophoblast incorporation into endothelial tubules in the presence and absence of TNF-α. Uterine endothelial cells were pre-incubated with lipid free apoA-I (final apoA-I concentration 1 mg/mL) for 16h prior to seeding on matrigel coated plates. Tubules formed within 4h. Fluorescence-labelled HTR-8/SVneo trophoblast cells were then co-cultured with the endothelial cells±TNF-α (final concentration of 0.2ng/mL). Bright field and fluorescent images were captured after 24h. The effect of TNF-α on HTR-8/SVneo cell invasion was quantified with Image J software. Integration of HTR-8/SVneo trophoblast cells into uterine endothelial tubular networks was also imaged using live cell imaging techniques (Zeiss Axiovert). TNF-α inhibited HTR-8/SVneo (trophoblast) cell integration into endothelial tubular structures by 24.1±3.7% pintegration of trophoblast into endothelial tubular structures in the presence

  17. Influence of ovarian manipulation on reproductive endocrinology in polycystic ovarian syndrome and regularly cycling women

    NARCIS (Netherlands)

    Hendriks, M.L.; König, T.E.; Soleman, R.S.; Korsen, T.; Schats, R.; Hompes, P.G.A.; Homburg, R.R.; Lambalk, C.B.

    2013-01-01

    Objective: Little is known about the function of the ovarian neuronal network in humans. In many species, copulation influences endocrinology through this network. As a first step, the possible influence of ovarian mechanical manipulation on pituitary and ovarian hormones was evaluated in polycystic

  18. Blood Glucose Monitoring as a Teaching Tool for Endocrinology: A New Perspective

    Science.gov (United States)

    Moats, Robert K., II

    2009-01-01

    The education of new allied health professionals and nurses in proper endocrine evaluation and care has become critical in recent years, especially considering the greatly increased prevalence of diabetes in adults and children. The evaluation of blood glucose levels in human volunteers over time is a powerful teaching tool for endocrinology that…

  19. Endocrinology Telehealth Consultation Improved Glycemic Control Similar to Face-to-Face Visits in Veterans.

    Science.gov (United States)

    Liu, Winnie; Saxon, David R; McNair, Bryan; Sanagorski, Rebecca; Rasouli, Neda

    2016-09-01

    Rates of diabetes for veterans who receive health care through the Veterans Health Administration are higher than rates in the general population. Furthermore, many veterans live in rural locations, far from Veterans Affairs (VA) hospitals, thus limiting their ability to readily seek face-to-face endocrinology care for diabetes. Telehealth (TH) technologies present an opportunity to improve access to specialty diabetes care for such patients; however, there is a lack of evidence regarding the ability of TH to improve glycemic control in comparison to traditional face-to-face consultations. This was a retrospective cohort study of all new endocrinology diabetes consultations at the Denver VA Medical Center over a 1-year period. A total of 189 patients were included in the analysis. In all, 85 patients had received face-to-face (FTF) endocrinology consultation for diabetes and 104 patients had received TH consultation. Subjects were mostly males (94.7%) and the mean age was 62.8 ± 10.1 years old. HbA1c improved from 9.76% (9.40% to 10.11%) to 8.55% (8.20% to 8.91%) (P Endocrinology TH consultations improved short-term glycemic control as effectively as traditional FTF visits in a veteran population with diabetes. © 2016 Diabetes Technology Society.

  20. Ernest Henry Starling: the history of cardiovascular endocrinology and the continuous need for developing animal models

    DEFF Research Database (Denmark)

    Henriksen, Jens Henrik Sahl

    2014-01-01

    The English physiologist, Ernest Henry Starling (1866–1927) (Fig. 1) in 1896, provided a quantitative explanation of the transcapillary transport of fluid. Six years later, he discovered the first hormone and introduced the concept of hormones in 1905, and at the time of the First World War, he f......’s achievements in cardiovascular physiology and endocrinology....

  1. Trends in the study of the comparative endocrinology of reproduction in vertebrates

    NARCIS (Netherlands)

    Oordt, G.J. van

    1962-01-01

    A couple of months ago the organizers of the present Conference asked me to deliver an opening address, which would review the development of comparative endocrinology in Europe, particularly with reference to my own work and experiences. Of course I accepted this invitation with very much

  2. Endocrinology in the 21st century: unmasking the mysteries of biology

    NARCIS (Netherlands)

    Romijn, J. A.

    1999-01-01

    The traditional concept of endocrinology has provided a model, that enabled to understand and treat endocrine diseases. Molecular and (patho)physiological differentiations of this concept will further improve the treatment of complex endocrine and metabolic diseases. Nature has lifted a tip of her

  3. Development of an e-learning portal for pediatric endocrinology : Educational considerations

    NARCIS (Netherlands)

    K. Grijpink-Van den Biggelaar; S.L.S. Drop (Stenvert); L. Schuwirth

    2010-01-01

    textabstractBackground: Global accessibility and dissemination of developments in pediatric endocrinology prompted to examine how to develop an educational interactive e-SPE web portal. Methods: A systematic approach was used to identify the relevant aspects of accessibility and dissemination. An

  4. Motivational interviewing in health care: results of a brief training in endocrinology.

    Science.gov (United States)

    Bean, Melanie K; Biskobing, Diane; Francis, Gary L; Wickham, Edmond

    2012-09-01

    Despite the importance of lifestyle change in disease management and the growing evidence supporting motivational interviewing (MI) as an effective counseling method to promote behavioral change, to date there are few published reports about MI training in graduate medical education. The study aimed to pilot the feasibility and effectiveness of a brief MI training intervention for endocrinology fellows and other providers. We used a pretest/posttest design to evaluate a brief MI training for 5 endocrinology fellows and 9 other providers. All participants completed subjective assessments of perceived confidence and beliefs about behavioral counseling at pretest and posttest. Objective assessment of MI was conducted using fellows' audiotaped patient encounters, which were coded using a validated tool for adherence to MI before and after the training. Paired t tests examined changes in objective and subjective assessments. The training intervention was well received and feasible in the endocrinology setting. At posttest, participants reported increased endorsement of the MI spirit and improved confidence in MI skills. Objective assessment revealed relative improvements in MI skills across several domains. However, most domains, as assessed by a validated tool, did not reach competency level after the training intervention. Although more intensive training may be needed to develop MI competence, the results of our pilot study suggest that brief, targeted MI training has short-term efficacy and is well received by endocrinology fellows and other providers.

  5. The neuro-endocrinological role of microbial glutamate and GABA signaling

    Directory of Open Access Journals (Sweden)

    Roberto Mazzoli

    2016-11-01

    Full Text Available Gut microbiota provides the host with multiple functions (e.g., by contributing to food digestion, vitamin supplementation and defense against pathogenic strains and interacts with the host organism through both direct contact (e.g., through surface antigens and soluble molecules, which are produced by the microbial metabolism. The existence of the so-called gut-brain axis of bi-directional communication between the gastrointestinal tract and the central nervous system also supports a communication pathway between the gut microbiota and neural circuits of the host, including the central nervous system. An increasing body of evidence has shown that gut microbiota is able to modulate gut and brain functions, including the mood, cognitive functions and behavior of humans. Nonetheless, given the extreme complexity of this communication network, its comprehension is still at its early stage. The present contribution will attempt to provide a state-of-the art description of the mechanisms by which gut microbiota can affect the gut-brain axis and the multiple cellular and molecular communication circuits (i.e., neural, immune and humoral. In this context, special attention will be paid to the microbial strains that produce bioactive compounds and display ascertained or potential probiotic activity. Several neuroactive molecules (e.g., catecholamines, histamine, serotonin and trace amines, will be considered, with special focus on Glu and GABA circuits, receptors and signaling. From the basic science viewpoint, microbial endocrinology deals with those theories in which neurochemicals, produced by both multicellular organisms and prokaryotes (e.g., serotonin, GABA, glutamate, are considered as a common shared language that enables interkingdom communication. With regards to its application, research in this area opens the way toward the possibility of the future use of neuroactive molecule-producing probiotics as therapeutic agents for the treatment of

  6. The Neuro-endocrinological Role of Microbial Glutamate and GABA Signaling.

    Science.gov (United States)

    Mazzoli, Roberto; Pessione, Enrica

    2016-01-01

    Gut microbiota provides the host with multiple functions (e.g., by contributing to food digestion, vitamin supplementation, and defense against pathogenic strains) and interacts with the host organism through both direct contact (e.g., through surface antigens) and soluble molecules, which are produced by the microbial metabolism. The existence of the so-called gut-brain axis of bi-directional communication between the gastrointestinal tract and the central nervous system (CNS) also supports a communication pathway between the gut microbiota and neural circuits of the host, including the CNS. An increasing body of evidence has shown that gut microbiota is able to modulate gut and brain functions, including the mood, cognitive functions, and behavior of humans. Nonetheless, given the extreme complexity of this communication network, its comprehension is still at its early stage. The present contribution will attempt to provide a state-of-the art description of the mechanisms by which gut microbiota can affect the gut-brain axis and the multiple cellular and molecular communication circuits (i.e., neural, immune, and humoral). In this context, special attention will be paid to the microbial strains that produce bioactive compounds and display ascertained or potential probiotic activity. Several neuroactive molecules (e.g., catecholamines, histamine, serotonin, and trace amines) will be considered, with special focus on Glu and GABA circuits, receptors, and signaling. From the basic science viewpoint, "microbial endocrinology" deals with those theories in which neurochemicals, produced by both multicellular organisms and prokaryotes (e.g., serotonin, GABA, glutamate), are considered as a common shared language that enables interkingdom communication. With regards to its application, research in this area opens the way toward the possibility of the future use of neuroactive molecule-producing probiotics as therapeutic agents for the treatment of neurogastroenteric and

  7. Permissive cytomegalovirus infection of primary villous term and first trimester trophoblasts.

    Science.gov (United States)

    Hemmings, D G; Kilani, R; Nykiforuk, C; Preiksaitis, J; Guilbert, L J

    1998-06-01

    Forty percent of women with primary cytomegalovirus (CMV) infections during pregnancy infect their fetuses with complications for the baby varying from mild to severe. How CMV crosses the syncytiotrophoblast, the barrier between maternal blood and fetal tissue in the villous placenta, is unknown. Virus may cross by infection of maternal cells that pass through physical breaches in the syncytiotrophoblast or by direct infection of the syncytiotrophoblast, with subsequent transmission to underlying fetal placental cells. In this study, we show that pure (>99.99%), long-term and healthy (>3 weeks) cultures of syncytiotrophoblasts are permissively infected with CMV. Greater than 99% of infectious progeny virus remained cell associated throughout culture periods up to 3 weeks. Infection of term trophoblasts required a higher virus inoculum, was less efficient, and progressed more slowly than parallel infections of placental and human embryonic lung fibroblasts. Three laboratory strains (AD169, Towne, and Davis) and a clinical isolate from a congenitally infected infant all permissively infected trophoblasts, although infection efficiencies varied. The infection of first trimester syncytiotrophoblasts with strain AD169 occurred at higher frequency and progressed more rapidly than infection of term cells but less efficiently and rapidly than infection of fibroblasts. These results show that villous syncytiotrophoblasts can be permissively infected by CMV but that the infection requires high virus titers and proceeds slowly and that progeny virus remains predominantly cell associated.

  8. Cytotoxicant-induced trophoblast dysfunction and abnormal pregnancy outcomes: role of zinc and metallothionein.

    Science.gov (United States)

    McAleer, Mary Frances; Tuan, Rocky S

    2004-12-01

    Normal trophoblast function, including implantation, hormone production, and formation of the selectively permeable maternofetal barrier, is essential for the establishment and maintenance of the fetoplacental unit and proper fetal development. Maternal cytotoxicant exposure causes the destruction of these cells, especially the terminally differentiated syncytiotrophoblasts, and results in a myriad of poor pregnancy outcomes. These outcomes range from intrauterine growth retardation and malformation to spontaneous abortion or stillbirth. There is recent evidence that the metal-binding protein, metallothionein, is involved in the protection of human trophoblastic cells from heavy metal-induced and severe oxidative stress-induced apoptosis. Metallothionein, with its unique biochemical structure, can both bind essential metal ions, such as the transcription modulator zinc, and yet allow their ready displacement by toxic nonessential metal ions or damaging free radicals. These properties suggest that metallothionein may be responsible not only for sequestering the cytotoxic agents, but also for altering signal transduction in the affected cells. Here, we review several identified causes of adverse pregnancy outcomes (specifically, prenatal exposure to cigarette smoke and alcohol, gestational infection, and exposure to environmental contaminants), discuss the role of zinc in modulating the cellular response to these toxic insults, and then propose how metallothionein may function to mediate this protective response. Published 2005 Wiley-Liss, Inc.

  9. miR-520 promotes DNA-damage-induced trophoblast cell apoptosis by targeting PARP1 in recurrent spontaneous abortion (RSA).

    Science.gov (United States)

    Dong, Xiujuan; Yang, Long; Wang, Hui

    2017-04-01

    The establishment and maintenance of successful pregnancy mainly depends on trophoblast cells. Their dysfunction has been implicated in recurrent spontaneous abortion (RSA), a major complication of pregnancy. However, the underlying mechanisms of trophoblasts dysfunction remain unclear. DNA-damage-induced cell apoptosis has been reported to play a vital role in cell death. In this study, we identified a novel microRNA (miR-520) in RSA progression via regulating trophoblast cell apoptosis. Microarray analysis showed that miR-520 was highly expressed in villus of RSA patients. By using flow cytometry analysis, we observed miR-520 expression was correlated with human trophoblast cell apoptosis in vitro, along with decreased poly (ADP-ribose) polymerase-1 (PARP1) expression. With the analysis of clinic samples, we observed that miR-520 level was negatively correlated with PARP1 level in RSA villus. In addition, overexpression of PARP1 restored the miR-520-induced trophoblast cell apoptosis in vitro. The status of chromosome in trophoblast implied that miR-520-promoted DNA-damage-induced cell apoptosis to regulate RSA progression. These results indicated that the level of miR-520 might associate with RSA by prompting trophoblast cell apoptosis via PARP1 dependent DNA-damage pathway.

  10. The clinical endocrinology workforce: current status and future projections of supply and demand.

    Science.gov (United States)

    Vigersky, Robert A; Fish, Lisa; Hogan, Paul; Stewart, Andrew; Kutler, Stephanie; Ladenson, Paul W; McDermott, Michael; Hupart, Kenneth H

    2014-09-01

    Many changes in health care delivery, health legislation, and the physician workforce that affect the supply and demand for endocrinology services have occurred since the first published workforce study of adult endocrinologists in 2003. The objective of the study was to assess the current adult endocrinology workforce data and provide the first analysis of the pediatric endocrinology workforce and to project the supply of and demand for endocrinologists through 2025. A workforce model was developed from an analysis of proprietary and publicly available databases, consultation with a technical expert panel, and the results of an online survey of board-certified endocrinologists. The Endocrine Society commissioned The Lewin Group to estimate current supply and to project gaps between supply and demand for endocrinologists. A technical expert panel of senior endocrinologists provided context, clinical information, and direction. The following were measured: 1) the current adult and pediatric endocrinology workforce and the supply of and demand for endocrinologists through 2025 and 2) the number of additional entrants into the endocrinology work pool that would be required to close the gap between supply and demand. Currently there is a shortage of approximately 1500 adult and 100 pediatric full-time equivalent endocrinologists. The gap for adult endocrinologists will expand to 2700 without an increase in the number of fellows trained. An increase in the prevalence of diabetes mellitus further expands the demand for adult endocrinologists. The gap can be closed in 5 and 10 years by increasing the number of fellowship positions by 14.4% and 5.5% per year, respectively. The gap between supply and demand for pediatric endocrinologists will close by 2016, and thereafter an excess supply over demand will develop at the current rate of new entrants into the work force. There are insufficient adult endocrinologists to satisfy current and future demand. A number of proactive

  11. Quantitative investigation of reproduction of gonosomal condensed chromatin during trophoblast cell polyploidization and endoreduplication in the east-european field vole Microtus rossiaemeridionalis

    Directory of Open Access Journals (Sweden)

    Bogdanova Margarita S

    2003-04-01

    Full Text Available Abstract Simultaneous determinations of DNA content in cell nuclei and condensed chromatin bodies formed by heterochromatized regions of sex chromosomes (gonosomal chromatin bodies, GCB have been performed in two trophoblast cell populations of the East-European field vole Microtus rossiaemeridionalis: in the proliferative population of trophoblast cells of the junctional zone of placenta and in the secondary giant trophoblast cells. One or two GCBs have been observed in trophoblast cell nuclei of all embryos studied (perhaps both male and female. In the proliferative trophoblast cell population characterized by low ploidy levels (2–16c and in the highly polyploid population of secondary giant trophoblast cells (32–256c the total DNA content in GCB increased proportionally to the ploidy level. In individual GCBs the DNA content also rose proportionally to the ploidy level in nuclei both with one and with two GCBs in both trophoblast cell populations. Some increase in percentage of nuclei with 2–3 GCBs was shown in nuclei of the placenta junctional zone; this may be accounted for by genome multiplication via uncompleted mitoses. In nuclei of the secondary giant trophoblast cells (16–256c the number of GCBs did not exceed 2, and the fraction of nuclei with two GCBs did not increase, which suggests the polytene nature of sex chromosomes in these cells. In all classes of ploidy the DNA content in trophoblast cell nuclei with the single GCB was lower than in nuclei with two and more GCBs. This can indicate that the single GCB in many cases does not derive from fusion of two GCBs. The measurements in individual GCBs suggest that different heterochromatized regions of the X- and Y-chromosome may contribute in GCB formation.

  12. Allelic imbalance modulates surface expression of the tolerance-inducing HLA-G molecule on primary trophoblast cells

    DEFF Research Database (Denmark)

    Djurisic, S; Teiblum, S; Tolstrup, C K

    2015-01-01

    The HLA-G molecule is expressed on trophoblast cells at the feto-maternal interface, where it interacts with local immune cells, and upholds tolerance against the semi-allogeneic fetus. Aberrant HLA-G expression in the placenta and reduced soluble HLA-G levels are observed in pregnancy complicati...

  13. Human Primary Trophoblast Cell Culture Model to Study the Protective Effects of Melatonin Against Hypoxia/reoxygenation-induced Disruption.

    Science.gov (United States)

    Sagrillo-Fagundes, Lucas; Clabault, Hélène; Laurent, Laetitia; Hudon-Thibeault, Andrée-Anne; Salustiano, Eugênia Maria Assunção; Fortier, Marlène; Bienvenue-Pariseault, Josianne; Wong Yen, Philippe; Sanderson, J Thomas; Vaillancourt, Cathy

    2016-07-30

    This protocol describes how villous cytotrophoblast cells are isolated from placentas at term by successive enzymatic digestions, followed by density centrifugation, media gradient isolation and immunomagnetic purification. As observed in vivo, mononucleated villous cytotrophoblast cells in primary culture differentiate into multinucleated syncytiotrophoblast cells after 72 hr. Compared to normoxia (8% O2), villous cytotrophoblast cells that undergo hypoxia/reoxygenation (0.5% / 8% O2) undergo increased oxidative stress and intrinsic apoptosis, similar to that observed in vivo in pregnancy complications such as preeclampsia, preterm birth, and intrauterine growth restriction. In this context, primary villous trophoblasts cultured under hypoxia/reoxygenation conditions represent a unique experimental system to better understand the mechanisms and signalling pathways that are altered in human placenta and facilitate the search for effective drugs that protect against certain pregnancy disorders. Human villous trophoblasts produce melatonin and express its synthesizing enzymes and receptors. Melatonin has been suggested as a treatment for preeclampsia and intrauterine growth restriction because of its protective antioxidant effects. In the primary villous cytotrophoblast cell model described in this paper, melatonin has no effect on trophoblast cells in normoxic state but restores the redox balance of syncytiotrophoblast cells disrupted by hypoxia/reoxygenation. Thus, human villous trophoblast cells in primary culture are an excellent approach to study the mechanisms behind the protective effects of melatonin on placental function during hypoxia/reoxygenation.

  14. Obstetric ultrasound aids prompt referral of gestational trophoblastic disease in marginalized populations on the Thailand-Myanmar border

    NARCIS (Netherlands)

    McGregor, Kathryn; Min, Aung Myat; Karunkonkowit, Noaeni; Keereechareon, Suporn; Tyrosvoutis, Mary Ellen; Tun, Nay Win; Rijken, Marcus J.; Hoogenboom, Gabie; Boel, Machteld; Chotivanich, Kesinee; Nosten, François; McGready, Rose

    2017-01-01

    Background: The use of obstetric ultrasound in the diagnosis of gestational trophoblastic disease (GTD) in high-income settings is well established, leading to prompt management and high survival rates. Evidence from low-income settings suggests ultrasound is essential in identifying complicated

  15. Role of ultrasound in the diagnosis and management of gestational trophoblastic disease in Rural health facilities- A case report

    International Nuclear Information System (INIS)

    Bach, J.F.H.

    2015-01-01

    Gestational trophoblastic disease (GTD) is a rare kind of proliferative disorder of trophoblastic cells which develops from the placenta in early pregnancy. It can be benign, premalignant or malignant. Molar pregnancy, also known as Hydatidiform Mole, is a form of benign GTD. The complete hydatidiform mole (CHM) sub-type which limited to endometrium is most common. It has excellent prognosis if early appropriate diagnosis and management are done. A well performed ultrasound(US) play a primordial role in the diagnosis of maternal health disorders during routine prenatal care. This helps in avoiding complications and consequently aids in achieving the objectives of the Millennium Development Goals (MDGs) in Rwanda. To understand the definition of Gestational trophoblastic disease(GTD) and to recognize key diagnostic findings of complete molar pregnancy on ultrasound and appropriate management in maternal follow up. Review the differential diagnosis for ultrasound findings seen with GTD and other modalities Ultrasound is the first modality to be used in all rural health facilities for diagnosis of suspected Gestational trophoblastic disease (GTD) for better results. It is available and free of radiation

  16. Hypoxic stress induces, but cannot sustain trophoblast stem cell differentiation to labyrinthine placenta due to mitochondrial insufficiency

    Directory of Open Access Journals (Sweden)

    Yufen Xie

    2014-11-01

    Full Text Available Dysfunctional stem cell differentiation into placental lineages is associated with gestational diseases. Of the differentiated lineages available to trophoblast stem cells (TSC, elevated O2 and mitochondrial function are necessary to placental lineages at the maternal–placental surface and important in the etiology of preeclampsia. TSC lineage imbalance leads to embryonic failure during uterine implantation. Stress at implantation exacerbates stem cell depletion by decreasing proliferation and increasing differentiation. In an implantation site O2 is normally ~2%. In culture, exposure to 2% O2 and fibroblast growth factor 4 (FGF4 enabled the highest mouse TSC multipotency and proliferation. In contrast, hypoxic stress (0.5% O2 initiated the most TSC differentiation after 24 h despite exposure to FGF4. However, hypoxic stress supported differentiation poorly after 4–7 days, despite FGF4 removal. At all tested O2 levels, FGF4 maintained Warburg metabolism; mitochondrial inactivity and aerobic glycolysis. However, hypoxic stress suppressed mitochondrial membrane potential and maintained low mitochondrial cytochrome c oxidase (oxidative phosphorylation/OxPhos, and high pyruvate kinase M2 (glycolysis despite FGF4 removal. Inhibiting OxPhos inhibited optimum differentiation at 20% O2. Moreover, adding differentiation-inducing hyperosmolar stress failed to induce differentiation during hypoxia. Thus, differentiation depended on OxPhos at 20% O2; hypoxic and hyperosmolar stresses did not induce differentiation at 0.5% O2. Hypoxia-limited differentiation and mitochondrial inhibition and activation suggest that differentiation into two lineages of the labyrinthine placenta requires O2 > 0.5–2% and mitochondrial function. Stress-activated protein kinase increases an early lineage and suppresses later lineages in proportion to the deviation from optimal O2 for multipotency, thus it is the first enzyme reported to prioritize differentiation.

  17. PP042. Anti-hypertensive drugs hydralazine, clonidine and labetalol improve trophoblast integration into endothelial cellular networks in vitro.

    Science.gov (United States)

    Xu, B; Charlton, F; Makris, A; Hennessy, A

    2012-07-01

    Preeclampsia is an exaggerated maternal inflammatory state with over-expression of placental soluble fms-like tyrosine kinase 1 (sFlt-1). It is also associated with shallow trophoblast invasion and inadequate transformation of uterine spiral arteries. Antihypertensive drugs administrated in preeclampsia to control blood pressure have been reported to regulate placental and circulating cytokine production from women with preeclampsia. Whether they could modulate the interaction between trophoblast and endothelial cells are not investigated. This study is to examine the effect of pharmacological dose of anti-hypertensive hydralazine, clonidine and labetalol on trophoblast cell integration into inflammatory TNF-a pre-exposed endothelial cellular networks. Human uterine myometrial microvascular endothelial cells (UtMVECs) were pre-incubated with (or without) low dose (0.5ng/ml) inflammatory TNF-a or TNF-a plus sFlt-1 (100ng/ml) for 24hours. These cells were labelled with red fluorescence and seeded on a 24-well culture plate coated with Matrigel. Endothelial tubular structures appeared within 4hours. Green fluorescent-labelled HTR-8/SVneo trophoblast cells were then co-cultured with endothelial cells, with (or without) hydralazine (10μg/ml), clonidine (1.0μg/ml) or labetalol (0.5μg/ml). Red and green fluorescent images were captured after 24hours. Drug effect on HTR-8 cells integration into endothelial cellular networks was quantified by Image Analysis software. The conditioned media were also collected to measure concentrations of free VEGF, PLGF and sFlt-1 by ELISA. When HTR-8/SVneo trophoblast cells were co-cultured with TNF-a pre-incubated endothelial cells, hydralazine and clonidine can significantly increase the trophoblast integration into endothelial cellular networks. This increase was not seen if co-cultured with normal endothelial cells (without TNF-a pre-incubation) or with TNF-a plus sFlt-1 treated endothelial cells. Labetalol could increase the HTR-8

  18. MiR-519d-3p suppresses invasion and migration of trophoblast cells via targeting MMP-2.

    Directory of Open Access Journals (Sweden)

    Jie Ding

    Full Text Available Our study was approved by the Medical Ethics Committee of Tang Du Hospital, Fourth Military Medical University and complied strictly with national ethical guidelines. Preeclampsia (PE is a specific clinical disorder characterized by gestational hypertension and proteinuria and is a leading cause of maternal and perinatal mortality worldwide. The miR-519d-3p is upregulated in the maternal plasma of patients with PE which indicates a possible association between this microRNA and the pathogenesis of PE. No studies to date have addressed the effect of miR-519d-3p on the invasion and migration of trophoblast cells. In our study, we found that miR-519d-3p expression was elevated in placental samples from patients with PE. In vitro, overexpression of miR-519d-3p significantly inhibited trophoblast cell migration and invasion, whereas transfection of a miR-519d-3p inhibitor enhanced trophoblast cell migration and invasion. Luciferase assays confirmed that matrix metalloproteinase-2 (MMP-2 is a direct target of miR-519d-3p. Quantitative real-time PCR and western blot assays showed that overexpression of miR-519d-3p downregulated MMP-2 mRNA and protein expression. Knockdown of MMP-2 using a siRNA attenuated the increased trophoblast migration and invasion promoted by the miR-519d-3p inhibitor. In placentas from patients with PE or normal pregnancies, a negative correlation between the expression of MMP-2 and miR-519d-3p was observed using the Pearson correlation and linear regression analysis. Our present findings suggest that upregulation of miR-519d-3p may contribute to the development of PE by inhibiting trophoblast cell migration and invasion via targeting MMP-2; miR-519d-3p may represent a potential predictive and therapeutic target for PE.

  19. The clinicopathological features of intermediate trophoblastic tumor in the pineal region

    Directory of Open Access Journals (Sweden)

    ZHANG Yun-xiang

    2012-08-01

    Full Text Available Objective To evaluate the clinicopathological features of intermediate trophoblastic tumor (ITT in the pineal region. Methods A retrospective study was performed to analyse the diagnostic and therapeutic process of 1 case with ITT in the pineal region. The specimen obtained from the surgery was dealt with common tissue processing mode and cut into slices. HE staining was performed to observe histophathological features. Immunohistochemical staining (SP two-step method was performed to analyse the expression of tumor markers. Related literatures were reviewed. Results A 6-year old boy with clinical manifestations of penis enlargement and rapid growth for more than one year, presented a mass in his pineal region through MRI. The tumor was surgically excised after it is refractory to 10 times experimental radiotherapy as germinoma. The level of β-human chorionic gonadotropin ( β-hCG in his postoperative blood was decreased to normal, but gradually increased, once again followed to normal after three times chemotherapy. Patient was normal almost postoperative 6 months later by follow -up. Pathological examination showed sheets necrosis with multiple calcification and scattered fresh blood cells, epithelioid tumor cells with solid growth pattern. The tumor cells were atypical mononuclear cells with relative uniform (between heterotypic cells and partially surrounding and invasing the vascular walls. The cytoplasm of tumor cells was eosinophilic or clear, the nucleus was round or irregular in shape and some with intranuclear pseudoinclusions, and its mitotic figures were rarely seen under light microscopy. The tumor cells showed strong positive for AE1/AE3, cell adhesion molecules 5.2 (CAM5.2, human placental lactogen (hPL, octamer-binding transcription factor 3/4 (Oct3/4, epidermal growth factor receptor (EGFR and E-cadherin. P53 was also expressed. The positive rate of Ki-67 was about 10%, and β-hCG was expressed in the extremely tumor cells. The

  20. Activation of PPAR{gamma} by Human Cytomegalovirus for de novo Replication Impairs Migration and Invasiveness of Cytotrophoblast from Early Placenta

    DEFF Research Database (Denmark)

    Rauwel, Benjamin; Mariamé, Bernard; Martin, Hélène

    2010-01-01

    , as assessed by using well-established in vitro models of invasive trophoblast i.e. primary cultures of EVCT isolated from first trimester placentas and the EVCT-derived cell line HIPEC. Our data provide new clues to explain how early infection during pregnancy could impair implantation, placentation...... and chromatin immunoprecipitation assays. Due to the key role of PPARgamma in placentation and its specific trophoblast expression within the human placenta, we then provided evidence that by activating PPARgamma human cytomegalovirus dramatically impaired early human trophoblast migration and invasiveness...

  1. Evaluation and Referral of Diabetic Eye Disease in the Endocrinology and Primary Care Office Settings.

    Science.gov (United States)

    Silva, Fabiana Q; Adhi, Mehreen; Wai, Karen M; Olansky, Leann; Lansang, M Cecilia; Singh, Rishi P

    2016-10-01

    The purpose of this study was to identify whether endocrinologists and primary care physicians (PCP) adequately screen for ophthalmic symptoms/signs within office visits and provide timely ophthalmology referrals in patients with diabetes. Patients between the ages of 18 years and 80 years with diabetes who underwent an office visit with an endocrinologist or a PCP between January 1, 2014, and December 31, 2014, were identified. Demographics, ophthalmic assessments, and referral information were collected. A total of 1,250 patient records were reviewed. Providers asked about ophthalmic symptoms/signs in 95.5% and 71% of endocrinology and primary care office encounters, respectively (P endocrinology and PCP visits, respectively (P < .0001). Ophthalmic complications from diabetes are not adequately screened, especially within the primary care setting, and further quality improvement measures may improve adherence to recommended screening protocols. [Ophthalmic Surg Lasers Imaging Retina. 2016;47:930-934.]. Copyright 2016, SLACK Incorporated.

  2. Polish Society of Endocrinology Position statement on endocrine disrupting chemicals (EDCs).

    Science.gov (United States)

    Rutkowska, Aleksandra; Rachoń, Dominik; Milewicz, Andrzej; Ruchała, Marek; Bolanowski, Marek; Jędrzejuk, Diana; Bednarczuk, Tomasz; Górska, Maria; Hubalewska-Dydejczyk, Alicja; Kos-Kudła, Beata; Lewiński, Andrzej; Zgliczyński, Wojciech

    2015-01-01

    With the reference to the position statements of the Endocrine Society, the Paediatric Endocrine Society, and the European Society of Paediatric Endocrinology, the Polish Society of Endocrinology points out the adverse health effects caused by endocrine disrupting chemicals (EDCs) commonly used in daily life as components of plastics, food containers, pharmaceuticals, and cosmetics. The statement is based on the alarming data about the increase of the prevalence of many endocrine disorders such as: cryptorchidism, precocious puberty in girls and boys, and hormone-dependent cancers (endometrium, breast, prostate). In our opinion, it is of human benefit to conduct epidemiological studies that will enable the estimation of the risk factors of exposure to EDCs and the probability of endocrine disorders. Increasing consumerism and the industrial boom has led to severe pollution of the environment with a corresponding negative impact on human health; thus, there is great necessity for the biomonitoring of EDCs in Poland.

  3. society for endocrinology, metabolism and diabetes of southern ...

    African Journals Online (AJOL)

    1971-05-29

    May 29, 1971 ... children, the effective renin activity was equivalent to 24 ng angiotensinjmlj4 h ..... D confirmed the suspicion that her osteomalacia was nutritional. ... Studies on patients with anorexia nervosa demonstrate· that food restri~tion ...

  4. Steroid hormones modulate galectin-1 in the trophoblast HTR-8/SVneocell line

    Directory of Open Access Journals (Sweden)

    Bojić-Trbojević Žanka

    2008-01-01

    Full Text Available The effects of steroids on galectin-1 (gal-1 were studied in HTR-8/SVneo cells by immunocytochemistry, cell-based ELISA, the MTT proliferation test and the Matrigel TM invasion test. Dexamethasone (DEX, progesterone (PRG, and mifepristone (RU486 were used. Gal-1 was modulated in a steroid- and dose-dependent manner by DEX, which mildly but significantly stimulated production at low concentrations (0.1-10 nM, and inhibited it at 100 nM, while the effects of PRG and RU486 were opposite. HTR-8/SVneo cell invasion of Matrigel was significantly decreased in the presence of DEX and lactose. The obtained data support the proposed regulatory role of steroids in trophoblast gal-1 production.

  5. Immunolocalization of progesterone receptors in binucleate trophoblast cells of the buffalo placenta (Bubalus bubalis

    Directory of Open Access Journals (Sweden)

    Carlos Eduardo Ambrósio

    2007-06-01

    Full Text Available The binucleate trophoblast cells (CTBs of the water buffalo placenta (Bubalus bubalis were studied with emphasis on the presence of progesterone receptor. Placentomal tissues from 27 buffalos (2-10 months of pregnancy were processed and embedded in paraplast (Paraplast Embedding Media – Paraplast Plus to locate the progesterone receptors using the immunohistochemistry technique. The immunohistochemical reaction for progesterone receptor through monoclonal antibody PgR Ab2 showed staining of CTBs, caruncular epithelial and estromal cells and blood vessel estromal pericitos present in the placentome throughout the entire gestational period analyzed. These results indicate the production of progesterone with autocrine and paracrine action in the placentome growth, differentiation and functional regulation.

  6. Elsevier Trophoblast Research Award lecture: The multifaceted role of Nodal signaling during mammalian reproduction.

    Science.gov (United States)

    Park, C B; Dufort, D

    2011-03-01

    Nodal, a secreted signaling protein in the transforming growth factor-beta (TGF-β) superfamily, has established roles in vertebrate development. However, components of the Nodal signaling pathway are also expressed at the maternal-fetal interface and have been implicated in many processes of mammalian reproduction. Emerging evidence indicates that Nodal and its extracellular inhibitor Lefty are expressed in the uterus and complex interactions between the two proteins mediate menstruation, decidualization and embryo implantation. Furthermore, several studies have shown that Nodal from both fetal and maternal sources may regulate trophoblast cell fate and facilitate placentation as both embryonic and uterine-specific Nodal knockout mouse strains exhibit disrupted placenta morphology. Here we review the established and prospective roles of Nodal signaling in facilitating successful pregnancy, including recent evidence supporting a potential link to parturition and preterm birth. Copyright © 2011 Elsevier Ltd. All rights reserved.

  7. Clinical characteristics and outcomes of placental site trophoblastic tumor: experience of single institution in Korea.

    Science.gov (United States)

    Lee, Hye-Joo; Shin, Wonkyo; Jang, Yun Jeong; Choi, Chel Hun; Lee, Jeong-Won; Bae, Duk-Soo; Kim, Byoung-Gie

    2018-05-01

    Placental site trophoblastic tumor (PSTT) is the rarest form of gestational trophoblastic disease (GTD) and the optimum management is still controversial. In this study, we analyzed the clinical features, treatment, and outcomes of 6 consecutive patients with PSTT treated in our institution. The electronic medical record database of Samsung Medical Center was screened to identify patients with PSTT from 1994 to 2017. Medical records for the details of each patient's clinical features and treatment were extracted and reviewed. This study was approved Institutional Review Board of our hospital. A total of 418 cases of GTD, 6 (1.4%) patients with PSTT were identified. The median age of the patients was 31 years. The antecedent pregnancy was term in all 5 cases with available antecedent pregnancy information and the median interval from pregnancy to diagnosis of PSTT was 8 months. The median titer of serum beta human chorionic gonadotropin (β-hCG) at diagnosis was 190.9 mIU/mL. Five (83.3%) patients presented with irregular vaginal bleeding and one (16.7%) had amenorrhea. All patients had disease confined to the uterus without metastasis at diagnosis and were successfully treated by hysterectomy alone. All of them were alive without disease during the follow-up period. In this study, we observed low level serum β-hCG titer and irregular vaginal bleeding with varying interval after antecedent term pregnancy were most common presenting features of PSTT. In addition, we demonstrated hysterectomy alone was successful for the treatment of stage I disease of PSTT.

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

    Science.gov (United States)

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

    2015-08-01

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

  9. Graded hyperthyroidism and serum human chorionic gonadotropin concentration in patients with trophoblastic disease

    International Nuclear Information System (INIS)

    Rajatanavin, R.

    1989-11-01

    Serum thyroid hormone and basal and post TRH stimulated levels of TSH were measured in 48 female subjects of mean age 29.3 ± 9.2 and mean gravida 2.9 ± 2.6 with trophoblastic disease (TD), both benign and malignant. Normal pregnant women (n=21) served as controls. Twenty-five patients showed a normal response to TRH (Group i) while the rest (Group ii) had subnormal response while thyroid hormone levels were increased. Two subgroups iiA and iiB were formed within Group ii on the basis of the free T 4 levels (measured by equilibrium dialysis) falling below or above the 25th percentile. hCG levels were higher in Group ii than in Group i and a stepwise significant increase in the mean level of this hormone was observed in Group i to iiA and iiB. Significant correlation between hCG levels and those of thyroxine, free thyroxine, and triiodothyronine were found in TD patients as a whole, but not within the different subgroups. Clinical signs were minimal, with proximal muscle weakness and fine finger tumours observed in 10 patients in Group iiB. The study shows that the incidence of biochemical hyperthyroidism is higher than was reported before sensitive methods for TSH measurement were available, and postulates that increased hCG concentrations in themselves and/or abnormal metabolic variants of hCG produced by trophoblastic tumours may act as thyroid stimulators in this condition. 64 refs, 5 figs, 4 tabs

  10. Outcome of Doctors Attending the European Society for Paediatric Endocrinology Winter Schools 2008-2014.

    Science.gov (United States)

    Donaldson, Malcolm D C

    2017-01-01

    Since 1995, the European Society for Paediatric Endocrinology (ESPE) has hosted Winter School (WS), a 5-day interactive meeting of 25 trainees and 7 teachers designed to cover all main endocrine topics. The aim of the present study was to determine subsequent outcome in ex-WS "students." A questionnaire was sent in August 2016 to all ESPE WS participants between 2008 and 2014. Information was requested on job/training status at WS attendance and in 2016, and subsequent involvement with ESPE. Of 174 participants (144 women, 30 men) including 5 attending two WS, 129 (74.5%) responded. At the time of WS/2016 survey 58/3 participants were junior trainees, 38/21 senior trainees, and 33/101 consultants. One hundred and seventeen (90.6%) responders were still involved with endocrinology, 107 (82%) rating WS as having a strong/very strong influence on their careers. Following WS, 80/174 (46%) participants had attended at least one ESPE main meeting, 28 (16%) had been awarded ESPE fellowships, and 34 (19%) had become ESPE members. The great majority of WS participants responding to the questionnaire are still involved with endocrinology and rated WS as influential. This favourable outcome supports the continuing funding of WS and similar educational programmes. © 2017 S. Karger AG, Basel.

  11. [Gregorio Marañón, a pioneer of endocrinology, 50 years after his death].

    Science.gov (United States)

    Zarate, Arturo

    2011-01-01

    Gregorio Maranon born and dead in Madrid (1887-1960), was a Spanish physician, scientist, historian, philosopher, humanist, and writer, considered one of the most brilliant Spanish intellectuals of the 20th century. He was also a Republican and fought the Primo de Rivera dictatorship, though later expressed his disagreement with communism. Maranon participated closely with the process of exile of Alfonso XIII. From a very early age he learned several foreign languages and was an avid reader, hence he became in contact with the intellectual circles of the time and cultivated a close friendship with Perez Galdos, Menendez-Pelayo, Ortega y Gasset, Pio Baroja, Unamuno, Lerroux among several outstanding and eminent figures of the famous Generation of 14. In Medical School he had great teachers such as Santiago Ramon y Cajal, and later he specialized in endocrinology and became professor of the specialty in the Complutense University in Madrid, moreover he founded the Institute of Medical Pathology and the Department of Experimental Endocrinology, henceforth he contributed to establish the relationship between endocrinology and psychology. At the beginning of the instauration of the Republic, Maranon became a member of the constituent assembly and the parliament, but soon became disillusioned of communism and left Spain before the initiation of the Civil War, remaining in France until 1942 when he returned to Spain to reestablish his private practice, and soon the medical teaching at the hospital which now bears his name. Late work about history, poetry was elaborated at his Toledo Cigarral de Menores.

  12. Microbial endocrinology: Host-microbiota neuroendocrine interactions influencing brain and behavior.

    Science.gov (United States)

    Lyte, Mark

    2014-01-01

    The ability of microorganisms, whether present as commensals within the microbiota or introduced as part of a therapeutic regimen, to influence behavior has been demonstrated by numerous laboratories over the last few years. Our understanding of the mechanisms that are responsible for microbiota-gut-brain interactions is, however, lacking. The complexity of the microbiota is, of course, a contributing factor. Nonetheless, while microbiologists approaching the issue of microbiota-gut-brain interactions in the behavior well recognize such complexity, what is often overlooked is the equal complexity of the host neurophysiological system, especially within the gut which is differentially innervated by the enteric nervous system. As such, in the search for common mechanisms by which the microbiota may influence behavior one may look for mechanisms which are shared by both host and microbiota. Such interkingdom signaling can be found in the shared production of neurochemical mediators that are found in both eukaryotes and prokaryotes. The study of the production and recognition of neurochemicals that are exactly the same in structure to those produced in the vertebrate organisms is known as microbial endocrinology. The examination of the microbiota from the vantage point of host-microbiota neuroendocrine interactions cannot only identify new microbial endocrinology-based mechanisms by which the microbiota can influence host behavior, but also lead to the design of interventions in which the composition of the microbiota may be modulated in order to achieve a specific microbial endocrinology-based profile beneficial to overall host behavior.

  13. [Assessment of a residency training program in endocrinology and nutrition by physicians: results of a survey].

    Science.gov (United States)

    Moreno-Fernández, Jesús; Gutiérrez-Alcántara, Carmen; Palomares-Ortega, Rafael; García-Manzanares, Alvaro; Benito-López, Pedro

    2011-12-01

    The current training program for resident physicians in endocrinology and nutrition (EN) organizes their medical learning. Program evaluation by physicians was assessed using a survey. The survey asked about demographic variables, EN training methods, working time and center, and opinion on training program contents. Fifty-one members of Sociedad Castellano-Manchega de Endocrinología, Nutrición y Diabetes, and Sociedad Andaluza de Endocrinología y Nutrición completed the survey. Forty-percent of them disagreed with the compulsory nature of internal medicine, cardiology, nephrology and, especially, neurology rotations (60%); a majority (>50%) were against several recommended rotations included in the program. The fourth year of residence was considered by 37.8% of respondents as the optimum time for outpatient and inpatient control and monitoring without direct supervision. The recommended monthly number of on-call duties was 3.8±1.2. We detected a positive opinion about extension of residence duration to 4.4±0.5 years. Doctoral thesis development during the residence period was not considered convenient by 66.7% of physicians. Finally, 97.8% of resident physicians would recommend residency in EN to other colleagues. Endocrinologists surveyed disagreed with different training program aspects such as the rotation system, skill acquisition timing, and on-call duties. Therefore, an adaptation of the current training program in EN would be required. Copyright © 2011 SEEN. Published by Elsevier Espana. All rights reserved.

  14. Detection of fetal-specific DNA after enrichment for trophoblasts using the monoclonal antibody LK26 in model systems but failure to demonstrate fetal DNA in maternal peripheral blood

    DEFF Research Database (Denmark)

    Hviid, T V; Sørensen, S; Morling, N

    1999-01-01

    Trophoblast cells can be detected in maternal blood during normal human pregnancy and DNA from these cells may be used for non-invasive prenatal diagnosis of inherited diseases. The possibility of enriching trophoblast cells from maternal blood samples using a monoclonal antibody (LK26) against...... a folate-binding protein, which recognizes trophoblast in normal tissues, in conjunction with immunomagnetic cell sorting was investigated. Verification of the presence of fetal DNA in the sorted samples was done by detection of fetal/paternal-specific short tandem repeat (STR) alleles using polymerase...... on peripheral maternal blood samples. However, it was not possible to detect fetal DNA sequences in these samples, most probably due to the extremely low number of trophoblast cells. Positive identification and retrieval of trophoblast cells in suspension or trophoblast nuclear material prepared on microscope...

  15. Journal of Endocrinology, Metabolism and Diabetes of South Africa ...

    African Journals Online (AJOL)

    Adrenocortical function in hospitalised patients with active pulmonary tuberculosis receiving a rifampicin-based regimen - a pilot study · EMAIL FREE FULL TEXT EMAIL FREE FULL TEXT DOWNLOAD FULL TEXT DOWNLOAD FULL TEXT. WD Francois Venter, Vanessa R Panz, Charles Feldman, Barry I Joffe, 16-21.

  16. Pioneer Valley Life Sciences Institute Program in Endocrinology and Metabolism

    Energy Technology Data Exchange (ETDEWEB)

    Schneyer, Alan; Brown, Melissa; Schwartz, Lawrence; Yadava, Nagendra; and Jerry, D Joseph

    2012-04-24

    Specific Aim - To determine the role of TGFBeta superfamily ligands in regulating Beta-cell function, proliferation, and survival (Drs. Schneyer and Brown) Specific Aim - To determine the feasibility of using respiratory activity and extracellular acidification rates of myoblasts to decipher the state of insulin resistance in cultured myoblastsMyoblast physiology (Drs. Schwartz and Yadava)

  17. Sera of patients with recurrent miscarriages containing anti-trophoblast antibodies (ATAB) reduce hCG and progesterone production in trophoblast cells in vitro.

    Science.gov (United States)

    von Schönfeldt, Viktoria; Rogenhofer, Nina; Ruf, Katharina; Thaler, Christian J; Jeschke, Udo

    2016-09-01

    Reproductive failure including RM has been suggested to correlate with antibodies that cross react with HLA-negative syncytiotrophoblasts and we have reported that 17% of women with 2 or more miscarriages and 34% of women with 3 or more miscarriages express anti-trophoblast antibodies (ATAB). Until now, the mechanism, how ATAB interfere with pregnancy success is not known. HCG and progesterone both play fundamental roles in supporting human pregnancy. Therefore we investigated the effects of sera of RM patients containing ATAB on the hCG and progesterone production of cells of the choriocarcinoma cell line JEG-3. In vitro study to investigate effects of patient sera with and without ATAB on hCG and progesterone secretion of JEG-3 cells. The presence of ATAB was detected as described earlier. Effects of sera from ATAB positive and ATAB negative RM patients on hCG and progesterone secretion by JEG-3 cells were analysed 12 and 24h after plating. Sera of women without pregnancy pathologies served as controls. Sera of ATAB-positive RM patients significantly inhibit hCG secretion of JEG-3 cells for 12h after plating compared to sera of healthy controls (p=0.019) and significantly reduce progesterone production for 12h (p=0.046) and 24h (p=0.027) of co-culture. Sera of ATAB-negative RM patient show no significant effect on progesterone secretion. Inhibition of hCG and progesterone production might point to a mechanism, how ATAB interfere with early pregnancies. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

  18. Elsevier Trophoblast Research Award Lecture: Unique properties of decidual T cells and their role in immune regulation during human pregnancy.

    Science.gov (United States)

    Tilburgs, T; Claas, F H J; Scherjon, S A

    2010-03-01

    Maternal lymphocytes at the fetal-maternal interface play a key role in the immune acceptance of the allogeneic fetus. Most studies focus on decidual NK cells and their interaction with fetal trophoblasts, whereas limited data are available on the mechanisms of fetus specific immune recognition and immune regulation by decidual T cells at the fetal-maternal interface. The aim of this review is to describe the phenotypic characteristics of decidual T cell subsets present at the fetal-maternal interface, their interaction with HLA-C expressed by fetal trophoblasts and their role in immune recognition and regulation at the fetal-maternal interface during human pregnancy. Copyright 2010 Elsevier Ltd. All rights reserved.

  19. Endocrinology and the brain: corticotropin-releasing hormone signaling.

    Science.gov (United States)

    Inda, Carolina; Armando, Natalia G; Dos Santos Claro, Paula A; Silberstein, Susana

    2017-08-01

    Corticotropin-releasing hormone (CRH) is a key player of basal and stress-activated responses in the hypothalamic-pituitary-adrenal axis (HPA) and in extrahypothalamic circuits, where it functions as a neuromodulator to orchestrate humoral and behavioral adaptive responses to stress. This review describes molecular components and cellular mechanisms involved in CRH signaling downstream of its G protein-coupled receptors (GPCRs) CRHR1 and CRHR2 and summarizes recent findings that challenge the classical view of GPCR signaling and impact on our understanding of CRHRs function. Special emphasis is placed on recent studies of CRH signaling that revealed new mechanistic aspects of cAMP generation and ERK1/2 activation in physiologically relevant contexts of the neurohormone action. In addition, we present an overview of the pathophysiological role of the CRH system, which highlights the need for a precise definition of CRHRs signaling at molecular level to identify novel targets for pharmacological intervention in neuroendocrine tissues and specific brain areas involved in CRH-related disorders. © 2017 The authors.

  20. Imprinted NanoVelcro Microchips for Isolation and Characterization of Circulating Fetal Trophoblasts: Toward Noninvasive Prenatal Diagnostics

    OpenAIRE

    Hou, Shuang; Chen, Jie-Fu; Song, Min; Zhu, Yazhen; Jan, Yu Jen; Chen, Szu Hao; Weng, Tzu-Hua; Ling, Dean-An; Chen, Shang-Fu; Ro, Tracy; Liang, An-Jou; Lee, Tom; Jin, Helen; Li, Man; Liu, Lian

    2017-01-01

    Circulating fetal nucleated cells (CFNCs) in maternal blood offer an ideal source of fetal genomic DNA for noninvasive prenatal diagnostics (NIPD). We developed a class of nanoVelcro microchips to effectively enrich a subcategory of CFNCs, i.e., circulating trophoblasts (cTBs) from maternal blood, which can then be isolated with single-cell resolution by a laser capture microdissection (LCM) technique for downstream genetic testing. We first established a nanoimprinting fabrication process to...

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

    Science.gov (United States)

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

    2012-01-01

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

  2. Gadd45 α expression in preeclampsia placenta and the effect of Gadd45 α on trophoblast HTR8/Svneo

    Directory of Open Access Journals (Sweden)

    Li Wang

    2016-01-01

    Full Text Available Objective: To study the expression of Gadd45 α in preeclampsia placenta and the regulating effect of Gadd45 α knockdown on trophoblast HTR8/Svneo. Methods: Preeclampsia placenta tissue and normal placenta tissue were collected, and mRNA contents and protein contents of Gadd45 α were detected by fluorescent quantitative PCR and Western blotting respectively; trophoblast cells HTR8/Svneo were cultured and after transfection of Gadd45 α siRNA, cell invasion ability and expression of invasion-assiotiated molecules were detected. Results: mRNA content and protein content of Gadd45 α in preeclampsia placenta tissue were higher than those in normal placenta tissue; after transfection of Gadd45 α siRNA, mRNA content and protein content of Gadd45 α in HTR8/Svneo cells significantly decreased, and the number of invasive cells as well as expression of MMP1, MMP2, MMP3 and MMP9 significantly increased. Conclusion: The expression of Gadd45 α in preeclampsia placenta abnormally increases; inhibting the expression of Gadd45 α in trophoblasts HTR8/Svneo can promote invasion and increase the expression of MMPs molecules.

  3. Sonographic image of cervix epithelioid trophoblastic tumor coexisting with mucinous adenocarcinoma in a postmenopausal woman: A case report.

    Science.gov (United States)

    Zhu, Yi; Zhang, Guo-Nan; Zhang, Rui-Bo; Shi, Yu; Wang, Deng-Feng; He, Rong

    2017-09-01

    Epithelioid trophoblastic tumor (ETT) is a distinctive but rare gestational trophoblastic neoplasia (GTN) composed of chorionic-type intermediate trophoblast cells. Approximately 50% ETT arose from the uterine cervix or lower uterine segment following a previous pregnancy with vaginal bleeding. With its unusual ability to simulate an invasive epithelioid neoplasm, ETT frequently poses a diagnostic challenge, especially involving the uterine cervix. We herein report the case of a 60-year-old female with persistent vaginal bleeding and middle-level elevation of serum human chorionic gonadotropin (hCG). Ultrasound revealed a 3.0 × 2.7 cm well-circumscribed, strongly echogenic lesion in the cervix, with a peripheral pattern of Doppler signals. The enhanced pattern by contrast-enhanced ultrasound displayed strong peripheral enhancement accompanied with globular appearance, then centripetal filling completely, and fading away rapidly. The final pathological diagnosis was ETT accompanying mucinous adenocarcinoma. Due to the pre-operative evaluation of a presumed IB2 cervix mucinous adenocarcinoma, the patient was treated with 2 courses of neoadjuvant chemotherapy followed by radical hysterectomy. The patient is currently disease-free for the past 1 year. This case report demonstrates that sonographic image of tumor shapes and blood flow could be helpful in differentiating ETT from another GTN and enable more accurate diagnosis before treatment.

  4. Roles of the insulinlike growth factor family in nonpregnant human endometrium and at the decidual: trophoblast interface.

    Science.gov (United States)

    Giudice, L C; Irwin, J C

    1999-01-01

    The insulinlike growth factor (IGF) family is believed to be important in endometrial development during the menstrual cycle and in the process of implantation. The mitogenic, differentiative, and antiapoptotic properties of the IGFs and their binding proteins, as well as their spatial and temporal expression in cycling endometrium, suggest that they may participate in endometrial growth, differentiation, apoptosis, and perhaps angiogenesis. IGFBP proteases, which increase IGF bioavailability, have been localized to endometrial stromal cells and to the human cytotrophoblast and likely play important roles in endometrial, decidual, and trophoblast physiology. IGFBP-1 is a major protein product of nonpregnant endometrium during the mid-late secretory phase and occurs in abundance in decidua. Its roles as an IGF-binding protein and as a trophoblast integrin ligand suggest that it may have multiple roles in endometrial development and in interactions between the decidua and the invading trophoblast. Recent evidence suggests that it may have a role in the process of shallow implantation in the clinical disorder of preclampsia. In contrast to knowledge about the roles of IGF peptides, IGFBP proteases, and IGFBPs in normal endometrial development and early human pregnancy, little information is available regarding this family in abnormal endometrial development, in occult endometrial defects, and in uterine receptivity and nonreceptivity.

  5. Regresión logística: Un ejemplo de su uso en Endocrinología Logistic regression: An example of its use in Endocrinology

    Directory of Open Access Journals (Sweden)

    Emma Domínguez Alonso

    2001-04-01

    Full Text Available Se intentó un acercamiento a la regresión logística, como una de las técnicas estadísticas multivariadas de más frecuente uso en las últimas décadas, para orientar a su uso correcto. Se consideraron cuestiones de tipo práctico como número de sujetos necesarios para aplicarla, situaciones en las que está indicado su uso, tipo de variables a las que es posible aplicarla y las formas en que puede ser incluida en el modelo, interpretación de los resultados, etc. Se mostró un ejemplo de la aplicación de esta técnica en una investigación en el campo de la Endocrinología. Se concluyó que la regresión logística resulta de gran utilidad para su aplicación en cualquier campo de la investigación médica cuando necesitamos precisar el efecto de un grupo de variables, consideradas potencialmente influyentes, sobre la ocurrencia de un determinado proceso.An approach to logistic regression , as one of the most used multivariate statistical techniques in the last decades, was made to recommend its correct use. Practical questions as the number of subjects necessary for its application, the situations in which it should be used, the type of variables to which it may be applied, the way it may be included in the model, the interpretation of the results, etc., were taken into consideration. An example of the application of this technique in the field of Endocrinology was given. It was concluded that the application of logistic regression is very useful in any field of medical research when we need to determine the effect of a group of variables, potentially considered as influential, on the ocurrence of a certain process.

  6. Animales de laboratorio en la endocrinología: Biomodelos de las enfermedades tiroideas Laboratory animals in endocrinology: Biomodels in thyroid diseases

    Directory of Open Access Journals (Sweden)

    Beatriz Hugues Hernandorena

    2002-12-01

    Full Text Available Los modelos animales que se utilizan en las investigaciones sobre el tiroides ayudan al estudio de los mecanismos patogénicos que conducen a la presentación de los desórdenes de esta glándula, dan la oportunidad de explorar nuevos tratamientos y formas de prevención. El objetivo de este trabajo fue brindar una información detallada sobre los biomodelos de enfermedades que afectan el tiroides, a partir de una revisión bibliográfica sobre el tema, que comprenda los que se obtienen de forma espontánea o inducida, exponiendo los factores ambientales que influyen sobre ellos. En conclusión, se expresaron las ventajas que ofrecen estos biomodelos para los investigadores que se dedican a estudiar esta rama de la endocrinología, aunque no constituyan un reflejo exacto de lo que ocurre en el hombre y no necesariamente reúnan todas las características distintivas de la patología tiroidea en cuestión.The animal models used in the investigations on thyroid help to study the pathogenic mechanisms leading to the appearance of disorders of this gland, and give the opportunity to find new treatments and ways of prevention. The objective of this paper was to provide a detailed information on the biomodels of diseases affecting the thyroid, starting from a bibliographic review on this topic, including those obtained in a spontaneous or induced way, and explaining the environmental factors influencing them. To conclude, the advantages of these biomodels for the researchers devoted to study this branch of endocrinology were stressed, although they are not an exact reflex of what happens in man and they do not necessarily have all the distinctive features of thyroid pathology.

  7. TRANSCULTURALIZATION RECOMMENDATIONS FOR DEVELOPING LATIN AMERICAN CLINICAL PRACTICE ALGORITHMS IN ENDOCRINOLOGY--PROCEEDINGS OF THE 2015 PAN-AMERICAN WORKSHOP BY THE AMERICAN ASSOCIATION OF CLINICAL ENDOCRINOLOGISTS AND AMERICAN COLLEGE OF ENDOCRINOLOGY.

    Science.gov (United States)

    Mechanick, Jeffrey I; Harrell, R Mack; Allende-Vigo, Myriam Z; Alvayero, Carlos; Arita-Melzer, Onix; Aschner, Pablo; Camacho, Pauline M; Castillo, Rogelio Zacarias; Cerdas, Sonia; Coutinho, Walmir F; Davidson, Jaime A; Garber, Jeffrey R; Garvey, W Timothy; González, Fernando Javier Lavalle; Granados, Denis O; Hamdy, Osama; Handelsman, Yehuda; Jiménez-Navarrete, Manuel Francisco; Lupo, Mark A; Mendoza, Enrique J; Jiménez-Montero, José G; Zangeneh, Farhad

    2016-04-01

    The American Association of Clinical Endocrinologists (AACE) and American College of Endocrinology (ACE) convened their first Workshop for recommendations to optimize Clinical Practice Algorithm (CPA) development for Latin America (LA) in diabetes (focusing on glycemic control), obesity (focusing on weight loss), thyroid (focusing on thyroid nodule diagnostics), and bone (focusing on postmenopausal osteoporosis) on February 28, 2015, in San Jose, Costa Rica. A standardized methodology is presented incorporating various transculturalization factors: resource availability (including imaging equipment and approved pharmaceuticals), health care professional and patient preferences, lifestyle variables, socio-economic parameters, web-based global accessibility, electronic implementation, and need for validation protocols. A standardized CPA template with node-specific recommendations to assist the local transculturalization process is provided. Participants unanimously agreed on the following five overarching principles for LA: (1) there is only one level of optimal endocrine care, (2) hemoglobin A1C should be utilized at every level of diabetes care, (3) nutrition education and increased pharmaceutical options are necessary to optimize the obesity care model, (4) quality neck ultrasound must be part of an optimal thyroid nodule care model, and (5) more scientific evidence is needed on osteoporosis prevalence and cost to justify intervention by governmental health care authorities. This 2015 AACE/ACE Workshop marks the beginning of a structured activity that assists local experts in creating culturally sensitive, evidence-based, and easy-to-implement tools for optimizing endocrine care on a global scale.

  8. Prognosis of patients treated with whole brain radiation therapy for metastatic gestational trophoblastic disease

    International Nuclear Information System (INIS)

    Schechter, Naomi R.; Mychalczak, Borys; Jones, Walter; Spriggs, David

    1996-01-01

    Purpose/Objective: To evaluate the effect of multiple treatment and disease related variables on the local control and survival of patients receiving whole brain radiation therapy for metastatic gestational trophoblastic disease. Materials and Methods: Between November 1967 and December 1994, 21 patients were treated at our institution for gestational trophoblastic disease metastatic to the brain. 29% ((6(21))) were diagnosed with their brain metastases before the onset of chemotherapy (early group). 79% ((15(21))) developed their brain metastases during or after the administration of first-line chemotherapy (late group). All patients were treated with whole brain radiation therapy. The total dose ranged from 200 cGy to 3600 cGy (median 2200 cGy). Sixteen patients (76%) received concurrent systemic chemotherapy. None of the patients received intrathecal chemotherapy as a component of their initial treatment. Survival and local control were calculated from the date of diagnosis of brain metastases. Follow-up ranged from 11 months to 170 months with a median of 77 months. Results: The median overall survival was 21 months, with 2- and 5-year actuarial survivals of 46% and 31%, respectively. Neither survival nor local control was significantly affected by age at diagnosis of brain metastases (<35 vs. ≥35 years), time of presentation of brain metastases (early vs. late), or use of concurrent chemotherapy. The total dose of radiation (<2200 cGy vs. ≥2200 cGy) significantly affected initial local control, but not survival. The 5-year actuarial local control of the initial brain metastases with ≥2200 cGy was 91%, as compared to 24% with <2200 cGy (p=0.05). Survival was significantly affected by control of disease at extracranial sites. The 2- and 5-year actuarial survivals of the 9 patients whose disease was controlled at extracranial sites were 100% and 83%, respectively, as compared to 8% and 0% for the 12 whose extracranial disease was not controlled (p=0

  9. Endocrinological analysis of 122 Japanese childhood cancer survivors in a single hospital

    International Nuclear Information System (INIS)

    Miyoshi, Yoko; Ohta, Hideaki; Hashii, Yoshiko; Tokimasa, Sadao; Namba, Noriyuki; Mushiake, Sotaro; Ozono, Keiichi; Hara, Junichi

    2008-01-01

    With recent improvements in the diagnosis and treatment of cancer, the number of childhood cancer survivors (CCSs) has been increasing in Japan. The importance of quality of life during the lifetime of CCSs has now been recognized, and the late effects of cancer treatments are essential and important issues. In this study we analyzed the endocrinological abnormalities of CCSs by retrospectively evaluating 122 outpatients (62 males and 60 females) who had been referred from pediatric oncologists to our follow-up clinic among 151 CCSs attending our hospital more than two years after their cancer treatment. Follow-up duration varied from 2 to 30 (median 8.0) years. Their average age was 17.3 (range 4-36, median 17.0) years, and 38 patients (31.1%) reached adulthood. Endocrinological abnormalities were found in 82 (67%) of 122 survivors. Gonadal dysfunction was observed in 60 patients (49%). Thirty-nine patients (32%) were short or grew at a slower rate. Twenty-six patients (21%) showed thyroid dysfunction. Other abnormalities were as follows: obesity in 20 patients (16%), leanness in 10 (8%), central diabetes insipidus in 11 (9%) and adrenocortical dysfunction in 9 (7%). Low bone mineral density was observed in 41 (42%) of 98 patients evaluated. These endocrinological abnormalities were caused by the combined effects of cancer itself and various treatments (chemotherapy, radiation therapy, surgery, and hematopoietic stem cell transplantation). Lifetime medical surveillance and continuous follow-up are necessary for CCSs, because treatment-related complications may occur during childhood and many years after the therapy as well. Endocrinologists should participate in long-term follow-up of these survivors in collaboration with pediatric oncologists. (author)

  10. Endocrinological analysis of 122 Japanese childhood cancer survivors in a single hospital.

    Science.gov (United States)

    Miyoshi, Yoko; Ohta, Hideaki; Hashii, Yoshiko; Tokimasa, Sadao; Namba, Noriyuki; Mushiake, Sotaro; Hara, Junichi; Ozono, Keiichi

    2008-12-01

    With recent improvements in the diagnosis and treatment of cancer, the number of childhood cancer survivors (CCSs) has been increasing in Japan. The importance of quality of life during the lifetime of CCSs has now been recognized, and the late effects of cancer treatments are essential and important issues. In this study we analyzed the endocrinological abnormalities of CCSs by retrospectively evaluating 122 outpatients (62 males and 60 females) who had been referred from pediatric oncologists to our follow-up clinic among 151 CCSs attending our hospital more than two years after their cancer treatment. Follow-up duration varied from 2 to 30 (median 8.0) years. Their average age was 17.3 (range 4-36, median 17.0) years, and 38 patients (31.1%) reached adulthood. Endocrinological abnormalities were found in 82 (67%) of 122 survivors. Gonadal dysfunction was observed in 60 patients (49%). Thirty-nine patients (32%) were short or grew at a slower rate. Twenty-six patients (21%) showed thyroid dysfunction. Other abnormalities were as follows: obesity in 20 patients (16%), leanness in 10 (8%), central diabetes insipidus in 11 (9%) and adrenocortical dysfunction in 9 (7%). Low bone mineral density was observed in 41 (42%) of 98 patients evaluated. These endocrinological abnormalities were caused by the combined effects of cancer itself and various treatments (chemotherapy, radiation therapy, surgery, and hematopoietic stem cell transplantation). Lifetime medical surveillance and continuous follow-up are necessary for CCSs, because treatment-related complications may occur during childhood and many years after the therapy as well. Endocrinologists should participate in long-term follow-up of these survivors in collaboration with pediatric oncologists.

  11. Systematic reviews of diagnostic tests in endocrinology: an audit of methods, reporting, and performance.

    Science.gov (United States)

    Spencer-Bonilla, Gabriela; Singh Ospina, Naykky; Rodriguez-Gutierrez, Rene; Brito, Juan P; Iñiguez-Ariza, Nicole; Tamhane, Shrikant; Erwin, Patricia J; Murad, M Hassan; Montori, Victor M

    2017-07-01

    Systematic reviews provide clinicians and policymakers estimates of diagnostic test accuracy and their usefulness in clinical practice. We identified all available systematic reviews of diagnosis in endocrinology, summarized the diagnostic accuracy of the tests included, and assessed the credibility and clinical usefulness of the methods and reporting. We searched Ovid MEDLINE, EMBASE, and Cochrane CENTRAL from inception to December 2015 for systematic reviews and meta-analyses reporting accuracy measures of diagnostic tests in endocrinology. Experienced reviewers independently screened for eligible studies and collected data. We summarized the results, methods, and reporting of the reviews. We performed subgroup analyses to categorize diagnostic tests as most useful based on their accuracy. We identified 84 systematic reviews; half of the tests included were classified as helpful when positive, one-fourth as helpful when negative. Most authors adequately reported how studies were identified and selected and how their trustworthiness (risk of bias) was judged. Only one in three reviews, however, reported an overall judgment about trustworthiness and one in five reported using adequate meta-analytic methods. One in four reported contacting authors for further information and about half included only patients with diagnostic uncertainty. Up to half of the diagnostic endocrine tests in which the likelihood ratio was calculated or provided are likely to be helpful in practice when positive as are one-quarter when negative. Most diagnostic systematic reviews in endocrine lack methodological rigor, protection against bias, and offer limited credibility. Substantial efforts, therefore, seem necessary to improve the quality of diagnostic systematic reviews in endocrinology.

  12. ASSESSING REFERRALS AND IMPROVING INFORMATION AVAILABILITY FOR CONSULTATIONS IN AN ACADEMIC ENDOCRINOLOGY CLINIC.

    Science.gov (United States)

    Hendrickson, Chase D; Saini, Saumya; Pothuloori, Avin; Mecchella, John N

    2017-02-01

    Outpatient specialty consultations rely on the timeliness and completeness of referral information to facilitate a valuable patient-specialist interaction. This project aimed to increase essential diagnostic information availability at the initial consultation for patients referred for common endocrine conditions frequently lacking such data-diabetes mellitus, thyroid nodule, thyrotoxicosis, and hypercalcemia. At an endocrinology clinic at an academic medical center in rural New England, providers see several thousand new patients annually, the majority of whom are referred by providers external to the clinic's healthcare system. Through consensus, endocrinology clinic providers agreed on the two or three data elements essential for a meaningful initial consultation for each. A quality improvement team employed a planned series of interventions based on previously published methods and an innovative approach: dissemination of a referral guideline, an assessment of referral adequacy in the endocrinology clinic workflow, coupled with focused requests for missing items, and a pre-visit lab appointment. Between April 2015 and March 2016, 762 referrals were reviewed. At baseline for the four conditions, referrals contained all essential elements only 27.5% (22 of 80) of the time. Over a 7-month period, the team implemented the interventions, with subsequent referrals containing all essential elements increasing to 75.5% (P<.0001), largely attributable to the pre-visit lab appointment. Incoming referrals that lack essential information are a significant problem in specialty care and may adversely affect patient experience, provider satisfaction, and clinic efficiency. Improvement may require innovative approaches, such as the potentially transferable and generalizable ones employed here. DHMC = Dartmouth-Hitchcock Medical Center EHR = electronic health record PDSA = Plan-Do-Study-Act.

  13. Endocrinological and Cardiological Late Effects Among Survivors of Childhood Acute Lymphoblastic Leukemia

    Directory of Open Access Journals (Sweden)

    Hale Ören

    2013-09-01

    Full Text Available Objective: Survival rates for childhood acute lymphoblastic leukemia (ALL have significantly improved and late effects of therapy have been important in the follow-up of survivors. The objective of this study is to identify the endocrinological and cardiological late effects of ALL patients treated in our pediatric hematology unit. Materials and Methods: Patients treated for ALL with BFM protocols after at least 5 years of diagnosis and not relapsed were included in the study. Endocrinological late effects (growth failure, obesity, insulin resistance, dyslipidemia, thyroid gland disorders, osteopenia/osteoporosis, and pubertal disorders and cardiological late effects were evaluated. The study group was evaluated with anthropometric measurements, body mass index, and laboratory testing of fasting glucose, insulin, serum lipids, thyroid functions, and bone mineral densities. Echocardiography and pulsed wave Doppler imaging were performed for analysis of cardiac functions. Results: Of the 38 ALL survivors, at least 1 adverse event occurred in 23 (60%, with 8 of them (21% having multiple problems. Six (16% of the survivors were obese and 8 (21% of them were overweight. Subjects who were overweight or obese at the time of diagnosis were more likely to be overweight or obese at last follow-up. Obesity was more frequently determined in patients who were younger than 6 years of age at the time of diagnosis. Insulin resistance was observed in 8 (21% subjects. Insulin resistance was more frequently seen in subjects who had family history of type 2 diabetes mellitus. Hyperlipidemia was detected in 8 (21% patients. Hypothyroidism or premature thelarche were detected in 2 children. Two survivors had osteopenia. Cardiovascular abnormalities occurred in one of the subjects with hypertension and cardiac diastolic dysfunction. Conclusion: We point out the necessity of follow-up of these patients for endocrinological and cardiological late effects, since at least

  14. Interprofessional Collaboration with Immune Checkpoint Inhibitor Therapy: the Roles of Gastroenterology, Endocrinology and Neurology.

    Science.gov (United States)

    Seery, Virginia

    2017-11-01

    To discuss immune checkpoint inhibitor therapy and identify opportunities for interprofessional collaboration in the management of toxicities in the areas of gastroenterology, endocrinology, and neurology. Published research and education articles in oncology, nursing, and various specialties. The use of immune checkpoint inhibitors is expanding; timely management of toxicity is critical for positive patient outcomes. There are many opportunities for interprofessional collaboration in the diagnosis and treatment of immune-related adverse events. Nurses play key roles in recognizing immune-related adverse events, providing patient education, and helping to facilitate interprofessional collaboration. Copyright © 2017 Elsevier Inc. All rights reserved.

  15. Microbial endocrinology: Why the intersection of microbiology and neurobiology matters to poultry health.

    Science.gov (United States)

    Villageliu, Daniel N; Lyte, Mark

    2017-08-01

    The union of microbiology and neurobiology has led to a revolution in the way we view the microbiome. Now recognized as important symbionts, the microorganisms which inhabit multiple niches in mammalian and avian (chicken) hosts, such as the intestinal tract and skin, serve and influence many important physiological functions. The realization that the gut microbiome serves as a kind of "microbial organ" has important implications for many areas of biology. In this paper advances in the field of microbial endocrinology which may hold relevance for the poultry industry are examined. © 2017 Poultry Science Association Inc.

  16. Cell-to-Cell Contact Results in a Selective Translocation of Maternal Human Immunodeficiency Virus Type 1 Quasispecies across a Trophoblastic Barrier by both Transcytosis and Infection

    Science.gov (United States)

    Lagaye, S.; Derrien, M.; Menu, E.; Coïto, C.; Tresoldi, E.; Mauclère, P.; Scarlatti, G.; Chaouat, G.; Barré-Sinoussi, F.; Bomsel, M.

    2001-01-01

    Mother-to-child transmission can occur in utero, mainly intrapartum and postpartum in case of breastfeeding. In utero transmission is highly restricted and results in selection of viral variant from the mother to the child. We have developed an in vitro system that mimics the interaction between viruses, infected cells present in maternal blood, and the trophoblast, the first barrier protecting the fetus. Trophoblastic BeWo cells were grown as a tight polarized monolayer in a two-chamber system. Cell-free virions applied to the apical pole neither crossed the barrier nor productively infected BeWo cells. In contrast, apical contact with human immunodeficiency virus (HIV)-infected peripheral blood mononuclear cells (PBMCs) resulted in transcytosis of infectious virus across the trophoblastic monolayer and in productive infection correlating with the fusion of HIV-infected PBMCs with trophoblasts. We showed that viral variants are selected during these two steps and that in one case of in utero transmission, the predominant maternal viral variant characterized after transcytosis was phylogenetically indistinguishable from the predominant child's virus. Hence, the first steps of transmission of HIV-1 in utero appear to involve the interaction between HIV type 1-infected cells and the trophoblastic layer, resulting in the passage of infectious HIV by transcytosis and by fusion/infection, both leading to a selection of virus quasispecies. PMID:11312350

  17. Human trophoblast survival at low oxygen concentrations requires metalloproteinase-mediated shedding of heparin-binding EGF-like growth factor.

    Science.gov (United States)

    Armant, D Randall; Kilburn, Brian A; Petkova, Anelia; Edwin, Samuel S; Duniec-Dmuchowski, Zophia M; Edwards, Holly J; Romero, Roberto; Leach, Richard E

    2006-02-01

    Heparin-binding EGF-like growth factor (HBEGF), which is expressed in the placenta during normal pregnancy, is down regulated in pre-eclampsia, a human pregnancy disorder associated with poor trophoblast differentiation and survival. This growth factor protects against apoptosis during stress, suggesting a role in trophoblast survival in the relatively low O(2) ( approximately 2%) environment of the first trimester conceptus. Using a well-characterized human first trimester cytotrophoblast cell line, we found that a 4-hour exposure to 2% O(2) upregulates HBEGF synthesis and secretion independently of an increase in its mRNA. Five other expressed members of the EGF family are largely unaffected. At 2% O(2), signaling via HER1 or HER4, known HBEGF receptors, is required for both HBEGF upregulation and protection against apoptosis. This positive-feedback loop is dependent on metalloproteinase-mediated cleavage and shedding of the HBEGF ectodomain. The restoration of trophoblast survival by the addition of soluble HBEGF in cultures exposed to low O(2) and metalloproteinase inhibitor suggests that the effects of HBEGF are mediated by autocrine/paracrine, rather than juxtacrine, signaling. Our results provide evidence that a post-transcriptional mechanism induced in trophoblasts by low O(2) rapidly amplifies HBEGF signaling to inhibit apoptosis. These findings have a high clinical significance, as the downregulation of HBEGF in pre-eclampsia is likely to be a contributing factor leading to the demise of trophoblasts.

  18. EEVD motif of heat shock cognate protein 70 contributes to bacterial uptake by trophoblast giant cells

    Directory of Open Access Journals (Sweden)

    Kim Suk

    2009-12-01

    Full Text Available Abstract Background The uptake of abortion-inducing pathogens by trophoblast giant (TG cells is a key event in infectious abortion. However, little is known about phagocytic functions of TG cells against the pathogens. Here we show that heat shock cognate protein 70 (Hsc70 contributes to bacterial uptake by TG cells and the EEVD motif of Hsc70 plays an important role in this. Methods Brucella abortus and Listeria monocytogenes were used as the bacterial antigen in this study. Recombinant proteins containing tetratricopeptide repeat (TPR domains were constructed and confirmation of the binding capacity to Hsc70 was assessed by ELISA. The recombinant TPR proteins were used for investigation of the effect of TPR proteins on bacterial uptake by TG cells and on pregnancy in mice. Results The monoclonal antibody that inhibits bacterial uptake by TG cells reacted with the EEVD motif of Hsc70. Bacterial TPR proteins bound to the C-terminal of Hsc70 through its EEVD motif and this binding inhibited bacterial uptake by TG cells. Infectious abortion was also prevented by blocking the EEVD motif of Hsc70. Conclusions Our results demonstrate that surface located Hsc70 on TG cells mediates the uptake of pathogenic bacteria and proteins containing the TPR domain inhibit the function of Hsc70 by binding to its EEVD motif. These molecules may be useful in the development of methods for preventing infectious abortion.

  19. Tegafur Substitution for 5-Fu in Combination with Actinomycin D to Treat Gestational Trophoblastic Neoplasm.

    Directory of Open Access Journals (Sweden)

    Mei Peng

    Full Text Available Although 5-fluorouracil (5-Fu combination chemotherapy provides a satisfactory therapeutic response in patients with gestational trophoblastic neoplasms (GTNs, it has severe side effects. The current study analyzed the therapeutic effects and side effects of tegafur plus actinomycin D (Act-D vs. 5-Fu plus Act-D for the treatment of GTNs based on controlled historical records. A total of 427 GTN cases that received tegafur and Act-D combination chemotherapy at the Second Xiangya Hospital of XiangYa Medical School between August 2003 and July 2013 were analyzed based on historical data. A total of 393 GTN cases that received 5-Fu plus Act-D between August 1993 and July 2003 at the same hospital were also analyzed, which constituted the control group. The therapeutic effects, toxicity and side effects after chemotherapy were compared between the groups. The overall response rate was 90.63% in the tegafur+Act-D group (tegafur group and 92.37% in the 5-Fu+Act-D group (5-Fu group; these rates were not significantly different (P > 0.05. However, the incidence rates of myelosuppression (white blood cell decline, gastrointestinal reactions (nausea, vomiting, dental ulcer, and diarrhea, skin lesions and phlebitis were lower in the tegafur group than in the 5-Fu group (P < 0.05. The results of this study may provide useful data for the clinical application of tegafur in GTN treatment.

  20. Current trends in follow-up of trophoblastic function in ruminant species.

    Science.gov (United States)

    Sousa, N M; Beckers, J F; Gajewski, Z

    2008-12-01

    During the pregnancy of ruminants, different hormones and proteins are secreted by placenta or corpus luteum allowing the follow up of gestation. Among them, progesterone (P4) and pregnancy-associated glycoproteins (PAG) were proposed as laboratory tools to establish or to confirm pregnancy diagnosis. In last years, PAG assay also provided useful information for researchers working in programs focused on the follow up of trophoblastic function. Concentrations of PAG appeared as altered after the use of embryo biotechnology (in vitro fertilization, cloning by nuclear transfer, inter-specific pregnancies), according to nutritional status of pregnant females (overnourished or undernourished), or consecutive to infectious diseases leading to pathologies affecting the pregnancy in cows (Actynomyces pyogenes and Neospora caninum) and goats (Toxoplasma gondii, Listeria monocytogenes and Trypanosoma congolense). As well, in numerous studies, the association of repeated ultrasound examinations with P4 and PAG determinations allowed a better understanding of mechanisms related to embryonic and fetal mortalities: failure after artificial insemination or embryo transfer techniques, large offspring syndrome after in vitro fecundation and cloning.

  1. Gestational trophoblastic neoplasia after spontaneous human chorionic gonadotropin normalization following molar pregnancy evacuation.

    Science.gov (United States)

    Braga, Antonio; Maestá, Izildinha; Matos, Michelle; Elias, Kevin M; Rizzo, Julianna; Viggiano, Maurício Guilherme Campos

    2015-11-01

    To evaluate the risk of gestational trophoblastic neoplasia (GTN) after spontaneous human chorionic gonadotropin normalization in postmolar follow-up. Retrospective chart review of 2284 consecutive cases of hydatidiform mole with spontaneous normalization of hCG following uterine evacuation treated at one of five Brazilian reference centers from January 2002 to June 2013. After hCG normalization, GTN occurred in 10/2284 patients (0.4%; 95% CI 0.2%-0.8%). GTN developed in 9/1424 patients (0.6%; 95% CI 0.3%-1.2%) after a complete hydatidiform mole, in 1/849 patients (0.1%; 95% CInormalization was 18months, and no diagnoses were made before six months of postmolar surveillance. Patients who required more than 56days to achieve a normal hCG value had a ten-fold increased risk of developing GTN after hCG normalization (9/1074; 0.8%; 95% CI 0.4%-1.6%) compared to those who reached a normal hCG level in fewer than 56days (1/1210;0.08%; 95% CInormalization following molar pregnancy is exceedingly rare, and the few patients who do develop GTN after achieving a normal hCG value are likely to be diagnosed after completing the commonly recommended six months of postmolar surveillance. Current recommendations for surveillance after hCG normalization should be revisited. Copyright © 2015 Elsevier Inc. All rights reserved.

  2. Elsevier Trophoblast Research Award Lecture: origin, evolution and future of placenta miRNAs.

    Science.gov (United States)

    Morales-Prieto, D M; Ospina-Prieto, S; Schmidt, A; Chaiwangyen, W; Markert, U R

    2014-02-01

    MicroRNAs (miRNAs) regulate the expression of a large number of genes in plants and animals. Placental miRNAs appeared late in evolution and can be found only in mammals. Nevertheless, these miRNAs are constantly under evolutionary pressure. As a consequence, miRNA sequences and their mRNA targets may differ between species, and some miRNAs can only be found in humans. Their expression can be tissue- or cell-specific and can vary time-dependently. Human placenta tissue exhibits a specific miRNA expression pattern that dynamically changes during pregnancy and is reflected in the maternal plasma. Some placental miRNAs are involved in or associated with major pregnancy disorders, such as preeclampsia, intrauterine growth restriction or preterm delivery and, therefore, have a strong potential for usage as sensitive and specific biomarkers. In this review we summarize current knowledge on the origin of placental miRNAs, their expression in humans with special regard to trophoblast cells, interspecies differences, and their future as biomarkers. It can be concluded that animal models for human reproduction have a different panel of miRNAs and targets, and can only partly reflect or predict the situation in humans. Copyright © 2013. Published by Elsevier Ltd.

  3. Brown-Sèquard, otro Precursor de la Endocrinología.

    Directory of Open Access Journals (Sweden)

    Alfredo Jácome Roca Rodriguez

    2008-03-01

    Admitimos que cada tejido y –más generalmente- cada célula del organismo, segregue por su propia cuenta productos o fermentos especiales que –derramados en la sangre- influyen por mediación de este líquido en todas las otras células, las cuales llegan a ser de este modo solidarias entre sí por un mecanismo diferente al del sistema nervioso… Como era frecuente que a aquellas glándulas sin conducto se les considerara un papel neutralizador de toxinas, propone su utilidad para el organismo, bien por este efecto antitóxico o por una influencia directa favorable. De cualquier manera, este sorpresivo pregón anunció el nacimiento de la endocrinología. Que -a juzgar por los avisos que hemos encontrado en el primer número de los Anales Franceses de Endocrinología en 1939- se interesaba mucho en las hormonas sexuales, las que en aquella época campeaban en la opoterapia.

  4. An interactive E-Learning Portal in Pediatric Endocrinology: Practical Experience

    Directory of Open Access Journals (Sweden)

    Stenvert L. S. Drop

    2013-10-01

    Full Text Available Based on educational considerations, the European Society for Paediatric Endocrinology (ESPE e-learning portal has been developed, providing an interactive learning environment for up-to-date information in pediatric endocrinology. From March 2011 to January 2012, five small-scale pilot studies were completed to assess the usefulness of the structure and content by senior experts, fellows, residents and medical students. Altogether, 8 cases and 4 chapters were studied by a total of 71 individuals: 18 senior experts, 21 fellows, 10 medical students, 9 regional pediatricians and 13 residents, resulting in a total of 127 evaluations. Participants considered the portal content interesting and appreciated the way of learning compared to traditional learning from literature and textbooks. Special attention was paid to assess the personalized feedback given by experts to fellows and residents who completed the portal. Feedback from experts included both medical understanding and communication skills demonstrated by fellows and residents. Users highly appreciated the feedback of the medical experts, who brought perspectives from another clinic. This portal also offers educational opportunities for medical students and regional pediatricians and can be used to develop various CanMEDS competencies, e.g., medical expert, health advocate, and scholar.

  5. Financial Analysis of Behavioral Health Services in a Pediatric Endocrinology Clinic.

    Science.gov (United States)

    Yarbro, Jessica L; Mehlenbeck, Robyn

    2016-09-01

    This article addresses a current need in psychological practice by describing a financially feasible model that moves toward integrated care of behavioral health services in a pediatric endocrinology clinic. Financial information (costs and revenue associated with behavioral health services) for the clinic, over an 18-month period (July 2012 to December 2013), was obtained through the hospital's financial department. The clinic meets one half day per week. Over the 18-month period, the behavioral health services generated a net gain of $3661.45 in the favor of the clinic. We determined that the psychologist and clinical psychology residents needed to see a total of four patients per half-day clinic for the clinic to "break-even." We describe one financially feasible way of integrating behavioral health services into a pediatric endocrinology clinic in the hope that this will be generalizable to other medical settings. © The Author 2015. Published by Oxford University Press on behalf of the Society of Pediatric Psychology. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

  6. Conservation endocrinology: A noninvasive tool to understand relationships between carnivore colonization and ecological carrying capacity

    Science.gov (United States)

    Berger, J.; Testa, J.W.; Roffe, T.; Monfort, S.L.

    1999-01-01

    Reproductive technology, especially the diagnosis of pregnancy by radioimmunoassay of fecal steroid metabolites, is an important component of captive propagation, but its role in our understanding of ecological interactions and in situ biological restoration has been more limited. Where large herbivores have been 'released' from predation by the extirpation of carnivores, controversy often exists about possible detrimental effects at the ecosystem level A related concern is that the reestablishment of large carnivores may decrease the availability of prey populations for human subsistence. We suggest that pregnancy assays can be a valuable tool to help distinguish between the roles of predation versus food-imposed limitations on population size and their effects on juvenile recruitment in wild species. We explored this issue through analyses of fecal progestagen concentration (FPC) levels to document pregnancy in moose (Alces alces) in the southern Greater Yellowstone Ecosystem, a site where wolves (Canis lupus) and grizzly bears (Ursus arctos) are recolonizing former habitats after an absence of more than 60 years. Pregnancy was clearly discernible (mean FPC for pregnant and nonpregnant females, respectively: 10.60 vs. 2.57 ??g/g; p endocrinology can be applied to issues involving reproductive events within an ecological context. They also affirm that noninvasive and generally inexpensive endocrinological procedures will be applicable to understanding interactions between recolonizing predators and prey, an issue that will continue to arise because of global restoration efforts, and to the study of rare ungulates in remote systems where data on reproductive events are difficult to obtain.

  7. SELECTION OF ENDOCRINOLOGY SUBSPECIALTY TRAINEES: WHICH APPLICANT CHARACTERISTICS ARE ASSOCIATED WITH PERFORMANCE DURING FELLOWSHIP TRAINING?

    Science.gov (United States)

    Natt, Neena; Chang, Alice Y; Berbari, Elie F; Kennel, Kurt A; Kearns, Ann E

    2016-01-01

    To determine which residency characteristics are associated with performance during endocrinology fellowship training as measured by competency-based faculty evaluation scores and faculty global ratings of trainee performance. We performed a retrospective review of interview applications from endocrinology fellows who graduated from a single academic institution between 2006 and 2013. Performance measures included competency-based faculty evaluation scores and faculty global ratings. The association between applicant characteristics and measures of performance during fellowship was examined by linear regression. The presence of a laudatory comparative statement in the residency program director's letter of recommendation (LoR) or experience as a chief resident was significantly associated with competency-based faculty evaluation scores (β = 0.22, P = .001; and β = 0.24, P = .009, respectively) and faculty global ratings (β = 0.85, P = .006; and β = 0.96, P = .015, respectively). The presence of a laudatory comparative statement in the residency program director's LoR or experience as a chief resident were significantly associated with overall performance during subspecialty fellowship training. Future studies are needed in other cohorts to determine the broader implications of these findings in the application and selection process.

  8. An Evaluation of Mobile Applications for Reproductive Endocrinology and Infertility Providers.

    Science.gov (United States)

    Shaia, Kathryn L; Farag, Sara; Chyjek, Kathy; Knopman, Jaime; Chen, Katherine T

    2017-03-01

    To identify and rate reproductive endocrinology and infertility (REI) mobile applications (apps) targeted toward REI providers. A list of REI apps was found in both the Apple iTunes and Google Play stores using the following seven MeSH terms: reproductive endocrinology, REI, infertility, fertility, In Vitro Fertilization, IVF, and embryology. Patient-centered apps were excluded. The remaining apps were then evaluated for accuracy using reliable references. Mobile technology. None. Accurate apps were evaluated for comprehensiveness (the extent of the ability to aid in clinical decision-making) and rated with objective and subjective components using the APPLICATIONS scoring system. Using the seven REI-related MeSH terms, 985 apps and 1,194 apps were identified in the Apple iTunes and Google Play stores, respectively. Of these unique apps, only 20 remained after excluding patient-centered apps. Upon further review for applicability to REI specifically and content accuracy, only seven apps remained. These seven apps were then rated using the APPLICATIONS scoring system. Only 0.32% of 2,179 apps reviewed for this study were useful to REI providers. There is potential for further mobile resource development in the area of REI, given the limited number and varying comprehensiveness and quality of available apps.

  9. Patients' poor communication with their doctors in the first visit of the gynecological endocrinology outpatient clinics.

    Science.gov (United States)

    Li, Xiao-Hong; Han, Zi-Yan; She, Wen-Jing; Lei, Hai-Ke

    2016-01-01

    To investigate patients' communication with their gynecologists in the first visit of the gynecological endocrinology outpatient clinics. We developed a questionnaire to evaluate 379 women' expectations of their first visit, information-giving about illness, and understanding of the consultation they encountered from April to August 2010. Descriptive statistics and multiple linear regression analysis were used to analyze the data. Before the first visit, 55% (208/379) of participants hoped to get the doctors' special attention, and 60% (227/379) of patients expected a very satisfying consultation. During the consultation, only 34% (129/379) of patients provided their case history clearly according to physicians' inquiry, 21% (81/379) of patients understood the examination and 28% (105/379) of patients understood the therapeutic regime after doctors' explanation. Correlation analysis showed that sociodemographic characteristics such as young age (under 20 years old), low level of education (primary school or less), and lack of medical knowledge affected patients' information-giving about illness and understanding of their first visit (all ps endocrinology outpatient clinics. They could not communicate well with their doctors, which was affected by age, education, and medical background.

  10. [Cardiovascular risk factor control in a population with longstanding diabetes attending endocrinology departments].

    Science.gov (United States)

    Comi-Diaz, Cristina; Miralles-García, José M; Cabrerizo, Lucio; Pérez, María; Masramon, Xavier; De Pablos-Velasco, Pedro

    2010-12-01

    To determine the degree of control of cardiovascular risk factors (CVRF) in a sample of patients with diabetes mellitus (DM) attending Endocrinology and Nutrition Departments in Spain. An epidemiological, cross-sectional, multicenter and observational study involving 41 Departments of Endocrinology and Nutrition in Spain. Each department selected patients with DM with over 10 years of evolution, which were treated in outpatient settings. Demographic, anthropometric, clinical and biochemical data, including medication, were collected for each participant. 1159 patients who met the inclusion criteria were recruited. 52% of the participants were patients with type 2 DM. The mean duration of DM was 19.6 years. A proportion of 37%, 44%, 27.6% and 25.5% had good control of their blood pressure (BP), low density cholesterol (LDLc), lipids and glucose, respectively, and only 4.3% did well in all factors evaluated. The percentage of poorly controlled BP was four times higher in type 2 than in type 1 DM. Obesity, low cultural level and aggregation of cardiovascular risk factors were associated with poorer control. The degree of control of CVRF in diabetic patients with long disease duration is insufficient. Copyright © 2010 SEEN. Published by Elsevier Espana. All rights reserved.

  11. Consensus statement for use and technical requirements of thyroid ultrasound in endocrinology units.

    Science.gov (United States)

    Martín-Hernández, Tomás; Díez Gómez, Juan José; Díaz-Soto, Gonzalo; Torres Cuadro, Alberto; Navarro González, Elena; Oleaga Alday, Amelia; Sambo Salas, Marcel; Reverter Calatayud, Jordi L; Argüelles Jiménez, Iñaki; Mancha Doblas, Isabel; Fernández García, Diego; Galofré, Juan Carlos

    2017-03-01

    Thyroid nodule detection has increased with widespread use of ultrasound, which is currently the main tool for detection, monitoring, diagnosis and, in some instances, treatment of thyroid nodules. Knowledge of ultrasound and adequate instruction on its use require a position statement by the scientific societies concerned. The working groups on thyroid cancer and ultrasound techniques of the Spanish Society of Endocrinology and Nutrition have promoted this document, based on a thorough analysis of the current literature, the results of multicenter studies and expert consensus, in order to set the requirements for the best use of ultrasound in clinical practice. The objectives include the adequate framework for use of thyroid ultrasound, the technical and legal requirements, the clinical situations in which it is recommended, the levels of knowledge and learning processes, the associated responsibility, and the establishment of a standardized reporting of results and integration into hospital information systems and endocrinology units. Copyright © 2017 SEEN. Publicado por Elsevier España, S.L.U. All rights reserved.

  12. AMERICAN ASSOCIATION OF CLINICAL ENDOCRINOLOGISTS, AMERICAN COLLEGE OF ENDOCRINOLOGY, AND ASSOCIAZIONE MEDICI ENDOCRINOLOGI MEDICAL GUIDELINES FOR CLINICAL PRACTICE FOR THE DIAGNOSIS AND MANAGEMENT OF THYROID NODULES--2016 UPDATE.

    Science.gov (United States)

    Gharib, Hossein; Papini, Enrico; Garber, Jeffrey R; Duick, Daniel S; Harrell, R Mack; Hegedüs, Laszlo; Paschke, Ralf; Valcavi, Roberto; Vitti, Paolo

    2016-05-01

    malignant or suspicious nodules. The present document updates previous guidelines released in 2006 and 2010 by the American Association of Clinical Endocrinologists (AACE), American College of Endocrinology (ACE) and Associazione Medici Endocrinologi (AME).

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

    DEFF Research Database (Denmark)

    Carter, Anthony Michael

    2011-01-01

    in the orangutan and became polymorphic in the lineage leading to gorilla, bonobo, chimpanzee, and human. Interaction between HLA-C1 and HLA-C2 on the surface of trophoblast and killer immunoglobulin-like receptors (KIRs) expressed by uterine natural killer cells are important regulators of trophoblast invasion....... Evolution of this system in great apes may have been one prerequisite for deep trophoblast invasion but seems to have come at a price. The evidence now suggests that certain combinations of maternal genotype for KIRs and fetal genotype for HLA-C imply an increased risk of preeclampsia, fetal growth...... restriction, and recurrent abortion. The fetal genotype is in part derived from the father providing an explanation for the paternal contribution to reproductive disorders....

  14. Hormonas, cerebro y conducta. Notas para la práctica de la Psicología en la Endocrinología Hormones, brain and behavior. Notes on the psychology practice in the field of Endocrinology

    Directory of Open Access Journals (Sweden)

    Alina Wong Carriera

    2013-04-01

    Full Text Available Las prácticas de los psicólogos en el campo de la Endocrinología y las de los propios endocrinólogos, requieren un mínimo de conocimientos sobre los efectos conductuales no endocrinos de las hormonas. La temporalidad es un concepto clave en Neurobiología, hecho que puede observarse con claridad en el efecto de las hormonas sobre la conducta, al tratarse de acciones moduladas por el período de maduración del sistema nervioso en que se ejercen. El mecanismo neural que facilita la ocurrencia de estas acciones en el tiempo es la plasticidad cerebral. Las hormonas, en su condición de factores epigenéticos, influyen en la conducta mediante los procesos de plasticidad, y provocan dos efectos principales: el organizador y el activador. El primero se refiere a la capacidad de las hormonas de influir en la citoarquitectura y estructura del cerebro de manera permanente durante el desarrollo, desde el período fetal hasta el final de la adolescencia, aunque algunos estudios sugieren que este efecto se mantiene más allá del período de la pubertad. El activador se relaciona con la activación de células diana para facilitar conductas en contextos específicos. Se trata de influencias transitorias, puntuales, que dependen de la concentración de las hormonas en cada instante. Solo conociendo la compleja relación entre el sustrato neural, las condiciones hormonales y el grado de maduración del sistema nervioso en general, y del cerebro en particular, se pueden diseñar estrategias terapéuticas correctas. El desconocimiento de estas interrelaciones lleva al riesgo de trabajar solo con la subjetividad del paciente y desconocer sus potencialidades y limitaciones.The practice of psychologists in the field of endocrinology and that of the endocrinologists as such require a minimum level of knowledge on the non-endocrine behavioral effects of hormones. Temporality is a key concept in neurobiology, a fact that can also be clearly observed in the

  15. Edaravone inhibits hypoxia-induced trophoblast-soluble Fms-like tyrosine kinase 1 expression: a possible therapeutic approach to preeclampsia.

    Science.gov (United States)

    Zhao, Y; Zheng, Y F; Luo, Q Q; Yan, T; Liu, X X; Han, L; Zou, L

    2014-07-01

    To investigate the effects of edaravone, a potent free radical scavenger used clinically, on hypoxia-induced trophoblast-soluble Fms-like tyrosine kinase 1 (sFlt-1) expression. A trophoblast cell line (HRT-8/SVneo) impaired by cobalt chloride (CoCl2) was used as the cell model under hypoxic conditions. 3-[4, 5-dimethylthiazol-2-yl]-2, 5-diphenyl tetrazolium bromide (MTT) was used to measure the viability of cells exposed to CoCl2 and edaravone. The levels of intracellular reactive oxygen species (ROS) were analyzed by flow cytometry. mRNA expression of sFlt-1, vascular endothelial growth factor (VEGF), and placental growth factor (PlGF) in trophoblasts was measured by real-time polymerase chain reaction, and the secretion of sFlt-1, VEGF, and PlGF proteins was analyzed by enzyme-linked immunosorbent assays (ELISAs). A human umbilical vein endothelial cell (HUVEC) tube-formation assay was performed to identify the effects of CoCl2 and edaravone on vascular development. CoCl2 treatment caused the loss of trophoblast viability, the formation of ROS, and sFlt-1 mRNA and protein expression in a dose-dependent manner. Pretreatment with edaravone significantly inhibited hypoxia-induced oxidative stress formation and sFlt-1 expression in trophoblasts. Neither PlGF nor VEGF mRNA or protein expression was increased by CoCl2. In the in vitro tube formation assay, edaravone showed a protective role in vascular development under hypoxic conditions. This study demonstrated that hypoxia leading to increased sFlt-1 release in trophoblasts may contribute to the placental vascular formation abnormalities observed in preeclampsia and suggested that the free radical scavenger edaravone could be a candidate for the effective treatment of preeclampsia. Copyright © 2014 Elsevier Ltd. All rights reserved.

  16. Characterization of fetal cells from the maternal circulation by microarray gene expression analysis - Could the extravillous trophoblasts be a target for future cell-based non-invasive prenatal diagnosis?

    DEFF Research Database (Denmark)

    Hatt, Lotte; Brinch, Marie; Singh, Ripudaman

    2014-01-01

    stem cell microarray analysis. Results: 39 genes were identified as candidates for unique fetal cell markers. More than half of these are genes known to be expressed in the placenta, especially in extravillous trophoblasts (EVTs). Immunohistochemical staining of placental tissue confirmed CD105......Introduction: Circulating fetal cells in maternal blood provide a tool for risk-free, non-invasive prenatal diagnosis. However, fetal cells in the maternal circulation are scarce, and to effectively isolate enough of them for reliable diagnostics, it is crucial to know which fetal cell type......(s) should be targeted. Materials and Methods: Fetal cells were enriched from maternal blood by magnetic-activated cell sorting using the endothelial cell marker CD105 and identified by XY fluorescence in situ hybridization. Expression pattern was compared between fetal cells and maternal blood cells using...

  17. Targeting and crossing of the human maternofetal barrier by Listeria monocytogenes: role of internalin interaction with trophoblast E-cadherin.

    Science.gov (United States)

    Lecuit, Marc; Nelson, D Michael; Smith, Steve D; Khun, Huot; Huerre, Michel; Vacher-Lavenu, Marie-Cécile; Gordon, Jeffrey I; Cossart, Pascale

    2004-04-20

    Listeria monocytogenes produces severe fetoplacental infections in humans. How it targets and crosses the maternofetal barrier is unknown. We used immunohistochemistry to examine the location of L. monocytogenes in placental and amniotic tissue samples obtained from women with fetoplacental listeriosis. The results raised the possibility that L. monocytogenes crosses the maternofetal barrier through the villous syncytiotrophoblast, with secondary infection occurring via the amniotic epithelium. Because epidemiological studies indicate that the bacterial surface protein, internalin (InlA), may play a role in human fetoplacental listeriosis, we investigated the cellular patterns of expression of its host receptor, E-cadherin, at the maternofetal interface. E-cadherin was found on the basal and apical plasma membranes of syncytiotrophoblasts and in villous cytotrophoblasts. Established trophoblastic cell lines, primary trophoblast cultures, and placental villous explants were each exposed to isogenic InlA+ or InlA- strains of L. monocytogenes, and to L. innocua expressing or not InlA. Quantitative assays of cellular invasion demonstrated that bacterial entry into syncytiotrophoblasts occurs via the apical membrane in an InlA-E-cadherin dependent manner. In human placental villous explants, bacterial invasion of the syncytiotrophoblast barrier and underlying villous tissue and subsequent replication produces histopathological lesions that mimic those seen in placentas of women with listeriosis. Thus, the InlA-E-cadherin interaction that plays a key role in the crossing of the intestinal barrier in humans is also exploited by L. monocytogenes to target and cross the placental barrier. Such a ligand-receptor interaction allowing a pathogen to specifically cross the placental villous trophoblast barrier has not been reported previously.

  18. Galectin-1 influences trophoblast immune evasion and emerges as a predictive factor for the outcome of pregnancy.

    Science.gov (United States)

    Tirado-González, Irene; Freitag, Nancy; Barrientos, Gabriela; Shaikly, Valerie; Nagaeva, Olga; Strand, Magnus; Kjellberg, Lennart; Klapp, Burghard F; Mincheva-Nilsson, Lucia; Cohen, Marie; Blois, Sandra M

    2013-01-01

    Galectin-1 (gal-1) is expressed at the feto-maternal interface and plays a role in regulating the maternal immune response against placental alloantigens, contributing to pregnancy maintenance. Both decidua and placenta contribute to gal-1 expression and may be important for the maternal immune regulation. The expression of gal-1 within the placenta is considered relevant to cell-adhesion and invasion of trophoblasts, but the role of gal-1 in the immune evasion machinery exhibited by trophoblast cells remains to be elucidated. In this study, we analyzed gal-1 expression in preimplantation human embryos and first-trimester decidua-placenta specimens and serum gal-1 levels to investigate the physiological role played by this lectin during pregnancy. The effect on human leukocyte antigen G (HLA-G) expression in response to stimulation or silencing of gal-1 was also determined in the human invasive, proliferative extravillous cytotrophoblast 65 (HIPEC65) cell line. Compared with normal pregnant women, circulating gal-1 levels were significantly decreased in patients who subsequently suffered a miscarriage. Human embryos undergoing preimplantation development expressed gal-1 on the trophectoderm and inner cell mass. Furthermore, our in vitro experiments showed that exogenous gal-1 positively regulated the membrane-bound HLA-G isoforms (HLA-G1 and G2) in HIPEC65 cells, whereas endogenous gal-1 also induced expression of the soluble isoforms (HLA-G5 and -G6). Our results suggest that gal-1 plays a key role in pregnancy maternal immune regulation by modulating HLA-G expression on trophoblast cells. Circulating gal-1 levels could serve as a predictive factor for pregnancy success in early human gestation.

  19. Endocrinología en la Javeriana. Recuerdos de una época.

    Directory of Open Access Journals (Sweden)

    Alfredo Jácome Roca

    2001-08-01

    Full Text Available

    La Facultad de Medicina de la Universidad Javeriana enseñó clínicas durante sus primeros 25 años de existencia en hospitales tradicionales de Bogotá tales como el San José, la Samaritana y el Instituto de Cancerología. La medicina en adultos era manejada por internistas generales como De Zubiría o Carrizosa o por cardiólogos como Consuegra.

    Poca cabida había para especialistas, los que con el tiempo empezaron a llegar del exterior. Cuando el Hospital San José se encargaba de la docencia en Medicina Interna, allí se rotaba por el servicio de endocrinología donde se formó como endocrinólogo el doctor Julio Gómez Afanador, quien ha sido casi que el secretario perpetuo de la Sociedad Colombiana de Endocrinología y quien es coautor de muchos de los estudios de bocio endémico y crecimiento producidos por este servicio; en 1965 él organizó una consulta de endocrinología en el Hospital San Ignacio, que a partir de 1968 empecé a dirigir.

    La endocrinología se enseñaba poco, que recuerde; hubo clases de fisiología endocrina por Hernán Mendoza y algunas pocas charlas que sobre el tema nos dio Bernardo Reyes en la Samaritana. Con mi amigo y colega Alvaro Mesa resolvimos indagar en un tema que se había puesto de moda merced a las investigaciones de los inmunólogos ingleses Deborah Doniach y su asociado el doctor Roitt: la autoinmunidad tiroidea.

    El Instituto de Cancerología nos pareció el sitio adecuado para trabajar en este proyecto que serviría para nuestra tesis de grado pues convocamos el grupo liderado por Jaime Cortázar, quien contaba con Efraím Otero como su asociado y a Jaime Ahumada como residente. Ellos habían sido pioneros en el manejo de los isótopos radioactivos en Colombia y el hecho de que aplicaran una novedosa e impactante tecnología, la gamagrafía en el diagnóstico tiroideo, les daba una aureola de científicos que sin duda nos atrajo.

    Tomando sueros de pacientes de su nutrida

  20. Serum depletion induces changes in protein expression in the trophoblast-derived cell line HTR-8/SVneo.

    Science.gov (United States)

    Novoa-Herran, Susana; Umaña-Perez, Adriana; Canals, Francesc; Sanchez-Gomez, Myriam

    2016-01-01

    How nutrition and growth factor restriction due to serum depletion affect trophoblast function remains poorly understood. We performed a proteomic differential study of the effects of serum depletion on a first trimester human immortalized trophoblast cell line. The viability of HTR-8/SVneo trophoblast cells in culture with 0, 0.5 and 10 % fetal bovine serum (FBS) were assayed via MTT at 24, 48 and 64 h. A comparative proteomic analysis of the cells grown with those FBS levels for 24 h was performed using two-dimensional electrophoresis (2DE), followed by mass spectrometry for protein spot identification, and a database search and bioinformatics analysis of the expressed proteins. Differential spots were identified using the Kolmogorov-Smirnov test ( n  = 3, significance level 0.10, D > 0.642) and/or ANOVA ( n  = 3, p  depletion differentially affect cell growth and protein expression. Differential expression was seen in 25 % of the protein spots grown with 0.5 % FBS and in 84 % of those grown with 0 % FBS, using 10 % serum as the physiological control. In 0.5 % FBS, this difference was related with biological processes typically affected by the serum, such as cell cycle, regulation of apoptosis and proliferation. In addition to these changes, in the serum-depleted proteome we observed downregulation of keratin 8, and upregulation of vimentin, the glycolytic enzymes enolase and pyruvate kinase (PKM2) and tumor progression-related inosine-5'-monophosphate dehydrogenase 2 (IMPDH2) enzyme. The proteins regulated by total serum depletion, but not affected by growth in 0.5 % serum, are members of the glycolytic and nucleotide metabolic pathways and the epithelial-to-mesenchymal transition (EMT), suggesting an adaptive switch characteristic of malignant cells. This comparative proteomic analysis and the identified proteins are the first evidence of a protein expression response to serum depletion in a trophoblast cell model. Our results show that

  1. Centrosome Clustering in the Development of Bovine Binucleate Trophoblast Giant Cells.

    Science.gov (United States)

    Klisch, Karl; Schraner, Elisabeth M; Boos, Alois

    2017-01-01

    Binucleate trophoblast giant cells (BNC) are the characteristic feature of the ruminant placenta. During their development, BNC pass through 2 acytokinetic mitoses and become binucleate with 2 tetraploid nuclei. In this study, we investigate the number and location of centrosomes in bovine BNC. Centrosomes typically consist of 2 centrioles surrounded by electron-dense pericentriolar material. Duplication of centrosomes is tightly linked to the cell cycle, which ensures that the number of centrosomes remains constant in proliferating diploid cells. Alterations of the cell cycle, which affect the number of chromosome sets, also affect the number of centrosomes. In this study, we use placentomal tissue from pregnant cows (gestational days 80-230) for immunohistochemical staining of γ-tubulin (n = 3) and transmission electron microscopy (n = 3). We show that mature BNC have 4 centrosomes with 8 centrioles, clustered in the angle between the 2 cell nuclei. During the second acytokinetic mitosis, the centrosomes must be clustered to form the poles of a bipolar spindle. In rare cases, centrosome clustering fails and tripolar mitosis leads to the formation of trinucleate "BNC". Generally, centrosome clustering occurs in polyploid tumor cells, which have an increased number of centrioles, but it is absent in proliferating diploid cells. Thus, inhibition of centrosome clustering in tumor cells is a novel promising strategy for cancer treatment. BNC are a cell population in which centrosome clustering occurs as part of the normal life history. Thus, they might be a good model for the study of the molecular mechanisms of centrosome clustering. © 2016 S. Karger AG, Basel.

  2. 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.

  3. Usefulness of low-dose CT in the detection of pulmonary metastasis of gestational trophoblastic tumours

    International Nuclear Information System (INIS)

    Xu, X.J.; Lou, F.L.; Zhang, M.M.; Pan, Z.M.; Zhang, L.

    2007-01-01

    Aim: To determine whether a low-dose spiral chest computed tomography (CT) examination could replace standard-dose chest CT in detecting pulmonary metastases in patients with gestational trophoblastic tumour (GTT). Materials and methods: In a prospective investigation, 67 chest CT examinations of 39 GTT patients were undertaken. All the patients underwent CT examinations using standard-dose (150 mAs, pitch 1, standard reconstruction algorithm) and low-dose (40 mAs, pitch 2, bone reconstruction algorithm) protocols. Two radiologists interpreted images independently. A metastasis was defined as a nodule within lung parenchyma that could not be attributed to a pulmonary vessel. The number of metastases detected with each protocol was recorded. The size of each lesion was measured and categorized as <5, 5-9.9, and ≥10 mm. Wilcoxon's signed rank test was used to assess the difference between the numbers of lesion detected by the two protocols. Results: The CT dose index (CTDI) for the standard-dose and low-dose CT protocols was 10.4 mGy and 1.4 mGy, respectively. One thousand, six hundred, and eighty-two metastases were detected by standard-dose CT, and 1460 lesions by the low-dose protocol. The numbers detected by low-dose CT were significantly less than those detected by standard-dose CT (Z = -3.776, p < 0.001), especially for nodules smaller than 5 mm (Z = -4.167, p < 0.001). However, the disease staging and risk score of the patients were not affected by use of the low-dose protocol. Conclusion: Low-dose chest CT can be used as a staging and follow-up procedure for patients with GTT

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

    International Nuclear Information System (INIS)

    Grimes, R.W.

    1990-01-01

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

  5. Management of gestational trophoblastic disease: a survey of New Zealand O&G practice.

    Science.gov (United States)

    Kladnitski, Maria; Kenwright, Diane

    2016-03-11

    The aim of the study was to obtain information on pathways for diagnosis and management of molar pregnancy/gestational trophoblastic disease (GTD) across New Zealand, the protocols used, and, in addition, to consider the view of O&G Specialists on a national GTD reference centre. An electronic survey approved by the RANZCOG Continues Professional Development Committee was distributed amongst registered O&G Specialists currently working in New Zealand. Data were analysed using Microsoft Excel 2011. Frequency distributions were used to determine the percentage of participants responding to the listed alternatives for each question. There were 234 potential responders, but only 68 complete questionnaires were received and available for analysis. The diagnosis of GTD requires histopathological analysis of pregnancy tissue, however only 79.7% of participants request this test routinely. Sixty-five percent of Fellows thought that a number of molar pregnancies can be missed with increasing proportion of medically-managed miscarriages, reliance on ultrasound and appearance of the tissue being contributing factors. Sixty-six percent of specialists were directly involved in the management of patients with GTD to various degrees. Follow-up responsibilities were divided between designated O&G specialists (52.3%), specialised gynaecology clinics (29.2%), acute assessment units (13.8%), nurse specialists (12%), O&G registrars (10.8%), GPs (6.2%), and others (6.2%). NZGCG guidelines were used by the majority of responders (54.8%), followed by local (29%) and RCOG (27.4%) guidelines. Seventy-two percent of specialists felt that some form of centralisation in the management of GTD is needed. In spite of the low response rate, our research demonstrates existing practice heterogeneity at every level of care. It also confirms that there is a desire for some form of centralisation in diagnosis and management of GTD, and a definite need for data collection in the form of a national

  6. A CRE/AP-1-like motif is essential for induced syncytin-2 expression and fusion in human trophoblast-like model.

    Directory of Open Access Journals (Sweden)

    Chirine Toufaily

    Full Text Available Syncytin-2 is encoded by the envelope gene of Endogenous Retrovirus-FRD (ERVFRD-1 and plays a critical role in fusion of placental trophoblasts leading to the formation of the multinucleated syncytiotrophoblast. Its expression is consequently regulated in a strict manner. In the present study, we have identified a forskolin-responsive region located between positions -300 to -150 in the Syncytin-2 promoter region. This 150 bp region in the context of a minimal promoter mediated an 80-fold induction of promoter activity following forskolin stimulation. EMSA analyses with competition experiments with nuclear extracts from forskolin-stimulated BeWo cells demonstrated that the -211 to -177 region specifically bound two forskolin-induced complexes, one of them containing a CRE/AP-1-like motif. Site-directed mutagenesis of the CRE/AP-1 binding site in the context of the Syncytin-2 promoter or a heterologous promoter showed that this motif was mostly essential for forskolin-induced promoter activity. Transfection experiments with dominant negative mutants and constitutively activated CREB expression vectors in addition to Chromatin Immunoprecipitation suggested that a CREB family member, CREB2 was binding and acting through the CRE/AP-1 motif. We further demonstrated the binding of JunD to this same motif. Similar to forskolin and soluble cAMP, CREB2 and JunD overexpression induced Syncytin-2 promoter activity in a CRE/AP-1-dependent manner and Syncytin-2 expression. In addition, BeWo cell fusion was induced by both CREB2 and JunD overexpression, while being repressed following silencing of either gene. These results thereby demonstrate that induced expression of Syncytin-2 is highly dependent on the interaction of bZIP-containing transcription factors to a CRE/AP-1 motif and that this element is important for the regulation of Syncytin-2 expression, which results in the formation of the peripheral syncytiotrophoblast layer.

  7. Physiology and Endocrinology Symposium: The current status of heat shock in early embryonic survival and reproductive efficiency

    Science.gov (United States)

    The Physiology and Endocrinology Symposium entitled “The Current Status of Heat Shock in Early Embryonic Survival and Reproductive Efficiency” was held at the Joint ADSA-CSAS-AMPA-WSAS-ASAS Meeting in Phoenix, Arizona, July 15 to 19, 2012. In recent years, data has accumulated suggesting a role for...

  8. Outcomes of androgen replacement therapy in adult male hypogonadism: recommendations from the Italian society of endocrinology.

    Science.gov (United States)

    Isidori, A M; Balercia, G; Calogero, A E; Corona, G; Ferlin, A; Francavilla, S; Santi, D; Maggi, M

    2015-01-01

    We developed clinical practice guidelines to assess the individual risk-benefit profile of androgen replacement therapy in adult male hypogonadism (HG), defined by the presence of specific signs and symptoms and serum testosterone (T) below 12 nmol/L. The task force consisted of eight clinicians experienced in treating HG, selected by the Italian Society of Endocrinology (SIE). The authors received no corporate funding or remuneration. Consensus was guided by a systematic review of controlled trials conducted on men with a mean T treatments for individuals at high risk for complications, such as those with osteoporosis and/or metabolic disorders. We recommend against using TS to improve cardiac outcome and limited mobility. We recommend against using TS in men with prostate cancer, unstable cardiovascular conditions or elevated haematocrit. The task force places a high value on the timely treatment of younger and middle-aged subjects to prevent the long-term consequences of hypoandrogenism.

  9. Early and late endocrinologic complications of the hematopoetic stem cell transplantation performed for hematologic malignancies

    Directory of Open Access Journals (Sweden)

    Murat Albayrak

    2012-03-01

    Full Text Available Hematopoietic stem cell transplantation (HSCT is usedfor various hematologic malignancies seen in childrenand adults. There may be several complications before,during, and after the HSCT. Just one of them is endocrinologiccomplications, since endocrine system (particularlythe pituitary gland, thyroid gland, adrenal glands, andgonads is highly sensitive against various stress. Chemotherapyand/or total body irradiation used as preparativeregimens and immunosuppressive agents (especiallycorticosteroids used for the graft-versus-host diseasecan cause hormonal disorders. Time elapsed after theHSCT, transplantation type (autologous or allogeneic,preparative regimen choice, age, and gender determinesthe complications. A multidisciplinary management containinga specialist of endocrinology for these patients ispreferred. In this report, we reviewed the endocrinologiccomplications that observed after the HSCT in childrenand adults referring to the recent literatures. J Clin ExpInvest 2012; 3(1: 149-156

  10. Study on reproductive endocrinological function in postmenopausal women treated with estriol

    International Nuclear Information System (INIS)

    Li Wenqi; Zhou Zhenli; Zhou Jiwen; Li Xin

    2002-01-01

    Objective: To investigate the reproductive endocrinological function in postmenopausal women treated with ultralente estriol for 3 years. Methods: Serum levels of six reproductive hormones (FSH, LH, PRL, T, E 2 , P) were measured with RIA in 1) 136 normal 1-5yrs post-menopausal women 2) 48 post-menopausal women treated with estriol for 3 years 3) 131 healthy women of child-bearing age during follicular and luteal phases. Results: Serum levels of the six reproductive hormones in women of child-bearing age at both follicular and luteal phases were significantly different from those in post-menopausal women (p 2 , P and T levels were not significant (p > 0.05). Conclusion: Serum reproductive hormones assay is important for monitoring hormone replacement therapy in aging women

  11. Diagnosis and treatment of hypoparathyroidism: a position statement from the Brazilian Society of Endocrinology and Metabolism.

    Science.gov (United States)

    Maeda, Sergio Setsuo; Moreira, Carolina Aguiar; Borba, Victória Zeghbi Cochenski; Bandeira, Francisco; Farias, Maria Lucia Fleiuss de; Borges, João Lindolfo Cunha; Paula, Francisco José Albuquerque de; Vanderlei, Felipe Augusto Brasileiro; Montenegro, Fábio Luiz de Menezes; Santos, Rodrigo Oliveira; Ferraz-de-Souza, Bruno; Lazaretti-Castro, Marise

    2018-02-01

    Objective To present an update on the diagnosis and treatment of hypoparathyroidism based on the most recent scientific evidence. Materials and methods The Department of Bone and Mineral Metabolism of the Sociedade Brasileira de Endocrinologia e Metabologia (SBEM; Brazilian Society of Endocrinology and Metabolism) was invited to prepare a document following the rules set by the Guidelines Program of the Associação Médica Brasileira (AMB; Brazilian Medical Association). Relevant papers were retrieved from the databases MEDLINE/PubMed, LILACS, and SciELO, and the evidence derived from each article was classified into recommendation levels according to scientific strength and study type. Conclusion An update on the recent scientific literature addressing hypoparathyroidism is presented to serve as a basis for the diagnosis and treatment of this condition in Brazil.

  12. [Thyroid dysfunction in pregnancy. Consensus document. Andalusian Society of Endocrinology and Nutrition (SAEN)].

    Science.gov (United States)

    Santiago Fernández, P; González-Romero, S; Martín Hernández, T; Navarro González, E; Velasco López, I; Millón Ramírez, M C

    2015-09-01

    A position statement on the diagnosis and treatment of thyroid dysfunction in pregnancy has been agreed on behalf of The Sociedad Andaluza de Endocrinología y Nutrición (SAEN), based on a review of the literature to date and all good clinical practice guidelines. The document is set out in different sections as regards the diagnosis and treatment of, overt and subclinical hypo- and hyperthyroidism, isolated hypothyroxinaemia and postpartum thyroiditis. It also justifies the implementation of universal screening for thyroid dysfunction in pregnancy, and provides practitioners who care for these patients with tool for rational decision making. Copyright © 2014 Sociedad Española de Médicos de Atención Primaria (SEMERGEN). Publicado por Elsevier España, S.L.U. All rights reserved.

  13. MECHANISMS IN ENDOCRINOLOGY: Skeletal muscle lipotoxicity in insulin resistance and type 2 diabetes: a causal mechanism or an innocent bystander?

    Science.gov (United States)

    Brøns, Charlotte; Grunnet, Louise Groth

    2017-02-01

    Dysfunctional adipose tissue is associated with an increased risk of developing type 2 diabetes (T2D). One characteristic of a dysfunctional adipose tissue is the reduced expandability of the subcutaneous adipose tissue leading to ectopic storage of fat in organs and/or tissues involved in the pathogenesis of T2D that can cause lipotoxicity. Accumulation of lipids in the skeletal muscle is associated with insulin resistance, but the majority of previous studies do not prove any causality. Most studies agree that it is not the intramuscular lipids per se that causes insulin resistance, but rather lipid intermediates such as diacylglycerols, fatty acyl-CoAs and ceramides and that it is the localization, composition and turnover of these intermediates that play an important role in the development of insulin resistance and T2D. Adipose tissue is a more active tissue than previously thought, and future research should thus aim at examining the exact role of lipid composition, cellular localization and the dynamics of lipid turnover on the development of insulin resistance. In addition, ectopic storage of fat has differential impact on various organs in different phenotypes at risk of developing T2D; thus, understanding how adipogenesis is regulated, the interference with metabolic outcomes and what determines the capacity of adipose tissue expandability in distinct population groups is necessary. This study is a review of the current literature on the adipose tissue expandability hypothesis and how the following ectopic lipid accumulation as a consequence of a limited adipose tissue expandability may be associated with insulin resistance in muscle and liver. © 2017 European Society of Endocrinology.

  14. [Pheochromocytoma in 8-year observation at a single endocrinological center in Wroclaw].

    Science.gov (United States)

    Bednarek-Tupikowska, Grazyna; Bucyk, Barbara; Daroszewski, Jacek; Bidzińska-Speichert, Bozena; Bohdanowicz-Pawlak, Anna; Szymczak, Jadwiga; Bednorz, Włodzimierz; Podgórski, Franciszek; Zareba-Bogdał, Elzbieta; Kuliczkowska-Płaksej, Justyna; Lenarcik, Agnieszka; Filus, Alicja; Kałuzny, Marcin; Kubicka, Eliza; Syrycka, Joanna; Tupikowska, Małgorzata; Lizurej, Oskar; Bolanowski, Marek; Milewicz, Andrzej

    2009-01-01

    Pheochromocytoma is rare tumor with a highly variable clinical presentation. This report provides clinical picture, efficiency of diagnostics and treatment of pheochromocytoma in 8-years in the endocrinological center in Wroclaw. The records of 37 patients with pheochromocytoma were identified, who were treated in 2000-2007 in the Department of Endocrinology, Diabetology and Isotope Treatment in Wroclaw. There were 23 women (age 23-75 year) and 14 men (age 17-74). We studied frequency of clinical signs, usefulness of diagnostic methods and efficacy of treatment. The duration of the clinical history ranged from 2 months to 16 years. The most frequent symptoms were: hypertension paroxysmal and constant, palpitations, headache, sweating and anxiety. The most sensitive diagnostic method was increased concentration of urinary metanephrine in 24-hour urine. Computed tomography was the most widely used method for tumor localization. Adrenal pheochromocytoma was detecting by CT in all patients, predominated in right adrenal, in 1 case in urinary bladder. Surgery caused remission of hypertension in 59%, improvement in 26.8%, and no changes in 13.9% of patients. Malignancy was reported in 2 cases, 1 woman died after surgery. MEN 2A occur in 21.6%. The diagnosis of pheochromocytma is usually made after long duration of the disease. The study confirms that clinical presentation of pheochromocytoma is variable and nonspecific, this finding makes the diagnosis very difficult. The most typical symptom is paroxysmal hypertension, which is present only in 40%, other symptoms are nonspecific. The measurement of 24-hour urinary metanephrines was the best indicator. CT was almost always successful in localizing the tumor. Patients with pheochromocytoma should be consider for other endocrine diseases especially medullary carcinoma, primary hyperparathyroidism and other component of MEN 2A.

  15. Exploring the Association between Alzheimer’s Disease, Oral Health, Microbial Endocrinology and Nutrition

    Science.gov (United States)

    Harding, Alice; Gonder, Ulrike; Robinson, Sarita J.; Crean, StJohn; Singhrao, Sim K.

    2017-01-01

    Longitudinal monitoring of patients suggests a causal link between chronic periodontitis and the development of Alzheimer’s disease (AD). However, the explanation of how periodontitis can lead to dementia remains unclear. A working hypothesis links extrinsic inflammation as a secondary cause of AD. This hypothesis suggests a compromised oral hygiene leads to a dysbiotic oral microbiome whereby Porphyromonas gingivalis, a keystone periodontal pathogen, with its companion species, orchestrates immune subversion in the host. Brushing and chewing on teeth supported by already injured soft tissues leads to bacteremias. As a result, a persistent systemic inflammatory response develops to periodontal pathogens. The pathogens, and the host’s inflammatory response, subsequently lead to the initiation and progression of multiple metabolic and inflammatory co-morbidities, including AD. Insufficient levels of essential micronutrients can lead to microbial dysbiosis through the growth of periodontal pathogens such as demonstrated for P. gingivalis under low hemin bioavailability. An individual’s diet also defines the consortium of microbial communities that take up residency in the oral and gastrointestinal (GI) tract microbiomes. Their imbalance can lead to behavioral changes. For example, probiotics enriched in Lactobacillus genus of bacteria, when ingested, exert some anti-inflammatory influence through common host/bacterial neurochemicals, both locally, and through sensory signaling back to the brain. Early life dietary behaviors may cause an imbalance in the host/microbial endocrinology through a dietary intake incompatible with a healthy GI tract microbiome later in life. This imbalance in host/microbial endocrinology may have a lasting impact on mental health. This observation opens up an opportunity to explore the mechanisms, which may underlie the previously detected relationship between diet, oral/GI microbial communities, to anxiety, cognition and sleep

  16. Exploring the Association between Alzheimer's Disease, Oral Health, Microbial Endocrinology and Nutrition.

    Science.gov (United States)

    Harding, Alice; Gonder, Ulrike; Robinson, Sarita J; Crean, StJohn; Singhrao, Sim K

    2017-01-01

    Longitudinal monitoring of patients suggests a causal link between chronic periodontitis and the development of Alzheimer's disease (AD). However, the explanation of how periodontitis can lead to dementia remains unclear. A working hypothesis links extrinsic inflammation as a secondary cause of AD. This hypothesis suggests a compromised oral hygiene leads to a dysbiotic oral microbiome whereby Porphyromonas gingivalis , a keystone periodontal pathogen, with its companion species, orchestrates immune subversion in the host. Brushing and chewing on teeth supported by already injured soft tissues leads to bacteremias. As a result, a persistent systemic inflammatory response develops to periodontal pathogens. The pathogens, and the host's inflammatory response, subsequently lead to the initiation and progression of multiple metabolic and inflammatory co-morbidities, including AD. Insufficient levels of essential micronutrients can lead to microbial dysbiosis through the growth of periodontal pathogens such as demonstrated for P. gingivalis under low hemin bioavailability. An individual's diet also defines the consortium of microbial communities that take up residency in the oral and gastrointestinal (GI) tract microbiomes. Their imbalance can lead to behavioral changes. For example, probiotics enriched in Lactobacillus genus of bacteria, when ingested, exert some anti-inflammatory influence through common host/bacterial neurochemicals, both locally, and through sensory signaling back to the brain. Early life dietary behaviors may cause an imbalance in the host/microbial endocrinology through a dietary intake incompatible with a healthy GI tract microbiome later in life. This imbalance in host/microbial endocrinology may have a lasting impact on mental health. This observation opens up an opportunity to explore the mechanisms, which may underlie the previously detected relationship between diet, oral/GI microbial communities, to anxiety, cognition and sleep patterns

  17. Economic impact of and satisfaction with a high resolution thyroid nodule clinic at the endocrinology department.

    Science.gov (United States)

    Díaz-Soto, Gonzalo; Torres, Beatriz; López Gómez, Juan Jose; Gómez Hoyos, Emilia; Villar, Aurelia; Romero, Enrique; de Luis, Daniel A

    2016-10-01

    No conclusive data exist on the value of a high resolution thyroid nodule clinic for management of nodular thyroid disease. The aim of this study was to evaluate the economic impact of and user satisfaction with a high resolution thyroid nodule clinic (HRTNC) in coordination with primary care. A prospective, observational, descriptive study was conducted to analyze data from 3,726 patients (mean age 61±12 years; 85% women) evaluated at an HRTNC during 2014 and 2015. Demographic data (sex and age), number of ultrasound examinations and fine needle aspiration cytologies (FNAC), referral center and consultation type were assessed. In 2014 and 2015, 3,726 neck ultrasound examinations and 926 FNACs (3.8% rated as non-diagnostic) were performed. Among the 1,227 patients evaluated for the first time, 21.5% did not require a second endocrine appointment, which resulted in mean estimated savings of 14,354.55 euros. Of all patients, 41.1% were referred from primary care, 33.4% from endocrinology, and 26.5% from other specialties. As compared to 2013, the number of thyroid ultrasound examinations requested decreased by 65.3% and 59.7% in 2014 and 2015 respectively, with mean estimated savings of 137,563.92 euros. Mean user satisfaction assessed was 4.0 points (95% confidence interval, 3.7-4.3) on a 5-point scale. HRTNCs at endocrinology departments, coordinated with primary care, are a viable, cost-effective alternative with a positive user perception. Copyright © 2016 SEEN. Publicado por Elsevier España, S.L.U. All rights reserved.

  18. European Society for Paediatric Endocrinology Consensus Guidelines on Screening, Diagnosis, and Management of Congenital Hypothyroidism

    Science.gov (United States)

    Léger, Juliane; Olivieri, Antonella; Donaldson, Malcolm; Torresani, Toni; Krude, Heiko; van Vliet, Guy; Polak, Michel

    2014-01-01

    Objective: The aim was to formulate practice guidelines for the diagnosis and management of congenital hypothyroidism (CH). Evidence: A systematic literature search was conducted to identify key articles relating to the screening, diagnosis, and management of CH. The evidence-based guidelines were developed with the Grading of Recommendations, Assessment, Development and Evaluation (GRADE) system, describing both the strength of recommendations and the quality of evidence. In the absence of sufficient evidence, conclusions were based on expert opinion. Consensus Process: Thirty-two participants drawn from the European Society for Paediatric Endocrinology and five other major scientific societies in the field of pediatric endocrinology were allocated to working groups with assigned topics and specific questions. Each group searched the literature, evaluated the evidence, and developed a draft document. These papers were debated and finalized by each group before presentation to the full assembly for further discussion and agreement. Recommendations: The recommendations include: worldwide neonatal screening, approaches to assess the cause (including genotyping) and the severity of the disorder, the immediate initiation of appropriate L-T4 supplementation and frequent monitoring to ensure dose adjustments to keep thyroid hormone levels in the target ranges, a trial of treatment in patients suspected of transient CH, regular assessments of developmental and neurosensory functions, consulting health professionals as appropriate, and education about CH. The harmonization of diagnosis, management, and routine health surveillance would not only optimize patient outcomes, but should also facilitate epidemiological studies of the disorder. Individuals with CH require monitoring throughout their lives, particularly during early childhood and pregnancy. PMID:24446653

  19. Exploring the Association between Alzheimer’s Disease, Oral Health, Microbial Endocrinology and Nutrition

    Directory of Open Access Journals (Sweden)

    Alice Harding

    2017-12-01

    Full Text Available Longitudinal monitoring of patients suggests a causal link between chronic periodontitis and the development of Alzheimer’s disease (AD. However, the explanation of how periodontitis can lead to dementia remains unclear. A working hypothesis links extrinsic inflammation as a secondary cause of AD. This hypothesis suggests a compromised oral hygiene leads to a dysbiotic oral microbiome whereby Porphyromonas gingivalis, a keystone periodontal pathogen, with its companion species, orchestrates immune subversion in the host. Brushing and chewing on teeth supported by already injured soft tissues leads to bacteremias. As a result, a persistent systemic inflammatory response develops to periodontal pathogens. The pathogens, and the host’s inflammatory response, subsequently lead to the initiation and progression of multiple metabolic and inflammatory co-morbidities, including AD. Insufficient levels of essential micronutrients can lead to microbial dysbiosis through the growth of periodontal pathogens such as demonstrated for P. gingivalis under low hemin bioavailability. An individual’s diet also defines the consortium of microbial communities that take up residency in the oral and gastrointestinal (GI tract microbiomes. Their imbalance can lead to behavioral changes. For example, probiotics enriched in Lactobacillus genus of bacteria, when ingested, exert some anti-inflammatory influence through common host/bacterial neurochemicals, both locally, and through sensory signaling back to the brain. Early life dietary behaviors may cause an imbalance in the host/microbial endocrinology through a dietary intake incompatible with a healthy GI tract microbiome later in life. This imbalance in host/microbial endocrinology may have a lasting impact on mental health. This observation opens up an opportunity to explore the mechanisms, which may underlie the previously detected relationship between diet, oral/GI microbial communities, to anxiety, cognition

  20. 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

  1. 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.

  2. The lncRNA TUG1 modulates proliferation in trophoblast cells via epigenetic suppression of RND3.

    Science.gov (United States)

    Xu, Yetao; Ge, Zhiping; Zhang, Erbao; Zuo, Qing; Huang, Shiyun; Yang, Nana; Wu, Dan; Zhang, Yuanyuan; Chen, Yanzi; Xu, Haoqin; Huang, Huan; Jiang, Zhiyan; Sun, Lizhou

    2017-10-12

    Due to limited treatment options, pre-eclampsia (PE) is associated with fetal perinatal and maternal morbidity and mortality. During the causes of PE, failure of uterine spiral artery remodeling which might be related to functioning abnormally of trophoblast cells, result in the occurrence and progression of PE. Recently, abnormal expression of long non-coding RNAs (lncRNAs), as imperative regulators involved in human diseases progression (included PE), which has been indicated by increasing evidence. In this research, we found that TUG1, a lncRNA, was markedly reduced in placental samples from patients with PE. Loss-function assays indicated that knockdown TUG1 significantly affected cell proliferation, apoptosis, migration and network formation in vitro. RNA-seq revealed that TUG1 could affect abundant genes, and then explore the function and regulatory mechanism of TUG1 in trophoblast cells. Furthermore, RNA immunoprecipitation and chromatin immunoprecipitation assays validated that TUG1 can epigenetically inhibit the level of RND3 through binding to EZH2, thus promoting PE development. Therefore, via illuminating the TUG1 mechanisms underlying PE development and progression, our findings might furnish a prospective therapeutic strategy for PE intervention.

  3. Dysregulated DNA Methyltransferase 3A Upregulates IGFBP5 to Suppress Trophoblast Cell Migration and Invasion in Preeclampsia.

    Science.gov (United States)

    Jia, Yuanhui; Li, Ting; Huang, Xiaojie; Xu, Xianghong; Zhou, Xinyao; Jia, Linyan; Zhu, Jingping; Xie, Dandan; Wang, Kai; Zhou, Qian; Jin, Liping; Zhang, Jiqin; Duan, Tao

    2017-02-01

    Preeclampsia is a unique multiple system disorder during human pregnancy, which affects ≈5% to 8% of pregnancies. Its risks and complications have become the major causes of maternal and fetal morbidity and mortality. Although abnormal placentation to which DNA methylation dysregulation is always linked is speculated to be one of the reasons causing preeclampsia, the underlying mechanisms still remain elusive to date. Here we revealed that aberrant DNA methyltransferase 3A (DNMT3A) plays a critical role in preeclampsia. Our results show that the expression and localization of DNMT3A are dysregulated in preeclamptic placenta. Moreover, knockdown of DNMT3A obviously inhibits trophoblast cell migration and invasion. Mechanistically, IGFBP5 (insulin-like growth factor-binding protein 5), known as a suppressor, is upregulated by decreased DNMT3A because of promoter hypomethylation. Importantly, IGFBP5 downregulation can rescue the defects caused by DNMT3A knockdown, thereby, consolidating the significance of IGFBP5 in the downstream of DNMT3A in trophoblast. Furthermore, we detected low promoter methylation and high protein expression of IGFBP5 in the clinical samples of preeclamptic placenta. Collectively, our study suggests that dysregulation of DNMT3A and IGFBP5 is relevant to preeclampsia. Thus, we propose that DNMT3A and IGFBP5 can serve as potential markers and targets for the clinical diagnosis and therapy of preeclampsia. © 2017 American Heart Association, Inc.

  4. Temporal and spatial expression of matrix metalloproteinase-2 and matrix metalloproteinase-9 in trophoblast and endometrial epithelium during pregnancy of pig

    Czech Academy of Sciences Publication Activity Database

    Georgieva, R.; Rashev, P.; Pěknicová, Jana; Michailova, A.

    2004-01-01

    Roč. 52, Suppl.1 (2004), s. 42-43 ISSN 1046-7408. [International Congress of Reproductive Immunology /9./. Hakone, 11.10.2004-15.10.2004] Institutional research plan: CEZ:AV0Z5052915 Keywords : matrix metalloproteinase * trophoblast * endometrium Subject RIV: EC - Immunology Impact factor: 1.808, year: 2004

  5. A Primary Human Trophoblast Model to Study the Effect of Inflammation Associated with Maternal Obesity on Regulation of Autophagy in the Placenta.

    Science.gov (United States)

    Simon, Bailey; Bucher, Matthew; Maloyan, Alina

    2017-09-27

    Maternal obesity is associated with an increased risk of adverse perinatal outcomes that are likely mediated by compromised placental function that can be attributed to, in part, the dysregulation of autophagy. Aberrant changes in the expression of autophagy regulators in the placentas from obese pregnancies may be regulated by inflammatory processes associated with both obesity and pregnancy. Described here is a protocol for sampling of villous tissue and isolation of villous cytotrophoblasts from the term human placenta for primary cell culture. This is followed by a method for simulating the inflammatory milieu in the obese intrauterine environment by treating primary trophoblasts from lean pregnancies with tumor necrosis factor alpha (TNFα), a proinflammatory cytokine that is elevated in obesity and in pregnancy. Through the implementation of the protocol described here, it is found that exposure to exogenous TNFα regulates the expression of Rubicon, a negative regulator of autophagy, in trophoblasts from lean pregnancies with female fetuses. While a variety of biological factors in the obese intrauterine environment maintain the potential to modulate critical pathways in trophoblasts, this ex vivo system is especially useful for determining if expression patterns observed in vivo in human placentas with maternal obesity are a direct result of TNFα signaling. Ultimately, this approach affords the opportunity to parse out the regulatory and molecular implications of inflammation associated with maternal obesity on autophagy and other critical cellular pathways in trophoblasts that have the potential to impact placental function.

  6. Mutations within the LINC-HELLP non-coding RNA differentially bind ribosomal and RNA splicing complexes and negatively affect trophoblast differentiation

    NARCIS (Netherlands)

    van Dijk, M.; Visser, A.; Buabeng, K.M.L.; Poutsma, A.; van der Schors, R.C.; Oudejans, C.B.M.

    2015-01-01

    LINC-HELLP, showing chromosomal linkage with the pregnancy-specific HELLP syndrome in Dutch families, reduces differentiation from a proliferative to an invasive phenotype of first-trimester extravillous trophoblasts. Here we show that mutations in LINC-HELLP identified in HELLP families negatively

  7. Role of prostate apoptosis response 4 in translocation of GRP78 from the endoplasmic reticulum to the cell surface of trophoblastic cells.

    Directory of Open Access Journals (Sweden)

    Marie Cohen

    Full Text Available Glucose-regulated protein 78 (GRP78 is an endoplasmic reticulum (ER molecular chaperone that belongs to the heat shock protein 70 family. GRP78 is also present on the cell surface membrane of trophoblastic cells, where it is associated with invasive or fusion properties of these cells. Impaired mechanism of GRP78 relocation from ER to the cell surface was observed in preeclamptic cytotrophoblastic cells (CTB and could take part in the pathogenesis of preeclampsia. In this study, we have investigated whether prostate apoptosis response 4 (Par-4, a protein identified as a partner of GRP78 relocation to the cell surface in prostate cancer cells, is present in trophoblastic cells and is involved in the translocation of GRP78 to the cell surface of CTB. Par-4 is indeed present in trophoblastic cells and its expression correlates with expression of membrane GRP78. Moreover, overexpression of Par-4 led to an increase of cell surface expression of GRP78 and decreased Par-4 gene expression reduced cell surface localization of GRP78 confirming a role of Par-4 in relocation of GRP78 from ER to the cell surface. Accordingly, invasive property was modified in these cells. In conclusion, we show that Par-4 is expressed in trophoblastic cells and is involved in transport of GRP78 to the cell surface and thus regulates invasive property of extravillous CTB.

  8. The STOX1 genotype associated with pre-eclampsia leads to a reduction of trophoblast invasion by alpha-T-catenin upregulation

    NARCIS (Netherlands)

    van Dijk, Marie; van Bezu, Jan; van Abel, Daan; Dunk, Caroline; Blankenstein, Marinus A.; Oudejans, Cees B. M.; Lye, Stephen J.

    2010-01-01

    By using complementary in vitro and ex vivo approaches, we show that the risk allele (Y153H) of the pre-eclampsia susceptibility gene STOX1 negatively regulates trophoblast invasion by upregulation of the cell-cell adhesion protein alpha-T-catenin (CTNNA3). This is effectuated at the crucial

  9. Identification of differences in gene expression in primary cell cultures of human endometrial epithelial cells and trophoblast cells following their interaction

    DEFF Research Database (Denmark)

    Høgh, Mette; Islin, Henrik; Møller, Charlotte

    2006-01-01

    The interaction between the cell types was simulated in vitro by growing primary cell cultures of human endometrial epithelial cells and trophoblast cells together (co-culture) and separately (control cultures). Gene expression in the cell cultures was compared using the Differential Display method and confirmed...

  10. Identification of patients with persistent trophoblastic disease after complete hydatidiform mole by using a normal 24-hour urine hCG regression curve

    NARCIS (Netherlands)

    Cromvoirt, S.M. van; Thomas, C.M.G.; Quinn, M.A.; McNally, O.M.; Bekkers, R.L.M.

    2014-01-01

    OBJECTIVE: The aim of this study was to establish a reference 24-hour urine human chorionic gonadotropin (hCG) regression curve in patients with complete hydatidiform mole (CHM) as diagnostic tool in the prediction of persistent trophoblastic disease (PTD). METHODS: From 2004 to 2011, 312 cases

  11. In Vivo Chromatin Targets of the Transcription Factor Yin Yang 2 in Trophoblast Stem Cells

    Science.gov (United States)

    Pérez-Palacios, Raquel; Macías-Redondo, Sofía; Climent, María; Contreras-Moreira, Bruno; Muniesa, Pedro; Schoorlemmer, Jon

    2016-01-01

    Background Yin Yang 2 (YY2) is a zinc finger protein closely related to the well-characterized Yin Yang 1 (YY1). YY1 is a DNA-binding transcription factor, with defined functions in multiple developmental processes, such as implantation, cell differentiation, X inactivation, imprinting and organogenesis. Yy2 has been treated as a largely immaterial duplication of Yy1, as they share high homology in the Zinc Finger-region and similar if not identical in vitro binding sites. In contrast to these similarities, gene expression alterations in HeLa cells with attenuated levels of either Yy1 or Yy2 were to some extent gene-specific. Moreover, the chromatin binding sites for YY2, except for its association with transposable retroviral elements (RE) and Endogenous Retroviral Elements (ERVs), remain to be identified. As a first step towards defining potential Yy2 functions matching or complementary to Yy1, we considered in vivo DNA binding sites of YY2 in trophoblast stem (TS) cells. Results We report the presence of YY2 protein in mouse-derived embryonic stem (ES) and TS cell lines. Following up on our previous report on ERV binding by YY2 in TS cells, we investigated the tissue-specificity of REX1 and YY2 binding and confirm binding to RE/ERV targets in both ES cells and TS cells. Because of the higher levels of expression, we chose TS cells to understand the role of Yy2 in gene and chromatin regulation. We used in vivo YY2 association as a measure to identify potential target genes. Sequencing of chromatin obtained in chromatin-immunoprecipitation (ChIP) assays carried out with αYY2 serum allowed us to identify a limited number of chromatin targets for YY2. Some putative binding sites were validated in regular ChIP assays and gene expression of genes nearby was altered in the absence of Yy2. Conclusions YY2 binding to ERVs is not confined to TS cells. In vivo binding sites share the presence of a consensus binding motif. Selected sites were uniquely bound by YY2 as

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

    Science.gov (United States)

    Carter, Anthony M

    2011-04-01

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

  13. Allelic imbalance modulates surface expression of the tolerance-inducing HLA-G molecule on primary trophoblast cells.

    Science.gov (United States)

    Djurisic, S; Teiblum, S; Tolstrup, C K; Christiansen, O B; Hviid, T V F

    2015-03-01

    The HLA-G molecule is expressed on trophoblast cells at the feto-maternal interface, where it interacts with local immune cells, and upholds tolerance against the semi-allogeneic fetus. Aberrant HLA-G expression in the placenta and reduced soluble HLA-G levels are observed in pregnancy complications, partly explained by HLA-G polymorphisms which are associated with differences in the alternative splicing pattern and of the stability of HLA-G mRNA. Of special importance is a 14 bp insertion/deletion polymorphism located in the 3'-untranslated region of the HLA-G gene. In the current study, we present novel evidence for allelic imbalance of the 14 bp insertion/deletion polymorphism, using a very accurate and sensitive Digital droplet PCR technique. Allelic imbalance in heterozygous samples was observed as differential expression levels of 14 bp insertion/deletion allele-specific mRNA transcripts, which was further associated with low levels of HLA-G surface expression on primary trophoblast cells. Full gene sequencing of HLA-G allowed us to study correlations between HLA-G extended haplotypes and single-nucleotide polymorphisms and HLA-G surface expression. We found that a 1:1 expression (allelic balance) of the 14 bp insertion/deletion mRNA alleles was associated with high surface expression of HLA-G and with a specific HLA-G extended haplotype. The 14 bp del/del genotype was associated with a significantly lower abundance of the G1 mRNA isoform, and a higher abundance of the G3 mRNA isoform. Overall, the present study provides original evidence for allelic imbalance of the 14 bp insertion/deletion polymorphism, which influences HLA-G surface expression on primary trophoblast cells, considered to be important in the pathogenesis of pre-eclampsia and other pregnancy complications. © The Author 2014. Published by Oxford University Press on behalf of the European Society of Human Reproduction and Embryology. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

  14. Decreased activation of placental mTOR family members is associated with the induction of intrauterine growth restriction by secondhand smoke in the mouse.

    Science.gov (United States)

    Mejia, Camilo; Lewis, Josh; Jordan, Clinton; Mejia, Juan; Ogden, Connor; Monson, Troy; Winden, Duane; Watson, Marc; Reynolds, Paul R; Arroyo, Juan A

    2017-02-01

    Cigarette smoke is known to be a risk for the development of intrauterine growth restriction (IUGR). Our objective was to assess the effects of secondhand smoke (SHS) during pregnancy and to what extent it regulates the activation of mTOR family members and murine trophoblast invasion. Mice were treated to SHS for 4 days. Placental and fetal weights were recorded at the time of necropsy. Immunohistochemistry was used to determine the level of placental trophoblast invasion. Western blots were utilized to assess the activation of caspase 3, XIAP, mTOR, p70 and 4EBP1 in treated and control placental lysates. As compared to controls, treated animals showed: (1) decreased placental (1.4-fold) and fetal (2.3-fold) weights (p smoke extract (CSE). Similar to primary smoking, SHS may induce IUGR via decreased activation of the mTOR family of proteins in the placenta. Increased activation of the placental XIAP protein could be a survival mechanism for abnormal trophoblast cells during SHS exposure. Further, CSE reduced trophoblast invasion, suggesting a direct causative effect of smoke on susceptible trophoblast cells involved in IUGR progression. These results provide important insight into the physiological consequences of SHS exposure and smoke-mediated placental disease.

  15. Progress in Pediatrics in 2012: choices in allergy, endocrinology, gastroenterology, hematology, infectious diseases, neurology, nutrition and respiratory tract illnesses.

    Science.gov (United States)

    Caffarelli, Carlo; Santamaria, Francesca; Vottero, Alessandra; Bernasconi, Sergio

    2013-05-08

    In this review, we summarize the progresses in allergy, endocrinology, gastroenterology, hematology, infectious diseases, neurology, nutrition and respiratory tract illnesses that have been published in The Italian Journal of Pediatrics in 2012. The induction of Treg activity by probiotics might be effective for promoting tolerance towards food allergens. Nasal cytology is useful in patients with rhinitis for diagnosing chronic non-allergic non-infectious diseases. Atopic eczema is associated both with an aberrant skin matrix and impaired systemic immune response. Therefore, isolated topical treatment may have suboptimal effect. Diagnostic work-up of exercise-induced anaphylaxis, including exercise challenge test, is necessary to reach a diagnosis. Studies may support a role for nutrition on prevention of asthma and cardiovascular diseases. Clinicians need to early identify adolescent menstrual abnormalities to minimize sequelae, and to promote health information. In Multiple Endocrine Neoplasia type 2B investigations include acetylcholinesterase study of rectal mucosa followed by the molecular analysis of RET mutation. Low adherence to gluten-free diet and osteopenia are common problems in children with diabetes mellitus type 1 and celiac disease. In infantile colic, laboratory tests are usually unnecessary and the treatment is based on reassurance. Prevalence of obesity and stunting is elucidated by several studies. Evidences are growing that dietetic measures are needed to prevent obesity in children with acute leukemia. Treatment studies for infectious diseases show promise for probiotics along with standard triple therapy in children with Helicobacter pilori infection, while zinc has no effect on pneumonia. Educational programs about the proper management of the febrile child are warranted. A new hour-specific total serum bilirubin nomogram has been shown to be able to predict newborns without hyperbilirubinemia after 48 to 72 hours of life. Newborns with

  16. Early studies reported extreme findings with large variability: a meta-epidemiologic study in the field of endocrinology.

    Science.gov (United States)

    Wang, Zhen; Alahdab, Fares; Almasri, Jehad; Haydour, Qusay; Mohammed, Khaled; Abu Dabrh, Abd Moain; Prokop, Larry J; Alfarkh, Wedad; Lakis, Sumaya; Montori, Victor M; Murad, Mohammad Hassan

    2016-04-01

    To evaluate the presence of extreme findings and fluctuation in effect size in endocrinology. We systematically identified all meta-analyses published in 2014 in the field of endocrinology. Within each meta-analysis, the effect size of the primary binary outcome was compared across studies according to their order of publication. We pooled studies using the DerSimonian and Laird random-effects method. Heterogeneity was evaluated using the I(2) and tau(2). Twelve percent of the included 100 meta-analyses reported the largest effect size in the very first published study. The largest effect size occurred in the first 2 earliest studies in 31% of meta-analyses. When the effect size was the largest in the first published study, it was three times larger than the final pooled effect (ratio of rates, 3.26; 95% confidence interval: 1.80, 5.90). The largest heterogeneity measured by I(2) was observed in 18% of the included meta-analyses when combining the first 2 studies or 17% when combing the first 3 studies. In endocrinology, early studies reported extreme findings with large variability. This behavior of the evidence needs to be taken into account when used to formulate clinical policies. Copyright © 2016 Elsevier Inc. All rights reserved.

  17. Frequency and clinical and molecular aspects of familial hypercholesterolemia in an endocrinology unit in Ciudad Bolívar, Venezuela.

    Science.gov (United States)

    Lima-Martínez, Marcos M; Paoli, Mariela; Vázquez-Cárdenas, Alejandra; Magaña-Torres, María Teresa; Guevara, Ornella; Muñoz, María Carolina; Parrilla-Alvarez, Alberto; Márquez, Yuliangelys; Medeiros, Ana; Bourbon, Mafalda

    2017-10-01

    To assess the frequency and the clinical, biochemical, and molecular aspects of familial hypercholesterolemia (FH) in subjects attending an endocrinology unit. An observational, descriptive study evaluating 3,140 subjects attending the endocrinology unit of Centro Médico Orinoco in Ciudad Bolívar, Venezuela, from 7 January 2013 to 9 December 2016. The index cases were selected using the Dutch Lipid Clinic Network criteria. Plasma lipid levels were measured, and a molecular analysis was performed by DNA sequencing of the LDLR and APOB genes. Ten (0.32%) of the 3,140 study patients had clinical and biochemical characteristics consistent with FH. All but one were female. Three had first-degree relatives with prior premature coronary artery; and none had a personal history of this condition. Three patients were obese; three had high blood pressure; and no one suffered from diabetes. Three patients had a history of tendon xanthomas, and one of corneal arcus. LDL-C levels ranged from 191 to 486mg/dL. Two patients were on statin therapy. The genetic causes of FH were identified in four patients, and were LDLR gene mutations in three of them and an APOB gene mutation in exon 26 in the other. Approximately, one out of every 300 people attending this endocrinology unit in those four years had FH, and LDLR gene mutations were the most prevalent cause. Copyright © 2017 SEEN. Publicado por Elsevier España, S.L.U. All rights reserved.

  18. [Diagnosis of congenital endocrinological disease in newborns with prolonged jaundice and hypoglycaemia].

    Science.gov (United States)

    Braslavsky, D; Keselman, A; Chiesa, A; Bergadá, I

    2012-03-01

    The association of prolonged neonatal jaundice and hypoglycaemia may be secondary to an endocrinological disease. Pituitary insufficiency and primary adrenal insufficiency are the most likely endocrine diseases that need to be ruled out. We retrospectively analysed the clinical and laboratory characteristics of thirteen patients referred to the Hospital de Niños Ricardo Gutiérrez between years 2003 and 2008 due to prolonged neonatal jaundice and hypoglycaemia secondary to pituitary insufficiency in twelve patients, and in one secondary to primary adrenal insufficiency. All patients had a history of neonatal hypoglycaemia. Ten patients had conjugated hyperbilirubinaemia and six also had elevated transaminases. Combined pituitary hormone deficiency was observed in the twelve hypopituitarism patients. Hormonal replacement normalised liver function and resolved the prolonged jaundice in all the patients. None of them underwent liver biopsy. Hypoglycaemia also remitted after hormonal therapy. Prolonged or cholestatic jaundice associated with neonatal hypoglycaemia is highly likely to be due to pituitary hormone deficiency or primary adrenal insufficiency. Early diagnosis and treatment of these children reverts the prolonged jaundice and prevents morbidity and mortality due to recurrent hypoglycaemia and hormone deficiencies. Copyright © 2011 Asociación Española de Pediatría. Published by Elsevier Espana. All rights reserved.

  19. Evolutionary medicine and its implications for endocrinological issues (e.g. menopause).

    Science.gov (United States)

    Kirchengast, Sylvia; Rühli, Frank

    2013-06-01

    Evolutionary medicine, which was formalized in the early 1990s, investigates evolutionary causes of recent human disease, disorders and malfunctions but also the influence of changing living conditions and modernization on health and disease. Evolutionary medicine can also provide insights into endocrinological disorders and in particular in the process of female reproductive senescence. Female reproductive senescence, i.e. menopausal transition is physiologically caused by the decline of estrogen secretion, which is associated with various somatic and psychic discomforts making this stage of life extremely uncomfortable. From the viewpoint of evolutionary medicine, these menopausal symptoms are the result from the sudden decrease of very high lifetime estrogen levels to zero during postmenopause, a situation which is quite new in our evolution and history. While women in recent developed countries experience menarche early, menopause late, few pregnancies, short periods of lactation and consequently low life time estrogen levels. The opposite is true of women living in traditional societies, whose living conditions may be interpreted as a mirror of the situation in our history. From this viewpoint we can conclude that menopausal symptoms may are the result of a mismatch between female reproductive physiology and recent living conditions. Copyright © 2013 Elsevier Inc. All rights reserved.

  20. Epidemiology of infertility and polycystic ovarian disease: endocrinological and demographic studies.

    Science.gov (United States)

    Hull, M G

    1987-09-01

    The frequency of polycystic ovarian disease (PCOD) as a cause of oligo-amenorrhea and infertility was determined, first by characterizing clinically occult PCOD using endocrinological methods, and secondly by estimating the frequency of overt and occult PCOD amongst infertile women residing in a particular area. Four groups of infertile women with oligo-amenorrhea due to 'functional' disorder were compared. The results show that by contrast with the groups having hyperprolactinemia or hypothalamic disorder the group with hirsutism (and therefore presumed PCOD) was closely resembled by a non-hirsute group in terms of estrogenization, LH level, LH/FSH ratio, prolactin level, body mass and responsiveness to clomiphene. The last group was therefore concluded to have a mild occult form of PCOD. The population studies revealed, first, that overt and occult PCOD accounted for 90% of patients with oligomenorrhea and 37% with amenorrhea, or 73% with oligo- or amenorrhea. Oligo- or amenorrhea accounted for 21% of couples with infertility and the annual incidence was 247 patients per million of the general population. The annual incidence of infertility due to PCOD per million was 41 with overt PCOD and 139 with occult PCOD (total 180). Of those, 140 appeared to respond well to clomiphene (78%) but 40 (22%) failed, requiring alternative therapy.

  1. Three patients with Schaaf-Yang syndrome exhibiting arthrogryposis and endocrinological abnormalities.

    Science.gov (United States)

    Enya, Takuji; Okamoto, Nobuhiko; Iba, Yoshinori; Miyazawa, Tomoki; Okada, Mitsuru; Ida, Shinobu; Naruto, Takuya; Imoto, Issei; Fujita, Atsushi; Miyake, Noriko; Matsumoto, Naomichi; Sugimoto, Keisuke; Takemura, Tsukasa

    2018-03-01

    MAGEL2 is the paternally expressed gene within Prader-Willi syndrome critical region at 15q11.2. We encountered three individuals in whom truncating mutations of MAGEL2 were identified. Patients 1 and 2, siblings born to healthy, non-consanguineous Japanese parents, showed generalized hypotonia, lethargy, severe respiratory difficulty, poor feeding, and multiple anomalies including arthrogryposis soon after birth. We carried out whole-exome sequencing, which detected a MAGEL2 mutation (c.1912C>T, p.Gln638*, heterozygous). The patients' father was heterozygous for the mutation. Patient 3 was a female infant, showed respiratory difficulty reflecting pulmonary hypoplasia, generalized hypotonia, feeding difficulty and multiple anomalies soon after birth. Targeted next-generation sequencing detected a novel heterozygous mutation in MAGEL2 (c.3131C>A, p.Ser1044*). This mutation was not found in the parents. MAGEL2 mutations, first reported to be the cause of the Prader-Willi like syndrome with autism by Schaaf et al. (2013) Nature Genetics, 45: 1405-1408 show the wide range of phenotypic spectrum from lethal arthrogryposis multiplex congenital to autism spectrum disorder (ASD) and mild intellectual disability (ID). Our results indicate that MAGEL2 mutations cause multiple congenital anomalies and intellectual disability accompanied by arthrogryposis multiplex congenita and various endocrinologic abnormalities, supporting that the view that clinical phenotypes of MAGEL2 mutations are variable. © 2018 Wiley Periodicals, Inc.

  2. Development of an e-learning portal for pediatric endocrinology: educational considerations.

    Science.gov (United States)

    Grijpink-van den Biggelaar, K; Drop, S L S; Schuwirth, L

    2010-01-01

    Global accessibility and dissemination of developments in pediatric endocrinology prompted to examine how to develop an educational interactive e-SPE web portal. A systematic approach was used to identify the relevant aspects of accessibility and dissemination. An orientation at the big idea was made, executed by an analysis of the needs of student and teacher pediatric endocrinologists, a definition of the learning objectives, a research in educational literature and an exploration of ICT design specifications. The intensive collaboration between medical, educational and information technology disciplines resulted in a portal design. The portal meets requirements of adult learning, stresses interaction between partners in learning and offers direct feedback during the learning process. The portal supports the development of not only knowledge but also competences both at junior and advanced levels. When the e-SPE portal is completed, the options for summative assessment will be examined as a medium for international certification in conjunction with local and national requirements (http://espe.elearning.nl). Copyright 2010 S. Karger AG, Basel.

  3. Mechanisms in endocrinology: vitamin D as a potential contributor in endocrine health and disease.

    Science.gov (United States)

    Muscogiuri, Giovanna; Mitri, Joanna; Mathieu, Chantal; Badenhoop, Klaus; Tamer, Gonca; Orio, Francesco; Mezza, Teresa; Vieth, Reinhold; Colao, Annamaria; Pittas, Anastassios

    2014-09-01

    It has been suggested that vitamin D may play a role in the pathogenesis of several endocrine diseases, such as hyperparathyroidism, type 1 diabetes (T1DM), type 2 diabetes (T2DM), autoimmune thyroid diseases, Addison's disease and polycystic ovary syndrome (PCOS). In this review, we debate the role of vitamin D in the pathogenesis of endocrine diseases. Narrative overview of the literature synthesizing the current evidence retrieved from searches of computerized databases, hand searches and authoritative texts. Evidence from basic science supports a role for vitamin D in many endocrine conditions. In humans, inverse relationships have been reported not only between blood 25-hydroxyvitamin D and parathyroid hormone concentrations but also with risk of T1DM, T2DM, and PCOS. There is less evidence for an association with Addison's disease or autoimmune thyroid disease. Vitamin D supplementation may have a role for prevention of T2DM, but the available evidence is not consistent. Although observational studies support a potential role of vitamin D in endocrine disease, high quality evidence from clinical trials does not exist to establish a place for vitamin D supplementation in optimizing endocrine health. Ongoing randomized controlled trials are expected to provide insights into the efficacy and safety of vitamin D in the management of endocrine disease. © 2014 European Society of Endocrinology.

  4. MRI findings and endocrinological dysfunction of apoplexy and silent hemorrhage in pituitary adenoma

    International Nuclear Information System (INIS)

    Kannuki, Seiji; Bando, Kazuhiko; Shirakawa, Norihito; Matsumoto, Keizo; Bando, Hiroshi; Saito, Shiro; Kusaka, Kazumasa.

    1993-01-01

    The study was designed to examine pathophysiology of endocrinological disturbance associated with diminished pituitary function by using magnetic resonance (MR) imaging. The subjects were 13 patients with hemorrhagic pituitary adenoma. According to clinical severity, the patients were classified as having (I) classical pituitary apoplexy (PA, n=2), (II) subacute PA (n=4), or (III) asymptomatic hemorrhagic pituitary adenoma (n=7). MR imaging and intraoperative findings revealed hemorrhagic PA in 7 patients and necrotic cyst formation in 5 patients. The cyst contents, either hemorrhagic or xanthochromic, were more accurately predicted by intensities on MR images than CT fidnings. Niveau formation was seen in 2 patients in Group I on MR images; however, MR imaging intensities differed in the two patients. In the first patient who developed classical PA during pregnancy, the upper and lower parts of the pituitary gland were seen as high intensity and iso-intensity, respectively. In the other patient, the upper and lower parts were seen as water-like and methemoglobin-like intensities, respectively. These findings have implications for the different etiology of niveau formation. In conclusion, diminished hypothalamic and pituitary function in pituitary hemorrhage seemed to be associated with disturbance of the connection between hypothalamus-anterior pituitary gland, or stalk of the pituitary gland. Hemorrhagic pituitary apoplexy manifested by various clinical features seemed to be attributed to venous hemorrhagic infarction due to pituitary portal compression. Pituitary apoplexy itself seemed to compress the portal system, leading to venous hemorrhage. (N.K.)

  5. The role of {sup 18}F-fluorodeoxyglucose positron emission tomography in gestational trophoblastic tumours: a pilot study

    Energy Technology Data Exchange (ETDEWEB)

    Chang, Ting Chang; Wu, Yen Ching; Wu, Tzu I. [University College of Medicine, Division of Gynecologic Oncology, Taoyuan (Taiwan); Yen, Tzu Chen; Chang, Yu.Cheng [Chang Gung Memorial Hospital, Department of Nuclear Medicine, Taoyuan (Taiwan); Li, Yiu Tai [Kuo General Hospital, Department of Obstetrics and Gynecology, Tainan (Taiwan); Ng, Koon Kwan [Chang Gung University College of Medicine, Departments of Diagnostic Radiology, Taoyuan (Taiwan); Jung, Shih Ming [Chang Gung Memorial Hospital, Anatomic Pathology, Taoyuan (Taiwan); Lai, Chyong Huey [University College of Medicine, Division of Gynecologic Oncology, Taoyuan (Taiwan); Chang Gung Memorial Hospital Linkou Medical Center, Department of Obstetrics and Gynecology, Taoyuan (Taiwan)

    2006-02-01

    We conducted a pilot trial to evaluate the value of {sup 18}F-fluorodeoxyglucose ({sup 18}F-FDG) positron emission tomography (PET) in gestational trophoblastic tumours (GTTs). Patients with placental site trophoblastic tumour (PSTT), high-risk GTT (World Health Organisation score {>=}8, disease onset at postpartum or greater than 6 months after antecedent pregnancy), metastatic GTT, recurrent/resistant GTT after chemotherapy, or post-molar GTT with unexplained abnormal {beta}-hCG regression and patients undergoing re-evaluation after salvage treatment were enrolled. PET was undertaken within 1 week after computed tomography (CT). Clinical impacts of additional PET were determined on a scan basis. A total of 14 patients were recruited. Sixteen PET scans were performed, with one patient having three serial studies. Benefits of additional PET were seen in 7 of 16 (43.8%) scans; these benefits included disclosure of chemotherapy-resistant lesions (n=2), exclusion of false-positive CT lesions (n=1), detection of an additional lesion not found by conventional imaging (n=1) in high-risk GTT at the start of primary chemotherapy, and confirmation of complete response to treatment for PSTT or to salvage therapy for recurrent/resistant GTT (n=3). On the other hand, in two instances there were false-negative PET findings, six scans yielded no benefit, and one showed an indeterminate lesion. Our preliminary results suggest that {sup 18}F-FDG PET is potentially useful in selected patients with GTT by providing precise mapping of metastases and tumour extent upfront, by monitoring treatment response and by localising viable tumours after chemotherapy. A larger study is necessary to further define the role of {sup 18}F-FDG PET in GTT. (orig.)

  6. Variable DAXX gene methylation is a common feature of placental trophoblast differentiation, preeclampsia, and response to hypoxia.

    Science.gov (United States)

    Novakovic, Boris; Evain-Brion, Danièle; Murthi, Padma; Fournier, Thiery; Saffery, Richard

    2017-06-01

    Placental functioning relies on the appropriate differentiation of progenitor villous cytotrophoblasts (CTBs) into extravillous cytotrophoblasts (EVCTs), including invasive EVCTs, and the multinucleated syncytiotrophoblast (ST) layer. This is accompanied by a general move away from a proliferative, immature phenotype. Genome-scale expression studies have provided valuable insight into genes that are associated with the shift to both an invasive EVCT and ST phenotype, whereas genome-scale DNA methylation analysis has shown that differentiation to ST involves widespread methylation shifts, which are counteracted by low oxygen. In the current study, we sought to identify DNA methylation variation that is associated with transition from CTB to ST in vitro and from a noninvasive to invasive EVCT phenotype after culture on Matrigel. Of the several hundred differentially methylated regions that were identified in each comparison, the majority showed a loss of methylation with differentiation. This included a large differentially methylated region (DMR) in the gene body of death domain-associated protein 6 ( DAXX ), which lost methylation during both CTB syncytialization to ST and EVCT differentiation to invasive EVCT. Comparison to publicly available methylation array data identified the same DMR as among the most consistently differentially methylated genes in placental samples from preeclampsia pregnancies. Of interest, in vitro culture of CTB or ST in low oxygen increases methylation in the same region, which correlates with delayed differentiation. Analysis of combined epigenomics signatures confirmed DAXX DMR as a likely regulatory element, and direct gene expression analysis identified a positive association between methylation at this site and DAXX expression levels. The widespread dynamic nature of DAXX methylation in association with trophoblast differentiation and placenta-associated pathologies is consistent with an important role for this gene in proper

  7. Relevance of the NR4A sub-family of nuclear orphan receptors in trophoblastic BeWo cell differentiation.

    Science.gov (United States)

    Malhotra, Sudha Saryu; Gupta, Satish Kumar

    2017-01-01

    Nur-77, a member of the NR4A sub-family of nuclear orphan receptors, is downregulated in the placentae of pre-eclamptic women. Here, we investigate the relevance of Nor-1, Nurr-1 and Nur-77 in trophoblastic cell differentiation. Their transcript levels were found to be significantly upregulated in BeWo cells treated with forskolin. The maximum increase was observed after 2 h, with a second peak in the expression levels after 48 h. The expression of NR4A sub-family members was also found to be upregulated in BeWo cells after treatment with hCG and GnRH. A similar significant increase was observed at the respective protein levels after 2 and 48 h of treatment with forskolin, hCG or GnRH. Silencing Nor-1, Nurr-1 or Nur-77 individually did not show any effect on forskolin-, hCG- and/or GnRH-mediated BeWo cell fusion and/or hCG secretion. After silencing any one member of the NR4A sub-family, an increase in the transcript levels of the other sub-family members was observed, indicating a compensatory effect due to their functional redundancy. Simultaneously silencing all three NR4A sub-family members significantly downregulated forskolin- and hCG-mediated BeWo cell fusion and/or hCG secretion. However, a considerable amount of cell death occurred after forskolin or hCG treatment as compared to the control siRNA-transfected cells. These results suggest that the NR4A sub-family of nuclear orphan receptors has a role in trophoblastic cell differentiation.

  8. Immunoglobulins from sera of APS patients bind HTR-8/SVneo trophoblast cell line and reduce additional mediators of cell invasion.

    Science.gov (United States)

    Jovanović Krivokuća, Milica; Abu Rabi, Tamara; Stefanoska, Ivana; Vrzić-Petronijević, Svetlana; Petronijević, Miloš; Vićovac, Ljiljana

    2017-12-01

    Immunoglobulins from sera of patients with antiphospholipid syndrome (APS) decrease trophoblast cell invasion in vitro. This study aimed to extend understanding of cellular effects of immunoglobulins from APS (aPL+) in HTR-8/SVneo cells. aPL+ IgG induced change in effector molecules important for cell invasion was investigated further. After 1h of culture 21% cells bound aPL+ IgG, as opposed to 6% in control (aPL-). This was accompanied by increase in phospho-p38 at 30min. After 24h treatment aPL+IgG decreased protein levels of integrin subunits α1 (78% of control; p<0.01), α4 (65% of control, p<0.01), α5 (76% of control; p<0.01) and β1 (80% of control; p<0.01), and secreted gal-1 (68% of control; p<0.05). ProMMP-9 was reduced to 70% of control (p<0.001). Treatment with inhibitor of p38 MAPK signaling SB202190 reversed inhibition in integrin β1 and secreted gal-1. Involvement of p38 MAPK signaling and decrease in integrin subunit α4 , proMMP-9, and secreted gal-1 in HTR-8/SVneo cells are novel and extend the list of mediators of trophoblast invasion affected by aPL. Copyright © 2017 Society for Biology of Reproduction & the Institute of Animal Reproduction and Food Research of Polish Academy of Sciences in Olsztyn. Published by Elsevier Urban & Partner Sp. z o.o. All rights reserved.

  9. The role of 18F-fluorodeoxyglucose positron emission tomography in gestational trophoblastic tumours: a pilot study

    International Nuclear Information System (INIS)

    Chang, Ting Chang; Wu, Yen Ching; Wu, Tzu I.; Yen, Tzu Chen; Chang, Yu.Cheng; Li, Yiu Tai; Ng, Koon Kwan; Jung, Shih Ming; Lai, Chyong Huey

    2006-01-01

    We conducted a pilot trial to evaluate the value of 18 F-fluorodeoxyglucose ( 18 F-FDG) positron emission tomography (PET) in gestational trophoblastic tumours (GTTs). Patients with placental site trophoblastic tumour (PSTT), high-risk GTT (World Health Organisation score ≥8, disease onset at postpartum or greater than 6 months after antecedent pregnancy), metastatic GTT, recurrent/resistant GTT after chemotherapy, or post-molar GTT with unexplained abnormal β-hCG regression and patients undergoing re-evaluation after salvage treatment were enrolled. PET was undertaken within 1 week after computed tomography (CT). Clinical impacts of additional PET were determined on a scan basis. A total of 14 patients were recruited. Sixteen PET scans were performed, with one patient having three serial studies. Benefits of additional PET were seen in 7 of 16 (43.8%) scans; these benefits included disclosure of chemotherapy-resistant lesions (n=2), exclusion of false-positive CT lesions (n=1), detection of an additional lesion not found by conventional imaging (n=1) in high-risk GTT at the start of primary chemotherapy, and confirmation of complete response to treatment for PSTT or to salvage therapy for recurrent/resistant GTT (n=3). On the other hand, in two instances there were false-negative PET findings, six scans yielded no benefit, and one showed an indeterminate lesion. Our preliminary results suggest that 18 F-FDG PET is potentially useful in selected patients with GTT by providing precise mapping of metastases and tumour extent upfront, by monitoring treatment response and by localising viable tumours after chemotherapy. A larger study is necessary to further define the role of 18 F-FDG PET in GTT. (orig.)

  10. A path model analysis on predictors of dropout (at 6 and 12 months) during the weight loss interventions in endocrinology outpatient division.

    Science.gov (United States)

    Perna, Simone; Spadaccini, Daniele; Riva, Antonella; Allegrini, Pietro; Edera, Chiara; Faliva, Milena Anna; Peroni, Gabriella; Naso, Maurizio; Nichetti, Mara; Gozzer, Carlotta; Vigo, Beatrice; Rondanelli, Mariangela

    2018-02-22

    This study aimed to identify the dropout rate at 6 and 12 months from the first outpatient visit, and to analyze dropout risk factors among the following areas: biochemical examinations, anthropometric measures, psychological tests, personal data, and life attitude such as smoking, physical activity, and pathologies. This is a retrospective longitudinal observational study. Patients undergo an outpatient endocrinology visit, which includes collecting biographical data, anthropometric measurements, physical and pathological history, psychological tests, and biochemical examinations. The sample consists of 913 subjects (682 women and 231 men), with an average age of 50.88 years (±15.80) for the total sample, with a BMI of 33.11 ± 5.65 kg/m 2 . 51.9% of the patients abandoned therapy at 6 months after their first visit, and analyzing the dropout rate at 12 months, it appears that 69.5% of subjects abandon therapy. The main predictor of dropout risk factors at 6 and 12 months is the weight loss during the first 3 months (p dropout at 12 months. Patients who introduced physical activity had a reduction of - 17% (at 6 months) and -13% (at 12 months) of dropout risk (p dropout vs. other categories of worker (i = 0.58; p Dropout risk at 12 months decrease in patients with a previous history of cancer, Endocrine and psychic and behavioral disorders (p dropout.

  11. [Clinical recommendations for sport practice in diabetic patients (RECORD Guide). Diabetes Mellitus Working Group of the Spanish Society of Endocrinology and Nutrition (SEEN)].

    Science.gov (United States)

    Gargallo-Fernández, Manuel; Escalada San Martín, Javier; Gómez-Peralta, Fernando; Rozas Moreno, Pedro; Marco Martínez, Amparo; Botella-Serrano, Marta; Tejera Pérez, Cristina; López Fernández, Judith

    2015-01-01

    Sporting activity is becoming a common practice in patients with diabetes mellitus (DM). This situation requires both a preliminary medical assessment and a wide range of changes in treatment which have scarcely been addressed in medical literature. To prepare a clinical guideline on the medical approach to patients with diabetes who practice sport regularly. An expert panel from the Diabetes Mellitus Working Group of the Spanish Society of Endocrinology and Nutrition (SEEN) reviewed the most relevant literature in each of the sections. Based both on this review and on data from the experience of a number of athletes with DM, a number of recommendations were agreed within each section. Finally, the Working Group and representatives of the SEEN jointly discussed all these recommendations. The guideline provides recommendations ranging from medical assessment before patients with DM start to practice sport to actions during and after physical activity. Recommendations are also given on aspects such as the impact of sport on blood glucose control, training schemes, or special risk situations. Copyright © 2015 SEEN. Published by Elsevier España, S.L.U. All rights reserved.

  12. AMERICAN ASSOCIATION OF CLINICAL ENDOCRINOLOGISTS AND AMERICAN COLLEGE OF ENDOCRINOLOGY POSITION STATEMENT ON MENOPAUSE-2017 UPDATE.

    Science.gov (United States)

    Cobin, Rhoda H; Goodman, Neil F

    2017-07-01

    EXECUTIVE SUMMARY This American Association of Clinical Endocrinologists (AACE)/American College of Endocrinology (ACE) Position Statement is designed to update the previous menopause clinical practice guidelines published in 2011 but does not replace them. The current document reviews new clinical trials published since then as well as new information regarding possible risks and benefits of therapies available for the treatment of menopausal symptoms. AACE reinforces the recommendations made in its previous guidelines and provides additional recommendations on the basis of new data. A summary regarding this position statement is listed below: New information available from randomized clinical trials and epidemiologic studies reported after 2011 was critically reviewed. No previous recommendations from the 2011 menopause clinical practice guidelines have been reversed or changed. Newer information enhances AACE's guidance for the use of hormone therapy in different subsets of women. Newer information helps to support the use of various types of estrogens, selective estrogen-receptor modulators (SERMs), and progesterone, as well as the route of delivery. Newer information supports the previous recommendation against the use of bioidentical hormones. The use of nonhormonal therapies for the symptomatic relief of menopausal symptoms is supported. Newer information enhances AACE's guidance for the use of hormone therapy in different subsets of women. Newer information helps to support the use of various types of estrogens, SERMs, and progesterone, as well as the route of delivery. Newer information supports the previous recommendation against the use of bioidentical hormones. The use of nonhormonal therapies for the symptomatic relief of menopausal symptoms is supported. New recommendations in this position statement include: 1. the use of menopausal hormone therapy in symptomatic postmenopausal women should be based on consideration of all risk factors for

  13. Efficacy of a hyperglycemia treatment program in a Vascular Surgery Department supervised by Endocrinology.

    Science.gov (United States)

    Caimari, Francisca; González, Cintia; Ramos, Analía; Chico, Ana; Cubero, José M; Pérez, Antonio

    2016-01-01

    The aim of this study was to evaluate the strategy and efficacy of a hyperglycemia treatment program supervised by Endocrinology. All patients with type 2 diabetes hospitalized at the vascular surgery department over a 12 month period were retrospectively reviewed. Clinical characteristics and hyperglycemia treatment during hospitalization, at discharge and 2-6 month after discharge were collected. Glycemic control was assessed using capillary blood glucose profiles and HbA1c at admission and 2-6 months post-discharge. A total of 140 hospitalizations of 123 patients were included. The protocol to choose the insulin regimen was applied in 96.4% of patients (22.8% correction dose, 23.6% basal-correction dose and 50% basal-bolus-correction dose [BBC]). Patients with BBC had higher HbA1c (7.7±1.5% vs. 6.7 ±0.8%; P<.001) and mean glycemia on the first day of hospitalization (184.4±59.2 vs. 140.5±31.4mg/dl; P<.001). Mean blood glucose was reduced to 162.1±41.8mg/dl in the middle and 160.8±43.3mg/dl in the last 24h of hospitalization in patients with BBC (P=.007), but did not change in the remaining patients. In 22.1% patients with treatment changes performed at discharge, HbA1c decreased from 8.2±1.6 to 6.8±1.6% at 2-6 months post-discharge (P=.019). The hyperglycemia treatment protocol applied by an endocrinologist in the hospital, allows the identification of the appropriate therapy and the improvement of the glycemic control during hospitalization and discharge, supporting its efficacy in clinical practice. Copyright © 2014 AEC. Publicado por Elsevier España, S.L.U. All rights reserved.

  14. Environmental influences on Adelie penguin breeding schedules, endocrinology, and chick survival.

    Science.gov (United States)

    Ninnes, C E; Waas, J R; Ling, N; Nakagawa, S; Banks, J C; Bell, D G; Bright, A; Carey, P W; Chandler, J; Hudson, Q J; Ingram, J R; Lyall, K; Morgan, D K J; Stevens, M I; Wallace, J; Möstl, E

    2011-08-01

    To understand how the social and physical environment influences behaviour, reproduction and survival, studies of underlying hormonal processes are crucial; in particular, interactions between stress and reproductive responses may have critical influences on breeding schedules. Several authors have examined the timing of breeding in relation to environmental stimuli, while others have independently described endocrine profiles. However, few studies have simultaneously measured endocrine profiles, breeding behaviour, and offspring survival across seasons. We measured sex and stress hormone concentrations (oestrogens, testosterone, and corticosterone), timing of breeding, and chick survival, in Adelie penguins (Pygoscelis adeliae) at two colonies in two different years. Clutch initiation at Cape Bird South (CBS; year 1, ~14,000 pairs) occurred later than at Cape Crozier East (CCE; year 2, ~ 25,000 pairs); however, breeding was more synchronous at CBS. This pattern was probably generated by the persistence of extensive sea ice at CBS (year 1). Higher corticosterone metabolite and lower sex hormone concentrations at CBS correlated with later breeding and lower chick survival compared to at CCE - again, a likely consequence of sea ice conditions. Within colonies, sub-colony size (S, 50-100; M, 200-300; L, 500-600; XL, >1000 pairs) did not influence the onset or synchrony of breeding, chick survival, or hormone concentrations. We showed that the endocrine profiles of breeding Adelie penguins can differ markedly between years and/or colonies, and that combining measures of endocrinology, behaviour, and offspring survival can reveal the mechanisms and consequences that different environmental conditions can have on breeding ecology. Copyright © 2011 Elsevier Inc. All rights reserved.

  15. Genetics in endocrinology: genetic variation in deiodinases: a systematic review of potential clinical effects in humans.

    Science.gov (United States)

    Verloop, Herman; Dekkers, Olaf M; Peeters, Robin P; Schoones, Jan W; Smit, Johannes W A

    2014-09-01

    Iodothyronine deiodinases represent a family of selenoproteins involved in peripheral and local homeostasis of thyroid hormone action. Deiodinases are expressed in multiple organs and thyroid hormone affects numerous biological systems, thus genetic variation in deiodinases may affect multiple clinical endpoints. Interest in clinical effects of genetic variation in deiodinases has clearly increased. We aimed to provide an overview for the role of deiodinase polymorphisms in human physiology and morbidity. In this systematic review, studies evaluating the relationship between deiodinase polymorphisms and clinical parameters in humans were eligible. No restrictions on publication date were imposed. The following databases were searched up to August 2013: Pubmed, EMBASE (OVID-version), Web of Science, COCHRANE Library, CINAHL (EbscoHOST-version), Academic Search Premier (EbscoHOST-version), and ScienceDirect. Deiodinase physiology at molecular and tissue level is described, and finally the role of these polymorphisms in pathophysiological conditions is reviewed. Deiodinase type 1 (D1) polymorphisms particularly show moderate-to-strong relationships with thyroid hormone parameters, IGF1 production, and risk for depression. D2 variants correlate with thyroid hormone levels, insulin resistance, bipolar mood disorder, psychological well-being, mental retardation, hypertension, and risk for osteoarthritis. D3 polymorphisms showed no relationship with inter-individual variation in serum thyroid hormone parameters. One D3 polymorphism was associated with risk for osteoarthritis. Genetic deiodinase profiles only explain a small proportion of inter-individual variations in serum thyroid hormone levels. Evidence suggests a role of genetic deiodinase variants in certain pathophysiological conditions. The value for determination of deiodinase polymorphism in clinical practice needs further investigation. © 2014 European Society of Endocrinology.

  16. The polycystic ovary syndrome: a position statement from the European Society of Endocrinology.

    Science.gov (United States)

    Conway, Gerard; Dewailly, Didier; Diamanti-Kandarakis, Evanthia; Escobar-Morreale, Héctor F; Franks, Stephen; Gambineri, Alessandra; Kelestimur, Fahrettin; Macut, Djuro; Micic, Dragan; Pasquali, Renato; Pfeifer, Marija; Pignatelli, Duarte; Pugeat, Michel; Yildiz, Bulent O

    2014-10-01

    Polycystic ovary syndrome (PCOS) is the most common ovarian disorder associated with androgen excess in women, which justifies the growing interest of endocrinologists. Great efforts have been made in the last 2 decades to define the syndrome. The presence of three different definitions for the diagnosis of PCOS reflects the phenotypic heterogeneity of the syndrome. Major criteria are required for the diagnosis, which in turn identifies different phenotypes according to the combination of different criteria. In addition, the relevant impact of metabolic issues, specifically insulin resistance and obesity, on the pathogenesis of PCOS, and the susceptibility to develop earlier than expected glucose intolerance states, including type 2 diabetes, has supported the notion that these aspects should be considered when defining the PCOS phenotype and planning potential therapeutic strategies in an affected subject. This paper offers a critical endocrine and European perspective on the debate on the definition of PCOS and summarises all major aspects related to aetiological factors, including early life events, potentially involved in the development of the disorder. Diagnostic tools of PCOS are also discussed, with emphasis on the laboratory evaluation of androgens and other potential biomarkers of ovarian and metabolic dysfunctions. We have also paid specific attention to the role of obesity, sleep disorders and neuropsychological aspects of PCOS and on the relevant pathogenetic aspects of cardiovascular risk factors. In addition, we have discussed how to target treatment choices based according to the phenotype and individual patient's needs. Finally, we have suggested potential areas of translational and clinical research for the future with specific emphasis on hormonal and metabolic aspects of PCOS. © 2014 European Society of Endocrinology.

  17. MECHANISMS IN ENDOCRINOLOGY: Aberrations of the X chromosome as cause of male infertility.

    Science.gov (United States)

    Röpke, Albrecht; Tüttelmann, Frank

    2017-11-01

    Male infertility is most commonly caused by spermatogenetic failure, clinically noted as oligo- or a-zoospermia. Today, in approximately 20% of azoospermic patients, a causal genetic defect can be identified. The most frequent genetic causes of azoospermia (or severe oligozoospermia) are Klinefelter syndrome (47,XXY), structural chromosomal abnormalities and Y-chromosomal microdeletions. Consistent with Ohno's law, the human X chromosome is the most stable of all the chromosomes, but contrary to Ohno's law, the X chromosome is loaded with regions of acquired, rapidly evolving genes, which are of special interest because they are predominantly expressed in the testis. Therefore, it is not surprising that the X chromosome, considered as the female counterpart of the male-associated Y chromosome, may actually play an essential role in male infertility and sperm production. This is supported by the recent description of a significantly increased copy number variation (CNV) burden on both sex chromosomes in infertile men and point mutations in X-chromosomal genes responsible for male infertility. Thus, the X chromosome seems to be frequently affected in infertile male patients. Four principal X-chromosomal aberrations have been identified so far: (1) aneuploidy of the X chromosome as found in Klinefelter syndrome (47,XXY or mosaicism for additional X chromosomes). (2) Translocations involving the X chromosome, e.g. nonsyndromic 46,XX testicular disorders of sex development (XX-male syndrome) or X-autosome translocations. (3) CNVs affecting the X chromosome. (4) Point mutations disrupting X-chromosomal genes. All these are reviewed herein and assessed concerning their importance for the clinical routine diagnostic workup of the infertile male as well as their potential to shape research on spermatogenic failure in the next years. © 2017 European Society of Endocrinology.

  18. [Treatment of obesity in a hospital endocrinology clinic. Influence of parental body mass index].

    Science.gov (United States)

    Regueras Santos, L; Díaz Moro, A; Iglesias Blázquez, C; Rodríguez Fernández, C; Quiroga González, R; de Paz Fernández, J A; Rodríguez Fernández, L M

    2015-11-01

    Parental obesity is a risk factor for childhood obesity. The aim of this study was to determine if parental obesity influences the adherence and success of obesity treatment in a hospital paediatric endocrinology clinic. An analytical, prospective, longitudinal study was conducted on obese children aged 4-14. An initial body mass index (BMI), and again at 6 months after receiving health, hygiene and dietary recommendations. Success was considered as a decrease of 0.5 in the BMI Z-score, and adherence to attending the 6-month review. Parental BMI was determined to identify overweight. The χ(2) test was used for qualitative variables and the T-Student test for quantitative (significance, p3). More than half (59%) of the children had one or both parents obese (41 fathers and 37 mothers were obese). Treatment was not adhered to by 25 children. Adherence was worse if both parents were obese OR 3.65 (1.3 to 10.5) (P<=.01) and adherence was better if the mother was not obese, although the father was (P=.01). The treatment had significant success in 40 patients. If the mother was the only obese one in the family, the possibility of treatment failure was greater OR 5.6 (1.4 to 22.4) (P<.01) CONCLUSIONS: A high percentage of children with severe obesity have obese parents. The mother has an important influence on adherence and response to treatment for the severely obese child. Copyright © 2014 Asociación Española de Pediatría. Published by Elsevier España, S.L.U. All rights reserved.

  19. More similar than you think: Frog metamorphosis as a model of human perinatal endocrinology.

    Science.gov (United States)

    Buchholz, Daniel R

    2015-12-15

    Hormonal control of development during the human perinatal period is critically important and complex with multiple hormones regulating fetal growth, brain development, and organ maturation in preparation for birth. Genetic and environmental perturbations of such hormonal control may cause irreversible morphological and physiological impairments and may also predispose individuals to diseases of adulthood, including diabetes and cardiovascular disease. Endocrine and molecular mechanisms that regulate perinatal development and that underlie the connections between early life events and adult diseases are not well elucidated. Such mechanisms are difficult to study in uterus-enclosed mammalian embryos because of confounding maternal effects. To elucidate mechanisms of developmental endocrinology in the perinatal period, Xenopus laevis the African clawed frog is a valuable vertebrate model. Frogs and humans have identical hormones which peak at birth and metamorphosis, have conserved hormone receptors and mechanisms of gene regulation, and have comparable roles for hormones in many target organs. Study of molecular and endocrine mechanisms of hormone-dependent development in frogs is advantageous because an extended free-living larval period followed by metamorphosis (1) is independent of maternal endocrine influence, (2) exhibits dramatic yet conserved developmental effects induced by thyroid and glucocorticoid hormones, and (3) begins at a developmental stage with naturally undetectable hormone levels, thereby facilitating endocrine manipulation and interpretation of results. This review highlights the utility of frog metamorphosis to elucidate molecular and endocrine actions, hormone interactions, and endocrine disruption, especially with respect to thyroid hormone. Knowledge from the frog model is expected to provide fundamental insights to aid medical understanding of endocrine disease, stress, and endocrine disruption affecting the perinatal period in humans

  20. miR-125b-1-3p inhibits trophoblast cell invasion by targeting sphingosine-1-phosphate receptor 1 in preeclampsia.

    Science.gov (United States)

    Li, Qinghua; Pan, Zhifang; Wang, Xuejian; Gao, Zhiqin; Ren, Chune; Yang, Weiwei

    2014-10-10

    Preeclampsia (PE) is the leading cause of maternal and perinatal mortality and morbidity. Understanding the molecular mechanisms underlying placentation facilitates the development of better intervention of this disease. MicroRNAs are strongly implicated in the pathogenesis of this syndrome. In current study, we found that miR-125b-1-3p was elevated in placentas derived from preeclampsia patients. Transfection of miR-125b-1-3p mimics significantly inhibited the invasiveness of human trophoblast cells, whereas miR-125b-1-3p inhibitor enhanced trophoblast cell invasion. Luciferase assays identified that S1PR1 was a novel direct target of miR-125b-1-3p in the placenta. Overexpression of S1PR1 could reverse the inhibitory effect of miR-125b-1-3p on the invasion of trophoblast cells. These findings suggested that abnormal expression of miR-125b-1-3p might contribute to the pathogenesis of preeclampsia. Copyright © 2014 Elsevier Inc. All rights reserved.

  1. Cell Adhesion Minimization by a Novel Mesh Culture Method Mechanically Directs Trophoblast Differentiation and Self-Assembly Organization of Human Pluripotent Stem Cells.

    Science.gov (United States)

    Okeyo, Kennedy Omondi; Kurosawa, Osamu; Yamazaki, Satoshi; Oana, Hidehiro; Kotera, Hidetoshi; Nakauchi, Hiromitsu; Washizu, Masao

    2015-10-01

    Mechanical methods for inducing differentiation and directing lineage specification will be instrumental in the application of pluripotent stem cells. Here, we demonstrate that minimization of cell-substrate adhesion can initiate and direct the differentiation of human pluripotent stem cells (hiPSCs) into cyst-forming trophoblast lineage cells (TLCs) without stimulation with cytokines or small molecules. To precisely control cell-substrate adhesion area, we developed a novel culture method where cells are cultured on microstructured mesh sheets suspended in a culture medium such that cells on mesh are completely out of contact with the culture dish. We used microfabricated mesh sheets that consisted of open meshes (100∼200 μm in pitch) with narrow mesh strands (3-5 μm in width) to provide support for initial cell attachment and growth. We demonstrate that minimization of cell adhesion area achieved by this culture method can trigger a sequence of morphogenetic transformations that begin with individual hiPSCs attached on the mesh strands proliferating to form cell sheets by self-assembly organization and ultimately differentiating after 10-15 days of mesh culture to generate spherical cysts that secreted human chorionic gonadotropin (hCG) hormone and expressed caudal-related homeobox 2 factor (CDX2), a specific marker of trophoblast lineage. Thus, this study demonstrates a simple and direct mechanical approach to induce trophoblast differentiation and generate cysts for application in the study of early human embryogenesis and drug development and screening.

  2. Differential effects of concomitant use of vitamins C and E on trophoblast apoptosis and autophagy between normoxia and hypoxia-reoxygenation.

    Directory of Open Access Journals (Sweden)

    Tai-Ho Hung

    2010-08-01

    Full Text Available Concomitant supplementation of vitamins C and E during pregnancy has been reportedly associated with low birth weight, the premature rupture of membranes and fetal loss or perinatal death in women at risk for preeclampsia; however, the cause is unknown. We surmise that hypoxia-reoxygenation (HR within the intervillous space due to abnormal placentation is the mechanism and hypothesize that concomitant administration of aforementioned vitamin antioxidants detrimentally affects trophoblast cells during HR.Using villous explants, concomitant administration of 50 microM of vitamins C and E was observed to reduce apoptotic and autophagic changes in the trophoblast layer at normoxia (8% oxygen but to cause more prominent apoptosis and autophagy during HR. Furthermore, increased levels of Bcl-2 and Bcl-xL in association with a decrease in the autophagy-related protein LC3-II were noted in cytotrophoblastic cells treated with vitamins C and E under standard culture conditions. In contrast, vitamin treatment decreased Bcl-2 and Bcl-xL as well as increased mitochondrial Bak and cytosolic LC3-II in cytotrophoblasts subjected to HR.Our results indicate that concomitant administration of vitamins C and E has differential effects on the changes of apoptosis, autophagy and the expression of Bcl-2 family of proteins in the trophoblasts between normoxia and HR. These changes may probably lead to the impairment of placental function and suboptimal growth of the fetus.

  3. [Evaluation of diabetic retinopathy screening using non-mydriatic fundus camera performed by physicians' assistants in the endocrinology service].

    Science.gov (United States)

    Barcatali, M-G; Denion, E; Miocque, S; Reznik, Y; Joubert, M; Morera, J; Rod, A; Mouriaux, F

    2015-04-01

    Since 2010, the High Authority for health (HAS) recommends the use of non-mydriatic fundus camera for diabetic retinopathy screening. The purpose of this study is to evaluate the results of screening for diabetic retinopathy using the non-mydriatic retinal camera by a physician's assistant in the endocrinology service. This is a retrospective study of all diabetic patients hospitalized in the endocrinology department between May 2013 and November 2013. For each endocrinology patient requiring screening, a previously trained physician's assistant performed fundus photos. The ophthalmologist then provided a written interpretation of the photos on a consultant's sheet. Of the 120 patients screened, 40 (33.3%) patients had uninterpretable photos. Among the 80 interpretable photos, 64 (53.4%) patients had no diabetic retinopathy, and 16 (13.3%) had diabetic retinopathy. No patient had diabetic maculopathy. Specific quality criteria were established by the HAS for screening for diabetic retinopathy using the non-mydriatic retinal camera in order to ensure sufficient sensitivity and specificity. In our study, the two quality criteria were not achieved: the rates of uninterpretable photos and the total number of photos analyzed in a given period. In our center, we discontinued this method of diabetic retinopathy screening due to the high rate of uninterpretable photos. Due to the logistic impossibility of the ophthalmologists taking all the fundus photos, we proposed that the ophthalmic nurses take the photos. They are better trained in the use of the equipment, and can confer directly with an ophthalmologist in questionable cases and to obtain pupil dilation as necessary. Copyright © 2015 Elsevier Masson SAS. All rights reserved.

  4. AMERICAN ASSOCIATION OF CLINICAL ENDOCRINOLOGISTS AND AMERICAN COLLEGE OF ENDOCRINOLOGY POSITION STATEMENT ON TESTING FOR AUTONOMIC AND SOMATIC NERVE DYSFUNCTION.

    Science.gov (United States)

    Vinik, Aaron I; Camacho, Pauline M; Davidson, Jaime A; Handelsman, Yehuda; Lando, Howard M; Leddy, Anne L; Reddy, Sethu K; Cook, Richard; Spallone, Vicenza; Tesfaye, Solomon; Ziegler, Dan

    2017-12-01

    This document represents the official position of the American Association of Clinical Endocrinologists and the American College of Endocrinology. Where there were no randomized controlled trials or specific U.S. FDA labeling for issues in clinical practice, the participating clinical experts utilized their judgment and experience. Every effort was made to achieve consensus among the committee members. Position statements are meant to provide guidance, but they are not to be considered prescriptive for any individual patient and cannot replace the judgment of a clinician.

  5. AMERICAN ASSOCIATION OF CLINICAL ENDOCRINOLOGISTS AND AMERICAN COLLEGE OF ENDOCRINOLOGY POSITION STATEMENT ON THE ASSOCIATION OF TESTOSTERONE AND CARDIOVASCULAR RISK.

    Science.gov (United States)

    Goodman, Neil; Guay, Andre; Dandona, Paresh; Dhindsa, Sandeep; Faiman, Charles; Cunningham, Glenn R

    2015-09-01

    This document represents the official position of the American Association of Clinical Endocrinologists and the American College of Endocrinology. Where there were no randomized controlled trials or specific U.S. FDA labeling for issues in clinical practice, the participating clinical experts utilized their judgment and experience. Every effort was made to achieve consensus among the committee members. Position statements are meant to provide guidance, but they are not to be considered prescriptive for any individual patient and cannot replace the judgment of a clinician.

  6. Combining Behavioral Endocrinology and Experimental Economics: Testosterone and Social Decision Making

    Science.gov (United States)

    2011-01-01

    Behavioral endocrinological research in humans as well as in animals suggests that testosterone plays a key role in social interactions. Studies in rodents have shown a direct link between testosterone and aggressive behavior1 and folk wisdom adapts these findings to humans, suggesting that testosterone induces antisocial, egoistic or even aggressive behavior2. However, many researchers doubt a direct testosterone-aggression link in humans, arguing instead that testosterone is primarily involved in status-related behavior3,4. As a high status can also be achieved by aggressive and antisocial means it can be difficult to distinguish between anti-social and status seeking behavior. We therefore set up an experimental environment, in which status can only be achieved by prosocial means. In a double-blind and placebo-controlled experiment, we administered a single sublingual dose of 0.5 mg of testosterone (with a hydroxypropyl-β-cyclodextrin carrier) to 121 women and investigated their social interaction behavior in an economic bargaining paradigm. Real monetary incentives are at stake in this paradigm; every player A receives a certain amount of money and has to make an offer to another player B on how to share the money. If B accepts, she gets what was offered and player A keeps the rest. If B refuses the offer, nobody gets anything. A status seeking player A is expected to avoid being rejected by behaving in a prosocial way, i.e. by making higher offers. The results show that if expectations about the hormone are controlled for, testosterone administration leads to a significant increase in fair bargaining offers compared to placebo. The role of expectations is reflected in the fact that subjects who report that they believe to have received testosterone make lower offers than those who say they believe that they were treated with a placebo. These findings suggest that the experimental economics approach is sensitive for detecting neurobiological effects as subtle

  7. A Resource for the Transcriptional Signature of Bona Fide Trophoblast Stem Cells and Analysis of Their Embryonic Persistence

    Directory of Open Access Journals (Sweden)

    Georg Kuales

    2015-01-01

    Full Text Available Trophoblast stem cells (TSCs represent the multipotent progenitors that give rise to the different cells of the embryonic portion of the placenta. Here, we analysed the expression of key TSC transcription factors Cdx2, Eomes, and Elf5 in the early developing placenta of mouse embryos and in cultured TSCs and reveal surprising heterogeneity in protein levels. We analysed persistence of TSCs in the early placenta and find that TSCs remain in the chorionic hinge until E9.5 and are lost shortly afterwards. To define the transcriptional signature of bona fide TSCs, we used inducible gain- and loss-of-function alleles of Eomes or Cdx2, and EomesGFP, to manipulate and monitor the core maintenance factors of TSCs, followed by genome-wide expression profiling. Combinatorial analysis of resulting expression profiles allowed for defining novel TSC marker genes that might functionally contribute to the maintenance of the TSC state. Analyses by qRT-PCR and in situ hybridisation validated novel TSC- and chorion-specific marker genes, such as Bok/Mtd, Cldn26, Duox2, Duoxa2, Nr0b1, and Sox21. Thus, these expression data provide a valuable resource for the transcriptional signature of bona fide and early differentiating TSCs and may contribute to an increased understanding of the transcriptional circuitries that maintain and/or establish stemness of TSCs.

  8. Heat shock cognate protein 70 contributes to Brucella invasion into trophoblast giant cells that cause infectious abortion

    Directory of Open Access Journals (Sweden)

    Furuoka Hidefumi

    2008-12-01

    Full Text Available Abstract Background The cell tropism of Brucella abortus, a causative agent of brucellosis and facultative intracellular pathogen, in the placenta is thought to be a key event of infectious abortion, although the molecular mechanism for this is largely unknown. There is a higher degree of bacterial colonization in the placenta than in other organs and many bacteria are detected in trophoblast giant (TG cells in the placenta. In the present study, we investigated mechanism of B. abortus invasion into TG cells. Results We observed internalization and intracellular growth of B. abortus in cultured TG cells. A monoclonal antibody that inhibits bacterial internalization was isolated and this reacted with heat shock cognate protein 70 (Hsc70. Depletion and over expression of Hsc70 in TG cells inhibited and promoted bacterial internalization, respectively. IFN-γ receptor was expressed in TG cells and IFN-γ treatment enhanced the uptake of bacteria by TG cells. Administering the anti-Hsc70 antibody to pregnant mice served to prevent infectious abortion. Conclusion B. abortus infection of TG cells in placenta is mediated by Hsc70, and that such infection leads to infectious abortion.

  9. Detection of circulating trophoblast particles in maternal blood using density gradient centrifugation in preeclampsia and in normotensive pregnancies.

    Science.gov (United States)

    Kuessel, Lorenz; Kasimir-Bauer, Sabine; Zeillinger, Robert; Pateisky, Petra; Ott, Johannes; Zeisler, Harald; Birdir, Cahit

    2016-08-01

    Preeclampsia (PE) is a frequent pregnancy-related disease and a major cause of maternal and fetal morbidity and mortality. Despite that, exact mechanisms of its pathophysiology remain largely unknown. In pregnancies complicated by PE, changes in the regulation of apoptosis seem to result in increased apoptotic shedding of trophoblast particles (TPs) into maternal circulation. Since the number of TP in peripheral blood is low, their detection necessitates pre-analytical enrichment. In this prospective multicenter pilot study we aimed to analyze TP in peripheral blood of 29 women with PE and of 13 unaffected controls using the OncoQuick®plus system for cell enrichment. Using immunocytochemistry, slides were evaluated microscopically for TP. Statistical analyses were performed using Welch's t-test or Fisher's exact test. TP were detected in 10 (34.5%) women with PE and in two (15.4%) of unaffected controls. More than one TP were only found in PE. Comparing the mean counts of TP between groups, we detected significantly more TP in PE (p = 0.046). The OncoQuick®plus system can be applied to detect TP in both women with PE and in normotensive pregnancies. Longitudinal studies investigating the role of TP as a screening method for patients at risk for PE are warranted.

  10. Paeonia lactiflora Enhances the Adhesion of Trophoblast to the Endometrium via Induction of Leukemia Inhibitory Factor Expression.

    Directory of Open Access Journals (Sweden)

    Hee-Jung Choi

    Full Text Available In the present study, we investigated the role of Paeonia lactiflora Pall. extract on embryo implantation in vitro and in vivo. A polysaccharides depleted-water extract of P. lactiflora (PL-PP increased LIF expression in human endometrial Ishikawa cells at non-cytotoxic doses. PL-PP significantly increased the adhesion of the human trophectoderm-derived JAr spheroids to endometrial Ishikawa cells. PL-PP-induced LIF expression was decreased in the presence of a p38 kinase inhibitor SB203580 and an MEK/ERK inhibitor U0126. Furthermore, endometrial LIF knockdown by shRNA reduced the expression of integrins β3 and β5 and adhesion of JAr spheroids to Ishikawa cells. In vivo administration of PL-PP restored the implantation of mouse blastocysts in a mifepristone-induced implantation failure mice model. Our results demonstrate that PL-PP increases LIF expression via the p38 and MEK/ERK pathways and favors trophoblast adhesion to endometrial cells.

  11. Ranking of MR tomography after transsphenoidal resection of the pituitary. Retrospective comparison between endocrinology, surgery and MRT

    International Nuclear Information System (INIS)

    Siewert, B.; Kaiser, W.A.; Hochstetter, A.; Solymosi, L.; Bootsveld, K.

    1994-01-01

    Postoperative magnetic resonance images of 40 patients after transsphenoidal surgery for pituitary adenoma were evaluated retrospectively. The signal intensities of packing material and residual tumour were analysed. T 1 -weighted spin-echo sequences were obtained in coronal and sagittal views with and without intravenous injection of contrast media. Residual tumour demonstrated homogeneous or inhomogeneous signal intensity on the native scan with homogeneous or inhomogeneous enhancement. Packing material demonstrated a homogeneous signal intensity on the images obtained without injection of contrast media with a peripheral enhancement or alternate layers of low and intermediate signal intensity with alternate enhancement after injection of contrast media. In 5 of 54 examinations different results were found in MRI, endocrinology and surgery (two false negative and one false positive MRI in correlation with endocrinology; two residual tumours on MRI where surgery was supposed to be complete). Application of intravenous contrast media facilitates the interpretation of postoperative examination of the pituitary gland as well as comparison with preoperative examinations and the knowledge of the intraoperative procedure. (orig.) [de

  12. Prevalence of dyslipidemia and its control in type 2 diabetes: A multicenter study in endocrinology clinics of China.

    Science.gov (United States)

    Yan, Li; Xu, Ming Tong; Yuan, Li; Chen, Bing; Xu, Zhang Rong; Guo, Qing Hua; Li, Qiang; Duan, Yu; Huang Fu, Jian; Wang, Yong Jian; Zhang, Miao; Luo, Zuo Jie; Zhao, Wei Gang; Wang, You Min; Yuan, Zhen Fang; Wang, Wei Qing; Wang, Peng Hua; Ran, Xing Wu; Wang, Yan Jun; Yang, Hua Zhang; Gao, Ling; Chen, Wei Qing; Ning, Guang

    2016-01-01

    The aim of this study was to assess the levels of serum lipid and awareness, treatment, and control of dyslipidemia in type 2 diabetes mellitus (T2DM) patients from top-ranked endocrinology clinics in large cities of China. A cross-sectional study in a representative sample of 4807 Chinese adults 40 to 75 years of age was conducted during 2010 to 2011 at 20 endocrinology clinics in top-ranked hospitals covering most of the major cities of China. Serum lipid levels were measured, and treatment of dyslipidemia was recorded and assessed. In the present study, the prevalence of dyslipidemia was 67.1% in T2DM subjects. Among those with dyslipidemia, the proportion of awareness and treatment was 68.7% and 55.9%. Among participants with lipid-lowering therapy, 686 subjects achieved the low-density lipoprotein cholesterol (LDL-C) control less than 2.60 mmol/L, with the rate being 39.4%. In those patients with previous cardiovascular disease, the percentage of participants who achieved LDL-C goal (1.80 mmol/L) was 15.3%. The prevalence of dyslipidemia is high, and the awareness, treatment, and control of dyslipidemia are relatively low in Chinese T2DM patients. This calls for the awareness and intervention of dyslipidemia in these patients. Copyright © 2016 National Lipid Association. Published by Elsevier Inc. All rights reserved.

  13. Global Application of the Assessment of Communication Skills of Paediatric Endocrinology Fellows in the Management of Differences in Sex Development Using the ESPE E-Learning.Org Portal

    DEFF Research Database (Denmark)

    Kranenburg, Laura J C; Reerds, Sam T H; Cools, Martine

    2017-01-01

    endocrinology. Guidelines are created for the assessment of communication between health professionals and individuals with DSD and their parents. METHODS: Paediatric endocrinology fellows worldwide were invited to study two interactive online cases (www.espe-elearning.org) and to describe a best practice...... as a separate key item to better reflect the qualitative differences in the replies and for simplicity of use by evaluators. CONCLUSIONS: E-learning can play an important role in assessing communication skills. A practical tool is provided to assess how information is shared with patients with DSD...

  14. Morbilidad en la consulta de endocrinología del Centro de Investigaciones Medicoquirúrgicas de Angola Morbidity at the Endocrinology outpatient department of the Center for Medicosurgical Research in Angola

    Directory of Open Access Journals (Sweden)

    Rubén S. Padrón Durán

    2006-04-01

    Full Text Available Los datos de la morbilidad en consulta externa pueden ser útiles para conocer las causas por las que los pacientes acuden al centro de salud, así como para planificar el ofrecimiento de consultas especiales y de exámenes complementarios. El objetivo de este estudio es presentar y analizar la morbilidad en la consulta externa de endocrinología del Centro de Investigaciones Medicoquirúrgicas de Angola (CIMECA. Se compilaron todos los diagnósticos de cada caso durante 28 meses consecutivos. Los diagnósticos específicos se clasificaron en 7 grandes grupos: 1 alteraciones de la glucemia, 2 obesidad y otros trastornos metabólicos, 3 medicina reproductiva, 4 trastornos del tiroides, 5 endocrinología pediátrica, 6 otras endocrinopatías y 7 sin endocrinopatías. Se atendieron 2 294 pacientes. Los grupos diagnósticos más frecuentes fueron: alteración de la glucemia (60,07 y obesidad y otros trastornos metabólicos (42,07; relativamente frecuentes fueron medicina reproductiva (19,4 y trastornos del tiroides (11,07. Sin embargo, los pacientes de endocrinología pediátrica (1,53 y otras endocrinopatías (0,22 fueron muy poco numerosos. Los diagnósticos específicos más comunes fueron la diabetes mellitus tipo 2 (DM2 y la obesidad exógena (53,01 y 24,72 respectivamente, seguidos por las hiperlipoproteinemias (11,73. En un rango entre 4,5 y 10 % observamos bocio difuso eutiroideo, glucemia en ayunas alterada, infertilidad femenina e hiperuricemia; el resto se halló en menos del 3 % del total de casos. Lo resultados y conclusiones más importantes del estudio son: a Los grupos diagnósticos más comunes fueron las alteraciones de la glucemia y la obesidad y otros trastornos metabólicos, entre ellos la DM2 y la obesidad exógena, b Los diagnósticos de medicina reproductiva y trastornos del tiroides fueron relativamente comunes, c Los trastornos endocrinos en edades pediátricas y otras endocrinopatías fueron muy poco frecuentes, d

  15. Pharmacoeconomic assessment of type 2 diabetes mellitus care on the base of Endocrinology Research Centre, Moscow

    Directory of Open Access Journals (Sweden)

    Ivan Ivanovich Dedov

    2012-09-01

    Full Text Available Aims. To assess the development of medical care and pharmacological treatment at Endocrine Research Centre (ERC, Moscow, forthe period of 2010-2011 years.Materials and Methods. We analyzed files of 100 patients with type 2 diabetes mellitus (T2DM, who underwent hospitalization to ERCafter January 1, 2010. Key parameters were assessed by means of a study chart, applied for every patient file. Mean values, medians,fractions and confidence intervals (CI were calculated for studied parameters. Various methods of parametric and non-parametricstatistics were used for comparison of acquired values. Results. Files of 100 patients with T2DM, hospitalized to Endocrinology Research Centre, were analyzed to obtain clinical characteristicsand evaluate initial (prior to hospitalization and optimized (after hospitalization therapeutic schemes, as well as spendingpatterns. Mean patient age exceeded 63 years, mean duration period of T2DM was greater than 14.4 years. 86% of patients weredecompensated for glycemic metabolism. 8% were diagnosed with less than 3 diabetes complications, 66% were found to have from 3to 6 complications. Almost all studied cases (98% featured elevated blood pressure, 63% - diabetic retinopathy on different stages,59% - IHD, 51% - cataract, 49% - CKD. Lower limb angiopathy was found in 30% of cases, diabetic foot syndrome - in 15%.2 patients lost their vision due to diabetic complications and 3 patients experienced lower limb amputation. Arterial hypertension wascompensated in 14 cases from total of 98.Correction of therapy decreased fraction of patients on oral hypoglycemic agents and intermediate acting insulin (NPH, while prescriptionfrequency of short acting insulin and rapid acting human insulin analogues (as well as long acting analogues showed oppositetrend. Optimization of therapy also included prescription of hypolipidemic drugs for majority of patients, as well as various agents forcorrection of coagulation abnormalities

  16. Co-dominant expression of the HLA-G gene and various forms of alternatively spliced HLA-G mRNA in human first trimester trophoblast

    DEFF Research Database (Denmark)

    Hviid, T V; Møller, C; Sørensen, S

    1998-01-01

    imprinting of the HLA-G locus could have implications for the interaction in the feto-maternal relationship. Restriction Fragment Length Polymorphism (RFLP), allele-specific amplification and Single Strand Conformation Polymorphism (SSCP) analysis followed by DNA sequencing were performed on Reverse...... Transcription (RT) Polymerase Chain Reaction (PCR) products of HLA-G mRNA to examine the expression of maternal and paternal alleles. Our results demonstrate that HLA-G is co-dominantly expressed in first trimester trophoblast cells. A "new" non-synonymous base substitution in exon 4 was detected. We also...

  17. Defective trophoblast invasion underlies fetal growth restriction and preeclampsia-like symptoms in the stroke-prone spontaneously hypertensive rat.

    Science.gov (United States)

    Barrientos, G; Pussetto, M; Rose, M; Staff, A C; Blois, S M; Toblli, J E

    2017-07-01

    What is the impact of chronic hypertension on placental development, fetal growth and maternal outcome in the stroke-prone spontaneously hypertensive rat (SHRSP)? SHRSP showed an impaired remodeling of the spiral arteries and abnormal pattern of trophoblast invasion during placentation, which were associated with subsequent maternal glomerular injury and increased baseline hypertension as well as placental insufficiency and asymmetric fetal growth restriction (FGR). A hallmark in the pathogenesis of preeclampsia (PE) is abnormal placentation with defective remodeling of the spiral arteries preceding the onset of the maternal syndrome. Pregnancies affected by chronic hypertension display an increased risk for PE, often associated with poor maternal and fetal outcomes. However, the impact of chronic hypertension on the placentation process as well as the nature of the factors promoting the development of PE in pregnant hypertensive women remain elusive. Timed pregnancies [n = 5] were established by mating 10-12-week-old SHRSP and Wistar Kyoto (WKY, normotensive controls) females with congenic males. Maternal systolic blood pressures (SBPs) were recorded pre-mating, throughout pregnancy (GD1-19) and post-partum by the tail-cuff method. On selected dates, 24 h urine- and blood samples were collected, and animals were euthanized for isolation of implantation sites and kidneys for morphometrical analyses. The 24 h proteinuria and the albumin:creatinine ratio were used for evaluation of maternal renal function. Renal injury was assessed on periodic acid Schiff, Masson's trichrome and Sirius red stainings. Placental and fetal weights were recorded on gestation day (GD)18 and GD20, followed by determination of fetal cephalization indexes and developmental stage, according to the Witschi scale. Morphometric analyses of placental development were conducted on hematoxylin-eosin stained tissue sections collected on GD14 and GD18, and complemented with immunohistochemical

  18. AMERICAN ASSOCIATION OF CLINICAL ENDOCRINOLOGISTS AND AMERICAN COLLEGE OF ENDOCRINOLOGY POSITION STATEMENT ON THE ASSOCIATION OF SGLT-2 INHIBITORS AND DIABETIC KETOACIDOSIS.

    Science.gov (United States)

    Handelsman, Yehuda; Henry, Robert R; Bloomgarden, Zachary T; Dagogo-Jack, Sam; DeFronzo, Ralph A; Einhorn, Daniel; Ferrannini, Ele; Fonseca, Vivian A; Garber, Alan J; Grunberger, George; LeRoith, Derek; Umpierrez, Guillermo E; Weir, Matthew R

    2016-06-01

    AACE = American Association of Clinical Endocrinologists ACE = American College of Endocrinology DKA = diabetic ketoacidosis EMA = European Medicines Agency FDA = U.S. Food and Drug Administration SGLT-2 = sodium glucosecotransporter 2 T1D = type 1 diabetes T2D = type 2 diabetes.

  19. Early expression of pregnancy-specific glycoprotein 22 (PSG22) by trophoblast cells modulates angiogenesis in mice.

    Science.gov (United States)

    Blois, Sandra M; Tirado-González, Irene; Wu, Julie; Barrientos, Gabriela; Johnson, Briana; Warren, James; Freitag, Nancy; Klapp, Burghard F; Irmak, Ster; Ergun, Suleyman; Dveskler, Gabriela S

    2012-06-01

    Mouse and human pregnancy-specific glycoproteins (PSG) are known to exert immunomodulatory functions during pregnancy by inducing maternal leukocytes to secrete anti-inflammatory cytokines that promote a tolerogenic decidual microenvironment. Many such anti-inflammatory mediators also function as proangiogenic factors, which, along with the reported association of murine PSG with the uterine vasculature, suggest that PSG may contribute to the vascular adaptations necessary for successful implantation and placental development. We observed that PSG22 is strongly expressed around the embryonic crypt on Gestation Day 5.5, indicating that trophoblast giant cells are the main source of PSG22 during the early stages of pregnancy. PSG22 treatment up-regulated the secretion of transforming growth factor beta 1 and vascular endothelial growth factor A (VEGFA) in murine macrophages, uterine dendritic cells, and natural killer cells. A possible role of PSGs in uteroplacental angiogenesis is further supported by the finding that incubation of endothelial cells with PSG22 resulted in the formation of tubes in the presence and absence of VEGFA. We determined that PSG22, like human PSG1 and murine PSG17 and PSG23, binds to the heparan sulfate chains in syndecans. Therefore, our findings indicate that despite the independent evolution and expansion of human and rodent PSG, members in both families have conserved functions that include their ability to induce anti-inflammatory cytokines and proangiogenic factors as well as to induce the formation of capillary structures by endothelial cells. In summary, our results indicate that PSG22, the most abundant PSG expressed during mouse early pregnancy, is likely a major contributor to the establishment of a successful pregnancy.

  20. Protective effect of nuclear factor E2-related factor 2 on inflammatory cytokine response to brominated diphenyl ether-47 in the HTR-8/SVneo human first trimester extravillous trophoblast cell line.

    Science.gov (United States)

    Park, Hae-Ryung; Loch-Caruso, Rita

    2014-11-15

    Polybrominated diphenyl ethers (PBDEs) are widely used flame retardants, and BDE-47 is a prevalent PBDE congener detected in human tissues. Exposure to PBDEs has been linked to adverse pregnancy outcomes in humans. Although the underlying mechanisms of adverse birth outcomes are poorly understood, critical roles for oxidative stress and inflammation are implicated. The present study investigated antioxidant responses in a human extravillous trophoblast cell line, HTR-8/SVneo, and examined the role of nuclear factor E2-related factor 2 (Nrf2), an antioxidative transcription factor, in BDE-47-induced inflammatory responses in the cells. Treatment of HTR-8/SVneo cells with 5, 10, 15, and 20μM BDE-47 for 24h increased intracellular glutathione (GSH) levels compared to solvent control. Treatment of HTR-8/SVneo cells with 20μM BDE-47 for 24h induced the antioxidant response element (ARE) activity, indicating Nrf2 transactivation by BDE-47 treatment, and resulted in differential expression of redox-sensitive genes compared to solvent control. Pretreatment with tert-butyl hydroquinone (tBHQ) or sulforaphane, known Nrf2 inducers, reduced BDE-47-stimulated IL-6 release with increased ARE reporter activity, reduced nuclear factor kappa B (NF-κB) reporter activity, increased GSH production, and stimulated expression of antioxidant genes compared to non-Nrf2 inducer pretreated groups, suggesting that Nrf2 may play a protective role against BDE-47-mediated inflammatory responses in HTR-8/SVneo cells. These results suggest that Nrf2 activation significantly attenuated BDE-47-induced IL-6 release by augmentation of cellular antioxidative system via upregulation of Nrf2 signaling pathways, and that Nrf2 induction may be a potential therapeutic target to reduce adverse pregnancy outcomes associated with toxicant-induced oxidative stress and inflammation. Copyright © 2014 Elsevier Inc. All rights reserved.

  1. Peace propaganda and biomedical experimentation: influential uses of radioisotopes in endocrinology and molecular genetics in Spain (1947-1971).

    Science.gov (United States)

    Santesmases, María Jesús

    2006-01-01

    A political discourse of peace marked the distribution and use of radioisotopes in biomedical research and in medical diagnosis and therapy in the post-World War II period. This occurred during the era of expansion and strengthening of the United States' influence on the promotion of sciences and technologies in Europe as a collaborative effort, initially encouraged by the policies and budgetary distribution of the Marshall Plan. This article follows the importation of radioisotopes by two Spanish research groups, one in experimental endocrinology and one in molecular biology. For both groups foreign funds were instrumental in the early establishment of their laboratories. The combination of funding and access to previously scarce radioisotopes helped position these groups at the forefront of research in Spain.

  2. CONTINUOUS GLUCOSE MONITORING: A CONSENSUS CONFERENCE OF THE AMERICAN ASSOCIATION OF CLINICAL ENDOCRINOLOGISTS AND AMERICAN COLLEGE OF ENDOCRINOLOGY.

    Science.gov (United States)

    Fonseca, Vivian A; Grunberger, George; Anhalt, Henry; Bailey, Timothy S; Blevins, Thomas; Garg, Satish K; Handelsman, Yehuda; Hirsch, Irl B; Orzeck, Eric A; Roberts, Victor Lawrence; Tamborlane, William

    2016-08-01

    Barriers to continuous glucose monitoring (CGM) use continue to hamper adoption of this valuable technology for the management of diabetes. The American Association of Clinical Endocrinologists and the American College of Endocrinology convened a public consensus conference February 20, 2016, to review available CGM data and propose strategies for expanding CGM access. Conference participants agreed that evidence supports the benefits of CGM in type 1 diabetes and that these benefits are likely to apply whenever intensive insulin therapy is used, regardless of diabetes type. CGM is likely to reduce healthcare resource utilization for acute and chronic complications, although real-world analyses are needed to confirm potential cost savings and quality of life improvements. Ongoing technological advances have improved CGM accuracy and usability, but more innovations in human factors, data delivery, reporting, and interpretation are needed to foster expanded use. The development of a standardized data report using similar metrics across all devices would facilitate clinician and patient understanding and utilization of CGM. Expanded CGM coverage by government and private payers is an urgent need. CGM improves glycemic control, reduces hypoglycemia, and may reduce overall costs of diabetes management. Expanding CGM coverage and utilization is likely to improve the health outcomes of people with diabetes. A1C = glycated hemoglobin AACE = American Association of Clinical Endocrinologists ACE = American College of Endocrinology ASPIRE = Automation to Simulate Pancreatic Insulin Response CGM = continuous glucose monitoring HRQOL = health-related quality of life ICER = incremental cost-effectiveness ratio JDRF = Juvenile Diabetes Research Foundation MARD = mean absolute relative difference MDI = multiple daily injections QALY = quality-adjusted life years RCT = randomized, controlled trial SAP = sensor-augmented pump SMBG = self-monitoring of blood glucose STAR = Sensor

  3. HCMV Infection of Human Trophoblast Progenitor Cells of the Placenta Is Neutralized by a Human Monoclonal Antibody to Glycoprotein B and Not by Antibodies to the Pentamer Complex

    Directory of Open Access Journals (Sweden)

    Martin Zydek

    2014-03-01

    Full Text Available Human cytomegalovirus (HCMV is the major viral cause of congenital infection and birth defects. Primary maternal infection often results in virus transmission, and symptomatic babies can have permanent neurological deficiencies and deafness. Congenital infection can also lead to intrauterine growth restriction, a defect in placental transport. HCMV replicates in primary cytotrophoblasts (CTBs, the specialized cells of the placenta, and inhibits differentiation/invasion. Human trophoblast progenitor cells (TBPCs give rise to the mature cell types of the chorionic villi, CTBs and multi-nucleated syncytiotrophoblasts (STBs. Here we report that TBPCs are fully permissive for pathogenic and attenuated HCMV strains. Studies with a mutant virus lacking a functional pentamer complex (gH/gL/pUL128-131A showed that virion entry into TBPCs is independent of the pentamer. In addition, infection is blocked by a potent human neutralizing monoclonal antibody (mAb, TRL345, reactive with glycoprotein B (gB, but not mAbs to the pentamer proteins pUL130/pUL131A. Functional studies revealed that neutralization of infection preserved the capacity of TBPCs to differentiate and assemble into trophospheres composed of CTBs and STBs in vitro. Our results indicate that mAbs to gB protect trophoblast progenitors of the placenta and could be included in antibody treatments developed to suppress congenital infection and prevent disease.

  4. ACCRETA COMPLICATING COMPLETE PLACENTA PREVIA IS CHARACTERIZED BY REDUCED SYSTEMIC LEVELS OF VASCULAR ENDOTHELIAL GROWTH FACTOR AND EPITHELIAL-TO-MESENCHYMAL TRANSITION OF THE INVASIVE TROPHOBLAST

    Science.gov (United States)

    Wehrum, Mark J.; Buhimschi, Irina A.; Salafia, Carolyn; Thung, Stephen; Bahtiyar, Mert O.; Werner, Erica F.; Campbell, Katherine H.; Laky, Christine; Sfakianaki, Anna K.; Zhao, Guomao; Funai, Edmund F.; Buhimschi, Catalin S.

    2011-01-01

    OBJECTIVE To characterize serum angiogenic factor profile of women with complete placenta previa and determine if invasive trophoblast differentiation characteristic of accreta, increta or percreta shares features of epitehelial-mesenchymal-transition (EMT). STUDY DESIGN We analyzed gestational age matched serum samples from 90 pregnant women with either complete placenta previa (n=45) or uncomplicated pregnancies (n=45). Vascular-endothelial-growth-factor (VEGF), placental-growth-factor (PlGF) and soluble fms-like-tyrosine-kinase-1 (sFlt-1) were immunoassayed. VEGF and phosphotyrosine (P-Tyr) immunoreactivity was surveyed in histological specimens relative to expression of vimentin and cytokeratin-7. RESULTS Women with previa and invasive placentation [accreta (n=5); increta (n=6); percreta (n=2)] had lower systemic VEGF (invasive previa: median [IQR]: 0.8[0.02–3.4] vs. control: 6.5[2.7–10.5] pg/mL, P=0.02). VEGF and P-Tyr immunostaining predominated in the invasive extravillous trophoblasts (EVT) which co-expressed vimentin and cytokeratin-7, a EMT feature and tumor-like cell phenotype. CONCLUSIONS Lower systemic free VEGF and a switch of the interstitial EVT to a metastable cell phenotype characterize placenta previa with excessive myometrial invasion. PMID:21316642

  5. Sulfur-containing heterocyclic compounds with potential antidiabetic activity

    Directory of Open Access Journals (Sweden)

    E. A. Savateeva

    2014-12-01

    Full Text Available The essential link in the pathogenesis of diabetes mellitus and its complications is a non-enzymatic glycosylation of proteins. However, modern endocrinology lacks of clinically effective pharmaceuticals for its correction. The screening of 23 derivatives of 1,3,4-thiadiazine the ability to inhibit the reaction of non-enzymatic glycosylation of proteins in vitro was held, and 11 the most active compounds of them were selected, also the relationship «structure – activity» was investigated. An essential part of the pathogenesis of diabetes mellitus and its complications is non-enzymatic glycosylation of proteins. However, modern endocrinology lacks clinically effective medicines for its correction.

  6. Obstetric ultrasound aids prompt referral of gestational trophoblastic disease in marginalized populations on the Thailand-Myanmar border.

    Science.gov (United States)

    McGregor, Kathryn; Myat Min, Aung; Karunkonkowit, Noaeni; Keereechareon, Suporn; Tyrosvoutis, Mary Ellen; Tun, Nay Win; Rijken, Marcus J; Hoogenboom, Gabie; Boel, Machteld; Chotivanich, Kesinee; Nosten, François; McGready, Rose

    2017-01-01

    The use of obstetric ultrasound in the diagnosis of gestational trophoblastic disease (GTD) in high-income settings is well established, leading to prompt management and high survival rates. Evidence from low-income settings suggests ultrasound is essential in identifying complicated pregnancies, but with limited studies reviewing specific conditions including GTD. The aim of this study is to review the role of ultrasound in diagnosis and management of GTD in a marginalized population on the Thailand-Myanmar border. Antenatal ultrasound became available in this rural setting in 2001 and care for women with GTD has been provided by Thailand public hospitals for 20 years. Retrospective record review. The incidence of GTD was 103 of 57,004 pregnancies in Karen and Burmese women on the Thailand-Myanmar border from 1993-2013. This equates to a rate of 1.8 (95% CI 1.5-2.2) per 1000 or 1 in 553 pregnancies. Of the 102 women with known outcomes, one (1.0%) died of haemorrhage at home. The median number of days between first antenatal clinic attendance and referral to hospital was reduced from 20 (IQR 5-35; range 1-155) to 2 (IQR 2-6; range 1-179) days (p = 0.002) after the introduction of ultrasound. The proportion of severe outcomes (death and total abdominal hysterectomy) was 25% (3/12) before ultrasound compared to 8.9% (8/90) with ultrasound (p = 0.119). A recurrence rate of 2.5% (2/80) was observed in the assessable population. The presence of malaria parasites in maternal blood was not associated with GTD. The rate of GTD in pregnancy in this population is comparable to rates previously reported within South-East Asia. Referral time for uterine evacuation was significantly shorter for those women who had an ultrasound. Ultrasound is an effective method to improve diagnosis of GTD in low-income settings and an effort to increase availability in marginalized populations is required.

  7. Decidual-secreted factors alter invasive trophoblast membrane and secreted proteins implying a role for decidual cell regulation of placentation.

    Directory of Open Access Journals (Sweden)

    Ellen Melaleuca Menkhorst

    Full Text Available Inadequate or inappropriate implantation and placentation during the establishment of human pregnancy is thought to lead to first trimester miscarriage, placental insufficiency and other obstetric complications. To create the placental blood supply, specialized cells, the 'extravillous trophoblast' (EVT invade through the differentiated uterine endometrium (the decidua to engraft and remodel uterine spiral arteries. We hypothesized that decidual factors would regulate EVT function by altering the production of EVT membrane and secreted factors. We used a proteomics approach to identify EVT membrane and secreted proteins regulated by decidual cell factors. Human endometrial stromal cells were decidualized in vitro by treatment with estradiol (10(-8 M, medroxyprogesterone acetate (10(-7 M and cAMP (0.5 mM for 14 days. Conditioned media (CM was collected on day 2 (non-decidualized CM and 14 (decidualized CM of treatment. Isolated primary EVT cultured on Matrigel™ were treated with media control, non-decidualized or decidualized CM for 16 h. EVT CM was fractionated for proteins <30 kDa using size-exclusion affinity nanoparticles (SEAN before trypsin digestion and HPLC-MS/MS. 43 proteins produced by EVT were identified; 14 not previously known to be expressed in the placenta and 12 which had previously been associated with diseases of pregnancy including preeclampsia. Profilin 1, lysosome associated membrane glycoprotein 1 (LAMP1, dipeptidyl peptidase 1 (DPP1/cathepsin C and annexin A2 expression by interstitial EVT in vivo was validated by immunhistochemistry. Decidual CM regulation in vitro was validated by western blotting: decidualized CM upregulated profilin 1 in EVT CM and non-decidualized CM upregulated annexin A2 in EVT CM and pro-DPP1 in EVT cell lysate. Here, non-decidualized factors induced protease expression by EVT suggesting that non-decidualized factors may induce a pro-inflammatory cascade. Preeclampsia is a pro

  8. A randomized controlled pilot trial comparing the impact of access to clinical endocrinology video demonstrations with access to usual revision resources on medical student performance of clinical endocrinology skills.

    Science.gov (United States)

    Hibbert, Emily J; Lambert, Tim; Carter, John N; Learoyd, Diana L; Twigg, Stephen; Clarke, Stephen

    2013-10-03

    Demonstrating competence in clinical skills is key to course completion for medical students. Methods of providing clinical instruction that foster immediate learning and potentially serve as longer-term repositories for on-demand revision, such as online videos demonstrating competent performance of clinical skills, are increasingly being used. However, their impact on learning has been little studied. The aim of this study was to determine the value of adjunctive on-demand video-based training for clinical skills acquisition by medical students in endocrinology. Following an endocrinology clinical tutorial program, 2nd year medical students in the pre-assessment revision period were recruited and randomized to either a set of bespoke on-line clinical skills training videos (TV), or to revision as usual (RAU). The skills demonstrated on video were history taking in diabetes mellitus (DMH), examination for diabetes lower limb complications (LLE), and examination for signs of thyroid disease (TE). Students were assessed on these clinical skills in an observed structured clinical examination two weeks after randomization. Assessors were blinded to student randomization status. For both diabetes related clinical skills assessment tasks, students in the TV group performed significantly better than those in the RAU group. There were no between group differences in thyroid examination performance. For the LLE, 91.7% (n = 11/12) of students randomized to the video were rated globally as competent at the skill compared with 40% (n = 4/10) of students not randomized to the video (p = 0.024). For the DMH, 83.3% (n = 10/12) of students randomized to the video were rated globally as competent at the skill compared with 20% (n = 2/10) of students not randomized to the video (p = 0.007). Exposure to high quality videos demonstrating clinical skills can significantly improve medical student skill performance in an observed structured clinical examination of these skills, when

  9. Practice patterns, satisfaction, and demographics of reproductive endocrinologists: results of the 2014 Society for Reproductive Endocrinology and Infertility Workforce Survey.

    Science.gov (United States)

    Barnhart, Kurt T; Nakajima, Steven T; Puscheck, Elizabeth; Price, Thomas M; Baker, Valerie L; Segars, James

    2016-05-01

    To identify the current and future state of the practice of reproductive medicine. Cross-sectional survey. Not applicable. None. Not applicable. The survey included 57 questions designed to assess practice patterns/metrics and professional satisfaction and morale. A total of 336/1,100 (31%) responded, and they were 38% women, 61% men, and 76% Caucasian, with a mean age of 54. Respondents averaged 2.3 jobs and averaged 53 hours of work per week: 44% work in academia and 50% in private groups. Average practice size was 5.5, with an average of 470 fresh IVF cycles performed per year. Percent effort included 63% infertility, 10% endocrinology, 10% surgery, and 9% research. Respondents performed an average of 13 major surgeries, 69 minor surgeries, and 128 oocyte retrievals per year. A total of 60% were salaried, and 40% were equity partners. Compensation was highly skewed. Greater than 84% had a positive morale and had a positive view of the future, and 92% would again choose REI as a career. The most satisfying areas of employment were patient interactions, intellectual stimulation, interactions with colleagues, and work schedule. The least satisfying areas were work schedule and financial compensation. Training was felt to be too focused on female factor infertility and basic research with insufficient training on embryology, genetics, male factor infertility, and clinical research. In the next 5 years, 57% suggested that the need for specialists would stay the same, while 20% predicted a decrease. A total of 58% felt we are training the correct number of fellows (37% felt we are training a surplus). Compared with academia, those in private practice reported higher compensation, less major surgery, more IVF, less endocrinology, and less research. Men worked more hours, conducted more surgery and IVF cycles, and had higher compensation than women. Morale was similar across age, gender, practice type, and geography. Our subspecialty has an extremely high morale. We

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

    Directory of Open Access Journals (Sweden)

    Barré-Sinoussi Françoise

    2009-05-01

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

  11. Position statement: Gender dysphoria in childhood and adolescence. Working Group on Gender Identity and Sexual Development of the Spanish Society of Endocrinology and Nutrition (GIDSEEN).

    Science.gov (United States)

    Esteva de Antonio, Isabel; Asenjo Araque, Nuria; Hurtado Murillo, Felipe; Fernández Rodríguez, María; Vidal Hagemeijer, Ángela; Moreno-Pérez, Oscar; Lucio Pérez, María Jesús; López Siguero, Juan Pedro

    2015-10-01

    Gender dysphoria (GD) in childhood and adolescence is a complex condition where early detection and comprehensive treatment are essential to improve quality of life, decrease mental comorbidity, and improve GD. In this position statement, the Working Group on Gender Identity and Sexual Development of the Spanish Society of Endocrinology and Nutrition (GIDSEEN), consisting of specialists in Endocrinology, Psychology, Psychiatry, Pediatrics and Sociology, sets out recommendations for evaluation and treatment of GD in children and adolescents. Interdisciplinary management of GD should be carried out at specialized units (UTIGs), considering that any clinical intervention should follow the principles of scientific rigor, experience, ethical and deontological principles, and the necessary caution in front of chronic, aggressive, and irreversible treatments. Copyright © 2015 SEEN. Published by Elsevier España, S.L.U. All rights reserved.

  12. The human leukocyte antigen G promotes trophoblast fusion and β-hCG production through the Erk1/2 pathway in human choriocarcinoma cell lines

    Energy Technology Data Exchange (ETDEWEB)

    Wang, Ji-meng [School of Medicine, Nankai University, Tianjin 300071 (China); State Key Laboratory of Reproductive Biology, Institute of Zoology, Chinese Academy of Sciences, Beijing 100101 (China); Zhao, Hong-xi [Department of Obstetrics and Gynecology, Tangdu Hospital, Fourth Military Medical University, Xi’an 710038 (China); Wang, Li [Department of Obstetrics and Gynecology, General Hospital of Chinese People’s Liberation Army, Beijing 100853 (China); Gao, Zhi-ying, E-mail: gaozy301@yahoo.com.cn [Department of Obstetrics and Gynecology, General Hospital of Chinese People’s Liberation Army, Beijing 100853 (China); Yao, Yuan-qing, E-mail: yqyao@126.com [Department of Obstetrics and Gynecology, General Hospital of Chinese People’s Liberation Army, Beijing 100853 (China)

    2013-05-10

    Highlights: •HLA-G expression promotes BeWo cells fusion and fusogenic gene expression. •HLA-G is capable of inducing β-hCG production in human choriocarcinoma cell lines. •Up-regulation of β-hCG production by HLA-G is mediated via the Erk1/2 pathway. -- Abstract: The human leukocyte antigen G (HLA-G) is expressed on the fetal–maternal interface and plays a role in protecting fetal-derived trophoblasts from the maternal immune response, allowing trophoblasts to invade the uterus. However, HLA-G also possesses immune suppressing-independent functions. We found that HLA-G expressing BeWo choriocarcinoma cells increased cell–cell fusion compared to control BeWo cells under forskolin treatment. Regardless of forskolin treatment, the expression of fusogenic gene mRNAs, including syncytin-1, the transcription factor glial cell missing 1 (Gcm1), and beta human chorionic gonadotropin (β-hCG) were elevated. HLA-G up-regulates β-hCG production in human choriocarcinoma cells because HLA-G knockdown in JEG-3 cells induces a dramatic decrease in β-hCG compared with control cells. The defect in β-hCG production in HLA-G knocked-down cells could not be completely overcome by stimulating hCG production through increasing intracellular cAMP levels. HLA-G expressing cells have increased phosphorylation levels for extracellular signal-regulated kinase1/2 (Erk1/2) in BeWo cells. The Erk1/2 pathway is inactivated after the inhibition of HLA-G expression in JEG-3 cells. Finally, Erk1/2 inhibition was able to suppress the increased hCG production induced by HLA-G expression. Together, these data suggest novel roles for HLA-G in regulating β-hCG production via the modulation of the Erk1/2 pathway and by inducing trophoblast cell fusion.

  13. WHO and national lists of essential medicines in Mexico, Central and South America, and the Caribbean: are they adequate to promote paediatric endocrinology and diabetes care?

    Science.gov (United States)

    Rowlands, Amanda; Acosta-Gualandri, Alejandra; Guevara-Aguirre, Jaime; Chanoine, Jean-Pierre

    2016-01-01

    Paediatric endocrinology and diabetes is a paediatric specialty with less common conditions and higher cost medicines. Access to medicines for our specialty in low and middle income countries remains limited. We analysed the content of the WHO (children and adults) and of all available national Model Lists of Essential Medicines (EMLs) for Mexico, the Caribbean, Central and South America from a paediatric endocrinology and diabetes standpoint. A master list of medicines deemed necessary in paediatric endocrinology and diabetes was established and compared with the WHO and national EMLs, taking into account the gross national income. The WHO EMLs, which are largely recognised as an international benchmark and drive the content of the national EMLs, included many but not all medicines present on our master list. Interestingly, several national EMLs from richer countries included medicines that were not present in the WHO EMLs. Our analysis suggests that these medicines could be considered by the WHO for inclusion in their EMLs, which may promote the adoption of more medicines by individual countries. We also propose several changes to the WHO and national EMLs that could facilitate access to medicines in our specialty: age cut-off for a child using physical maturity rather than a set age limit; greater standardisation of the formatting of the national EMLs for easier comparison and collaborations between countries; greater emphasis on age-specificity and population-specificity for some medicines; and formatting of the EMLs in a disease-focused manner rather than as individual medicines. PMID:28588968

  14. Feasibility and patient acceptability of a novel artificial intelligence-based screening model for diabetic retinopathy at endocrinology outpatient services: a pilot study.

    Science.gov (United States)

    Keel, Stuart; Lee, Pei Ying; Scheetz, Jane; Li, Zhixi; Kotowicz, Mark A; MacIsaac, Richard J; He, Mingguang

    2018-03-12

    The purpose of this study is to evaluate the feasibility and patient acceptability of a novel artificial intelligence (AI)-based diabetic retinopathy (DR) screening model within endocrinology outpatient settings. Adults with diabetes were recruited from two urban endocrinology outpatient clinics and single-field, non-mydriatic fundus photographs were taken and graded for referable DR ( ≥ pre-proliferative DR). Each participant underwent; (1) automated screening model; where a deep learning algorithm (DLA) provided real-time reporting of results; and (2) manual model where retinal images were transferred to a retinal grading centre and manual grading outcomes were distributed to the patient within 2 weeks of assessment. Participants completed a questionnaire on the day of examination and 1-month following assessment to determine overall satisfaction and the preferred model of care. In total, 96 participants were screened for DR and the mean assessment time for automated screening was 6.9 minutes. Ninety-six percent of participants reported that they were either satisfied or very satisfied with the automated screening model and 78% reported that they preferred the automated model over manual. The sensitivity and specificity of the DLA for correct referral was 92.3% and 93.7%, respectively. AI-based DR screening in endocrinology outpatient settings appears to be feasible and well accepted by patients.

  15. Progress in pediatrics in 2013: choices in allergology, endocrinology, gastroenterology, hypertension, infectious diseases, neonatology, neurology, nutrition and respiratory tract illnesses.

    Science.gov (United States)

    Caffarelli, Carlo; Santamaria, Francesca; Vottero, Alessandra; Dascola, Carlotta Povesi; Mirra, Virginia; Sperli, Francesco; Bernasconi, Sergio

    2014-07-12

    This review will provide new information related to pathophysiology and management of specific diseases that have been addressed by selected articles published in the Italian Journal of Pediatrics in 2013, focusing on allergology, endocrinology, gastroenterology, hypertension, infectious diseases, neonatology, neurology, nutrition and respiratory tract illnesses in children. Recommendations for interpretation of skin prick test to foods in atopic eczema, management of allergic conjunctivitis, hypertension and breastfeeding in women treated with antiepileptic drugs and healthy breakfast have been reported. Epidemiological studies have given emphasis to high incidence of autoimmune disorders in patients with Turner syndrome, increasing prevalence of celiac disease, frequency of hypertension in adolescents, incidence and risk factor for retinopathy of prematurity. Advances in prevention include elucidation of the role of probiotics in reducing occurrence of allergies and feeding intolerance, and events of foetal life that influence later onset of diseases. Mechanistic studies suggested a role for vitamin D deficiency in asthma and type 1 diabetes and for reactivation of Varicella-Zoster virus in aseptic meningitis. Regarding diagnosis, a new mean for the diagnosis of hyperbilirubinaemia in newborns, a score for recognition of impaired nutritional status and growth and criteria for early Dyke-Davidoff-Masson Syndrome have been suggested. New therapeutic approaches consist of use of etanercept for reducing insulin dose in type 1 diabetes, probiotics in atopic eczema, and melatonin in viral infections.

  16. MECHANISMS IN ENDOCRINOLOGY: Exogenous insulin does not increase muscle protein synthesis rate when administered systemically: a systematic review.

    Science.gov (United States)

    Trommelen, Jorn; Groen, Bart B L; Hamer, Henrike M; de Groot, Lisette C P G M; van Loon, Luc J C

    2015-07-01

    Though it is well appreciated that insulin plays an important role in the regulation of muscle protein metabolism, there is much discrepancy in the literature on the capacity of exogenous insulin administration to increase muscle protein synthesis rates in vivo in humans. To assess whether exogenous insulin administration increases muscle protein synthesis rates in young and older adults. A systematic review of clinical trials was performed and the presence or absence of an increase in muscle protein synthesis rate was reported for each individual study arm. In a stepwise manner, multiple models were constructed that excluded study arms based on the following conditions: model 1, concurrent hyperaminoacidemia; model 2, insulin-induced hypoaminoacidemia; model 3, supraphysiological insulin concentrations; and model 4, older, more insulin resistant, subjects. From the presented data in the current systematic review, we conclude that: i) exogenous insulin and amino acid administration effectively increase muscle protein synthesis, but this effect is attributed to the hyperaminoacidemia; ii) exogenous insulin administered systemically induces hypoaminoacidemia which obviates any insulin-stimulatory effect on muscle protein synthesis; iii) exogenous insulin resulting in supraphysiological insulin levels exceeding 50, 000  pmol/l may effectively augment muscle protein synthesis; iv) exogenous insulin may have a diminished effect on muscle protein synthesis in older adults due to age-related anabolic resistance; and v) exogenous insulin administered systemically does not increase muscle protein synthesis in healthy, young adults. © 2015 European Society of Endocrinology.

  17. MECHANISMS IN ENDOCRINOLOGY: Kidney involvement in patients with primary hyperparathyroidism: an update on clinical and molecular aspects.

    Science.gov (United States)

    Verdelli, C; Corbetta, S

    2017-01-01

    Primary hyperparathyroidism (PHPT) is the third most common endocrine disease. Kidney is a target of both chronic elevated PTH and calcium in PHPT. The classic PHPT complications of symptomatic kidney stones and nephrocalcinosis have become rare and the PHPT current presentation is asymptomatic with uncertain and long-lasting progression. Nonetheless, the routine use of imaging and of biochemical determinations have revealed the frequent occurrence of asymptomatic kidney stones, hypercalciuria and reduced kidney function in asymptomatic PHPT patients. Though the pathogenesis is far from being elucidated, PHPT is associated with reduced renal function, in terms of estimated glomerular filtration rate, and related increased morbidity and mortality. In the last decade, the effort of the Kidney Disease: Improving Global Outcomes (KDIGO) panel of experts highlighted that even mild reduction of kidney function is associated with increased risk of cardiovascular disease. These considerations provided the basis for the Fourth Workshop recommendations of a more extensive diagnostic workout about kidney features and of wider criteria for parathyroid surgery including asymptomatic kidney disease. Moreover, kidney involvement in PHPT is likely to be affected by variants of genes coding the key molecules regulating the calcium and ions renal handling; these features might have clinical relevance and should be considered both during diagnostic workout and follow-up. Finally, the effects of parathyroid surgery and of medical treatment on kidney involvement of PHPT are reviewed. © 2017 European Society of Endocrinology.

  18. Embryo transfer simulation improves pregnancy rates and decreases time to proficiency in Reproductive Endocrinology and Infertility fellow embryo transfers.

    Science.gov (United States)

    Heitmann, Ryan J; Hill, Micah J; Csokmay, John M; Pilgrim, Justin; DeCherney, Alan H; Deering, Shad

    2017-05-01

    To design and evaluate an ET simulator to train Reproductive Endocrinology and Infertility (REI) fellows' techniques of ET. Simulation model development and retrospective cohort analysis. Not applicable. Patients undergoing IVF. Simulation model evaluation and implementation of ET simulation training. Pregnancy rates. The REI fellow and faculty evaluation responses (n = 19/21 [90%]) of the model demonstrated realistic characteristics, with evaluators concluding the model was suitable for training in almost all evaluated areas. A total of 12 REI fellows who performed ET were analyzed: 6 before ET trainer and 6 after ET trainer. Pregnancy rates were 31% in the initial 10 ETs per fellow before simulator vs. 46% after simulator. One of six pre-ET trainer fellows (17%) had pregnancy rates ≥40% in their first 10 ETs; whereas four of six post-ET trainer fellows had pregnancy rates ≥40% in their first 10 ETs. The average number of ETs to obtain >40% pregnancy efficiency was 27 ETs before trainer vs. 15 ETs after trainer. Pregnancy rates were similar in the two groups after 20 ETs, and collective terminal pregnancy rates were >50% after 40 ETs. Embryo transfer simulation improved REI fellow pregnancy rates in their first 10 transfers and led to a more rapid ET proficiency. These data suggest potential value in adopting ET simulation, even in programs with a robust history of live ET in fellowship training. Published by Elsevier Inc.

  19. Associations Between Waiting Times, Service Times, and Patient Satisfaction in an Endocrinology Outpatient Department: A Time Study and Questionnaire Survey.

    Science.gov (United States)

    Xie, Zhenzhen; Or, Calvin

    2017-01-01

    The issue of long patient waits has attracted increasing public attention due to the negative effects of waiting on patients' satisfaction with health care. The present study examined the associations between actual waiting time, perceived acceptability of waiting time, actual service time, perceived acceptability of service time, actual visit duration, and the level of patient satisfaction with care. We conducted a cross-sectional time study and questionnaire survey of endocrinology outpatients visiting a major teaching hospital in China. Our results show that actual waiting time was negatively associated with patient satisfaction regarding several aspects of the care they received. Also, patients who were less satisfied with the sociocultural atmosphere and the identity-oriented approach to their care tended to perceive the amounts of time they spent waiting and receiving care as less acceptable. It is not always possible to prevent dissatisfaction with waiting, or to actually reduce waiting times by increasing resources such as increased staffing. However, several improvements in care services can be considered. Our suggestions include providing clearer, more transparent information to keep patients informed about the health care services that they may receive, and the health care professionals who are responsible for those services. We also suggest that care providers are encouraged to continue to show empathy and respect for patients, that patients are provided with private areas where they can talk with health professionals and no one can overhear, and that hospital staff treat the family members or friends who accompany patients in a courteous and friendly way.

  20. Dissecting the workforce and workplace for clinical endocrinology, and the work of endocrinologists early in their careers.

    Science.gov (United States)

    Desjardins, Claude; Bach, Mark A; Cappola, Anne R; Seely, Ellen W; Ehrenberg, Ronald G

    2011-04-01

    The United States lacks timely reliable mechanisms for assessing the professional work of subspecialty physicians. The aim was to use early-career members of The Endocrine Society as a model to estimate subspecialty physician involvement in patient care, teaching, research, and administration among clinical, academic, federal, and pharmaceutical/biotech workplaces and to assess the workforce for research within individual workplaces. Physicians joining The Endocrine Society from 1991-2005 and residing in North America were invited to complete a Web-based survey. This report relies on 817 early-career endocrinologists or 29.6% of eligible respondents. Respondents from all types of workplaces engaged in patient care, teaching, research, and administration. The time committed to the four tasks, however, differed significantly among workplaces. Research (basic, translational, disease, patient, population, and prevention) was accomplished within all workplaces, but the scope and scale of investigative work was employer dependent. Recipients of National Institutes of Health K08/23 awards succeeded in receiving federal research project grants (P Women in academic settings earned less than men (P < 0.01) and were less likely to occupy tenure-eligible positions (P < 0.01). Web-based surveys offer a simple tool for estimating the work of subspecialty physicians and provide a framework for improving biomedical investigation. Several interventions should be considered for endocrinology: recruit physicians from underrepresented demographic groups, increase K08/23 awards, incentivize investigative careers, and improve the national infrastructure for biomedical research.

  1. Lapse in embryo transfer training does not negatively affect clinical pregnancy rates for reproductive endocrinology and infertility fellows.

    Science.gov (United States)

    Kresowik, Jessica; Sparks, Amy; Duran, Eyup H; Shah, Divya K

    2015-03-01

    To compare rates of clinical pregnancy (CPR) and live birth (LBR) following embryo transfer (ET) performed by reproductive endocrinology and infertility (REI) fellows before and after a prolonged lapse in clinical training due to an 18-month research rotation. Retrospective cohort study. Not applicable. All women undergoing in vitro fertilization (IVF) and IVF-intracytoplasmic sperm injection (ICSI) cycles with ET performed by REI fellows from August 2003 to July 2012. Eighteen-month lapse in clinical training of REI fellows. CPR and LBR before and after the lapse in clinical training were calculated and compared per fellow and as a composite group. Alternating logistic regression models were used to calculate the odds of clinical pregnancy and live birth following transfers performed before and after the lapse in training. Unadjusted odds of clinical pregnancy and live birth were similar between the two time periods both for individual fellows and for the composite group. Alternate logistic regression analysis revealed no significant difference in CPR (odds ratio [OR] 0.94, 95% confidence interval [CI] 0.83-1.07) or LBR (OR 1.05, 95% CI 0.94-1.18) after the lapse in training compared with before. A research rotation is common in REI fellowship training programs. This prolonged departure from clinical training does not appear to negatively affect pregnancy outcome following fellow ET. Copyright © 2015 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.

  2. Progress in pediatrics in 2011. Choices in endocrinology, gastroenterology, hemato-oncology, infectious diseases, otolaryngology, pharmacotherapy and respiratory tract illnesses

    Directory of Open Access Journals (Sweden)

    Caffarelli Carlo

    2012-06-01

    Full Text Available Abstract Main progresses in endocrinology, gastroenterology, hemato-oncology, infectious diseases, otolaryngology, pharmacotherapy, and respiratory tract illnesses selected from articles published in The Italian Journal of Pediatrics in 2011 were reviewed. Risk factors for gastroenteritis and appendicitis in developing countries may be useful in improving our understanding of these diseases. Childhood hearing impairment is a world-wide problem which continues to have an high prevalence in newborns. Among the mechanisms of diseases, obese children often have asthma and high hepcidin levels that may reduce serum iron concentrations. In cystic fibrosis, 18q distal deletion has been described as a novel mutation. Hypothyroidism in children with central nervous system infections may increase mortality rates. Infrared tympanic thermometer (IRTT in oral mode for the measurement of body temperature may be useful in fever screening in a busy setup. In newborns, the transmission of CMV infection through breast milk may be prevented through freezing or pasteurization. Recent advances in treatment of constipation, urinary tract infections, leukemia, pain in children with cancer, neonates with sepsis or difficult weaning from mechanical ventilation will likely contribute towards optimizing management of these common disorders. The work of the Family Pediatricians Medicines for Children Research Network aims to develop competence, infrastructure, networking and education for pediatric clinical trials.

  3. MECHANISMS IN ENDOCRINOLOGY: Neurodevelopmental disorders in children born to mothers with thyroid dysfunction: evidence of fetal programming?

    Science.gov (United States)

    Andersen, Stine Linding; Carlé, Allan; Karmisholt, Jesper; Pedersen, Inge Bülow; Andersen, Stig

    2017-07-01

    Fetal programming is a long-standing, but still evolving, concept that links exposures during pregnancy to the later development of disease in the offspring. A fetal programming effect has been considered within different endocrine axes and in relation to different maternal endocrine diseases. In this critical review, we describe and discuss the hypothesis of fetal programming by maternal thyroid dysfunction in the context of fetal brain development and neurodevelopmental disorders in the offspring. Thyroid hormones are important regulators of early brain development, and evidence from experimental and observational human studies have demonstrated structural and functional abnormalities in the brain caused by the lack or excess of thyroid hormone during fetal brain development. The hypothesis that such abnormalities introduced during early fetal brain development increase susceptibility for the later onset of neurodevelopmental disorders in the offspring is biologically plausible. However, epidemiological studies on the association between maternal thyroid dysfunction and long-term child outcomes are observational in design, and are challenged by important methodological aspects. © 2017 European Society of Endocrinology.

  4. Mechanisms in endocrinology: the crosstalk between thyroid gland and adipose tissue: signal integration in health and disease.

    Science.gov (United States)

    Santini, Ferruccio; Marzullo, Paolo; Rotondi, Mario; Ceccarini, Giovanni; Pagano, Loredana; Ippolito, Serena; Chiovato, Luca; Biondi, Bernadette

    2014-10-01

    Obesity and thyroid diseases are common disorders in the general population and they frequently occur in single individuals. Alongside a chance association, a direct relationship between 'thyroid and obesity' has been hypothesized. Thyroid hormone is an important determinant of energy expenditure and contributes to appetite regulation, while hormones and cytokines from the adipose tissue act on the CNS to inform on the quantity of energy stores. A continuous interaction between the thyroid hormone and regulatory mechanisms localized in adipose tissue and brain is important for human body weight control and maintenance of optimal energy balance. Whether obesity has a pathogenic role in thyroid disease remains largely a matter of investigation. This review highlights the complexity in the identification of thyroid hormone deficiency in obese patients. Regardless of the importance of treating subclinical and overt hypothyroidism, at present there is no evidence to recommend pharmacological correction of the isolated hyperthyrotropinemia often encountered in obese patients. While thyroid hormones are not indicated as anti-obesity drugs, preclinical studies suggest that thyromimetic drugs, by targeting selected receptors, might be useful in the treatment of obesity and dyslipidemia. © 2014 European Society of Endocrinology.

  5. Radioisotopic methods of investigation in endocrinology. Radioizotopnye metody issledovaniya v endokrinologii

    Energy Technology Data Exchange (ETDEWEB)

    Malenchenko, A F; Matveenko, E G; Livshits, I B; Seregin, V V; Spesivtseva, V G

    1976-01-01

    A description is given of research on iodine metabolism both under normal and pathological conditions employing the method of clinical dynamic radiometry. Possible uses of radioisotopes are indicated for evaluating the function of the parathyroid glands, the pancreas, and the pituitary-adrenal system. Data are given on the practical use of radio-immune, radio-receptor methods as well as the competitive bonding method for determining a number of hormonal and other biologically active metabolites and substances with low antigen activity in various pathological states both clinically and in experiments. The use of neutron-activation methods in biology and medicine is demonstrated. The book is intended for endocrinologists, biologists, and scientific associates interested in the study of the functional state of endocrine glands by radioisotopic methods. 46 figures, 16 tables.

  6. Protective effect of nuclear factor E2-related factor 2 on inflammatory cytokine response to brominated diphenyl ether-47 in the HTR-8/SVneo human first trimester extravillous trophoblast cell line

    International Nuclear Information System (INIS)

    Park, Hae-Ryung; Loch-Caruso, Rita

    2014-01-01

    Polybrominated diphenyl ethers (PBDEs) are widely used flame retardants, and BDE-47 is a prevalent PBDE congener detected in human tissues. Exposure to PBDEs has been linked to adverse pregnancy outcomes in humans. Although the underlying mechanisms of adverse birth outcomes are poorly understood, critical roles for oxidative stress and inflammation are implicated. The present study investigated antioxidant responses in a human extravillous trophoblast cell line, HTR-8/SVneo, and examined the role of nuclear factor E2-related factor 2 (Nrf2), an antioxidative transcription factor, in BDE-47-induced inflammatory responses in the cells. Treatment of HTR-8/SVneo cells with 5, 10, 15, and 20 μM BDE-47 for 24 h increased intracellular glutathione (GSH) levels compared to solvent control. Treatment of HTR-8/SVneo cells with 20 μM BDE-47 for 24 h induced the antioxidant response element (ARE) activity, indicating Nrf2 transactivation by BDE-47 treatment, and resulted in differential expression of redox-sensitive genes compared to solvent control. Pretreatment with tert-butyl hydroquinone (tBHQ) or sulforaphane, known Nrf2 inducers, reduced BDE-47-stimulated IL-6 release with increased ARE reporter activity, reduced nuclear factor kappa B (NF-κB) reporter activity, increased GSH production, and stimulated expression of antioxidant genes compared to non-Nrf2 inducer pretreated groups, suggesting that Nrf2 may play a protective role against BDE-47-mediated inflammatory responses in HTR-8/SVneo cells. These results suggest that Nrf2 activation significantly attenuated BDE-47-induced IL-6 release by augmentation of cellular antioxidative system via upregulation of Nrf2 signaling pathways, and that Nrf2 induction may be a potential therapeutic target to reduce adverse pregnancy outcomes associated with toxicant-induced oxidative stress and inflammation. - Highlights: • BDE-47 stimulated ARE reporter activity and GSH production. • BDE-47 resulted in differential

  7. Protective effect of nuclear factor E2-related factor 2 on inflammatory cytokine response to brominated diphenyl ether-47 in the HTR-8/SVneo human first trimester extravillous trophoblast cell line

    Energy Technology Data Exchange (ETDEWEB)

    Park, Hae-Ryung, E-mail: heaven@umich.edu; Loch-Caruso, Rita

    2014-11-15

    Polybrominated diphenyl ethers (PBDEs) are widely used flame retardants, and BDE-47 is a prevalent PBDE congener detected in human tissues. Exposure to PBDEs has been linked to adverse pregnancy outcomes in humans. Although the underlying mechanisms of adverse birth outcomes are poorly understood, critical roles for oxidative stress and inflammation are implicated. The present study investigated antioxidant responses in a human extravillous trophoblast cell line, HTR-8/SVneo, and examined the role of nuclear factor E2-related factor 2 (Nrf2), an antioxidative transcription factor, in BDE-47-induced inflammatory responses in the cells. Treatment of HTR-8/SVneo cells with 5, 10, 15, and 20 μM BDE-47 for 24 h increased intracellular glutathione (GSH) levels compared to solvent control. Treatment of HTR-8/SVneo cells with 20 μM BDE-47 for 24 h induced the antioxidant response element (ARE) activity, indicating Nrf2 transactivation by BDE-47 treatment, and resulted in differential expression of redox-sensitive genes compared to solvent control. Pretreatment with tert-butyl hydroquinone (tBHQ) or sulforaphane, known Nrf2 inducers, reduced BDE-47-stimulated IL-6 release with increased ARE reporter activity, reduced nuclear factor kappa B (NF-κB) reporter activity, increased GSH production, and stimulated expression of antioxidant genes compared to non-Nrf2 inducer pretreated groups, suggesting that Nrf2 may play a protective role against BDE-47-mediated inflammatory responses in HTR-8/SVneo cells. These results suggest that Nrf2 activation significantly attenuated BDE-47-induced IL-6 release by augmentation of cellular antioxidative system via upregulation of Nrf2 signaling pathways, and that Nrf2 induction may be a potential therapeutic target to reduce adverse pregnancy outcomes associated with toxicant-induced oxidative stress and inflammation. - Highlights: • BDE-47 stimulated ARE reporter activity and GSH production. • BDE-47 resulted in differential

  8. The African catfish, Clarias gariepinus, a model for the study of reproductive endocrinology in teleosts

    NARCIS (Netherlands)

    Oordt, P.G.W.J. van; Goos, H.J.Th.

    1987-01-01

    In their natural habitat African catfish, Clarias gariepinus, show a discontinuous reproductive cycle. This cycle follows changes in the gonadotropic activity of the pituitary. Gonadotropin release has been shown to be under dual hypothalamic control, i.e. a gonadotropin-releasing hormone (GnRH) and

  9. Utilizing a Rat Delayed Implantation Model to Teach Integrative Endocrinology and Reproductive Biology

    Science.gov (United States)

    Geisert, Rodney D.; Smith, Michael F.; Schmelzle, Amanda L.; Green, Jonathan A.

    2018-01-01

    In this teaching laboratory, the students are directed in an exercise that involves designing and performing an experiment to determine estrogen's role in regulating delayed implantation (diapause) in female rats. To encourage active participation by the students, a discussion question is provided before the laboratory exercise in which each…

  10. Reading Habits of Third-Year Medical Students during an Integrated Endocrinology Course.

    Science.gov (United States)

    Friedberg, Mark; Mahanaimi, David; Lev-Zion, Rafael; Sidi, Aviel; Glick, Shimon

    1998-01-01

    Independent reading by medical students beyond formal classroom activities is considered central to medical education. This study examines self-directed study among third-year students in a six-year medical program. Students averaged 151 minutes daily on independent study using lecture notes, textbooks, and reading articles. Suggests ways to…

  11. An investigative study into psychological and fertility sequelae of gestational trophoblastic disease: the impact on patients' perceived fertili